Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial.

BACKGROUND & AIMS: Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We investigated the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least 4 red blood cell (RBC) units or parental iron infusions, or both, in the year preceding randomization. Patients were allocated (1:1) to 40-mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was 1 year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least 1 octreotide injection or followed standard of care for at least 1 month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up. RESULTS: We enrolled 62 patients (mean age, 72 years; 32 men) from 17 Dutch hospitals in the octreotide (n = 31) and standard of care (n = 31) groups. Patients required a mean number of 20.3 (standard deviation, 15.6) transfusion units and 2.4 (standard deviation, 2.0) endoscopic procedures in the year before enrollment. The total number of transfusions was lower with octreotide (11.0; 95% confidence interval [CI], 5.5-16.5) compared with standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5). CONCLUSIONS: Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia. CLINICALTRIALS: gov, NCT02384122.

A Prediction Model for Successful Increase of Adalimumab Dose Intervals in Patients with Crohn's Disease: Secondary Analysis of the Pragmatic Open-Label Randomised Controlled Non-inferiority LADI Trial.

BACKGROUND: In the pragmatic open-label randomised controlled non-inferiority LADI trial we showed that increasing adalimumab (ADA) dose intervals was non-inferior to conventional dosing for persistent flares in patients with Crohn's disease (CD) in clinical and biochemical remission. AIMS: To develop a prediction model to identify patients who can successfully increase their ADA dose interval based on secondary analysis of trial data. METHODS: Patients in the intervention group of the LADI trial increased ADA intervals to 3 and then to 4 weeks. The dose interval increase was defined as successful when patients had no persistent flare (> 8 weeks), no intervention-related severe adverse events, no rescue medication use during the study, and were on an increased dose interval while in clinical and biochemical remission at week 48. Prediction models were based on logistic regression with relaxed LASSO. Models were internally validated using bootstrap optimism correction. RESULTS: We included 109 patients, of which 60.6% successfully increased their dose interval. Patients that were active smokers (odds ratio [OR] 0.90), had previous CD-related intra-abdominal surgeries (OR 0.85), proximal small bowel disease (OR 0.92), an increased Harvey-Bradshaw Index (OR 0.99) or increased faecal calprotectin (OR 0.997) were less likely to successfully increase their dose interval. The model had fair discriminative ability (AUC = 0.63) and net benefit analysis showed that the model could be used to select patients who could increase their dose interval. CONCLUSION: The final prediction model seems promising to select patients who could successfully increase their ADA dose interval. The model should be validated externally before it may be applied in clinical practice. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, number NCT03172377.

The added value of predictive biomarkers in treat-to-target strategies for rheumatoid arthritis patients: a conceptual modelling study.

OBJECTIVES: To quantify the additional value of a hypothetical biomarker predicting response to treatment for RA regarding efficacy and costs by using a modelling design. METHODS: A Markov model was built comparing a usual care T2T strategy with a biomarker-steered strategy for RA patients starting biologic therapy. Outcome measures include time spent in remission or low disease activity (LDA) and costs. Four additional scenario analyses were performed by varying biomarker or clinical care characteristics: (i) costs of the biomarker; (ii) sensitivity and specificity of the biomarker; (iii) proportion of eligible patients tapering; and (iv) medication costs. RESULTS: In the base model, patients spent 2.9 months extra in LDA or remission in the biomarker strategy compared with usual care T2T over 48 months. Total costs were €43 301 and €42 568 for, respectively, the usual care and biomarker strategy, and treatment costs accounted for 91% of total costs in both scenarios. Cost savings were driven due to patients in the biomarker strategy experiencing remission or LDA earlier, and starting tapering sooner. Cost-effectiveness was not so much driven by costs or test characteristics of the biomarker (scenario 1/2), but rather by the level of early and proactive tapering and drug costs (scenarios 3/4). CONCLUSIONS: The use of a biomarker for prediction of response to b/tsDMARD treatment in RA can be of added value to current treat-to-target clinical care. However, gains in efficacy are modest and cost gains are depending on a combination of early proactive tapering and high medication costs.

