Morquio A syndrome is an ultra-rare, inherited lysosomal storage disorder associated with progressive, multi-systemic clinical impairments, causing gradual loss of functional capacity and endurance, impaired quality of life, and early mortality. Studies in Morquio A patients have used the 6-min walk test (6MWT) to assess functionality and endurance and to evaluate disease progression or efficacy of treatment. The objective of the present study was to review minimal clinically important differences (MCIDs) for the 6MWT reported for disease states that widely use the 6MWT to evaluate clinical benefit and to discuss the results in view of the challenges in estimating MCID for ultra-rare diseases, using the case of elosulfase alfa in Morquio A patients. A systematic literature search was performed using Embase and Medline to identify studies specifically estimating the MCID using either anchor-based or distribution-based methods. A total of 19 publications on 17 studies were identified; none of these included patients with Morquio A syndrome or the wider disease category of lysosomal storage disorders. Therefore, the MCIDs determined by studies in patients with respiratory, cardiovascular, or musculoskeletal disease were compared to changes in the 6MWT seen in Morquio A patients in the pivotal phase 3 clinical trial of elosulfase alfa enzyme replacement therapy. The literature review showed a mean MCID for the 6MWT of 7% change (range 3–15%) in studies using anchor-based methods and a 9% change (range 4–16%) using distribution-based methods. Results of the elosulfase alfa clinical trial and its extension showed a placebo-adjusted 14.9% improvement in the 6MWT from baseline at week 24, which was greater than the mean MCID based on the results of the systematic literature review. After 2 years, 6MWT distance increased by a mean of 20.7% from baseline in a modified per-protocol population, versus a reduction of 6.9% in comparable untreated patients from the MorCAP natural history study over the same period. Although further research is required to establish the MCID of the 6MWT in Morquio A patients, the presented data provide further evidence for the positive effect of elosulfase alfa in this patient population.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-017-0633-1) contains supplementary material, which is available to authorized users.

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SUMMARYThe long-term effect of prednisone in Crohn's disease has been examined in a doubleblind controlled trial. Clinical relapse, recurrence, and extension of the disease were examined in 64 patients followed-up for up to three years. Fourteen patients were withdrawn because of severe symptoms (eight on prednisone and six controls); the withdrawal rate in both groups was 30 % at three years. Nine other patients had radiological recurrence or extension of disease (five prednisone and four controls). Prednisone did not improve the relapse rate, nor did it affect recurrence or extension of disease.

Objective To evaluate the association between the degree of response to placebo in migraine studies and the observed difference between drug and placebo across studies of preventative treatments for migraine. Methods A systematic review was performed using MEDLINE and the Cochrane Central Register of Controlled Clinical Trials from January 1988 to June 2019. Randomized, double-blind, parallel-group, placebo-controlled trials on oral or injection preventative treatments for migraine were included. Single- and multi-variable linear regression analyses were performed on the placebo-subtracted response rate (i.e. placebo responders subtracted from active responders), and the proportion of placebo responders. Fisher’s exact tests were performed on the level of placebo response and the success in meeting the study’s primary endpoint. Results After adjusting for route of administration and number of randomized subjects, there was a statistically significant association between the proportion of patients who were placebo responders and the placebo-subtracted response rate (b = −0.27, p = 0.02). There was a statistically significant difference in trial success rate (60%) between studies with ≤20% placebo responders and studies with > 30% placebo responders ( p = 0.03). Conclusion Considering the detrimental impact that high placebo response can have on clinical trials, it is imperative to find effective solutions to decrease the placebo response and increase assay sensitivity.

