Satisfaction With and Adherence to Off-Label Corticosteroids in Adolescents and Adults With Eosinophilic Esophagitis: Results of a Web-Based Survey in the United States.

GOALS: We assessed satisfaction with and adherence to off-label corticosteroids in patients with eosinophilic esophagitis (EoE) in the United States. BACKGROUND: EoE is a chronic inflammatory disease for which there are currently no US Food and Drug Administration-approved swallowed topical corticosteroids. STUDY: This noninterventional, cross-sectional, web-based survey included caregivers of adolescents (aged 11 to 17 y) and adults (aged 18 years or older) with a self-reported [or caregiver-reported (adolescents)] physician diagnosis of EoE who were receiving corticosteroids. Participants were recruited through 2 nonprofit, patient advocacy groups. The 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) was used to assess satisfaction across effectiveness, convenience, and global satisfaction domains (scale: 1 to 100 per domain); higher scores indicated greater satisfaction. The 4-item Morisky Green Levine Medication Adherence Scale (MGL-4) was used to assess adherence; an MGL-4 score of <3 indicated adherence. Participants also reported reasons for nonadherence. RESULTS: Overall, 201 participants (caregivers of adolescents, n=98; adults, n=103) were included in this study. Mean TSQM-9 scores indicated low satisfaction with off-label corticosteroids across all 3 satisfaction domains in adolescents (≤61.1) and adults (≤55.7). Slightly fewer adolescents (37.1%) than adults (40.8%) were considered adherent. Forgetfulness was the most frequently reported reason for nonadherence; some patients chose not to take their medications, owing to poor palatability (adolescents), difficulty taking medications at specific times (adults), or feeling depressed/overwhelmed (adolescents and adults). CONCLUSIONS: Satisfaction with and adherence to off-label corticosteroids were low in this web-based survey of adolescents and adults with EoE in the United States.

Clinical Outcomes Before and After Prucalopride Treatment: An Observational Study in Patients With Chronic Idiopathic Constipation in the United States.

INTRODUCTION: This real-world US-based claims study compared constipation-related symptoms and complications 6 months before and after prucalopride initiation in adults with chronic idiopathic constipation (CIC). METHODS: This observational, retrospective cohort analysis used the IBM MarketScan Commercial Claims and Encounters Database and the Medicare Supplemental Database (January 2015-June 2020). Prucalopride-treated patients (≥18 years old) who had ≥1 constipation-related International Classification of Diseases, Tenth Revision, Clinical Modification ( ICD-10-CM ) diagnosis code during the baseline or study period were included. The proportions of patients with constipation-related symptoms (abdominal pain, abdominal distension [gaseous], incomplete defecation, and nausea) and constipation-related complications (anal fissure and fistula, intestinal obstruction, rectal prolapse, hemorrhoids, perianal venous thrombosis, perianal/perirectal abscess, and rectal bleeding) were examined. Constipation-related symptoms and complications were identified using ICD-10-CM , ICD-10 - Procedure Coding System , or Current Procedural Terminology codes. Data were stratified by age (overall, 18-64 years, and ≥65 years). RESULTS: This study included 690 patients: The mean (SD) patient age was 48.0 (14.7) years, and 87.5% were women. The proportions of patients overall with constipation-related symptoms decreased 6 months after prucalopride initiation (abdominal pain [50.4% vs 33.3%, P < 0.001]; abdominal distension [gaseous] [23.9% vs 13.3%, P < 0.001]; and nausea [22.6% vs 17.7%, P < 0.01]; no improvements observed for incomplete defecation). Similarly, the proportions of patients overall with constipation-related complications decreased 6 months after prucalopride initiation (intestinal obstruction [4.9% vs 2.0%, P < 0.001]; hemorrhoids [10.7% vs 7.0%, P < 0.05]; and rectal bleeding [4.1% vs 1.7%, P < 0.05]). DISCUSSION: This study suggests that prucalopride may be associated with improved constipation-related symptoms and complications 6 months after treatment initiation.

Pooled Phase 2 and 3 Efficacy and Safety Data on Budesonide Oral Suspension in Adolescents with Eosinophilic Esophagitis.

OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of budesonide oral suspension (BOS) in adolescents with eosinophilic esophagitis (EoE). METHODS: This post hoc analysis pooled data from two 12-week, randomized, double-blind, placebo-controlled studies of BOS 2.0 mg twice daily (b.i.d.) (phase 2, NCT01642212; phase 3, NCT02605837) in patients aged 11-17 years with EoE and dysphagia. Efficacy endpoints included histologic (≤6, ≤1, and <15 eosinophils per high-power field [eos/hpf]), dysphagia symptom (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] scores from baseline), and clinicopathologic (≤6 eos/hpf and ≥30% reduction in DSQ scores from baseline) responses at week 12. Change from baseline to week 12 in peak eosinophil counts, DSQ scores, EoE Histology Scoring System (EoEHSS) grade (severity) and stage (extent) total score ratios (TSRs), and total EoE Endoscopic Reference Scores (EREFS) were assessed. Safety outcomes were also examined. RESULTS: Overall, 76 adolescents were included (BOS, n = 45; placebo, n = 31). Significantly more patients who received BOS than placebo achieved histologic responses (≤6 eos/hpf: 46.7% vs 6.5%; ≤1 eos/hpf: 42.2% vs 0.0%; <15 eos/hpf: 53.3% vs 9.7%; P < 0.001) and a clinicopathologic response (31.1% vs 3.2%; P = 0.003) at week 12. More BOS-treated than placebo-treated patients achieved a dysphagia symptom response at week 12 (68.9% vs 58.1%; not statistically significant P = 0.314). BOS-treated patients had significantly greater reductions in EoEHSS grade and stage TSRs ( P < 0.001) and total EREFS ( P = 0.021) from baseline to week 12 than placebo-treated patients. BOS was well tolerated, with no clinically meaningful differences in adverse events versus placebo. CONCLUSIONS: BOS 2.0 mg b.i.d. significantly improved most efficacy outcomes in adolescents with EoE versus placebo.

Effects of treatment cessation and re-treatment in randomized controlled trials of prucalopride in patients with chronic idiopathic constipation.

BACKGROUND: Prucalopride is a selective, high-affinity serotonin type 4 receptor agonist approved for the treatment of chronic idiopathic constipation (CIC) in adults. We investigated the impact of prucalopride cessation and re-treatment on efficacy and safety. METHODS: Data were from two randomized controlled trials in adults with CIC. In a dose-finding trial, complete spontaneous bowel movements (CSBMs) and treatment-emergent adverse events (TEAEs) were assessed during a 4-week run-out period after a 4-week treatment period (TP; prucalopride 0.5-4 mg once daily or placebo). In a re-treatment trial, CSBMs and TEAEs were assessed during two 4-week TPs (prucalopride 4 mg once daily or placebo) separated by a 2- or 4-week washout period. KEY RESULTS: In the dose-finding trial (N = 234; 43-48 patients/group), mean CSBMs/week and the proportion of responders (≥3 CSBMs/week) were higher with prucalopride than placebo during the TP, but similar in all groups 1-4 weeks after treatment cessation. TEAEs were less frequent following treatment cessation. In the re-treatment trial (efficacy analyses: prucalopride, n = 189; placebo, n = 205), the proportion of responders was similar in both TPs and significantly higher (p ≤ 0.001) with prucalopride (TP1, 38.6%; TP2, 36.0%) than placebo (TP1, 10.7%; TP2, 11.2%). Most patients who responded to prucalopride in TP1 responded again in TP2 (71.2%). TEAEs were less frequent in TP2 than TP1. CONCLUSIONS AND INFERENCES: Prucalopride cessation resulted in a loss of clinical effect to baseline levels within 7 days. Similar efficacy and safety were observed between TP1 and TP2 after prucalopride was re-initiated following a washout period.

A Review of the Cardiovascular Safety of Prucalopride in Patients With Chronic Idiopathic Constipation.

Prokinetic agents, specifically 5-hydroxytryptamine type 4 (5-HT 4 ) receptor agonists, have been shown to provide relief in chronic idiopathic constipation (CIC). The first-generation 5-HT 4 agonists were initially withdrawn from use owing to associations with serious cardiovascular (CV) events. This review summarizes CV safety data for prucalopride, a high-affinity 5-HT 4 agonist approved in the United States in 2018 for adults with CIC. No significant effects of prucalopride on CV safety were observed in animal models or early-phase clinical studies, including a thorough QT study at therapeutic (2 mg) or supratherapeutic (10 mg) doses. Among 1,750 patients with CIC who received prucalopride (2-4 mg) in 5 phase 3 studies, no trends in CV adverse events, electrocardiogram parameters, or blood pressure were documented; ≤1.0%-2.0% of patients had prolonged QT interval corrected for heart rate (HR) using Fridericia formula after placebo or prucalopride treatment, and low HR occurred in ≤6.1% and ≤3.3% of these patients, respectively. In two 24-month observational studies among 2,468 patients, changes in electrocardiogram parameters over time were minor, except at occasional time points when significant changes from baseline were reported for HR or QT interval. In a real-world European CV safety study among 35,087 patients (prucalopride, 5,715; polyethylene glycol 3350 [PEG3350], 29,372), results were consistent for no evidence of increased risk of major adverse CV events among patients treated with prucalopride vs PEG3350 (incidence rate ratio = 0.64; 95% confidence interval 0.36-1.14). Studies to date have not raised concerns regarding the impact of prucalopride treatment on CV parameters.