Patient-preferred outcomes in patients with vestibular schwannoma: a qualitative content analysis of symptoms, side effects and their impact on health-related quality of life.

PURPOSE: During counseling and management of patients with vestibular schwannoma (VS), the emphasis is shifting from tumour control and nerve preservation towards maintaining or improving health-related quality of life (HRQoL). Understanding the patients' perspective and impact of VS is, therefore, of utmost importance. The current study aimed to identify treatment outcomes preferred by patients and to explore the patient-reported VS symptoms and management-related side effects and their impact on HRQoL. METHODS: Patients with VS were contacted through the Dutch VS association Stichting Hoormij and questioned using a semi-structured, cross-sectional online survey. Patients were asked to report and rank symptoms and side effects, with their impact on HRQoL and frequency of occurrence. Results were structured through qualitative content analysis. Coded symptoms, side effects, impacts, frequencies, and patient-preferred outcomes were analysed and summarized with descriptive statistics. RESULTS: Of the 231 respondents, 71% were actively treated. Hearing (symptoms vs. side effects: 78.8% vs. 63.6%), balance (62.3%; 48.8%), and energy issues (33.8%; 32.6%) were the most frequently mentioned symptoms and management-related side effects. Fatigue, deafness, headaches, and hearing loss had the highest impact on HRQoL. The majority of patients identified hearing preservation (61%), balance preservation (38.5%), and reduced tinnitus (34.6%) to be the patient-preferred outcomes. CONCLUSION: This qualitative study demonstrates that in this population many patients with VS encounter participation difficulties in their daily physical and social activities and value hearing and balance preservation, reduced tinnitus, and restored energy as preferred outcomes as they are hampered by symptoms and side effects related to hearing, balance, and energy. Healthcare professionals should consider these key points and use these and the patient-preferred outcomes in consultation, shared decision making, treatment, and follow-up to optimize patient-centred care.

A first exploration of the economic consequences of an autonomous surgical robot for lateral skull base surgery: an early health technology assessment.

OBJECTIVES: Lateral skull base procedures, such as translabyrinthine approach (TLA), are challenging. An autonomous surgical robot might be a solution to these challenges. Our aim is to explore in an early phase the economic consequences of an autonomous surgical robot compared with conventional TLA. METHODS: An early decision analytic model was constructed in order to perform a step-wise threshold analyses and a sensitivity analysis to analyze the impact of the several factors on the incremental costs. RESULTS: Using surgical robot results in incremental costs - EUR 5,562 per procedure - compared to conventional TLA. These costs are most reduced by higher number of procedures, followed by lower price of the robot, saved operation time, and reduced risk of complication, respectively. CONCLUSIONS: The incremental costs of using an autonomous surgical robot can be decreased by choosing applications with a high turnover rate, a long operation time, and a high complication rate.

The potential of individualized dosing of ravulizumab to improve patient-friendliness of paroxysmal nocturnal haemoglobinuria treatment at reduced costs.

Ravulizumab is a very expensive complement C5-inhibitor for the treatment of paroxysmal nocturnal haemoglobinuria, with a fixed-dosing interval of 8 weeks. For lifelong treatment, a cost-effective and patient-friendly dosing strategy is preferred. We therefore explored alternative ravulizumab dosing regimens in silico based on the thorough dose-finding studies of the manufacturer. Extending the interval to 10 weeks or individually extending the interval to a mean of 12.8 weeks based on pharmacokinetic monitoring resulted in noninferior efficacy in terms of lactate dehydrogenase normalization, with drug cost savings up to 37%. We here show the potential of individualized ravulizumab dosing to improve patient-friendliness at reduced costs.

What determines quality of life in patients with vestibular schwannoma?

