Development of a Single Vial Mass Flow Rate Monitor to Assess Pharmaceutical Freeze Drying Heterogeneity.

During pharmaceutical lyophilization processes, inter-vial drying heterogeneity remains a significant obstacle. Due to differences in heat and mass transfer based on vial position within the freeze drier, edge vials freeze differently, are typically warmer and dry faster than center vials. This vial position-dependent heterogeneity within the freeze dryer leads to tradeoffs during process development. During primary drying, process developers must be careful to avoid shelf temperatures that would result in overheating of edge vials causing the product sublimation interface temperature to rise above the critical (collapse) temperature. However, at lower shelf temperatures, center vials require longer to complete primary drying, risking collapse or melt-back due to incomplete drying. Both situations may result in poor product quality affecting drug stability, activity, and reconstitution times. We present a new approach for monitoring vial location-specific water vapor mass flow based on Tunable Diode Laser Absorption Spectroscopy (TDLAS). The single vial monitor enables measurement of the gas flow velocity, water vapor temperature, and gas concentration from the sublimating ice, enabling the calculation of the mass flow rate which can be used in combination with a heat and mass transfer model to determine vial heat transfer coefficients and product resistance to drying. These parameters can in turn be used for robust and rapid process development and control.

Impact of withdrawal time on adenoma detection rate: results from a prospective multicenter trial.

BACKGROUND AND AIMS: Performing a high-quality colonoscopy is critical for optimizing the adenoma detection rate (ADR). Colonoscopy withdrawal time (a surrogate measure) of ≥6 minutes is recommended; however, a threshold of a high-quality withdrawal and its impact on ADR are not known. METHODS: We examined withdrawal time (excluding polyp resection and bowel cleaning time) of subjects undergoing screening and/or surveillance colonoscopy in a prospective, multicenter, randomized controlled trial. We examined the relationship of withdrawal time in 1-minute increments on ADR and reported odds ratio (OR) with 95% confidence intervals. Linear regression analysis was performed to assess the maximal inspection time threshold that impacts the ADR. RESULTS: A total of 1142 subjects (age, 62.3 ± 8.9 years; 80.5% men) underwent screening (45.9%) or surveillance (53.6%) colonoscopy. The screening group had a median withdrawal time of 9.0 minutes (interquartile range [IQR], 3.3) with an ADR of 49.6%, whereas the surveillance group had a median withdrawal time of 9.3 minutes (IQR, 4.3) with an ADR of 63.9%. ADR correspondingly increased for a withdrawal time of 6 minutes to 13 minutes, beyond which ADR did not increase (50.4% vs 76.6%, P < .01). For every 1-minute increase in withdrawal time, there was 6% higher odds of detecting an additional subject with an adenoma (OR, 1.06; 95% confidence interval, 1.02-1.10; P = .004). CONCLUSIONS: Results from this multicenter, randomized controlled trial underscore the importance of a high-quality examination and efforts required to achieve this with an incremental yield in ADR based on withdrawal time. (Clinical trial registration number: NCT03952611.).

Safety of same-day discharge after peroral endoscopic myotomy.

There are limited data on the safety of same-day discharge (SDD) after peroral endoscopic myotomy (POEM). The aim of our study is to assess the frequency and relationship to POEM for emergency department (ED) visits and hospitalizations after SDD in these patients. We retrospectively identified consecutive patients between November 2019 and August 2021 who underwent POEM with SDD and at least 6 months follow-up. Criteria for SDD includes: (1) no serious procedure-related adverse event; (2) post-POEM esophagram without leak; (3) stable vital signs; (4) ability to take liquids orally; (5) pain controlled without IV analgesia; (6) adequate social support; (7) American Society of Anesthesiologists (ASA) class I-III. A causative relationship between POEM and ED visits and hospitalizations was assigned by consensus. Out of 185 POEMs performed, 78 (41.7%, 42M, mean 51±16 years) had SDD. Within 30 days of POEM, 8 ED visits occurred in 7/78 (9%) patients and 2 (25%) were considered related to POEM; hospitalization was required in 3 (38%). After 30 days, 11 ED visits occurred in 10/78 (12.8%) patients and 1 (9%) was considered related to POEM; hospitalization was required in 5 (45%). In this study of consecutive SDD patients after POEM, 3/19 (16%) ED visits and 2/8 (25%) hospitalizations within 6 months were considered related to the procedure. Therefore, eligible patients who follow and fulfill a strict protocol after POEM may be safely discharged the same day.

