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Ellyn K Dunbar,1 Jami L Saloman,2 Anna Evans Phillips,3 David C Whitcomb4 1Departments of Human Genetics and Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA; 2Departments of Neurobiology and Medicine, Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA, USA; 3Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA; 4Departments of Human Genetics, Cell Biology and Molecular Physiology, and Medicine, Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA, USACorrespondence: David C WhitcombDivision of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh and UPMC, Room 401.4, 3708 Fifth Ave, Pittsburgh, PA, 15213, USATel +1 412 578 9515Email whitcomb@pitt.eduAbstract: Pain is the most distressing and disruptive feature of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) resulting in low quality of life (QOL) and disabilities. There is no single, characteristic pain pattern in patients with RAP and CP. Abdominal imaging features of CP accurately reflect morphologic features but they do not correlate with pain. Pain is the major driver of poor quality of life (QOL) and it is the constant pain, rather than intermittent pain that drives poor QOL. Furthermore, the most severe constant pain experience in CP is also a complex condition. The ability to target the etiopathogenesis of severe pain requires new methods to detect the exact pain mechanisms in an individual at cellular, tissue, system and psychiatric levels. In patients with complex and severe disease, it is likely that multiple overlapping mechanisms are simultaneously driving pain, anxiety and depression. Quantitative sensory testing (QST) shows promise in detecting alterations in central processing of pain signals and to classify patients for mechanistic and therapeutic studies. New genetic research suggests that genetic loci for severe pain in CP overlap with genetic loci for depression and other psychiatric disorders, providing additional insights and therapeutic targets for individual patients with severe CP pain. Well-designed clinical trials that integrate clinical features, QST, genetics and psychological assessments with targeted treatment and assessment of responses are required for a quantum leap forward. A better understanding of the context and mechanisms contributing to severe pain experiences in individual patients is predicted to lead to better therapies and quality of life.Keywords: pancreatitis, pain management, mental health, depression, genetic research

Background: After two decades of mass drug administration (MDA) for schistosomiasis in Burkina Faso, an impact assessment was conducted in 16 health districts (HDs) between February 2023 to March 2024 to determine the epidemiological situation of schistosomiasis in school-aged children and facilitate the decision for sub-district level treatment decision., Methodology/principal Findings: A cross-sectional cluster survey was conducted with randomly selected children aged 5-14 years. Haemastix reagent strips were used to detect microhaematuria in urine, and urine filtration was used to detect and quantify Schistosoma haematobium eggs in children with microhaematuria. The Kato-Katz was used to detect and quantify S. mansoni eggs in fecal samples. The prevalence of infection and the prevalence of heavy-intensity (HI) infections were calculated. The overall prevalence of schistosomiasis was 2.4% (range: 0-11.1%) in 16 HDs, with the overall prevalence of HI infection of 0.9% (range: 0-4.2%). Four HDs (Tenkodogo, Batié, Sig-Nonghin, and Karangasso-Vigué) had a prevalence of HI infection from 1.3% to 4.2%. Forty-seven health areas still had an overall prevalence of 1.4-62.5%, with seven health areas in five HDs >10%, and 29 health areas had a prevalence of HI infection from 1.4% to 22.9%. Boys had a higher prevalence of HI infections than girls. The prevalence of microhaematuria at 5.8% was significantly higher than that of S. haematobium infection by urine filtration at 2.3%, and Haemastix results were significantly associated with the intensity of infection., Conclusions/significance: The results showed that progress has been made in eliminating schistosomiasis as a public health problem in the 16 HDs in Burkina Faso after two decades of mass treatment. However, hotspots of infections remain, with 29 health areas having a prevalence of HI infection above the 1% threshold. The results provide evidence for planning targeted sub-district-level treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Zongo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Opioids are used to treat pain in chronic pancreatitis (CP), but little is known about current use patterns. The aims of this study were to characterize the utilization of opioids, and associations with clinical characteristics in adult patients with CP., Methods: This cross-sectional analysis utilized baseline data from participants with definite CP enrolled in a cohort study in the US (PROCEED). Data on demographics, pain medication use, health care utilization, disability, and pain patterns were systematically collected in case report forms while quality of life (QOL) was assessed with patient-reported outcome instruments. Opioid use was classified according to strength (weak or strong) and frequency (scheduled or as-needed)., Results: A total of 681 participants (n=364, 53% male) were included: 299 (44%) were current opioid users (22% only weak opioids and 22% at least one strong opioid). Increasing