OBJECTIVES: Patients with a vestibular schwannoma (VS) experience a reduced quality of life (QoL). The main objective of this study was to determine the strongest predictors reducing physical and mental QoL from the disease-specific Penn Acoustic Neuroma Quality of Life (PANQOL) questionnaire in patients with VS. DESIGN: Observational study. SETTING: Radboudumc Skull Base Centre, Nijmegen. PARTICIPANTS: Patients newly diagnosed with VS between 2014 and 2017 managed with either observation, stereotactic radiosurgery or microsurgery. MAIN OUTCOME MEASURES: Quality of life was assessed using the disease-specific PANQOL and general Short-Form (36) Health Survey (SF-36). Multiple linear regression models with PANQOL domains as predictors were used to determine the strongest predictors for SF-36 QoL physical and mental health scores. Standardised beta coefficients (ß) were used for ranking. RESULTS: A total of 174 patients (50% females, mean age 58.9 years) returned the questionnaires, providing a 69% response rate. Fifteen patients (9%) were treated with microsurgery, 29 (17%) with stereotactic radiosurgery and 130 patients (75%) were observed in a wait and scan strategy. A lack of energy (ß = .28; P ≤ .001), lower general health (ß = .22; P ≤ .001), headache (ß = .16; P ≤ .001), anxiety (ß = .15; P ≤ .001) and balance problems (ß = .10; P ≤ .001) are the strongest predictors affecting physical health, while mental health is most affected by anxiety (ß = .37; P ≤ .001), a lack of energy (ß = .34; P ≤ .001), facial nerve dysfunction (ß = .07; P ≤ .001), balance problems (ß = .04; P ≤ .001) and headaches (ß = .04; P ≤ .001). CONCLUSION: A lack of energy, anxiety, headache and balance problems are the strongest predictors of both SF-36 physical and mental QoL in patients with VS. More awareness and supportive care regarding energy, anxiety, headache and balance in informing, evaluating and treating patients with VS could improve QoL.

Lanreotide Reduces Liver Growth In Patients With Autosomal Dominant Polycystic Liver and Kidney Disease.

BACKGROUND & AIMS: Polycystic liver disease is the most common extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). There is need for robust long-term evidence for the volume-reducing effect of somatostatin analogues. We made use of data from an open-label, randomized trial to determine the effects of lanreotide on height-adjusted liver volume (hTLV) and combined height-adjusted liver and kidney volume (hTLKV) in patients with ADPKD. METHODS: We performed a 120-week study comparing the reno-protective effects of lanreotide vs standard care in 305 patients with ADPKD (the DIPAK-1 study). For this analysis, we studied the 175 patients with polycystic liver disease with hepatic cysts identified by magnetic resonance imaging and liver volume ≥2000 mL. Of these, 93 patients were assigned to a group that received lanreotide (120 mg subcutaneously every 4 weeks) and 82 to a group that received standard care (blood pressure control, a sodium-restricted diet, and antihypertensive agents). The primary endpoint was percent change in hTLV between baseline and end of treatment (week 120). A secondary endpoint was change in hTLKV. RESULTS: At 120 weeks, hTLV decreased by 1.99% in the lanreotide group (95% confidence interval [CI], -4.21 to 0.24) and increased by 3.92% in the control group (95% CI, 1.56-6.28). Compared with the control group, lanreotide reduced the growth of hTLV by 5.91% (95% CI, -9.18 to -2.63; P < .001). Growth of hTLV was still reduced by 3.87% at 4 months after the last injection of lanreotide compared with baseline (95% CI, -7.55 to -0.18; P = .04). Lanreotide reduced growth of hTLKV by 7.18% compared with the control group (95% CI, -10.25 to -4.12; P < .001). CONCLUSIONS: In this subanalysis of a randomized trial of patients with polycystic liver disease due to ADPKD, lanreotide for 120 weeks reduced the growth of liver and combined liver and kidney volume. This effect was still present 4 months after the last injection of lanreotide. ClinicalTrials.gov, Number: NCT01616927.

Health Economic Consequences of a Tightly Controlled Dose Reduction Strategy for Adalimumab, Etanercept and Ustekinumab Compared with Standard Psoriasis Care: A Cost-utility Analysis of the CONDOR Study.