High-Definition Colonoscopy Compared With Cuff- and Cap-Assisted Colonoscopy: Results From a Multicenter, Prospective, Randomized Controlled Trial.

BACKGROUND AND AIMS: Mucosal exposure devices including distal attachments such as the cuff and cap have shown variable results in improving adenoma detection rate (ADR) compared with high-definition white light colonoscopy (HDWLE). METHODS: We performed a prospective, multicenter randomized controlled trial in patients undergoing screening or surveillance colonoscopy comparing HDWLE to 2 different types of distal attachments: cuff (CF) (Endocuff Vision) or cap (CP) (Reveal). The primary outcome was ADR. Secondary outcomes included adenomas per colonoscopy, advanced adenoma and sessile serrated lesion detection rate, right-sided ADR, withdrawal time, and adverse events. Continuous variables were compared using Student's t test and categorical variables were compared using chi-square or Fisher's exact test using statistical software Stata version16. A P value <.05 was considered significant. RESULTS: A total of 1203 subjects were randomized to either HDWLE (n = 384; mean 62 years of age; 81.3% males), CF (n = 379; mean 62.7 years of age; 79.9% males) or CP (n = 379; mean age 62.1 years of age; 80.5% males). No significant differences were found among 3 groups for ADR (57.3%, 59.1%, and 55.7%; P = .6), adenomas per colonoscopy (1.4 ± 1.9, 1.6 ± 2.4, and 1.4 ± 2; P = .3), advanced adenoma (7.6%, 9.2%, and 8.2%; P = .7), sessile serrated lesion (6.8%, 6.3%, and 5.5%; P = .8), or right ADR (48.2%, 49.3%, and 46.2%; P = .7). The number of polyps per colonoscopy were significantly higher in the CF group compared with HDWLE and CP group (2.7 ± 3.4, 2.3 ± 2.5, and 2.2 ± 2.3; P = .013). In a multivariable model, after adjusting for age, sex, body mass index, withdrawal time, and Boston Bowel Preparation Scale score, there was no impact of device type on the primary outcome of ADR (P = .77). In screening patients, CF resulted in more neoplasms per colonoscopy (CF: 1.7 ± 2.6, HDWLE: 1.3 ± 1.7, and CP: 1.2 ± 1.8; P = .047) with a shorter withdrawal time. CONCLUSIONS: Results from this multicenter randomized controlled trial do not show any significant benefit of using either distal attachment devices (CF or CP) over HDWLE, at least in high-detector endoscopists. The Endocuff may have an advantage in the screening population. (ClinicalTrials.gov, Number: NCT03952611).

Symptom Association for Gastroesophageal Reflux Disease by pH Monitoring After Peroral Endoscopic Myotomy.

INTRODUCTION: There are limited data correlating symptoms with reflux episodes during pH studies after peroral endoscopic myotomy. METHODS: Consecutive patients who underwent POEM followed up ≥6 months later by 48-hour ambulatory wireless pH testing off antisecretory therapy were identified. Reflux symptom association was defined as symptom association probability >95%. RESULTS: The most frequent symptoms of heartburn (47.2%), cough (45.1%), and chest pain (39.6%) were associated with a positive reflux symptom association (symptom association probability >95%) in 20.9%, 17.1%, and 19.4%, respectively. DISCUSSION: There is poor correlation between reported symptoms and esophageal acid exposure during pH testing after POEM.

Comparison of functional lumen imaging probe and high-resolution manometry to assess response after peroral endoscopic myotomy.