Safety of an investigational formulation of budesonide (budesonide oral suspension) for eosinophilic oesophagitis: an integrated safety analysis of six phase 1-3 clinical trials.

BACKGROUND: Questions remain regarding the safety of swallowed topical corticosteroids in eosinophilic oesophagitis (EoE). AIM: To assess the safety of an investigational formulation of budesonide (budesonide oral suspension; BOS) from six trials. METHODS: Safety data were integrated from six trials (healthy adults: SHP621-101 [phase 1]; patients with EoE: MPI 101-01 and MPI 101-06 [phase 2]; SHP621-301, SHP621-302 and SHP621-303 [phase 3]) for participants who received ≥1 dose of study drug (BOS 2.0 mg twice daily [b.i.d.], BOS any dose [including BOS 2.0 mg b.i.d.] and placebo). Adverse events (AEs), laboratory testing, bone density and adrenal AEs were assessed. Exposure-adjusted incidence rates were calculated for AEs and AEs of special interest (AESIs). RESULTS: Overall, 514 unique participants were included (BOS 2.0 mg b.i.d., n = 292; BOS any dose, n = 448; placebo, n = 168). The BOS 2.0 mg b.i.d., BOS any dose and placebo groups totalled 93.7, 122.4 and 25.0 participant-years of exposure (PY), respectively. Proportions of treatment-emergent AEs (TEAEs) and AESIs (any) reported were higher for BOS than placebo; however, most were mild/moderate in severity. The most commonly reported AESIs (exposure-adjusted incidence rates [per 100 PY]) in the BOS 2.0 mg b.i.d., BOS any dose and placebo groups were infections (133.5, 154.4 and 136.2, respectively) and gastrointestinal AEs (84.3, 80.9 and 92.1, respectively). Adrenal AEs were more frequent with BOS 2.0 mg b.i.d. and BOS any dose than placebo (44.8, 34.3 and 24.0, respectively). TEAEs and AESIs related to study drug or leading to discontinuation were infrequent. CONCLUSIONS: BOS was well-tolerated; most TEAEs with BOS were mild/moderate in severity. GOV NUMBERS: SHP621-101 (no clinical trials registration number), MPI 101-01 (NCT00762073), MPI 101-06 (NCT01642212), SHP621-301 (NCT02605837), SHP621-302 (NCT02736409) and SHP621-303 (NCT03245840).

Heterogeneity of Randomized Controlled Trials of Fecal Microbiota Transplantation in Recurrent Clostridioides difficile Infection.

INTRODUCTION: Clinical trials have demonstrated the efficacy of FMT for reduction in CDI recurrences (rCDI), but this treatment and its reporting in the literature has significant heterogeneity. Recent publications (e.g., Ramai et al. in Dig Dis Sci 2020. https://doi.org/10.1007/s10620-020-06185-7 ) present the clinical outcomes for different FMT methodologies. However, to understand, compare, and contextualize outcomes, this heterogeneity in methods and reporting must be understood. METHODS: We performed a literature review of randomized controlled trials (RCTs) of FMT for rCDI to evaluate heterogeneity among trials. A methodical search between January 2010 and May 2019 of Medline, Embase, and Cochrane was conducted for studies investigating FMT in adults with rCDI. RCTs were evaluated for a variety of methodological and reporting criteria. RESULTS: Eight RCTs were identified, wherein 14 different FMT preparations were considered (each with distinct protocols for processing, storage, administration, and dosing). Sample sizes were generally small, with only two studies performing FMT in more than 100 patients. Three studies used non-FMT controls (vancomycin), while the remaining compared FMT with differing routes of administration or formulations. Across the identified studies, there was no standardized manner for reporting the timing of the FMT procedure. All studies tracked adverse events; however, follow-up periods were limited. CONCLUSIONS: Considerable variability exists among RCTs, with marked differences in study design, control groups, and outcome assessment. Lack of a standard-of-care control in many trials may impact reproducibility of FMT trial outcomes in patients with rCDI. Widespread use of FMT for rCDI is still investigational; therefore, these foundational studies provide opportunities to optimize future trials.

Health care resource utilization and costs of recurrent Clostridioides difficile infection in the elderly: a real-world claims analysis.