frequency and severity of pain was associated with increase of weak, strong, as-needed, or scheduled opioids. Neuromodulators were used by ∼40% of participants; increasing use was associated with increasing frequency and severity of pain. On multivariate analysis, independent predictors associated with strength and frequency of current opioid use were pain patterns (ORs 1.84-8.32 and ORs 1.92-8.52, respectively, p<0.001) and prior celiac plexus block (OR 3.54, 95% CI 1.82-6.87) and (OR 3.42, 95% CI 1.76-6.64), respectively. Participants using opioids had higher prevalence of disability, healthcare utilization and poorer QOL., Conclusions: Opioid use in CP is common and associated with increased pain severity and constancy. These data provide foundational estimates for future trials that can elucidate the complex interactions between patient factors, pain, and interventions., (Copyright © 2025 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Abstract: Both the clinical management and study of recurrent acute pancreatitis and chronic pancreatitis are complicated by significant heterogeneity in the etiology, mechanisms, symptoms, and complications of pancreatitis. The National Institutes of Diabetes and Digestive and Kidney Disease recently convened a workshop to address current knowledge and knowledge gaps in the field. Preclinical models that better replicate human disease are important for development of new therapies. Pain is often the most common and most difficult symptom to treat, as the causes are multifactorial and effective treatment may vary depending on whether pain is neuropathic or nociceptive in origin, and the placebo effect can complicate evaluation of the efficacy of medical and procedural interventions. Novel technologies like functional magnetic resonance imaging and virtual reality may offer novel means for assessing and treating pain, respectively. Clinical trial designs will need to consider best approaches to addressing the heterogeneity of chronic pancreatitis, including careful attention to designing eligibility criteria, and establishing accepted and validated core outcomes criteria for the field. The latter may be informed by consensus in pain research. Recruitment of participants into clinical trials has been challenging, often requiring multiple centers. Establishment of a clinical trials network would facilitate greater opportunities for therapeutic trials in pancreatitis., Competing Interests: D.Y. is a consultant for Pfizer, Inc and has received research support from AbbVie Pharmaceuticals. M.D.B. has served on advisory or monitoring boards for Vertex, Novo Nordisk, and Bridge Bio and received research support from ViaCyte and Dexcom. C.E.F. is a consultant for Nestle Health and has received research support from AbbVie Pharmaceuticals. G.I.P. has received research support by AbbVie Pharmaceuticals. S.J.S. is a consultant for UpToDate (Wolters, Inc). J.E. is a consultant for Boston Scientific Co. L.M. is President of Mission Cure Capital but no financial support or conflict of interest. F.G.S.T. has served as consultant for Sanofi. W.G.P. is a consultant for Pfizer, Arctx Medical, Ariel Medicine, Capsovision, Horizon Therapeutics, Nestle, and Olympus, and has received research support from AbbVie. A.J.F. is a consultant for BridgeBio, has received research funding from Anagram Therapeutics, and is a board member for CAPER. V.K.S. is a consultant to Panafina and Amgen; advisory board participant to Amgen and Ionis; and equity holder and scientific advisory board to Solv Endotherapy, Origin Endoscopy, and Kyttaro. D.C.W. is a consultant for Nestlé and Ariel Precision Medicine and is co-founder and chief scientific officer at Ariel Precision Medicine, Pittsburgh, PA. V.A. is a consultant for Olympus Medical, Dragonfly Endoscopy, and is a co-founder for Origin Endoscopy Inc, Solv Endotherapy Inc, and Sotelix Endoscopy Inc. All other authors have no conflict of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Disclosures: No declared conflict of interests

Objectives: Pain is the foremost complication of chronic pancreatitis (CP), affecting about 70% of patients. However, the pathophysiological understanding and management of CP-related pain are complex, likely as patients have diverse "pain phenotypes" responding differently to treatment. This study aims to develop a bedside test panel to identify distinct pain phenotypes, investigate the temporal evolution, and determine whether they can be used to predict treatment response., Methods: The INPAIN study is an international, multicenter, observational, longitudinal cohort study consisted of 4 substudies. The studies will prospectively enroll 400 CP patients (50 without pain and 350 with pain) and 50 control subjects, conducting biannual observations for 4 years. The test panel is consisted of comprehensive subjective and objective assessment parameters. Statistical analysis strategies differ across the substudies. A model to predict treatment efficacy will be developed using various machine learning techniques, including an artificial intelligence approach, with internal cross-validation. Trajectories in pain parameters will be characterized by graphical analysis and mixed effect models., Discussion: The INPAIN study aims to comprehensively understand pain in CP through a test panel developed for routine clinical use. This tool has the potential to personalize treatments, improve clinical practice, enhance patient care, improve quality of life, and minimize