A dose reduction strategy for adalimumab, etanercept and ustekinumab in patients with psoriasis who have stable and low disease activity has recently been compared with usual care in the CONDOR study (CONtrolled DOse Reduction) of biologics in patients with psoriasis with low disease activity. The aim of the current study was to perform a cost-utility analysis with a 12-month time horizon alongside this trial, using prospectively measured healthcare costs and quality-adjusted life years, based on Short-Form Six-Dimension utilities. Bootstrap analys-es were used to calculate the decremental cost-utility ratio and the incremental net monetary benefit. The dose reduction strategy resulted in a mean cost saving of €3,820 (95th percentile -€3,099 to -€4,509) per patient over a period of 12 months. There was an 83% chance that dose reduction would result in a reduction in quality adjusted life years (mean -0.02 (95th percentile -0.06 to 0.02). In conclusion, dose reduction of biologics resulted in substantial cost savings with an acceptable reduction in quality of life.

Incidence of Progression of Persistent Nondysplastic Barrett's Esophagus to Malignancy.

BACKGROUND & AIMS: The risk of esophageal adenocarcinoma (EAC) in patients with non-dysplastic Barrett's esophagus (NDBE) is low, so there is debate over the role of ongoing surveillance for patients with NDBE. It is important to identify patients at low risk for progression. We assessed cancer risk based on the subsequent number of endoscopies showing persistence of NDBE in a nationwide study in the Netherlands. METHODS: In a population-based study, patients with a first diagnosis of NDBE were selected from the Dutch nationwide registry of histopathology. We calculated incidence rates and incidence rate ratios (IRR) for high-grade dysplasia (HGD) and EAC to determine whether the number of endoscopies negative for dysplasia and the persistence of NDBE over time associate with progression to malignancy. RESULTS: We identified 12,728 patients with NDBE during 2003 and 2013. HGD or EAC developed in 436 patients (3.4%) during 64,537 person-years of follow up (median, 4.9 years). The rate of progression to HGD or EAC was 0.68 (95% CI, 0.61-0.74) per 100 person-years. In patients with 2 consecutive endoscopies showing NDBE, the rate of progression to HGD or EAC decreased to 0.55 (95% CI, 0.46-0.64) per 100 person-years (IRR, 0.72; 95% CI, 0.60-0.87). Overall, the incidence of HGD or EAC decreased by 14% for each year of progression-free follow-up (IRR, 0.86; 95% CI, 0.81-0.92). CONCLUSION: In a population-based study in the Netherlands, we found patients with stable NDBE to have a low risk of progression to HGD or EAC. These findings indicate that surveillance intervals might be lengthened or even discontinued in subgroups patients with persistent NDBE.

An economic model of the cost-utility of pre-emptive genetic testing to support pharmacotherapy in patients with major depression in primary care.

The pharmacokinetics of many antidepressants (tricyclic antidepressants (TCA) or selective serotonin re-uptake inhibitors (SSRI)) are influenced by the highly polymorphic CYP2D6 enzyme. Therefore, pharmacogenetics could play an important role in the treatment of depressive patients. The potential cost-utility of screening patients is however still unknown. Therefore, a Markov model was developed to compare the strategy of screening for CYP2D6 and subsequently adjust antidepressant treatment according to a patient's metabolizer profile of poor, extensive, or ultra metabolizer, with the strategy of no screening ('one size fits all' principle). Each week a patient had a probability of side effects, which was followed by dosage titration or treatment switching. After 6 weeks treatment effect was evaluated followed by treatment adjustments if necessary, with a total time horizon of the model of 12 weeks. The analysis was performed from a societal perspective. The strategy of screening compared with no screening resulted in incremental costs of €91 (95 percentiles: €39; €152) more expensive but also more effect with 0.001 quality adjusted life years (QALYs) (95 percentiles: 0.001; 0.002) gain. The incremental cost-effectiveness ratio (ICER) was therefore €77,406 per QALY gained, but varied between €22,500 and €377,500 depending on the price of screening and productivity losses. According to our model, we cannot unequivocally conclude that screening for CYP2D6 in primary care patients using antidepressants is be cost-effective, as the results are surrounded by large uncertainty. Therefore, information from ongoing studies should be used to reduce these uncertainties.