BACKGROUND: Clostridioides difficile infection (CDI) affected an estimated 365,000 persons in the United States in 2017. Despite a nationally decreasing trend of CDI cases, the population incidence of recurrent CDI (rCDI) has not improved. Elderly individuals (aged ≥ 65 years) are at higher risk of CDI, rCDI, and complicated CDI compared with younger individuals. OBJECTIVE: To analyze Medicare fee-for-service data for 12 months after an initial CDI episode, in order to obtain real-world data on health care resource utilization (HRU) and costs for elderly patients with CDI and rCDI. METHODS: A retrospective cohort study of patients who were aged ≥ 65 years and had a first (index) CDI diagnosis from January 1, 2010, to December 31, 2016, and continuous enrollment in Medicare Parts A, B, and D during the 12-month pre-index and 12-month post-index periods was conducted. A CDI episode was identified by either an inpatient stay with CDI diagnosis code or an outpatient medical claim with a CDI diagnosis code plus a CDI treatment. Each CDI episode was followed by a 14-day CDI claim-free period after the last CDI claim or end of CDI treatment. rCDI was a second or subsequent episode of CDI that occurred within an 8-week window after the 14-day CDI claim-free period. The number of CDI and rCDI episodes, HRU, time to recurrence, and total all-cause direct medical costs were calculated over the 12-month pre-index (baseline) and 12-month follow-up periods and stratified by number of rCDI episodes (No rCDI, 1 rCDI, 2 rCDI, 3+ rCDI). RESULTS: A total of 268,762 patients with an index CDI were included. Mean age was 78.3 years, and 69.0% were female. HRU was higher during the 6 months immediately pre-index versus 7-12 months pre-index, including a higher proportion of patients with a hospital admission (55.1% vs. 27.5%) or emergency department visit (41.3% vs. 27.4%), respectively. Moreover, 34.7% of the study population experienced rCDI. Of those who experienced 1 recurrence, 59.1% had a second recurrence, and of those who had 2 recurrences, 58.4% had a third. During the 12-month follow-up, postacute care was used by at least 70% of each rCDI cohort. The proportion of patients with ≥ 4 hospital admissions during follow-up was highest for the 3+ rCDI cohort (24.9% of patients). During the 12-month follow-up, mean total all-cause direct costs were $76,024, $99,348, $96,148, and $96,517 for the No rCDI, 1 rCDI, 2 rCDI, and 3+ rCDI cohorts, respectively, largely driven by inpatient costs. Adjusted all-cause total costs were significantly higher for all 3 rCDI cohorts compared with the No rCDI cohort. CONCLUSIONS: Elderly individuals experienced high rates of recurrence after their first CDI episode, and especially after a prior recurrence. The intensity of HRU during follow-up was higher for patients who suffered recurrences. Patients with rCDI had the burden of higher costs of care, including the patient out-of-pocket responsibility, versus patients with a single CDI episode. DISCLOSURES: Funding for this study was provided by Ferring Pharmaceuticals. Nelson is an employee of Ferring Pharmaceuticals, and Scott, Boules, and Unni were employees of Ferring Pharmaceuticals at the time of this study. Teigland and Parente are employees of Avalere Health and provided consulting services to Ferring Pharmaceuticals. Feuerstadt has served as a consultant to and on the speakers bureau for Merck and Co. and has served as a consultant for Ferring Pharmaceuticals and Roche Pharmaceuticals. Portions of the data contained in this study appeared as an abstract/ePoster for the AMCP Annual Meeting 2020, April 2020.

Clinical complications in patients with primary and recurrent Clostridioides difficile infection: A real-world data analysis.

OBJECTIVE: Clostridioides difficile infection and recurrent C. difficile infection result in substantial economic burden and healthcare resource use. Sepsis and bowel surgery are known to be serious complications of C. difficile infection. This study evaluated clinical complications in patients with C. difficile infection and recurrent C. difficile infection during a 12-month period following the primary C. difficile infection. METHODS: A retrospective analysis of commercial claims data from the IQVIA PharMetrics Plus™ database was conducted for patients aged 18-64 years with an index C. difficile infection episode requiring inpatient stay or an outpatient visit for C. difficile infection followed by a C. difficile infection treatment. Each C. difficile infection episode ended after a 14-day C. difficile infection-claim-free period was observed. Recurrent C. difficile infection was defined as a further C. difficile infection episode within an 8-week window following the claim-free period. Clinical complications were documented over 12 months of follow-up and stratified by the number of recurrent C. difficile infection episodes (0 rCDI, 1 rCDI, 2 rCDI, and 3+ rCDI). RESULTS: In total, 46,571 patients with index C. difficile infection episode were included. During the 6-month pre-index, the mean (standard deviation) baseline Charlson comorbidity index score, by increasing the recurrent C. difficile infection group, was 1.2 (1.9), 1.5 (2.2), 1.8 (2.3), and 2.3 (2.5). During the 12-month follow-up, sepsis occurred in 16.5%, 27.3%, 33.1%, and 43.3% of patients, and subtotal colectomy or diverting loop ileostomy was performed in 4.6%, 7.3%, 8.9%, and 10.5% of patients, respectively, by increasing the recurrent C. difficile infection group. CONCLUSIONS: Reduction in recurrent C. difficile infection is an important step to reduce the burden of serious clinical complications, and new treatments are needed to reduce C. difficile infection recurrence.

