BackgroundPrucalopride is a 5-HT4 receptor agonist with gastrointestinal prokinetic activities. This integrated analysis of data from three 12-week, double-blind trials evaluated the effect of prucalopride 2 mg q.d. on common constipation symptoms in women in whom laxatives had failed to provide adequate relief. The effect of prucalopride on bowel function was outside the scope of the analysis and has been described elsewhere.MethodsWomen with self-reported inadequate relief from laxatives and included in the prucalopride 2 mg or placebo arm of the trials were selected for analysis. Symptom severity was determined with the Patient Assessment of Constipation Symptoms (PAC–SYM) questionnaire. Observed changes from baseline in individual item scores were also evaluated by calculating Cohen's D effect sizes using baseline standard deviation (SD) (>0.2–0.5, >0.5–0.8 and >0.8 for small, moderate and large effects, respectively).Key ResultsData were analyzed for 936 women. The proportion of women with a PAC-SYM severity score >2 at baseline was 50.0% for abdominal symptoms, 71.4% for stool symptoms, and 15.5% for rectal symptoms. Excluding the women without presence of a symptom at baseline from the effect size calculations showed that prucalopride 2 mg had a large effect (>0.8) on all PAC-SYM items, including abdominal pain, abdominal discomfort, bloating, straining, and painful bowel movements. For abdominal symptoms and stool symptoms, effect sizes with prucalopride 2 mg were 1.3–2.3 times larger than those with placebo.Conclusions & InferencesPrucalopride 2 mg q.d. for 12 weeks alleviates common constipation symptoms in women in whom laxatives had failed to provide adequate relief.

Methylphenidate is effective in treating children with epilepsy and ADHD and safe in children who are seizure free. Caution is warranted for those still having seizures while receiving AED therapy.

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PurposeThe Weiss Functional Impairment Rating Scale-Parent Form (WFIRS-P) is a 50-item scale that assesses functional impairment on six clinically relevant domains typically affected in attention-deficit/hyperactivity disorder (ADHD). As functional impairment is central to ADHD, the WFIRS-P offers potential as a tool for assessing functional impairment in ADHD. These analyses were designed to examine the overall performance of WFIRS-P in differentiating ADHD and non-ADHD cases using receiver operating characteristics (ROC) analysis. This is the first attempt to empirically determine the level of functional impairment that differentiates ADHD children from normal controls.MethodsThis observational study comprised 5–19-year-olds with physician-diagnosed ADHD (n = 476) and non-ADHD controls (n = 202). ROC analysis evaluated the ability of WFIRS-P to discriminate between ADHD and non-ADHD, and identified a WFIRS-P cut-off score that optimises correct classification. Data were analysed for the complete sample, for males versus females and for participants in two age groups (5–12 versus 13–19 years).ResultsArea under the curve (AUC) was 0.91 (95% confidence interval 0.88–0.93) for the overall WFIRS-P score, suggesting highly accurate classification of ADHD distinct from non-ADHD. Sensitivity (0.83) and specificity (0.85) were maximal for a mean overall WFIRS-P score of 0.65, suggesting that this is an appropriate threshold for differentiation. DeLong’s test found no significant differences in AUCs for males versus females or 5–12 versus 13–19 years, suggesting that WFIRS-P is an accurate classifier of ADHD across gender and age.ConclusionsWhen assessing function, WFIRS-P appears to provide a simple and effective basis for differentiating between individuals with/without ADHD in terms of functional impairment.ClassificationDisease-specific applications of QOL research.

SummaryBackgroundThe Patient Assessment of Constipation‐Symptoms (PAC‐SYM) questionnaire is frequently used in clinical trials of constipation. However, the threshold for reduction in total PAC‐SYM score used to define a clinical response on this 0‐4 point scale has not undergone formal appraisal, and its relationship with clinical benefit as perceived by patients has not been defined.AimTo determine the minimal important difference in PAC‐SYM score, and the optimum cut‐off value for defining responders.MethodsThe minimal important difference was estimated using data from six international phase 3/4, double‐blind, randomised controlled trials of prucalopride in patients with chronic constipation (NCT01147926, NCT01424228, NCT01116206, NCT00485940, NCT00483886, NCT00488137), with anchor‐ and distribution‐based approaches. Five appropriate patient‐reported outcomes were selected as anchors. In addition, receiver operating characteristics (ROC) curve analyses were used to investigate responder discrimination for each anchor.ResultsData from 2884 patients were included. Minimal important difference estimates ranged from –0.52 to –0.63 across the five anchors. Estimates were not affected by study location but were consistently lower for rectal symptoms than for abdominal and stool symptoms. Distribution‐based estimates were considerably lower than anchor‐based estimates. ROC curve analyses showed optimum cut‐off scores for discriminating responders to be similar to anchor‐based minimal important difference estimates.ConclusionsAnchor‐based methods gave consistent results for the minimal important difference, at approximately –0.6, and this value was close to the ROC‐determined optimal cut‐off scores for responder discrimination. This value could be considered in clinical practice. A slightly more conservative threshold (eg –0.75) could be used in clinical trials to reduce the placebo response rate.