Long-term efficacy and cost-effectiveness of blended cognitive behavior therapy for high fear of recurrence in breast, prostate and colorectal Cancer survivors: follow-up of the SWORD randomized controlled trial.

BACKGROUND: Blended cognitive behaviour therapy (bCBT) is an effective treatment for fear of cancer recurrence (FCR) in curatively-treated breast, colorectal and prostate cancer survivors with high FCR. However, long-term outcomes are unknown. This study investigated the long-term efficacy and cost-effectiveness of bCBT compared with care as usual (CAU). METHODS: Eighty-eight cancer survivors with high FCR (Cancer Worry Scale ≥14) were randomly assigned to bCBT (n = 45) or CAU (n = 43). Data were collected at baseline and at three, nine and fifteen months from baseline and analysed by modified intention-to-treat. Efficacy was investigated with linear mixed-effects models. Cost-effectiveness was investigated from a societal perspective by comparing costs with quality-adjusted life-years (QALYs). RESULTS: Participants who received bCBT reported significantly lower FCR compared with CAU (mean difference of - 1.787 [95% CI -3.251 to - 0.323, p = 0.017] at 15 months follow-up), and proportionally greater self-rated and clinically significant improvement at each follow-up measurement. Total QALYs were non-significantly different between conditions when adjusted for utility score baseline differences (0.984 compared to 0.957, p = 0.385), while total costs were €631 lower (95% CI -1737 to 2794, p = 0.587). Intervention costs of bCBT were €466. The incremental cost-effectiveness ratio amounted to an additional €2049 per QALY gained, with a 62% probability that bCBT is cost-effective at a willingness to pay (WTP) threshold of €20,000 per QALY. Results were confirmed in sensitivity analyses. CONCLUSIONS: bCBT for cancer survivors with FCR is clinically and statistically more effective than CAU on the long-term. In addition, bCBT is a relatively inexpensive intervention with similar costs and QALYs as CAU. TRIAL REGISTRATION: The RCT was registered in the Dutch National Trial Register ( NTR4423 ) on 12-Feb-2014. This abstract was previously presented at the International Psycho-Oncology Society conference of 2018 and published online. (Psycho-oncology, 27(S3):8-55; 2018).

Endosheath ultrathin transnasal endoscopy is a cost-effective method for screening for Barrett's esophagus in patients with GERD symptoms.

BACKGROUND AND AIMS: Barrett's esophagus (BE) screening is currently not considered to be cost effective in the general population but may be effective in high-risk subgroups, such as 50-year-old white men with chronic reflux disease (GERD). A new modality for screening is unsedated transnasal endoscopy using endosheath technology (uTNE), which has been shown to be safe and effective in clinical practice. In this study, we determined the cost-utility of uTNE in a high-risk subgroup compared with no screening or screening with standard endoscopy. METHODS: A Markov model was used to simulate screening of 50-year-old white men with symptoms of GERD with either uTNE or standard endoscopy compared with no screening, over a lifetime horizon. Input variables were based on the literature and recent data on uTNE screening for BE. The study was designed from a healthcare payer perspective by using direct costs. Primary outcome measures were costs, quality-adjusted life years (QALYs), and the incremental cost-utility ratio (ICUR) of uTNE and standard endoscopy compared with no screening. Sensitivity analysis was performed for several factors, such as prevalence of BE. RESULTS: Costs of uTNE, standard endoscopy, and no screening were estimated at, $2495, $2957, and $1436, respectively. Compared with no screening, uTNE screening resulted in an overall QALY increase of 0.039 (95% percentile 0.018; 0.063) and an ICUR of $29,446 per QALY gained (95% confidence interval [CI], 18.516-53.091), whereas standard endoscopy compared with no screening resulted in a QALY increase of 0.034 (95% CI, 0.015-0.056) and an ICUR of $47,563 (95% CI, 31,036-82,970). CONCLUSION: Both uTNE and standard endoscopy seem to be cost-effective screening methods in a screening cohort of 50-year-old white men with GERD at a willingness-to-pay cutoff of $50,000.