treatment side effects., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Gastrointestinal (GI) symptoms and weight loss develop during and after acute pancreatitis (AP), but remain understudied. In this prospective, multicenter study, we aim to assess GI symptom burden and weight loss and their correlation with exocrine function up to 12-mo post-AP., Methods: GI symptom burden, anthropometrics, and exocrine pancreatic function were systematically measured in adults (≥18 years) with AP at predefined intervals: hospitalization (enrollment), 3-months (3-mo), and 12-mo post-AP. Symptoms were evaluated using a 15-item tracker, including abdominal symptoms, stool characteristics, and activities of daily living; higher scores indicating greater symptom burden (range 0-45). Exocrine function was assessed with fecal elastase-1 (FE-1) levels., Results: GI symptoms were collected in 97 participants with 12-mo follow-up. The median (IQR) GI-symptom score was 7 (3-12) with 55 participants (57%) experiencing at least one symptom frequently ("often" or "almost always"). In multivariable linear regression, younger age, lower Charlson Comorbidity Index, smoking, recurrent AP, and alcoholic or idiopathic etiologies were associated with significantly higher GI-symptom burden at 12-mo. A significant negative correlation was found between GI symptoms and FE-1 levels during hospitalization ((ρ)=-0.288; p=0.015) and at 12-mo (ρ=-0.219; p=0.046). Eighteen participants (18.6%) lost ≥10% body weight between hospitalization and 12-mo, and had significantly lower median FE-1 levels at 12-mo compared to the group without weight-loss (166 vs. 332 µg/g, p=0.016)., Conclusions: This is the first study to prospectively assess GI-symptom burden and exocrine function post-AP. Lower exocrine pancreatic function at 12-mo was associated with increased symptom burden and weight loss. These findings support further investigations to define and improve patient-reported outcomes post-AP., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Dietary fat malabsorption contributes to poor nutritional status in patients with cystic fibrosis (CF) and exocrine pancreatic insufficiency (EPI). Prescribing gastric acid-reducing agents such as proton-pump inhibitors (PPI) as an adjunct to pancreatic enzyme replacement therapy (PERT) to improve dietary fat absorption has been accepted in clinical practice despite limited evidence., Aims: This was a pilot randomized, double-blind, placebo-controlled crossover trial of subjects aged 12 and older with CF and EPI assessed on placebo and omeprazole to determine if PPI improved the efficacy of PERT as indicated by measures of dietary fat absorption., Methods: Fat malabsorption via stool coefficient of fat absorption (CFA) and malabsorption blood test (MBT), gastrointestinal pH (wireless motility capsule [WMC]), and quality of life (QOL) were assessed after 14 days on both placebo or PPI (omeprazole)., Results: Total 19 subjects enrolled, 13 were randomized, and 9 provided paired results on placebo and PPI. The 3 subject results for CFA were as follows: 1 increased, 1 decreased, and 1 was within the reference range in both tests for fat absorption. For 9 MBT subjects, 7 decreased and 2 increased fat absorption. For the 4 WMC studies, no change in transit times, nor in pH profiles were noted. No differences were seen in the domains of the two QOL questionnaires comparing placebo and PPI., Conclusions: These limited descriptive pilot study results in participants with CF and EPI on PERT evaluated by stool, blood, and QOL tests did not suggest improvement in fat absorption attributable to PPI., Competing Interests: Declarations Conflict of interest All authors disclose they have no conflicts of interest related to this project and manuscript. The funding sources had no role in study design, analysis, or drafting of the manuscript., (© 2024. The Author(s).)

Background: Spontaneous pancreatic portal vein fistula (PPVF) - a rare complication of pancreatic inflammation - varies widely in presentation and means of diagnosis but has been previously associated with bleeding complications and mortality. A systematic review of published literature was performed to assess the frequency of outcomes., Methods: A search of electronic databases (PubMed, Ovid MEDLINE, Scopus, EMBASE, gray literature) resulted in 1667 relevant unique manuscripts; 52 met inclusion criteria., Results: A total of 74 unique (male n = 47, 63.5 %) patients were included. Mean age was 53.5 (±11.9) years. History of alcohol use was reported in 55 (74.3 %). Underlying chronic pancreatitis (CP) was present in 49 (66.2 %). In cases where presenting symptoms were reported (n = 57, 77.4 %), the most frequent were abdominal pain (63.5 %), weight loss (14.9 %), rash (12.2 %), nausea/vomiting (12.2 %), and polyarthritis (9.5 %). Computed tomography was the most common imaging modality used to confirm the diagnosis (n = 20, 27.0 %), followed by magnetic resonance cholangiopancreatography (n = 14, 18.9 %). Portal vein thrombosis was reported in 57 (77.0 %), and bleeding events (luminal, variceal, or intra-pseudocyst) were reported in 13(17.6 %) patients. Younger age was associated with higher risk of bleeding events. Mortality was reported in 12 (16.2 %) patients at any time during follow up. Older age and polyarthritis at presentation were associated with mortality., Conclusions: PPVF is a rare and potentially fatal condition, though rates of bleeding complication and death were relatively