Pediatric bowel preparation: Sodium picosulfate, magnesium oxide, citric acid vs polyethylene glycol, a randomized trial.

BACKGROUND: Bowel preparation in children can be challenging. AIM: To describe the efficacy, safety, and tolerability of sodium picosulfate, magnesium oxide, and citric acid (SPMC) bowel preparation in children. METHODS: Phase 3, randomized, assessor-blinded, multicenter study of low-volume, divided dose SPMC enrolled children 9-16 years undergoing elective colonoscopy. Participants 9-12 years were randomized 1:1:1 to SPMC ½ dose × 2, SPMC 1 dose × 2, or polyethylene glycol (PEG). Participants 13-16 years were randomized 1:1 to SPMC 1 dose × 2 or PEG. PEG-based bowel preparations were administered per local protocol. Primary efficacy endpoint for quality of bowel preparation was responders (rating of 'excellent' or 'good') by modified Aronchick Scale. Secondary efficacy endpoint was participant's tolerability and satisfaction from a 7-item questionnaire. Safety assessments included adverse events (AEs) and laboratory evaluations. RESULTS: 78 participants were randomized, 48 were 9-12 years, 30 were 13-16 years. For the primary efficacy endpoint in 9-12 years, 50.0%, 87.5%, and 81.3% were responders for SPMC ½ dose × 2, SPMC 1 dose × 2, and PEG groups, respectively. Responder rates for 13-16 years were 81.3% for SPMC 1 dose × 2 and 85.7% for PEG. Overall, 43.8% of participants receiving SPMC 1 dose × 2 reported it was 'very easy' or 'easy' to drink, compared with 20.0% receiving PEG. Treatment-emergent AEs were reported by 45.5% of participants receiving SPMC 1 dose × 2 and 63.0% receiving PEG. CONCLUSION: SPMC was an efficacious and safe for bowel preparation in children 9-16 years, with comparable efficacy to PEG. Tolerability for SPMC was higher compared to PEG.

Efficacy, safety, and tolerability of a ready-to-drink bowel preparation in overweight and obese adults: subanalysis by body mass index from a phase III, assessor-blinded study.

BACKGROUND: We performed a post hoc secondary analysis for the effect of body mass index (BMI) on the efficacy, tolerability, and safety of ready-to-drink sodium picosulfate, magnesium oxide, and citric acid (SPMC oral solution) bowel preparation. METHODS: A phase III, randomized, assessor-blinded, multicenter, noninferiority study was conducted comparing split-dose, low-volume SPMC oral solution with a powder formulation for oral solution. A post hoc secondary analysis assessed efficacy, safety, and tolerability of SPMC oral solution stratified by BMI. BMI was classified by Centers for Disease Control and Prevention definitions (underweight and normal weight: BMI < 25 kg/m2; overweight: BMI 25-29.9 kg/m2; class I obesity: BMI 30-34.9 kg/m2; class II obesity: BMI 35-39.9 kg/m2; class III/severe obesity: BMI ⩾40 kg/m2). Prespecified primary efficacy endpoint ('responders') was the proportion of participants with 'excellent' or 'good' ratings on a modified Aronchick Scale (AS). Secondary efficacy outcomes were the quality of cleansing of the right colon as assessed by the Boston Bowel Preparation Scale (BBPS); as well as selected findings from the Mayo Clinic Bowel Prep Tolerability Questionnaire. Safety assessments included adverse events (AEs) and laboratory evaluations. RESULTS: Between 82.8% and 92.5% of participants in any BMI group were responders by AS, and between 91.3% and 100% were responders by BBPS in the right colon. Efficacy was consistent across BMI groups, with no clear trends. Greater than 83% of participants in any BMI group found the preparation 'easy' or 'acceptable' to ingest, and the majority (>58%) rated SPMC oral solution as 'better' than a prior bowel preparation. In all BMI groups, safety data were similar to the overall cohort. Commonly reported, drug-related, treatment-emergent AEs were, by ascending BMI group, nausea (1.1%, 5.3%, 1.0%, 5.7%, and 0%) and headache (1.1%, 4.1%, 1.0%, 5.7%, and 0%). CONCLUSIONS: Ready-to-drink SPMC oral solution had consistent, good quality colon cleansing, and favorable tolerability among participants of all BMI groups. CLINICALTRIALSGOV REGISTRATION: NCT03017235.

Efficacy, safety, and tolerability of a ready-to-drink bowel preparation: subanalysis by age from a phase III, assessor-blinded study.