BACKGROUND AND AIMS: Outcomes after peroral endoscopic myotomy (POEM) are assessed clinically by the Eckardt score (ES) or objectively by high-resolution manometry (HRM) and functional lumen imaging probe (FLIP). This study compared HRM and FLIP to evaluate clinical response after POEM. METHODS: This was a single tertiary center retrospective study of consecutive patients who underwent POEM for treatment-naive achalasia and with ≥6 months of follow-up. Baseline and follow-up testing in all patients included ES, HRM, and FLIP of the esophagogastric junction (EGJ). A normal post-POEM (or normalized) EGJ distensibility index (EGJ-DI) >2.8 mm2/mm Hg, maximum EGJ diameter (MxEGJD) ≥14 mm, and integrated relaxation pressure (IRP) <15 mm Hg were compared with a clinical response, defined as ES ≤3. RESULTS: Eighty-seven patients (58% men, mean age 51 ± 17 years) were included. Overall clinical response by ES, IRP, MxEGJD, and EGJ-DI were 97.7%, 86.2%, 75.9%, and 92.0%, respectively. The sensitivity of a normal IRP (87.1% [95% confidence interval {CI}, 78.0-93.4]) was similar to the sensitivity of a normal MxEGJD (75.3% [95% CI, 64.7-84.0], P = .053) and normal EGJ-DI (91.8% [95% CI, 83.8%-96.6%], P = .39) after POEM to predict clinical response. However, the sensitivity of a normal post-POEM EGJ-DI was superior to a normal post-POEM MxEGJD (P = .001) to predict clinical response. There was no difference in the area under the curve of a normal MxEGJD or EGJ-DI to predict a normal IRP (P = .956) after POEM. CONCLUSIONS: Normal FLIP metrics ≥6 months after POEM for achalasia show good to excellent sensitivity but are equivalent to a normalized IRP by HRM to predict clinical response by ESs. FLIP may be used as an alternative to HRM to assess lower esophageal sphincter response to POEM in these patients. (Clinical trial registration number: NCT02770859.).

The role of female endoscopists: are women gastroenterologists better at obtaining biopsies for celiac disease than men?

OBJECTIVES: Celiac disease (CD) is commonly found in women. Given the sex differences in diagnosed patients, we hypothesized sex differences in physicians obtaining biopsies for CD may exist. MATERIALS AND METHODS: We retrospectively reviewed duodenal biopsies for suspected CD excluding pre-existing CD patients. Appropriate biopsy practice was defined as ≥5 specimens per ACG guidelines. RESULTS: We included 125 patients (females, 92). There were 85 properly (68%) biopsied. Presence of a female endoscopist was associated with better adherence to biopsy guidelines (OR, 2.99, 95% CI, 1.19-7.54; p = .02) which remained significant after multivariable adjustment (adjusted OR, 2.7; p = .047). CONCLUSIONS: Physician sex-based differences in biopsy patterns may exist.

Pacific western boundary currents and their roles in climate.

Pacific Ocean western boundary currents and the interlinked equatorial Pacific circulation system were among the first currents of these types to be explored by pioneering oceanographers. The widely accepted but poorly quantified importance of these currents-in processes such as the El Niño/Southern Oscillation, the Pacific Decadal Oscillation and the Indonesian Throughflow-has triggered renewed interest. Ongoing efforts are seeking to understand the heat and mass balances of the equatorial Pacific, and possible changes associated with greenhouse-gas-induced climate change. Only a concerted international effort will close the observational, theoretical and technical gaps currently limiting a robust answer to these elusive questions.

A Compact Model for Lyophilizer Equipment Capability Estimation.

This work presents a compact model for the equipment capability limit of a common configuration of pharmaceutical lyophilizers, a product chamber separated from the condenser by a duct and isolation valve, at a wide range of design parameters. The equipment capability limit is one of the most important characteristics determining the lyophilization design space for a particular product, container, and equipment combination. Experimental measurements of equipment capability are time-consuming and expensive, especially at the production scale. Numerical modeling using computational fluid dynamics may reduce the number of experiments and provide insights into the physics of the process with high resolution. The computational fluid dynamics (CFD) modeling has been used in this work to develop a compact model for lyophilizer equipment capability. This eliminates the need for end users to create a full CFD model of the equipment and process. Full CFD and compact model simulations for laboratory and pilot-scale lyophilizers have been compared with tunable diode laser absorption spectroscopy measurements of the water vapor mass flow during ice slab tests. The compact model results average deviation from the experimental data is within 10%, whereas the full CFD simulations are within 5%. The compact model is based on several key parameters which are the main characteristics of a lyophilizer affecting the equipment capability curve. These parameters are discussed, and their effect on the modeling results is shown.

A Software Tool for Lyophilization Primary Drying Process Development and Scale-up Including Process Heterogeneity, I: Laboratory-Scale Model Testing.