low in this population. High-quality observational studies are needed to better understand the pathophysiology and natural history of this diagnosis., Competing Interests: Declaration of competing interest AEP: Board Member, National Pancreas Foundation. All other authors declare no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose of Review: The burdens of pancreatic ductal adenocarcinoma (PDAC) and acute pancreatitis are increasing globally. We reviewed current literature on whether acute pancreatitis is a causal factor for PDAC and examined clinical manifestations of PDAC-associated acute pancreatitis., Recent Findings: Recent findings detail the timing of acute pancreatitis before and after PDAC occurrence, further solidifying the evidence for PDAC-associated acute pancreatitis and for acute pancreatitis as a causal risk factor for PDAC. The risk of PDAC remains elevated above the general population in patients with distant history of acute pancreatitis. PDAC risk also increases with recurrent acute pancreatitis episodes, independent of smoking and alcohol. Mechanisms linking acute pancreatitis to PDAC include inflammation and neutrophil infiltration, which can be attenuated by suppressing inflammation and/or epigenetic modulation, thus slowing the progression of acinar-to-ductal metaplasia. Clinical presentation and management of acute pancreatitis in the context of PDAC are discussed, including challenges acute pancreatitis poses in the diagnosis and treatment of PDAC, and novel interventions for PDAC-associated acute pancreatitis., Summary: PDAC risk may be reduced with improved acute pancreatitis prevention and treatment, such as antiinflammatories or epigenetic modulators. Increased acute pancreatitis and PDAC burden warrant more research on better diagnosis and management of PDAC-associated acute pancreatitis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Exocrine Pancreatic insufficiency (EPI) occurs following acute pancreatitis (AP) at variably reported rates and with unclear recovery timeline. The aim of this study was to establish the prevalence and predictors of EPI at 12 months after AP in a prospective cohort., Methods: In this prospective, multicentre, longitudinal cohort study, adult participants (≥18 years) admitted to the hospital with an AP attack (defined by Revised Atlanta Classification) were enrolled in a United States multi-centre longitudinal cohort (Sites: The Ohio State University, University of Pittsburgh, and Johns Hopkins University). Patients were excluded if they had pancreatic cancer, chronic pancreatitis, or malabsorptive disease (including previously diagnosed EPI). Participant data was obtained by interview and by review of the electronic medical record. EPI was assessed by stool fecal elastase (FE-1) levels collected at baseline, 3 months, and 12 months (primary endpoint). EPI was defined by FE-1 <200 μg/g; severe FE-1 level ≤100 μg/g; mild FE-1 101-200 μg/g. Multivariable logistic regression was used to identify predictors of EPI at 12 months. This study is registered with ClinicalTrials.gov, NCT03063398., Findings: EPI was observed in 29 (34.1%) of the 85 participants [44 (51.8%) male, mean age 54.7 ± 14.1 years] who provided stool samples at 12 months. For the study overall, participants were recruited between June 22, 2017 and October 18, 2021. A total of 5794 individuals were screened, 311 of whom were eligible for the study. 112 participants provided stool samples at baseline, 79 completed stool samples at 3 months, and 85 completed samples at 12 months. 64 participants included samples at all 3 timepoints. In univariable analysis, factors significantly associated with EPI at 12 months included recurrent (versus index) AP, pre-existing diabetes, alcohol, and idiopathic etiologies, and increasing severity of AP. In multivariable analysis, the odds of having EPI at 12 months increased 4-fold with idiopathic AP etiology (Odds Ratio 4.095, 95% Confidence Interval [CI] 1.418, 11.826), and 3-fold with moderately severe or severe AP (Odds Ratio 3.166, 95% CI 1.156, 8.670), and baseline diabetes mellitus (Odds Ratio 3.217, 95% CI 1.113, 9.298). Even individuals with an index mild attack of AP (n = 39) developed severe EPI at 12 months (prevalence 12.8%)., Interpretation: EPI as diagnosed by FE-1 is present in over one third of prospectively assessed patients at 12 months post-AP. Since EPI develops in patients with mild AP, investigations are needed to understand the mechanisms of injury and identify methods for tailored screening., Funding: This study was supported by an Investigator Initiated Research Grant from AbbVie, Inc., Competing Interests: VKS declares being a Consultant to Ariel Precision Medicine, Panafina, and Horizon Therapeutics; a Scientific Advisory Board Member of and equity holder in Kyttaro, Origin Endoscopy and Solv Endotherapy. SC declares funding for research, including salary, paid to her institution by Abbvie. MLR declares support from the Cystic Fibrosis Foundation and the American Society for Parenteral and Enteral Nutrition, and position as Chair for the Young Trainees Committee for the Collaborative Alliance for Pancreatic Education and Research (CAPER). PJL declares the Investigator Initiated Research funding from Abbvie for the project execution and administration. GIP declares the Investigator Initiated Research funding that supported this study from Abbvie. All other authors declare no financial or other conflicts of interest., (© 2024 The Authors.)

