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\"Go behind the scenes of seven of today's most popular narrative radio shows and podcasts, including This American Life and RadioLab, in graphic narrative. Every week, millions of devoted fans tune in to or download This American Life, The Moth, Radiolab, Planet Money, Snap Judgment, Serial, Invisibilia and other narrative radio shows. Using personal stories to breathe life into complex ideas and issues, these beloved programs help us to understand ourselves and our world a little bit better. Each has a distinct style, but every one delivers stories that are brilliantly told and produced. Out on the Wire offers an unexpected window into this new kind of storytelling--one that literally illustrates the making of a purely auditory medium. With the help of This American Life's Ira Glass, Jessica Abel, a cartoonist and devotee of narrative radio, uncovers just how radio producers construct narrative, spilling some juicy insider details. Jad Abumrad of RadioLab talks about chasing moments of awe with scientists, while Planet Money's Robert Smith lets us in on his slightly goofy strategy for putting interviewees at ease. And Abel reveals how mad--really mad--Ira Glass becomes when he receives edits from his colleagues. Informative and engaging, Out on the Wire demonstrates that narrative radio and podcasts are creating some of the most exciting and innovative storytelling available today\"-- Provided by publisher.

Chronic idiopathic constipation (CIC) is a prevalent functional gastrointestinal disorder diagnosed based on patient-reported symptoms and the absence of structural gastrointestinal abnormalities. Individuals with CIC typically institute dietary changes and use stool softeners or over-the-counter (OTC) laxatives, possibly at the direction of a healthcare provider, before prescription medications for CIC are initiated. Although highly prevalent, there is limited information regarding CIC patient experiences with OTC medications. This post-hoc analysis used patient-reported data from a questionnaire administered during patient screening for a prospective linaclotide Phase 3b clinical trial in patients with CIC (N = 1482 screened). The questionnaire asked patients to report their experiences with OTC CIC medications over the preceding 6 months. Among patients with screening responses (N = 1423), most were female (85%) and white (66%), with a mean age of 48.9 years. A high proportion of patients had used one or more OTC medications (70% had ≥1 OTC; 19% had ≥3 OTCs), with the majority being bisacodyl (33%) and polyethylene glycol (30%). The most commonly cited reason for stopping an OTC medication was insufficient symptom relief (17-40%). The majority of patients taking OTC medications reported no or little satisfaction with the medication's effect on their constipation (62%) and CIC-specific abdominal symptoms (78%). Many patients had little to no confidence in bowel movement (BM) frequency after taking OTC medications and their confidence in their ability to predict BM timing was also low (49-81% not at all confident). Treatment effects on individual CIC symptoms, predictability of bowel habits, and satisfaction with treatment are all important factors for healthcare providers and patients to consider when establishing an effective treatment regimen for CIC. NCT01642914.

Linaclotide improves abdominal pain and constipation in patients with constipation-predominant irritable bowel syndrome (IBS-C). Patients report additional bothersome abdominal symptoms of bloating and discomfort. The intention of this study was to evaluate linaclotide's efficacy in relieving IBS-C-related abdominal symptoms (bloating, discomfort, and pain) using a novel multi-item Abdominal Score (AS). Patients with IBS-C with abdominal pain ≥3 (0-10 scale) were randomized to linaclotide 290 μg or placebo daily for 12 weeks. The AS, derived from the Diary for IBS Symptoms-Constipation, is the average of abdominal bloating, discomfort, and pain at their worst (0 = none, 10 = worst possible). The primary end point was overall change from baseline (CFB) in AS. Secondary end points included CFB in 12-week AS evaluated using cumulative distribution function and 6-week/12-week AS responder (AS improvement ≥2 points for ≥6-week/12-week). Overall, 614 patients (mean age 46.7 years; 81% female) were randomized. All prespecified end points showed significant benefit of linaclotide vs placebo. The mean overall CFB AS reduction for linaclotide was -1.9 vs -1.2 for placebo (P < 0.0001); the 6-week/12-week AS responder rate was 40.5% for linaclotide vs 23.4% for placebo (odds ratio = 2.2 [95% confidence interval, 1.55-3.12; P < 0.0001]). Diarrhea was the most common treatment-emergent adverse event (linaclotide = 4.6%, placebo = 1.6%). Linaclotide significantly reduced multiple abdominal symptoms important to patients with IBS-C (bloating, discomfort, and pain) compared with placebo, as measured by a novel multi-item AS. The AS, derived from the Diary for IBS Symptoms-Constipation, should be considered for use in future IBS-C clinical studies to measure clinically meaningful improvements beyond traditional end points.