Aims: Opioids do not represent standard therapy for endometriosis; however, women with endometriosis are frequently prescribed an opioid to manage related abdominal or pelvic pain. The aim of this study was to evaluate the impact of opioid use on endometriosis-related economic and healthcare burden in the United States. Materials and methods: We performed a retrospective, propensity-matched cohort analysis of the Truven MarketScan Commercial database from 1 January 2011 to 31 December 2016. Eligible women had at least 1 inpatient or 2 outpatient codes for endometriosis and 12 months of continuous enrollment before and after the index date (i.e. first recorded endometriosis diagnosis). The primary analysis examined healthcare costs and utilization for 12 months after the index date in women who filled at least 1 opioid prescription versus those who did not. The secondary analysis examined healthcare costs and utilization by the pattern of opioid use. Results: The primary analysis matched 43,516 women across 2 groups and the secondary analysis matched 13,230 women across 5 groups. In the primary analysis, total 12-month healthcare costs were significantly higher in the opioid group compared to the non-opioid group ($29,236.00 vs. $18,466.00, respectively; p < .001); the same pattern was observed for all healthcare utilization parameters. In the secondary analysis, higher morphine equivalent daily dose and proportion of days covered were associated with the highest healthcare costs and utilization compared to the non-opioid group. Limitations: Retrospective design and inability to confirm whether filled opioid prescriptions were actually taken. Conclusions: Filling an opioid prescription within 1 year after an endometriosis diagnosis was associated with significant excess healthcare burden. Patients prescribed an opioid may experience inadequate symptom management and benefit from the use of disease-specific, non-opioid therapies.

To determine the prevalence and pattern of opioid use in endometriosis and the characteristics of patients prescribed an opioid using medical insurance claims data. Design: We performed a retrospective cohort analysis of data from the Truven MarketScan Commercial database for the period of January 1, 2011 to December 31, 2016. Setting: The Truven database includes inpatient, outpatient, and prescription claims covering more than 115 million unique individuals and over 36 million inpatient hospital discharges across multiple payer types and all 50 states. Patients: Women with endometriosis were defined as those with 1 inpatient or 2 outpatient codes for endometriosis. Interventions: No interventions were assigned. Women who filled an opioid prescription within 12 months of diagnosis were placed in the opioid cohort and women who did not fill an opioid prescription were placed in the nonopioid cohort. Measurements and Main Results: Baseline characteristics were evaluated 12 months preindex (date of the first diagnosis) and opioid use was assessed for 12 months after the index date. The dataset included 58 472 women with endometriosis. Of these, 61.7% filled an opioid prescription during the study period. More than 95% filled prescriptions for short-acting opioids (SAOs) only, 4.1% filled prescriptions for both SAOs and extended-release/long-acting opioids (LAOs), and 0.6% filled prescriptions for LAOs only. Patients who filled an opioid prescription had higher baseline comorbidities (especially gynecologic and chronic pain comorbidities) and endometriosis-related medication use compared with patients who did not fill an opioid prescription during the study period. Patients who filled both LAO and SAO prescriptions had the highest total days' supply of opioids, the proportion of days covered by prescriptions, and morphine equivalent daily dose. These patients also had the highest proportions of opioid switching and dose augmentation. Statistical trends in data were not substantially altered when analyses excluded patients with chronic pain comorbidities or surgical opioid prescriptions. Conclusion: Although opioids are not a recommended treatment for endometriosis, more than half of our cohort filled an opioid prescription within 1 year after a first recorded diagnosis of endometriosis. Patients who filled an opioid prescription tended to use more endometriosis-related medications and have a higher comorbidity burden. Additional research is necessary to better understand the reasons and outcomes associated with opioid utilization in endometriosis and to determine if there is a more effective pain management treatment plan for patients taking opioids. Journal of Minimally Invasive Dr. As-Sanie receives royalties from UpToDate and is a consultant for AbbVie Inc., Myovant Sciences, Merck, and Bayer. Dr. Soliman is an AbbVie Inc. employee and may own AbbVie stock or stock options. Drs. Evans and Katz are employees of Analgesic Solutions and provide consulting services to AbbVie Inc. Drs. Erpelding and Lanier are former ...

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Aim The aim of this study was to report clinical outcomes following the use of a pediatric day-case laparoscopic cholecystectomy (DCLC) clinical care pathway. The pathway was modified in September 2009 and we compare the clinical outcomes before and after this modification. Methods A care pathway for DCLC was introduced in 2008 with emphasis on the day of admission, timing of surgery, choice of anesthetic agents, analgesia, postoperative feeding, mobilization, and pain scoring. Demographic and clinical data were recorded prospectively from