This work introduces a completely rewritten version of the program RMCProfile (version 7), big-box, reverse Monte Carlo modelling software for analysis of total scattering data. The major new feature of RMCProfile7 is the ability to refine multiple phases simultaneously, which is relevant for many current research areas such as energy materials, catalysis and engineering. Other new features include improved support for molecular potentials and rigid-body refinements, as well as multiple different data sets. An empirical resolution correction and calculation of the pair distribution function as a back-Fourier transform are now also available. RMCProfile7 is freely available for download at https://rmcprofile.ornl.gov/., (© Wojciech A. Sławiński et al. 2024.)

Background: Baseline mapping showed that schistosomiasis was highly/moderately endemic in nine districts in Sierra Leone. Mass drug administration (MDA) with praziquantel started in 2009, and after multiple rounds of treatment, an impact assessment was conducted in 2016 followed by a second re-assessment in 2022 using cluster sampling to provide more granular data for refining chiefdom (sub-district) treatment strategies., Methods: On average, 20 rural villages were systematically selected per district by probability proportional to population size across the nine districts. Surveys were conducted in schools, and 24 school children aged between 5 and 14 years were randomly selected, with an equal number of boys and girls. One stool sample and one urine sample were collected per child. Two Kato-Katz slides were examined per stool for Schistosoma mansoni infection. Hemastix strips were used as a proxy for S. haematobium infection with urine filtration used for egg counts on hematuria-positive samples., Results: In total, 4,736 stool samples and 4,618 urine samples were examined across 200 schools in 125 chiefdoms. Overall, the prevalence of S. mansoni was 16.3% (95% CI: 15.3-17.4%), while the overall prevalence of S. haematobium was 2.0% (95% CI: 1.6-2.4%) by hematuria. The prevalence of heavy infections for S. mansoni and S. haematobium was 1.5% (95% CI: 1.1-1.9%) and 0.02% (95% CI: 0.0-0.14%), respectively. Among 125 chiefdoms surveyed, the overall schistosomiasis prevalence was <10% in 65 chiefdoms, 10-49.9% in 47 chiefdoms, and ≥ 50% in 13 chiefdoms. There was a mixed relationship between schistosomiasis in school children and WASH access in schools., Conclusion: Sierra Leone has made significant progress in reducing schistosomiasis prevalence across the country after a decade of MDA intervention. However, high prevalence remains in some hotspot chiefdoms. The next steps are for the national program to investigate and address any potential issues such as low coverage or poor knowledge of schistosomiasis risk behaviors and, where appropriate, consider broadening to community-wide treatment in hotspot chiefdoms or communities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kargbo-Labour, Redwood-Sawyerr, Conteh, Chop, Bah, Koroma, Kabia, Klein, Juneja, Houck, Reid, Evans, Weaver, Phillips and Zhang.)

Exocrine pancreatic dysfunction (EPD) is a malabsorptive complication of pancreatic disorders that can lead to a host of symptoms ranging from flatulence to diarrhea and contribute to weight loss and metabolic bone disease. It is increasingly recognized to occur after acute pancreatitis (AP), including episodes with mild severity. The risk of developing EPD after AP is influenced by a range of factors, including the degree of acinar cell destruction and inflammation during AP, and persistent structural derangements following AP. In this article, we discuss the epidemiology, pathophysiology, and clinical management of EPD after AP while highlighting key knowledge gaps., Competing Interests: Declaration of competing interest No conflicts of interest exist., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Gastrointestinal hospitalisations in the USA cause over US$130 billion in expenditures, and acute pancreatitis is a leading cause of these hospitalisations. Adequate pain control is one of the primary treatment goals for acute pancreatitis. Though opioids are commonly used for analgesia in these patients, there have been concerns about short-term and long-term side effects of using opioids. Recently, non-opioid medications have been studied to treat pain in patients with acute pancreatitis. This systematic review and network meta-analysis aims to assess the comparative efficacy of analgesic medication for non-severe, acute pancreatitis., Methods and Analysis: We will search multiple electronic databases for randomised controlled trials that study pain management in patients with non-severe, acute pancreatitis. The intervention will be any analgesic for acute pancreatitis in the hospital setting. The comparison group will be patients who received