Background Patient-reported outcomes (PROs) are required to assess the efficacy of treatments for functional constipation (FC), which is one of the most common functional gastrointestinal disorders in children. A novel PRO, the Pediatric Functional Constipation Symptom Diary (PFCSD), was developed to assess 7 core symptoms of FC (stool frequency, stool consistency, incomplete evacuation, straining, abdominal pain, abdominal bloating, and fecal incontinence) in pediatric FC patients. Here, we describe the psychometric analyses of the PFCSD using data from a phase 3 clinical trial of linaclotide (LIN-MD-64; NCT04026113) in children with FC. Methodology This psychometric evaluation assessed the measurement properties (reliability, validity, responsiveness) and meaningful within-patient change thresholds for symptom scores derived from the PFCSD. Since spontaneous bowel movement (SBM) frequency and stool consistency (measured using the pediatric Bristol Stool Form Scale in the PFCSD) were key endpoints for the phase 3 clinical trial of linaclotide, scores from these 2 items were the primary focus of these psychometric analyses. Daily and weekly responses on the PFCSD were assessed across a 14-week period from 328 pediatric patients aged 6 to 17 years who met the modified Rome III criteria for child/adolescent FC. Results Test-retest reliability, construct validity, and responsiveness of SBM frequency and stool consistency scores on the PFCSD were supported by this psychometric evaluation. Using intraclass correlation coefficients (ICCs), PFCSD scores on items measuring SBM frequency (ICC = 0.91) and stool consistency (ICC = 0.56) were consistent across repeated administrations. Convergent and discriminant correlations underscored the validity of SBM frequency and stool consistency scores on the PFCSD. The meaningful change threshold for weekly SBM frequency was identified as a change from baseline of ≥ 2 SBMs. For stool consistency, the meaningful change threshold ranged between + 0.8 to + 1.7 on the pediatric Bristol Stool Form Scale. Conclusions The PFCSD is a novel, fit-for-purpose PRO measure evaluating key symptoms experienced by patients with FC aged 6 to 17 years. These analyses support the reliability, validity, and responsiveness of SBM frequency rate and stool consistency scores on the PFCSD in this target population and provide further guidance for interpreting meaningful changes in these scores at the individual level.

This study aimed to evaluate gold nanoparticles (GNPs) and photobiomodulation (PBM), associated with antibothropic serum (AS), to treat a muscle lesion induced by Bothrops jararaca venom. Methods: 108 Swiss male mice were used, divided into nine groups ( n  = 12) with different combinations of treatments. Animals were inoculated with 250 µg of B. jararaca venom at the right gastrocnemius muscle. The treatment started 12 h after the venom injection and occurred daily for 7 days. AS was administered as recommended by the Ministry of Health. Low-power aluminum gallium indium phosphide (AlGaInP) with continuous emission (wavelength 660 nm; average power 30 mW ± 20%; beam size of 0.06310 cm 2 ; and dose of 2 J for ± 1 min per point). Irradiation was applied to five distinct areas surrounding the wound, at a perpendicular angle to the skin. The groups treated with GNPs received treatment through the application of 1 mL of 20 nm GNPs (30 mg/L). Muscle, heart, and kidneys were removed for histological and biochemical analysis. Results: GNPs can improve the results achieved by PBM and the standard treatment, presenting significant benefits in histological parameters, such as the increase of new blood vessels, fibroblasts, collagen, and a reduction of inflammatory infiltrate. Conclusion: GNPs can be considered an option to accelerate the recovery of Bothrops lesions. Graphical Abstract

Purpose Irritable bowel syndrome with diarrhea (IBS-D) significantly impacts health-related quality of life (HRQOL). This post hoc analysis of two phase III trials evaluated the effects of eluxadoline treatment on disease-specific HRQOL among patients with IBS-D. Methods Adult patients meeting Rome III criteria for IBS-D were randomized to oral eluxadoline (75 mg or 100 mg) or placebo twice daily in two phase III clinical trials for 52 weeks (IBS-3001) and 26 weeks (IBS-3002). The Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire assessed disease-specific HRQOL throughout the study. Changes from baseline to Week 26 in IBS-QOL total and subscale scores were analyzed using an analysis of covariance model. Percentages of IBS-QOL responders with ≥ 14- and 20-point changes were evaluated for IBS-QOL total and subscale scores. A longitudinal mixed-effects model was fitted to evaluate mean IBS-QOL total scores. A cumulative distribution function for change from baseline to Week 26 in IBS-QOL total score was plotted. Results Mean changes from baseline to Week 26 for the IBS-QOL total and all subscale scores were significantly higher for patients treated with eluxadoline (both doses) compared to placebo. A significantly greater proportion of eluxadoline-treated patients were responders compared to placebo. Mean and mixed-effects model estimated mean IBS-QOL total scores were consistently higher for eluxadoline versus placebo over 52 weeks. Conclusions Compared to placebo, twice-daily eluxadoline treatment significantly improved HRQOL among patients with IBS-D in two phase III trials.