BACKGROUND: The incidence and mortality of colorectal cancer (CRC) increase with age and, therefore, it is recommended that adults undergo regular CRC screening, ideally by colonoscopy, with some new guidelines recommending screening begin at 45 years. Effective bowel preparation is a critical step to a successful colonoscopy. Of concern is that older adults may have poorer quality of bowel preparation or reduced tolerability for the bowel preparation. Here, we performed a post hoc secondary analysis for the effect of age on the efficacy, tolerability, and safety of ready-to-drink sodium picosulfate, magnesium oxide, and citric acid (SPMC oral solution) bowel preparation. METHODS: A phase III, randomized, assessor-blinded, multicenter, non-inferiority study was conducted comparing split-dose, low-volume SPMC oral solution with split-dose, low-volume sodium picosulfate, magnesium oxide, and citric acid powder for oral solution. A post hoc secondary analysis was performed to assess efficacy, safety, and tolerability of SPMC oral solution by age group (<50 years, 50-64 years, ⩾65 years). The prespecified primary efficacy endpoint ('responders') was the proportion of participants with 'excellent' or 'good' ratings on a modified Aronchick Scale (AS). Secondary efficacy outcomes were the quality of cleansing of the right colon as assessed by the Boston Bowel Preparation Scale (BBPS); as well as selected findings from the Mayo Clinic Bowel Prep Tolerability Questionnaire. Safety assessments included adverse events (AEs) and laboratory evaluations. RESULTS: Within age groups, at least 83.9% of participants were responders by the AS, and at least 91.1% of participants were responders by the BBPS in the right colon. On both scales, responder rates were highest in the youngest age group and decreased with increasing age. Greater than 88% of participants in any age group found the preparation 'easy' or 'acceptable' to ingest, with rates of 'easy' being highest in the oldest age group. No new safety signals were seen in any age group. The most commonly reported drug-related, treatment-emergent AEs were, by ascending age group, nausea (7.0%, 3.2%, 0.8%), headache (4.2%, 2.8%, 1.6%) and vomiting (2.8%, 1.2%, 0.8%). CONCLUSION: Ready-to-drink SPMC oral solution showed good efficacy of overall colon cleansing and tolerability in adults across different age groups, including those ⩾65 years.ClinicalTrials.gov identifier: NCT03017235.

Effect of Surgical Weight Loss on Plantar Fasciitis and Health-Care Use.

BACKGROUND:: Plantar fasciitis (PF) is one of the most common causes of heel pain. Obesity is recognized as a major factor in PF development, possibly due to increased mechanical loading of the foot due to excess weight. The benefit of bariatric surgery is documented for other comorbidities but not for PF. METHODS:: A retrospective medical record review was performed for patients with PF identified from a prospectively maintained database of the Cleveland Clinic Bariatric and Metabolic Institute. Age, sex, surgery, excess weight loss, body mass index (BMI), and health-care use related to PF treatment were abstracted. Comparative analyses were stratified by surgery type. RESULTS:: Two hundred twenty-eight of 10,305 patients (2.2%) had a documented diagnosis of PF, of whom 163 underwent bariatric surgery and were included in the analysis. Eighty-five percent of patients were women, mean ± SD age was 52.2 ± 9.9 years, and mean ± SD preintervention BMI was 45 ± 7.7. Postoperatively, mean ± SD BMI and excess weight loss were 34.8 ± 7.8 and 51.0% ± 20.4%, respectively. One hundred forty-six patients (90%) achieved resolution of PF and related symptoms. The mean ± SD number of treatment modalities used for PF per patient preoperatively was 1.9 ± 1.0 ( P = .25). After surgery, the mean ± SD number of treatment modalities used per patient was reduced to 0.3 ± 0.1 ( P = .01). CONCLUSIONS:: We present new evidence suggesting that reductions in BMI after bariatric surgery may be associated with decreasing the number of visits for PF and may contribute to symptomatic improvement.

Completion Gastrectomy with Esophagojejunostomy for Management of Complications of Benign Foregut Surgery.