a placebo or other active interventions for pain management. The primary outcomes of interest include pain scores and the need for supplementary analgesia. The secondary outcomes will be serious adverse events, local complications, progression to severe pancreatitis, transfer to the intensive care unit, length of hospitalisation, time to start enteral feeds, 30-day all-cause mortality and Quality of Life Scale scores. If sufficient homogeneity exists among included studies, the findings will be pooled using a traditional pairwise and network meta-analysis. The risk of bias in randomised control trials will be evaluated using the Cochrane Risk of Bias Tool 2.0. The Grading of Recommendations, Assessment, Development, and Evaluation approach will be used to report the certainty of evidence., Ethics and Dissemination: This systematic review will not involve direct contact with human subjects. The findings of this review will be published in a peer-reviewed journal. They will give healthcare providers a better awareness of the optimal analgesic medication for pain treatment in non-severe, acute pancreatitis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Psychiatric comorbidity measured by screening instruments is common in patients with chronic pancreatitis (CP) but whether this accurately reflects clinical diagnosis of psychiatric comorbidity is unknown and the prevalence of psychotropic medication prescription in CP remains largely unexplored., Methods: Adult patients (≥18 years) with definite CP were enrolled and completed the Hospital Anxiety and Depression Scale (HADS). Demographics, clinical characteristics and medications were retrieved from case report forms and the electronic health record (EHR). Clinical diagnosis of depression or anxiety was determined by presence of ICD-10 code or inclusion in the patient's EHR problem list or treatment plan. Comparisons were made between patients with and without clinical psychiatric comorbidity., Results: Total of 81 patients (48, 59.3% male; mean age 57.6 ± 14.3 years) were included. Clinical diagnoses of anxiety and depression were each noted in 47 (58%) patients, with overlap in 42 (51.9%). Compared to clinical diagnoses, the sensitivity and specificity of a positive screen for anxiety (HADS >7) were 76.6% and 91.2%; for depression 55.3% and 88.2%. Patients with anxiety and/or depression were more frequently female (51.9% v 20.7%), younger (53.6 v 64.9 years), and had alcohol etiology (51.9% v 27.6%) (all p < 0.01). In those with psychiatric comorbidity, 42 (80.8%) were prescribed psychotropic medication, most commonly gabapentinoid (24, 57.1%), selective serotonin reuptake inhibitor (n = 22, 52.4%) or benzodiazepine (n = 20, 47.6%)., Conclusions: Psychiatric comorbidities are common among CP patients and many receive psychotropic medications. Further studies are needed to evaluate the impact of these medications on CP symptoms., Competing Interests: Declaration of competing interest The authors report that they have no relevant conflicts of interest., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: The mainstay of soil-transmitted helminth (STH) control is repeated mass drug administration (MDA) of anthelmintics to endemic populations. Individual longitudinal compliance treatment patterns are important for identifying pockets of infected individuals who remain untreated and serve as infection reservoirs., Methods: The Geshiyaro Project censused the study population in Wolaita, Ethiopia at baseline in 2018. Individual longitudinal compliance was recorded for six rounds of community-wide MDA (cMDA). The probability distribution of treatment frequency was analysed by age and gender stratifications. Probabilities of transmission interruption for different compliance patterns were calculated using an individual-based stochastic model of Ascaris lumbricoides transmission., Results: The never-treated (0.42%) population was smaller than expected from a random positive binomial distribution. The observed compliance frequency was well described by the beta-binomial distribution. Preschool-age children (odds ratio [OR] 10.1 [95% confidence interval {CI} 6.63 to 15.4]) had the highest never-treated proportion of the age groups. Conversely, school-age children (SAC) and adults (OR 1.03 [95% CI 0.98 to 1.09]) had the highest always-treated proportion of the age groups., Conclusions: The study reports the largest dataset of individual longitudinal compliance to cMDA for STH control. Clear pattens are shown in the age-dependent distribution of individual compliance behaviour. The impact of compliance on the probability of elimination is significant, highlighting the importance of recording the full frequency distribution, not just the never-treated proportion., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Society of Tropical Medicine and Hygiene.)