Based on the literature and collective experience and consensus of the authors, this article provides a definition for an event-driven electronic diary (EDeD), outlines considerations for the use of EDeDs, and provides best practice recommendations for their design and implementation in clinical trials. This is a much-needed resource to optimize data quality in clinical trials and to support a necessary level of standardization using this form of data capture.

Introduction: Treatment of patients with chronic idiopathic constipation and irritable bowel syndrome with constipation (IBS-C) may provide symptom improvement, which is associated with increased quality of life (QOL), a key factor impacting patients perception of treatment satisfaction. This analysis assessed patient-reported outcomes before and on/after initiating linaclotide, based on survey data from the Chronic Constipation and IBS-C Treatment and Outcomes Real-world Research Platform (CONTOR). Methods: CONTOR participants included fully insured patients aged >8 years, identified via claims from a large, geographically diverse US health insurer, with: >1 medical claim for constipation (ICD-9-CM diagnosis code: 564.0x); or >1 claim for IBS (564.1x) or abdominal pain (789.0x) plus >1 pharmacy claim for a stool softener/laxative; or >1 claim for linaclotide or lubiprostone. Over the 1-year study period, participants completed self-administered baseline/quarterly surveys, which assessed treatment satisfaction, symptoms (Patient Assessment of Constipation Symptoms [PAC-SYM]), and QOL (PAC-QOL). Participants reporting over-the-counter (OTC) constipation treatment who then reported initiating linaclotide regardless of continued OTC treatment were included; those reporting any concomitant lubiprostone use were excluded. Outcomes were measured before and on/after the initiation of linaclotide and for daily and non-daily linaclotide use. Results: 124 participants reported initiating linaclotide after taking an OTC treatment, with ics similar to 2052 participants in the overall CONTOR population (Table 1). Linaclotide frequency of use at initiation was daily (53.2%), as needed (33.9%), every other day (8.9%), or weekly (4.0%). A greater proportion of participants were satisfied with their treatment on/after initiating linaclotide vs. before (39.2% vs. 30.2%). Mean PAC-SYM and PAC-QOL scores were lower on/after initiating linaclotide vs. before, indicating better QOL and fewer symptoms, respectively (Table 2). Greater changes in outcomes were observed among patients who reported daily linaclotide use. Conclusion: Among CONTOR participants initiating linaclotide after reporting OTC use, overall treatment satisfaction increased on/after initiating linaclotide, with mild improvement in symptoms and QOL. These results warrant further investigation to assess whether outcomes continue to improve with longer linaclotide use.

Introduction: Understanding how patients with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) treat their disease and what drives treatment satisfaction or discontinuation is important when considering new treatment options. Treatment choice may be difficult, due in part to the heterogeneity and/or severity of these disorders. This analysis of the Chronic Constipation and IBS-C Treatment and Outcomes Real-world Research Platform (CONTOR) study examined treatment patterns and outcomes among participants with IBS-C or CIC. Methods: CONTOR included fully insured US patients with: both medical and pharmacy benefits and >1 medical claim for constipation (ICD-9-CM diagnosis code: 564.0x); or >1 claim for IBS (564.1x) or abdominal pain (789.0x) plus >1 pharmacy claim for a stool softener/laxative; or >1 claim for linaclotide or lubiprostone (October 2014 to November 2016). Over the 12-month study period, participants completed a baseline and quarterly survey, which included the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire and an assessment of overall treatment satisfaction. Monthly surveys collected patient-reported new or discontinued IBS-C/CIC treatments. Association between quality of life and changes in treatment satisfaction was determined by multivariate analyses. Results: Of 2052 CONTOR participants, 93.8% (n=1922) were female; the mean (SD) age was 46.7 (11.9) years. At baseline, the majority of participants reported their IBS-C/CIC treatment included over-thecounter (OTC) medication use (65.4%), while 22.2% reported OTC and prescription treatment (Table 1). The concomitant use of prescription and OTC treatments remained consistent over the study period. The most common reasons for discontinuing any treatment were failure to improve constipation (41.4%), bloating (39.4%), and pain (34.7%); improved symptoms no longer required medication in 28.7% of participants. The odds of becoming satisfied with treatment were higher in participants with improved PACQOL total scores (defined as >0.5 improvement from baseline) compared to those with no improvement (p<0.001) (Table 2). Conclusion: The majority of participants with IBS-C or CIC used a variety of treatments to manage their disease. Improved quality of life was associated with treatment satisfaction.