A novel device for intracolonoscopy cleansing of inadequately prepared colonoscopy patients: a feasibility study.

BACKGROUND: The importance of high quality preprocedural bowel preparation is widely acknowledged, but suboptimal bowel cleansing still occurs in up to 20 % of all colonoscopy patients. The aim of this study was to evaluate the performance of a novel intraprocedural cleaning device for cleaning poorly prepared colons. METHODS: This multicenter feasibility study included patients aged 18 - 75 years who were referred for colonoscopy. Intraprocedural cleaning was performed in patients after a limited preprocedural bowel preparation regimen (2 days of dietary restrictions and 2 × 10 mg bisacodyl). The primary outcome was the proportion of adequately prepared patients (Boston Bowel Preparation scale [BBPS] ≥ 2 in each segment) before and after segmental washing with the new device. Secondary outcomes included: cecal intubation rate, procedure time, system usability, patient satisfaction, and safety. RESULTS: 47 patients (42.6 % male), with a median age of 61 years (interquartile range [IQR] 46 - 67 years), were included at three clinical sites. Cecal intubation was achieved in 46/47 patients (97.9 %). The cleaning device significantly improved the proportion of patients with adequate bowel cleansing (from 19.1 % to 97.9 %; P < 0.001) and median BBPS score (from 3.0 [IQR 0.0 - 5.0] to 9.0 [IQR 8.0 - 9.0]). Median cecal intubation time and total procedure time were 16.5 minutes (IQR 9.0-28.3) and 34.0 minutes (IQR 25.0 - 42.8), respectively. Physicians were satisfied with the ease of use of the device and it was well tolerated by patients. No severe adverse events occurred during the study period. CONCLUSIONS: This feasibility study suggests that the intraprocedural cleaning device appears to be safe and effective in cleaning poorly prepared colons to an adequate level, allowing a thorough colorectal examination.

Severity in polycystic liver disease is associated with aetiology and female gender: Results of the International PLD Registry.

BACKGROUND & AIMS: Polycystic liver disease (PLD) occurs in two genetic disorders, autosomal-dominant polycystic kidney disease (ADPKD) and autosomal-dominant polycystic liver disease (ADPLD). The aim of this study is to compare disease severity between ADPKD and ADPLD by determining the association between diagnosis and height-adjusted total liver volume (hTLV). METHODS: We performed a cross-sectional analysis with hTLV as endpoint. Patients were identified from the International PLD Registry (>10 liver cysts) and included in our analysis when PLD diagnosis was made prior to September 2017, hTLV was available before volume-reducing therapy (measured on computed tomography or magnetic resonance imaging) and when patients were tertiary referred. Data from the registry were retrieved for age, diagnosis (ADPKD or ADPLD), gender, height and hTLV. RESULTS: A total of 360 patients (ADPKD n = 241; ADPLD n = 119) met our inclusion criteria. Female ADPKD patients had larger hTLV compared with ADPLD (P = 0.008). In a multivariate regression analysis, ADPKD and lower age at index CT were independently associated with larger hTLV in females, whereas in males a higher age was associated with larger hTLV. Young females (≤51 years) had larger liver volumes compared with older females (>51 years) in ADPKD. CONCLUSION: Aetiology is presented as a new risk factor associated with PLD severity. Young females with ADPKD represent a subgroup of PLD patients with the most severe phenotype expressed in hTLV.

Symptom relief and not cyst reduction determines treatment success in aspiration sclerotherapy of hepatic cysts.