Introduction: Treatment for abdominal pain in patients with chronic pancreatitis (CP) remains challenging in the setting of central nervous system sensitisation, a phenomenon of remodelling and neuronal hyperexcitability resulting from persistent pain stimuli. This is suspected to render affected individuals less likely to respond to conventional therapies. Endotherapy or surgical decompression is offered to patients with pancreatic duct obstruction. However, the response to treatment is unpredictable. Pancreatic quantitative sensory testing (P-QST), an investigative technique of standardised stimulations to test the pain system in CP, has been used for phenotyping patients into three mutually exclusive groups: no central sensitisation, segmental sensitisation (pancreatic viscerotome) and widespread hyperalgesia suggestive of supraspinal central sensitisation. We will test the predictive capability of the pretreatment P-QST phenotype to predict the likelihood of pain improvement following invasive treatment for painful CP., Methods and Analysis: This observational clinical trial will enrol 150 patients from the University of Pittsburgh, Johns Hopkins and Indiana University. Participants will undergo pretreatment phenotyping with P-QST. Treatment will be pancreatic endotherapy or surgery for clearance of painful pancreatic duct obstruction., Primary Outcome: average pain score over the preceding 7 days measured by Numeric Rating Scale at 6 months postintervention. Secondary outcomes will include changes in opioid use during follow-up, and patient-reported outcomes in pain and quality of life at 3, 6 and 12 months after the intervention. Exploratory outcomes will include creation of a model for individualised prediction of response to invasive treatment., Ethics and Dissemination: The trial will evaluate the ability of P-QST to predict response to invasive treatment for painful CP and develop a predictive model for individualised prediction of treatment response for widespread use. This trial was approved by the University of Pittsburgh Institutional Review Board. Data and results will be reported and disseminated in conjunction with National Institutes of Health policies., Trial Registration Number: NCT04996628., Competing Interests: Competing interests: AEP: Board Member, National Pancreas Foundation. VKS: Consultant to Abbvie, Ariel Precision Medicine, Horizon Therapeutics and Panafina; Medical Advisory Board participant to Organon; Scientific advisory board participant for Kyttaro, Origin Endoscopy and Solv Endoscopy; Equity holder in Kyttaro, Origin Endoscopy, Solv Endoscopy. The other authors have no financial or personal competing interests to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Abdominal pain is the most common symptom of chronic pancreatitis (CP) and is often debilitating for patients and very difficult to treat. To date, there exists no cure for the disease. Treatment strategies focus on symptom management and on mitigation of disease progression by reducing toxin exposure and avoiding recurrent inflammatory events. Traditional treatment protocols start with medical management followed by consideration of procedural or surgical intervention on selected patients with severe and persistent pain. The incorporation of adjuvant therapies to treat comorbidities including psychiatric disorders, exocrine pancreatic insufficiency, mineral bone disease, frailty, and malnutrition, are in its early stages. Recent clinical studies and animal models have been designed to improve investigation into the pathophysiology of CP pain, as well as to improve pain management. Despite the array of tools available, many therapeutic options for the management of CP pain provide incomplete relief. There still remains much to discover about the neural regulation of pancreas-related pain. In this review, we will discuss research from the last 5 years that has provided new insights into novel methods of pain phenotyping and the pathophysiology of CP pain. These discoveries have led to improvements in patient selection for optimization of outcomes for both medical and procedural management, and identification of potential future therapies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Chinese Medical Association, Published by Wolters Kluwer Health, Inc.)

Samarium hexaboride, SmB 6 , is a negative thermal expansion (NTE) material whose structure is similar to other known NTE materials such as the family of Prussian blues. In the Prussian blues, NTE is due to a phonon mechanism, but we recently showed from DFT calculations that this is unlikely in SmB 6 (Li et al. , Phys. Chem. Chem. Phys . 2023, 25 , 10749). We now report experimental X-ray diffraction and pair distribution function analysis of this material in the temperature range 20-300 K. The interatomic distances shown by both methods are consistent with the NTE instead arising from an electronic effect, by which the samarium atoms lose electrons and thus have a smaller ionic radius as the temperature increases.

Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were compared between CP subjects with and without pain. Only platelet-derived growth factor B (PDGF-B) stood out, with levels significantly higher in the CP pain group as compared to subjects with no pain. Subjects with pain were then stratified into 4 pain subtypes (Neuropathic, Nociceptive, Mixed, and Unclassified). A comparison of putative biomarker concentration among 5 groups (no pain and 4 pain subtypes) identified unique proteins that were correlated with pain subtypes. Serum transforming growth factor beta 1 (TGFβ1) level was significantly higher in the Nociceptive pain group compared to the No pain group, suggesting that TGFβ1 may be a biomarker for nociceptive pain. The Neuropathic pain only group was too small to detect statistical differences. However, glycoprotein 130 (GP130), a coreceptor for interleukin 6, was significantly higher in the Mixed pain group compared to the groups lacking a neuropathic pain component. These data suggest that GP130 may be a biomarker for neuropathic pain in CP. PERSPECTIVE: Serum TGFβ1 and GP130 may be biomarkers for nociceptive and neuropathic CP pain, respectively. Preclinical data suggest inhibiting TGFβ1 or GP130 reduces CP pain in rodent models, indicating that additional translational and clinical studies may be warranted to develop a precision medicine approach to the management of pain in CP., (Copyright © 2023 United States Association for the Study of Pain, Inc. All rights reserved.)

