What Can Be Learned From Crowdsourced Population Asparagus Urinary Odor Kinetics?

Asparagus consumption is associated with the production of malodorous urine. Interindividual variability was previously characterized by an American Society for Clinical Pharmacology and Therapeutics crowdsourced study. To further characterize urinary odor kinetics, we conducted a study with consenting participants from Takeda Pharmaceutical International Company. The participants were randomized to consume a specified number of asparagus spears and asked to record urine odor. A kinetic-pharmacodynamic model characterized the data from both the newly conducted Takeda study (N = 42) and the previously analyzed American Society for Clinical Pharmacology and Therapeutics studies (total N = 139). The updated model included the identification of an absorption process with a half-life of 25 minutes. We estimated the elimination half-life of the asparagus effect on malodorous urine to be 7.2 hours, which was 44% longer in our study. We built on previous experience using an improved R-Shiny app for conducting the crowdsourcing experiment, further demonstrating the utility of this population kinetics approach in organizational and educational settings.

Randomized controlled trial of full and brief cognitive-behaviour therapy and wait-list for paediatric obsessive-compulsive disorder.

BACKGROUND: Reviews and practice guidelines for paediatric obsessive-compulsive disorder (OCD) recommend cognitive-behaviour therapy (CBT) as the psychological treatment of choice, but note that it has not been sufficiently evaluated for children and adolescents and that more randomized controlled trials are needed. The aim of this trial was to evaluate effectiveness and optimal delivery of CBT, emphasizing cognitive interventions. METHODS: A total of 96 children and adolescents with OCD were randomly allocated to the three conditions each of approximately 12 weeks duration: full CBT (average therapist contact: 12 sessions) and brief CBT (average contact: 5 sessions, with use of therapist-guided workbooks), and wait-list/delayed treatment. The primary outcome measure was the child version of the semi-structured interviewer-based Yale-Brown Obsessive Compulsive Scale. CLINICAL TRIAL REGISTRATION: http://www.controlled-trials.com/ISRCTN/; unique identifier: ISRCTN29092580. RESULTS: There was statistically significant symptomatic improvement in both treatment groups compared with the wait-list group, with no significant differences in outcomes between the two treatment groups. Controlled treatment effect sizes in intention-to-treat analyses were 2.2 for full CBT and 1.6 for brief CBT. Improvements were maintained at follow-up an average of 14 weeks later. CONCLUSIONS: The findings demonstrate the benefits of CBT emphasizing cognitive interventions for children and adolescents with OCD and suggest that relatively lower therapist intensity delivery with use of therapist-guided workbooks is an efficient mode of delivery.

An iontophoretic fentanyl patient-activated analgesic delivery system for postoperative pain: a double-blind, placebo-controlled trial.

An iontophoretic fentanyl HCl patient-activated transdermal system (fentanyl HCl PATS) is under development for the treatment of acute postoperative pain. The fentanyl HCl PATS is a needle-free, credit card-sized, preprogrammed system that is applied to the patient's upper outer arm or chest. The fentanyl HCl PATS was demonstrated to be superior to placebo in a previous trial; however, the randomization scheme used and the lack of control of entry pain level may have contributed to the lack of robust findings. We compared the fentanyl HCl PATS with placebo for acute postoperative pain management in a larger trial that addressed the limitations of the previous study. Adult patients admitted to the postanesthesia care unit after major surgery were titrated to comfort with opioids and randomized 1:1 to receive the fentanyl HCl PATS 40 microg or placebo for 24 hours. Supplemental IV fentanyl was available to patients upon request in both treatment groups for the first 3 hours after enrollment. The primary efficacy end-point was the percentage of patients who discontinued participation in the study because of inadequate analgesia. Pain intensity scores, patient global assessments (PGA), and investigator global assessments (IGA) were collected. Four-hundred-eighty-four patients (PATS, n = 244; placebo, n = 240) were enrolled. Fewer patients receiving the fentanyl HCl PATS discontinued because of inadequate analgesia compared with placebo (28.7% versus 60.0%; P < 0.0001). Mean last pain intensity scores were 3.5 and 5.4 for the fentanyl HCl PATS and placebo groups, respectively. Patients (73.4%, PGA) and investigators (72.1%, IGA) considered the fentanyl HCl PATS a good or excellent method of pain control. Treatment-related adverse events were similar between groups. This study demonstrated the superiority of the iontophoretic fentanyl HCl PATS over placebo for acute postoperative pain management.

Randomized, double-blind, dose-ranging study of pentosan polysulfate sodium for interstitial cystitis.

OBJECTIVES: To compare the current recommended dose of pentosan polysulfate sodium (PPS) with doses two to three times higher. METHODS: We evaluated three dosages (300, 600, and 900 mg) of PPS in a randomized, double-blind, double-dummy, parallel-group, multicenter, 32-week study. Adults (n = 380) with a diagnosis of interstitial cystitis (IC) as determined by a positive cystoscopic examination combined with bladder pain and urgency or a history of IC symptoms for at least 6 months were enrolled. Participants completed the Patient's Overall Rating of Symptom Index (PORIS) and the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) at baseline (ICSI only) and during follow-up visits at 4, 8, 12, 16, 24, and 32 weeks. RESULTS: Mean ICSI scores improved significantly during the 32 weeks for all dosages (baseline 11.2, 11.9, and 11.9 to endpoint 8.2, 8.1, 8.6 for 300, 600, and 900 mg, respectively; P <0.001) but the response to treatment was not dose dependent (no statistically significant difference in response among the three dosages). At baseline, 3.2%, 62.2%, and 34.6% reported mild, moderate, and severe symptoms, respectively, as assessed by the ICSI. At study end, 27.5%, 56.9%, and 15.7% reported mild, moderate, and severe symptoms, respectively. The PORIS scores improved within 4 weeks with 15.8% to 21.1% of all patients classified as responders (50% or greater improvement on PORIS). At 32 weeks, 49.6%, 49.6%, and 45.2% of all patients were responders at a dose of 300, 600, and 900 mg, respectively. Most adverse events were mild and resolved without intervention. CONCLUSIONS: For all three dosages of PPS, a clinically significant but similar response was demonstrated. The duration of therapy appears to be more important than the dosage.