BACKGROUND: With the worldwide epidemic of obesity, an increasing number of bariatric operations and antireflux fundoplications are being performed. Despite low morbidity of the primary foregut surgery, completion gastrectomy may be necessary as a definitive procedure for complications of prior foregut surgery; however, the literature evaluating outcomes after completion gastrectomy with esophagojejunostomy (EJ) for benign diseases is limited. We present our experience of completion gastrectomy with Roux-en-Y EJ in the setting of benign disease at a single tertiary center. METHODS AND PROCEDURES: All patients who underwent total, proximal, or completion gastrectomy with EJ for complications of benign foregut surgery from January 2006 to December 2015 were retrospectively identified. All cancer operations were excluded. RESULTS: There were 23 patients who underwent gastrectomy with EJ (13 laparoscopic EJ [LEJ] and 10 open EJ). The index operations included 12 antireflux, 9 bariatric, and 2 peptic ulcer disease surgeries. Seventy-eight percent of patients had surgical or endoscopic interventions before EJ, with a median of one prior intervention and a median interval from the index operation to EJ of 25 months (interquartile range 9-87). The 30-day perioperative complication rate was 30% with 17% classified being major (Clavien-Dindo ≥ III) and no 30-day perioperative mortality. Comparing laparoscopic and open approaches showed similar operative times, estimated blood loss, and overall complication rate. LEJ was associated with a shorter length of stay (LOS) (P < .001), fewer postoperative ICU days (P = .002), fewer 6-month complication rates (P < .007), and decreased readmission rate (P = .024). CONCLUSION: Our series demonstrates that EJ is a reasonable option for reoperative foregut surgery. The laparoscopic approach appears to be associated with decreased LOS and readmissions.

Comparative Outcomes of Bariatric Surgery in Patients With and Without Human Immunodeficiency Virus.

BACKGROUND: Paradoxically, advances in anti-retroviral therapy that has increased survival for patients with human immunodeficiency virus (HIV) have resulted in greater numbers of HIV+ patients developing other chronic diseases, including obesity. Little comparative literature exists detailing perioperative or metabolic outcomes of bariatric surgery in the HIV+ population compared to HIV negative (HIV-) controls. METHODS: This is a retrospective case-control study with both HIV+ (case) and HIV- control patients. Individuals undergoing sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) between January 1, 2006 and December 31, 2015 were included. HIV+ status was defined as any individual with documented history of HIV. RESULTS: Eleven HIV+ patients underwent RYGB or SG during the study period. After matching (1:5 HIV+: HIV-) both cohorts had similar mean age (42 years), gender distribution (63% female), and preoperative BMI (48 kg/m2), as well as comorbidities. There were no differences in postoperative length of stay, or all cause 30-day morbidity. There were 63.7% HIV+ and 76.4% with 1-year follow-up available. Both percent excess weight loss (56% HIV+ vs. 60% HIV-) and BMI (32 HIV+ vs. 34 kg/m2 HIV-) were similar in both groups. There were minimal changes to CD4 count or HIV viral load in the patients during the follow-up period. CONCLUSION: Bariatric surgery is safe and feasible in HIV-infected population well controlled on anti-retroviral medication. The short-term surgical and metabolic outcomes are similar to HIV- controls with minimal effect on the CD4 count and viral load in HIV+ cohort for long-term follow-up.

Laparoscopic duodenojejunostomy for superior mesenteric artery syndrome: intermediate follow-up results and a review of the literature.

BACKGROUND: Superior mesenteric artery syndrome (SMAS) is a rare condition caused by partial obstruction of the third portion of the duodenum by the SMA anteriorly and aorta posteriorly. Laparoscopic duodenojejunostomy has been described as a safe and feasible surgical intervention with favorable short-term outcomes. However, descriptions of intermediate outcomes are lacking in the literature. METHODS: A retrospective chart review was performed on patients who underwent minimally invasive duodenojejunostomy from March 2005 to August 2015 at our healthcare system with greater than 6-month follow-up. RESULTS: Eighteen patients with mean age of 31.2 were identified. There were 4 men and 14 women. Patients' diagnosis was made by clinical presentation with radiographic confirmation. Mean weight loss preoperatively was 13.9 kg, representing 24.1 % total body weight loss. There were no intraoperative complications. Postoperatively, 2 patients developed prolonged ileus. One underwent exploratory laparotomy and washout for presumed leak, but none was identified. Three patients were readmitted within 30 days; 2 for intolerance to enteral intake with dehydration, and 1 for closed-loop obstruction requiring laparoscopic lysis of adhesions. The average and median length of follow-up were 27.7 and 26.0 months, respectively. Patients gained an average of 2.2 kg with an increase in body mass index of from 19.6 to 20.4 m/kg2. Although 14 of 18 patients reported initial symptom improvement, at latest follow-up, only 6 patients reported symptomatic improvement or resolution. Three were diagnosed with global dysmotility, and 1 underwent intestinal transplant. Two were diagnosed with gastroparesis, and 1 underwent a laparoscopic gastric electric stimulator placement and pyloroplasty. There were no mortalities. CONCLUSION: Duodenojejunostomy is the most common surgical intervention in management of SMAS. Our intermediate follow-up reveals infrequent improvement and rare resolution of preoperative symptomatology. Patients had a modest average weight gain postoperatively. This may suggest that different preoperative workup and treatment is indicated.

Laparoscopic versus open inguinal hernia repair in patients with obesity: an American College of Surgeons NSQIP clinical outcomes analysis.