Freeze-drying is a deceptively complex operation requiring sophisticated design of a robust and efficient process that includes understanding and planning for heterogeneity across the batch and shifts in parameters due to vial or lyophilizer changes. A software tool has been designed to assist in process development and scale-up based on a model that includes consideration of the process heterogeneity. Two drug formulations were used to test the ability of the new tool to develop a freeze-drying cycle and correctly predict product temperatures and drying times. Model inputs were determined experimentally, and the primary drying heterogeneous freeze-drying model was used to design drying cycles that provided data to verify the accuracy of model-predicted product temperature and primary drying time. When model inputs were accurate, model-predicted primary drying times were within 0.1 to 15.9% of experimentally measured values, and product temperature accuracy was between 0.2 and 1.2°C for three vial locations, center, inner edge, and outer edge. However, for some drying cycles, differences in vial heat transfer coefficients due to changes in shelf and product temperature as well as altered product resistance due to product temperature-dependent microcollapse increased inaccuracy (up to 28.6% difference in primary drying time and 5.1°C difference in product temperature). This highlights the need for careful determination of experimental conditions used to calculate model inputs. In future efforts, full characterization of location- and shelf temperature-dependentKv as well as location- and product temperature-dependentRp will enhance the accuracy of the predictions by the model within the user-friendly software.

Impact of a ring-fitted cap on insertion time and adenoma detection: a randomized controlled trial.

BACKGROUND AND AIMS: Devices for flattening colon folds can improve polyp detection at colonoscopy. However, there are few data on the endoscopic ring-fitted cap (EndoRings; EndoAid, Caesarea, Israel). We sought to compare adenoma detection with EndoRings with that of standard high-definition colonoscopy. METHODS: This was a single-center, randomized controlled trial of 562 patients (284 randomized to EndoRings and 278 to standard colonoscopy) at 2 outpatient endoscopy units in the Indiana University Hospital system. Adenoma detection was the primary outcome measured as adenoma detection rate (ADR) and adenomas per colonoscopy (APC). We also compared sessile serrated polyp detection rate, insertion times, withdrawal times, and ease of passage through the sigmoid colon. RESULTS: EndoRings was superior to standard colonoscopy in terms of APC (1.46 vs 1.06, P = .025), but there were no statistically significant differences in ADR or sessile serrated polyp detection rate. Mean withdrawal time (in patients with no polyps) was shorter and insertion time (all patients) was longer in the EndoRings arm by 1.8 minutes and 0.75 minutes, respectively. One provider had significantly higher detection with Endo-Rings and contributed substantially to the overall results. CONCLUSIONS: EndoRings can increase adenoma detection without a significant increase in procedure time, but the effect varies between operators. The use of EndoRings slows colonoscope insertion. (Clinical trial registration number: NCT03418662.).

A comparison of 2 distal attachment mucosal exposure devices: a noninferiority randomized controlled trial.

BACKGROUND AND AIMS: Endocuff (Arc Medical Design, Leeds, UK) and Endocuff Vision (Arc Medical Design, Leeds, UK) are effective mucosal exposure devices for improving polyp detection during colonoscopy. AmplifEYE (Medivators Inc, Minneapolis, Minn, USA) is a device that appears similar to the Endocuff devices but has received minimal clinical testing. METHODS: We performed a randomized controlled clinical trial using a noninferiority design to compare Endocuff Vision with AmplifEYE. RESULTS: The primary endpoint of adenomas per colonoscopy was similar in AmplifEYE at 1.63 (standard deviation 2.83) versus 1.51 (2.29) with Endocuff Vision (P = .535). The 95% lower confidence limit was 0.88 for ratio of means, establishing noninferiority of AmplifEYE (P = .008). There was no difference between the arms for mean insertion time, and mean inspection time (withdrawal time minus polypectomy time and time for washing and suctioning) was shorter with AmplifEYE (6.8 minutes vs 6.9 minutes, P = .042). CONCLUSIONS: AmplifEYE is noninferior to Endocuff Vision for adenoma detection. The decision on which device to use can be based on cost. Additional comparisons of AmplifEYE with Endocuff by other investigators are warranted. (Clinical trial registration number: NCT03560128.).

A phase III, multicenter, prospective, single-blinded, noninferiority, randomized controlled trial on the performance of a novel esophageal stent with an antireflux valve (with video).