OBJECTIVE: To assess whether quantitative assessment of symptom reduction is a better outcome parameter than cyst volume reduction for treatment success in patients treated by aspiration sclerotherapy. METHODS: We included patients with symptomatic, large (> 5 cm), hepatic cysts from a randomized controlled trial (NCT02048319). At baseline and 6 months after treatment, symptoms were assessed with the polycystic liver disease questionnaire (PLD-Q) and we measured cyst volume using ultrasonography. Patient-reported change in health was assessed on a 5-point Likert scale (much worse to much better) after 6 months. We tested whether PLD-Q scores and cyst volumes changed after aspiration sclerotherapy (responsiveness). Changes in PLD-Q scores and cyst volume were compared with change in health as a measure of treatment success (discriminative ability). As secondary analysis, we compared baseline characteristics between responders (improved) and non-responders (not improved). RESULTS: We included 32 patients. Six months after treatment, 23 patients (72%) improved. Both PLD-Q score and cyst volume significantly decreased (median 38 to 18 points, p < 0.001, and 479 to 68 mL, p < 0.001). Larger improvement in PLD-Q score was associated with a positive change in health (p = 0.001), while larger proportional reduction in cyst volume was not significantly associated with health improvement after treatment (p = 0.136). Responders had larger baseline cyst volumes compared to non-responders (median 624 mL [IQR 343-1023] vs. 322 mL [IQR 157-423] p = 0.008). CONCLUSION: Cyst diameter reduction does not reflect treatment success in aspiration sclerotherapy from patients' perspective, while symptoms measured with the PLD-Q can be used as a reliable outcome measure. KEY POINTS: • Cyst diameter reduction poorly reflects treatment success in aspiration sclerotherapy. • Symptoms measured by the polycystic liver disease questionnaire (PLD-Q) is a better outcome measure than cyst volume reduction for treatment success after aspiration sclerotherapy. • Particularly patients with larger cysts (≥ 529 mL) benefit from aspiration sclerotherapy.

Optimizing the dose in patients treated with imatinib as first line treatment for gastrointestinal stromal tumours: A cost-effectiveness study.

AIMS: Patients with metastatic gastrointestinal stromal tumours (GIST) are treated in first line with the oral tyrosine kinase inhibitor, imatinib, until progressive disease. With this fixed dosing regimen, only approximately 40% of patients reach adequate plasma levels within the therapeutic index. Therapeutic drug monitoring (TDM) is a solution to reach plasma levels within the therapeutic index. However, introducing TDM will also increase costs, due to prolonged imatinib use and laboratory costs. The aim of this study was to evaluate the cost-effectiveness of TDM in patients with metastatic/unresectable GIST treated with imatinib as a first line treatment, compared with fixed dosing. METHODS: A survival model was created to simulate progression, mortality and treatment costs over a 5-year time horizon, comparing fixed dosing vs TDM-guided dosing. The outcomes measured were treatments costs, life-years and quality-adjusted life-years. RESULTS: Total costs over the 5-year time horizon were estimated to be €106 994.85 and €150 477.08 for fixed dosing vs TDM-guided dosing, respectively. A quality-adjusted life year gain of 0.74 (95% confidence interval 0.66-0.90) was estimated with TDM-guided dosing compared to fixed dosing. An average incremental cost-effectiveness ratio of €58 785.70 per quality-adjusted life year gained was found, mainly caused by longer use and higher dosages of imatinib. CONCLUSION: Based on the currently available data, this analysis suggests that TDM-guided dosing may be a cost-effective intervention for patients with metastatic/unresectable GIST treated with imatinib which will be improved when imatinib losses its patency.

Social media monitoring on the perceived safety of medication use during pregnancy: A case study from the Netherlands.