INTRODUCTION: The laparoscopic approach to inguinal hernia repair (IHR) has proven beneficial in reducing postoperative pain and facilitating earlier return to normal activity. Except for indications such as recurrent or bilateral inguinal hernias, there remains a paucity of data that specifically identities patient populations that would benefit most from the laparoscopic approach to IHR. Nevertheless, previous experience has shown that obese patients have increased wound morbidity following open surgical procedures. The aim of this study was to investigate the effect of a laparoscopic versus open surgical approach to IHR on early postoperative morbidity and mortality in the obese population using the National Surgical Quality Improvement Program (NSQIP) database. METHODS: All IHRs were identified within the NSQIP database from 2005 to 2013. Obesity was defined as a body mass index ≥30 kg/m2. A propensity score matching technique between the laparoscopic and open approaches was used. Association of obesity with postoperative outcomes was investigated using an adjusted and unadjusted model based on clinically important preoperative variables identified by the propensity scoring system. RESULTS: A total of 7346 patients met inclusion criteria; 5573 patients underwent laparoscopic IHR, while 1773 patients underwent open IHR. On univariate analysis, obese patients who underwent laparoscopic IHR were less likely to experience a deep surgical site infection, wound dehiscence, or return to the operating room compared with those who underwent an open IHR. In both the adjusted and unadjusted propensity score models, there was no difference in outcomes between those who underwent laparoscopic versus open IHR. CONCLUSIONS: The laparoscopic approach to IHR in obese patients has similar outcomes as an open approach with regard to 30-day wound events. Preoperative risk stratification of obese patients is important to determining the appropriate surgical approach to IHR. Further studies are needed to investigate the long-term effects of the open and laparoscopic approaches to IHR in the obese population.

Primary Inadequate Weight Loss After Roux-en-Y Gastric Bypass Is not Associated with Poor Cardiovascular or Metabolic Outcomes: Experience from a Single Institution.

BACKGROUND: It is well accepted that bariatric surgery has cardiovascular and metabolic effects independent of weight loss. METHODS: Weight loss outcomes of patients undergoing Roux-en-Y gastric bypass (RYGB) at a high volume referral center were collected at 1 year postoperatively. Patients with failed primary weight loss were identified. Primary inadequate weight loss was defined as total body weight loss less than 15 %. Changes in hypertension (HTN), dyslipidemia, type 2 diabetes mellitus (T2DM), and metabolic syndrome profiles were investigated using Student's t test. RESULTS: A total of 2500 patients underwent RYGB from the years 2001-2013 at our institution. One hundred five (4.2 %) patients had primary inadequate weight loss. Within this cohort, 81 (77.1 %) patients had hypertension, 67 (63.8 %) had dyslipidemia, 53 (50.5 %) had type 2 diabetes mellitus, and 66 (62.9 %) patients had metabolic syndrome. At 1 year postoperatively, all metabolic parameters were significantly improved. Measures of metabolic disease included high-density lipoprotein (HDL) (46.3 ± 11.6 versus 54.1 ± 12.7 mg/dL, p < 0.01), low-density lipoprotein (LDL) (103.6 ± 35.8 versus 89.2 ± 30.0 mg/dL, p < 0.01), triglycerides (177.3 ± 139.1 versus 117.6 ± 59.3 mg/dL, p < 0.01), mean plasma glucose (128.9 ± 55.3 versus 102.7 ± 27.3 mg/dL, p < 0.01), and hemoglobin A1C (7.3 ± 1.9 versus 6.1 ± 1.0 %, p < 0.01). HTN was noted to improve in 27 (33.3 %) patients based on a decrease in the number of anti-hypertensives used (1.7 ± 1.0 versus 1.3 ± 1.3, p < 0.01), and 21 (31.8 %) patients had resolution of their metabolic syndrome. CONCLUSION: Improvement in cardiometabolic comorbidities still occurs despite suboptimal weight loss following RYGB.

Endoscopic management of post-bariatric surgery complications.

Understanding the technical constructs of bariatric surgery is important to the treating endoscopist to maximize effective endoluminal therapy. Post-operative complication rates vary widely based on the complication of interest, and have been reported to be as high as 68% following adjustable gastric banding. Similarly, there is a wide range of presenting symptoms for post-operative bariatric complications, including abdominal pain, nausea and vomiting, dysphagia, gastrointestinal hemorrhage, and weight regain, all of which may provoke an endoscopic assessment. Bleeding and anastomotic leak are considered to be early (< 30 d) complications, whereas strictures, marginal ulcers, band erosions, and weight loss failure or weight recidivism are typically considered late (> 30 d) complications. Treatment of complications in the immediate post-operative period may require unique considerations. Endoluminal therapies serve as adjuncts to surgical and radiographic procedures. This review aims to summarize the spectrum and efficacy of endoscopic management of post-operative bariatric complications.