BACKGROUND AND AIMS: Self-expanding metal stents (SEMSs) when deployed across the gastroesophageal junction (GEJ) can lead to reflux with risks of aspiration. A SEMS with a tricuspid antireflux valve (SEMS-V) was designed to address this issue. The aim of this study was to evaluate the efficacy and safety of this stent. METHODS: A phase III, multicenter, prospective, noninferiority, randomized controlled trial was conducted on patients with malignant dysphagia requiring SEMSs to be placed across the GEJ. Patients were randomized to receive SEMSs with no valve (SEMS-NV) or SEMS-V. Postdeployment dysphagia score at 2 weeks and Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) questionnaire score at 4 weeks were measured. Patients were followed for 24 weeks. RESULTS: Sixty patients were randomized (SEMS-NV: 30 patients, mean age 67 ± 13 years; SEMS-V: 30 patients, mean age 65 ± 12 years). Baseline dysphagia scores (SEMS-NV, 2.5 ± .8; SEMS-V, 2.5 ± .8) and GERD-HRQL scores (SEMS-NV, 11.1 ± 8.2; SEMS-V, 12.8 ± 8.3) were similar. All SEMSs were successfully deployed. A similar proportion of patients in both arms improved from advanced dysphagia to moderate to no dysphagia (SEMS-NV, 71%; SEMS-V, 74%; 95% confidence interval, 1.93 [-17.8 to 21.7]). The dysphagia scores were also similar across all follow-up time points. Mean GERD-HRQL scores improved by 7.4 ± 10.2 points in the SEMS-V arm and by 5.2 ± 8.3 in the SEMS-NV group (P = .96). The GERD-HRQL scores were similar across all follow-up time points. Aspiration pneumonia occurred in 3.3% in the SEMS-NV arm and 6.9% in the SEMS-V arm (P = .61). Migration rates were similar (SEMS-NV, 33%; SEMS-V, 48%; P = .29). Two SEMS-V spontaneously fractured. There was no perforation, food impaction, or stent-related death in either group. CONCLUSIONS: The SEMS-V was equally effective in relieving dysphagia as compared with the SEMS-NV. Presence of the valve did not increase the risks of adverse events. GERD symptom scores were similar between the 2 stents, implying either that the valve was not effective or that all patients on proton pump inhibitors could have masked the symptoms of GERD. Studies with objective evaluations such as fluoroscopy and/or pH/impedance are recommended. (Clinical trial registration number: NCT02159898.).

Development of a Mini-Freeze Dryer for Material-Sparing Laboratory Processing with Representative Product Temperature History.

The goal of the work described in this publication was to evaluate a new, small, material-sparing freeze dryer, denoted as the "mini-freeze dryer or mini-FD", capable of reproducing the product temperature history of larger freeze dryers, thereby facilitating scale-up. The mini-FD wall temperatures can be controlled to mimic loading procedures and dryer process characteristics of larger dryers. The mini-FD is equipped with a tunable diode laser absorption spectroscopy (TDLAS) water vapor mass flow monitor and with other advanced process analytical technology (PAT) sensors. Drying experiments were performed to demonstrate scalability to larger freeze dryers, including the determination of vial heat transfer coefficients, K v . Product temperature histories during K v runs were evaluated and compared with those obtained with a commercial laboratory-scale freeze dryer (LyoStar II) for sucrose and mannitol product formulations. When the mini-FD wall temperature was set at the LyoStar II band temperature (- 20°C) to mimic lab dryer edge vials, edge vial drying in the mini-FD possessed an average K v within 5% of those obtained during drying in the LyoStar II. When the wall temperature of the mini-FD was set equal to the central vial product temperature, edge vials behaved as center vials, possessing a K v value within 5% of those measured in the LyoStar II. During both K v runs and complete product freeze drying runs, the temperature-time profiles for the average edge vials and central vial in the mini-FD agreed well with the average edge and average central vials of the LyoStar II.

Recommended Best Practices for Process Monitoring Instrumentation in Pharmaceutical Freeze Drying-2017.

Recommended best practices in monitoring of product status during pharmaceutical freeze drying are presented, focusing on methods that apply to both laboratory and production scale. With respect to product temperature measurement, sources of uncertainty associated with any type of measurement probe are discussed, as well as important differences between the two most common types of temperature-measuring instruments-thermocouples and resistance temperature detectors (RTD). Two types of pressure transducers are discussed-thermal conductivity-type gauges and capacitance manometers, with the Pirani gauge being the thermal conductivity-type gauge of choice. It is recommended that both types of pressure gauge be used on both the product chamber and the condenser for freeze dryers with an external condenser, and the reasoning for this recommendation is discussed. Developing technology for process monitoring worthy of further investigation is also briefly reviewed, including wireless product temperature monitoring, tunable diode laser absorption spectroscopy at manufacturing scale, heat flux measurement, and mass spectrometry as process monitoring tools.