Patient-controlled transdermal fentanyl hydrochloride vs intravenous morphine pump for postoperative pain: a randomized controlled trial.

CONTEXT: Patient-controlled analgesia (PCA) with morphine is commonly used to provide acute postoperative pain control after major surgery. The fentanyl hydrochloride patient-controlled transdermal system eliminates the need for venous access and complicated programming of pumps. OBJECTIVE: To assess the efficacy and safety of an investigational patient-controlled iontophoretic transdermal system using fentanyl hydrochloride compared with a standard intravenous morphine patient-controlled pump. DESIGN, SETTING, AND PATIENTS: Prospective randomized controlled parallel-group trial conducted between September 2000 and March 2001 at 33 North American hospitals, enrolling 636 adult patients who had just undergone major surgery. INTERVENTIONS: In surgical recovery rooms, patients were randomly assigned to intravenous morphine (1-mg bolus every 5 minutes; maximum of 10 mg/h) by a patient-controlled analgesia pump (n = 320) or iontophoretic fentanyl hydrochloride (40- microg infusion over 10 minutes) by a patient-controlled transdermal system (n = 316). Supplemental analgesia (morphine or fentanyl intravenous boluses) was administered as needed before and for the first 3 hours after activation of the PCA treatments. Patients then used the PCA treatments without additional analgesics for up to 72 hours. MAIN OUTCOME MEASURES: The primary efficacy variable was patient global assessment of the method of pain control during the first 24 hours. Additional efficacy measures were the proportion of patients discontinuing the study because of inadequate analgesia for any reason, patient-reported pain intensity scores on a 100-mm visual analog scale (VAS), and patient global assessments at 48 and 72 hours. Adverse effects were also recorded. RESULTS: Ratings of good or excellent after 24 hours of treatment for the method of pain control were given by 73.7% of patients (233/316) who used transdermal fentanyl PCA and 76.9% of patients (246/320) who used intravenous morphine PCA; treatment difference was -3.2% (95% confidence interval, -9.9% to 3.5%; P =.36). Early patient discontinuations (25.9% fentanyl vs 25.0% morphine; P =.78) and last pain intensity scores (32.7 fentanyl vs 31.1 morphine on the VAS; P =.45) were not different between the 2 treatments. With continued treatment for up to 48 or 72 hours, more than 80% of patient assessments in each treatment group were good or excellent. The incidence of opioid-related adverse events was similar between the groups. CONCLUSION: An investigational PCA transdermal system using iontophoresis to deliver fentanyl provided postsurgical pain control equivalent to that of a standard intravenous morphine regimen delivered by a PCA pump.

Effect of pentosan polysulfate therapy on intravesical potassium sensitivity.

OBJECTIVES: To evaluate further the intravesical potassium sensitivity test (PST) as an indicator of the epithelial leak of interstitial cystitis (IC) and determine whether successful pentosan polysulfate (PPS; Elmiron) treatment is associated with a change in PST results. Most individuals with IC appear to have an abnormally permeable epithelium that allows urinary solutes such as potassium to penetrate to the bladder interstitium, provoking symptoms. METHODS: Data were from an optimal dose trial of PPS in IC. Patients underwent a PST before and after a 32-week trial of 300, 600, or 900 mg PPS/day. The response to PPS treatment was measured using the Patient Overall Rating of Improvement in Symptoms scale. The before and after treatment PSTs and Patient Overall Rating of Improvement of Symptoms scores were compared. RESULTS: Of 377 patients with IC at 28 centers, 302 (80%) had a positive PST at entry. Of the 198 patients who completed the study, 153 were PST positive at entry and 92 (60%) showed clinical improvement at exit. Clinically improved patients had significant improvement on the PST analog pain and urgency scales (3.2 to 1.3 and 3.6 to 1.9, respectively; P <0.0001). In contrast, patients with no clinical improvement had no significant change in pain (3.1 to 2.7) or urgency (3.6 to 3.2). CONCLUSIONS: PST shows abnormal epithelial permeability in most patients with IC and a significant reduction in this permeability after successful PPS therapy. PST appears to be a valid indicator of epithelial abnormality and a reliable test in the diagnosis of IC.

Long-term safety of extended-release oxybutynin chloride in a community-dwelling population of participants with overactive bladder: a one-year study.

In this multicenter, open-label study of extended- and immediate-release oxybutynin chloride, community-dwelling participants were studied for up to 12 months to evaluate the long-term safety profile of extended-release oxybutynin. Quality-of-life assessments designed to measure the impact of incontinence and evaluate treatment outcome were used to study subjective improvement. A total of 904 women and 163 men (mean age 64 years, range 29-91 years) were enrolled. The majority of discontinuations were in the first 3 months (25.5%); of those who continued after 3 months, 62% remained on extended-release oxybutynin chloride for one year. The majority of discontinuations were for adverse events; dry mouth was the most frequently cited event leading to discontinuation (8.4%). Significant improvements were seen in QOL measures. Long-term therapy with extended-release oxybutynin chloride was generally well tolerated and effective, improving quality of life significantly in participants with overactive bladder over 3-12 months of therapy.