AIMS: An increasing number of women trust the Internet for information about medication safety during pregnancy. This study aimed to evaluate the availability and accuracy of social media content on the perceived safety of medication use in pregnancy. METHODS: We performed a systematic search of posts related to medication safety during pregnancy in the Dutch language published on social media, blogs and forums between May 2011 and April 2016 using Coosto, a tool for social media monitoring. The perceived safety in the posts was compared with the Dutch Teratology Information Service (TIS) safety classifications. RESULTS: We included 1224 online posts, which described 1441 scenarios about medication safety in pregnancy. A total of 820 (57%) scenarios were in line with the TIS classification. Incorrect perception was higher for prescription medication compared to medication available over-the-counter (60 vs 25%). Furthermore, the safety classification of medications with a TIS classification on strict indication or second-line drugs (93%) and medications with insufficient knowledge on their safety during pregnancy (76%) was more likely to be incorrectly perceived by the public compared to medications with the TIS classification safe (24%). CONCLUSIONS: Social media monitoring may be useful for surveillance of potentially unsafe use of medications in pregnancy. Many social posts related to medication safety during pregnancy provide inaccurate information. As this information may affect women's perceptions and decisions, accurate communication between healthcare providers and pregnant women regarding the benefits and risks of medications is vital.

Clinical response after laparoscopic fenestration of symptomatic hepatic cysts: a systematic review and meta-analysis.

BACKGROUND: Laparoscopic fenestration is one of the treatment options for symptomatic hepatic cysts, either solitary or in context of polycystic liver disease (PLD), but indications, efficacy and surgical techniques are under debate. METHODS: A systematic literature search (1950-2017) of PubMed, Embase, Web of Science and the Cochrane Library was performed (CRD42017071305). Studies assessing symptomatic relief or symptomatic recurrence after laparoscopic fenestration in patients with symptomatic, non-parasitic, hepatic cysts were included. Complications were scored according to Clavien-Dindo. Methodological quality was assessed by Newcastle-Ottawa scale (NOS) for cohort studies. Pooled estimates were calculated using a random effects model for meta-analysis. RESULTS: Out of 5277 citations, 62 studies with a total of 1314 patients were included. Median NOS-score was 6 out of 9. Median follow-up duration was 30 months. Symptomatic relief after laparoscopic fenestration was 90.2% (95% CI 84.3-94.9). Symptomatic recurrence was 9.6% (95% CI 6.9-12.8) and reintervention rate was 7.1% (95% CI 5.0-9.4). Post-operative complications occurred in 10.8% (95% CI 8.1-13.9) and major complications in 3.3% (95% CI 2.1-4.7) of patients. Procedure-related mortality was 1.0% (95% CI 0.5-1.6). In a subgroup analysis of PLD patients (n = 146), symptomatic recurrence and reintervention rates were significantly higher with respective rates of 33.7% (95% CI 18.7-50.4) and 26.4% (95% CI 12.6-43.0). Complications were more frequent in PLD patients, with a rate of 29.3% (95% CI 16.0-44.5). CONCLUSIONS: Laparoscopic fenestration is an effective procedure for treatment of symptomatic hepatic cysts with a low symptomatic recurrence rate. The symptomatic recurrence rate and risk of complications are significantly higher in PLD patients.

Nail Involvement as a Predictor of Disease Severity in Paediatric Psoriasis: Follow-up Data from the Dutch ChildCAPTURE Registry.

Little is known about the relationship between nail psoriasis and psoriasis severity in children, and there has been no longitudinal assessment of psoriasis severity related to nail psoriasis. The aim of this study was to assess whether nail psoriasis could serve as a predictor for a more severe disease course. De-identified data were obtained from the ChildCAPTURE registry, a daily clinical practice cohort of children with psoriasis, from September 2008 to November 2015. Cross-sectional analyses were performed at baseline. Longitudinal data until 2-year follow-up were analysed by linear mixed models. Nail psoriasis was present in 19.0% of all 343 patients at baseline and cross-sectionally associated with higher Psoriasis Area and Severity Index (PASI) (p = 0.033). Longitudinal analysis demonstrated higher PASI (p <0.001) during 2-year follow-up in patients with nail involvement at baseline. These findings suggest that nail psoriasis is a potential clinical predictor for more severe disease course over time in paediatric psoriasis.