Narrow-band imaging versus white light for the detection of proximal colon serrated lesions: a randomized, controlled trial.

BACKGROUND: The value of narrow-band imaging (NBI) for detecting serrated lesions is unknown. OBJECTIVE: To assess NBI for the detection of proximal colon serrated lesions. DESIGN: Randomized, controlled trial. SETTING: Two academic hospital outpatient units. PATIENTS: Eight hundred outpatients 50 years of age and older with intact colons undergoing routine screening, surveillance, or diagnostic examinations. INTERVENTIONS: Randomization to colon inspection in NBI versus white-light colonoscopy. MAIN OUTCOME MEASUREMENTS: The number of serrated lesions (sessile serrated polyps plus hyperplastic polyps) proximal to the sigmoid colon. RESULTS: The mean inspection times for the whole colon and proximal colon were the same for the NBI and white-light groups. There were 204 proximal colon lesions in the NBI group and 158 in the white light group (P = .085). Detection of conventional adenomas was comparable in the 2 groups. LIMITATIONS: Lack of blinding, endoscopic estimation of polyp location. CONCLUSION: NBI may increase the detection of proximal colon serrated lesions, but the result in this trial did not reach significance. Additional study of this issue is warranted. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01572428.).

Long-term follow-up results of endoscopic treatment of gastroesophageal reflux disease with the MUSE™ endoscopic stapling device.

BACKGROUND: The initial 6-month data for MUSE™ (Medigus, Omer, Israel) endoscopic stapling device were reported (Zacherl et al. in Surg Endosc 29:220-229, 2015). The current study aims to evaluate the long-term clinical outcome of 37 patients who received endoscopic gastroesophageal reflux disease (GERD) treatment with the MUSE™ device. METHODS: Efficacy and safety data for 37 patients were analyzed at baseline, 6 months, and 4 years post-procedure. In one center (IU), efficacy and safety data were evaluated at baseline, 6 months post-procedure, and then annually up to 4 years. RESULTS: No new complications have been reported in our long-term analysis. The proportions of patients who remained off daily PPI were 83.8 % (31/37) at 6 months and 69.4 % (25/36) at 4 years post-procedure. GERD-Health Related Quality of Life (HRQL) scores (off PPI) were significantly decreased from baseline to 6 months and 4 years post-procedure. The daily dosage of GERD medications, measured as omeprazole equivalents (mean ± SD, mg), decreased from 66.1 ± 33.2 at baseline to 10.8 ± 15.9 at 6 months and 12.8 ± 19.4 at 4 years post-procedure (P < 0.01). CONCLUSIONS: In our multi-center prospective study, the MUSE™ stapling device appears to be safe and effective in improving symptom scores as well as reducing PPI use in patients with GERD. These results appeared to be equal to or better than those of the other devices for endoluminal GERD therapy. Future studies with larger patient series, sham control group, and greater number of staples are awaited.

Endoscopic anterior fundoplication with the Medigus Ultrasonic Surgical Endostapler (MUSE™) for gastroesophageal reflux disease: 6-month results from a multi-center prospective trial.

BACKGROUND: Both long-term proton pump inhibitor (PPI) use and surgical fundoplication have potential drawbacks as treatments for chronic gastroesophageal reflux disease (GERD). This multi-center, prospective study evaluated the clinical experiences of 69 patients who received an alternative treatment: endoscopic anterior fundoplication with a video- and ultrasound-guided transoral surgical stapler. METHODS: Patients with well-categorized GERD were enrolled at six international sites. Efficacy data was compared at baseline and at 6 months post-procedure. The primary endpoint was a ≥ 50 % improvement in GERD health-related quality of life (HRQL) score. Secondary endpoints were elimination or ≥ 50 % reduction in dose of PPI medication and reduction of total acid exposure on esophageal pH probe monitoring. A safety evaluation was performed at time 0 and weeks 1, 4, 12, and 6 months. RESULTS: 66 patients completed follow-up. Six months after the procedure, the GERD-HRQL score improved by >50 % off PPI in 73 % (48/66) of patients (95 % CI 60-83 %). Forty-two patients (64.6 %) were no longer using daily PPI medication. Of the 23 patients who continued to take PPI following the procedure, 13 (56.5 %) reported a ≥ 50 % reduction in dose. The mean percent of total time with esophageal pH <4.0 decreased from baseline to 6 months (P < 0.001). Common adverse events were peri-operative chest discomfort and sore throat. Two severe adverse events requiring intervention occurred in the first 24 subjects, no further esophageal injury or leaks were reported in the remaining 48 enrolled subjects. CONCLUSIONS: The initial 6-month data reported in this study demonstrate safety and efficacy of this endoscopic plication device. Early experience with the device necessitated procedure and device changes to improve safety, with improved results in the later portion of the study. Continued assessment of durability and safety are ongoing in a three-year follow-up study of this patient group.

Treatment of esophageal leaks, fistulae, and perforations with temporary stents: evaluation of efficacy, adverse events, and factors associated with successful outcomes.

BACKGROUND: Factors associated with successful endoscopic therapy with temporary stents for esophageal leaks, fistulae, and perforations (L/F/P) are not well known. OBJECTIVES: To evaluate the safety, efficacy, and outcomes of esophageal stenting in these patients and identify factors associated with successful closure. DESIGN: Retrospective. SETTING: Academic tertiary referral center. PATIENTS: All patients with attempted stent placement for esophageal L/F/P between January 2003 and May 2012. INTERVENTION: Esophageal stent placement and removal. MAIN OUTCOME MEASUREMENTS: Factors predictive of therapeutic success defined as complete closure after index stent removal (primary closure) or after further endoscopic stenting (secondary closure). RESULTS: Sixty-seven patients with 132 attempted stents for esophageal L/F/P were considered; 13 patients were excluded. Among the remaining 54 patients, 117 stents were placed for leaks (29 patients; 64 stents), fistulae (15 patients; 36 stents), and perforations (10 patients; 17 stents). Procedural technical success was achieved in all patients (100%). Primary closure was successful in 40 patients (74%) and secondary closure in an additional 5 (83% overall). On short-term (<3 months) follow-up, 27 patients (50%) were asymptomatic, whereas 22 (41%) had technical adverse events, including stent migration in 15 patients (28%). Factors associated with successful primary closure include a shorter time between diagnosis of esophageal L/F/P and initial stent insertion (9.03 vs 22.54 days; P = .003), and a smaller luminal opening size (P = .002). LIMITATIONS: Retrospective, single-center study. CONCLUSIONS: Temporary stents are safe and effective in treating esophageal L/F/P. Defect opening size and time from diagnosis to stent placement appear to be candidate predictors for successful closure.

Associations of seasonally available global positioning systems-derived walkability and objectively measured sleep in the Nurses' Health Study 3 Mobile Health Substudy.

Background: Sleep is influenced by the environments that we experience while awake and while asleep. Neighborhood walkability has been linked with chronic disease and lifestyle factors, such as physical activity; however, evidence for the association between walkability and sleep is mixed. Extant studies assign walkability based on residential addresses, which does not account for mobility. We examined the association between walkability and sleep in the Nurses' Health Study 3 (NHS3) Mobile Health Substudy (MHS). Methods: From 2018 to 2020, individuals in the United States-based NHS3 prospective cohort participated in the MHS, in which minute-level global positioning systems (GPS) data and objective sleep duration and efficiency measures were collected via a custom smartphone application and Fitbit, respectively, for four 7-day periods across a year to capture seasonal variability. Census tract walkability was calculated by summing z-scores of population density (2015-2019 American Community Survey), business density (2018 Infogroup), and intersection density (2018 TIGER/Line road shapefiles). We ran generalized additive mixed models with penalized splines to estimate the association between walkability and sleep, adjusting for individual-level covariates as well as GPS-based exposure to environmental and contextual factors. Results: The average main sleep period duration was 7.9 hours and the mean sleep efficiency was 93%. For both sleep duration and sleep efficiency, we did not observe an association with daily average walkability exposure. Conclusion: In this study of women across the United States, we found that daily GPS-based neighborhood walkability exposure during wake time was not associated with objective wearable-derived sleep duration or sleep efficiency.