Background: The Geshiyaro project aims to assess the feasibility of interrupting transmission of soil-transmitted helminths (STH) and schistosome (SCH) infection in the Wolaita zone of southern Ethiopia through high coverage community-wide mass drug administration (MDA), in combination with improved water, sanitation, and hygiene services and behaviour change communication delivered through the existing health care infrastructure. To accurately measure treatment coverage a population census was conducted enrolling individuals with biometric fingerprinting and barcoded ID cards. This paper details the baseline census and parasitology surveys conducted before the start of any interventions., Methods: The census was conducted in five of the 15 Wolaita districts between October 2018 and December 2019, enrolling all consenting participants from every household. Simultaneously, a cross-sectional parasitology survey was conducted in 130 out of 361 randomly selected communities from all 15 districts, with 100 individuals across all age groups (infant to adult) per community providing stool and urine for analysis by duplicate Kato-Katz and a point-of-care circulating cathodic antigen (POC-CCA) to test for Schistosoma mansoni and STH, and microhaematuria and urine filtration for Schistosoma haematobium. Of the 130 communities, 30 were randomly selected for annual, longitudinal parasitological monitoring, with 150 randomly selected individuals from infant to adult providing two days of stool and urine samples for analysis by the same diagnostic tests per community., Results: In total 97,919 households participated in the baseline census enrolling 466,071 individuals, with parasitological data obtained from 10,785 people. At baseline, 15.5% were infected with at least one STH species, with Ascaris lumbricoides (9.5%), followed by hookworm (7.2%) and Trichuris trichiura (1.8%). Substantial heterogeneity in STH prevalence was observed between communities ranging from 0% to 61% where most infections were low intensity. Schistosoma mansoni infection was the dominant schistosome infection (0.85% by Kato-Katz and 13.3% by POC-CCA trace negative and 21.5% trace positive), with few Schistosoma haematobium infections identified (2.77% haematuria positive and 0.13% positive by urine filtration)., Conclusions: While the national control program in Ethiopia has made good progress in reducing prevalence of STH and SCH in Wolaita since it was launched in 2015, there remain areas of persistent infection suggesting the existence of environmental or behavioural risk factors that contribute to ongoing transmission. This project aims to identify the most efficient intervention strategies to reduce community burden and reach interruption of transmission., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MS is the Director of Monitoring, Evaluation and Learning at the Children’s Investment Fund Foundation, the project’s funder., (Copyright: © 2023 Phillips et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Due to the burden of schistosomiasis (SCH) and soil-transmitted helminths (STH), Togo Ministry of Health launched a program for Preventive Chemotherapy Neglected Tropical Diseases (PC-NTDs) in 2009, initiating integrated mass drug administration (MDA) the following year for the three PC-NTDs: SCH, STH and onchocerciasis. Significant reduction of infection across the country was noted in 2015 during the first impact assessment, following 5 years of high-coverage MDA implemented at the sub-district level for SCH and district level for STH. After another 5 years of effective MDA, a second survey was conducted in 2021 to re-evaluate the situation of SCH and STH., Methods: A cross-section of school-aged children was taken across ten districts of Togo. A total of 302 schools in 92 sub-districts were sampled, with 24 school-aged children per school resulting in 7248 children surveyed. Urine samples were tested by haemastix® for Schistosoma haematobium, with urine filtration for the presence of eggs conducted on haematuria-positive samples. Stool samples were collected in a subset of 34 sub-districts in seven out of the ten surveyed districts, where STH and Schistosoma mansoni endemicity was high during the 2015 impact assessment. Duplicate (two) Kato-Katz analysis was performed for each stool sample. Sociodemographic and school-level water, sanitation and hygiene information was also collected., Results: Overall, SCH prevalence was 5.90% (95% CI: 5.4-6.5), with 5.09% (95% CI: 4.64-5.67) for S. haematobium and 2.56% (95% CI: 1.98-3.29) for S. mansoni. STH prevalence was 19.7% (95% CI: 18.2-21.4), with 19.6% (95% CI: 18.1-21.3) hookworm, 0.08% (95% CI: 2.2-5.8) Trichuris trichiura and 0.04% (95% CI: 0.01-0.33) Ascaris lumbricoides. Compared to baseline, a significant reduction in both SCH (22.2% to 5.90%) and STH (29.2% t0 19.7%) prevalence was observed. Children aged 5-9 years were less infected than older peers aged 10-14 years: 4.76% vs. 7.53% (P < 0.01) for SCH and 17.2% vs. 23.0% (P < 0.01) for STH., Conclusions: After 10 years of high coverage integrated MDA, Togo has achieved low prevalence SCH infection through the sub-district MDA implementation with considerable infection heterogeneity within sub-districts. As STH infection has not reached a level where the infections are not a public health problem, the sub-district treatment strategy could also be adopted in addition to improvement of treatment coverage among preschool age children and hygiene and sanitation practices., (© 2023. BioMed Central Ltd., part of Springer Nature.)

During acute pancreatitis (AP), free fatty acids (FFAs) are liberated from circulating triglycerides (TG) and injured adipocytes by pancreatic lipase. Circulating FFAs have been suspected as a source of systemic lipotoxicity in AP. However, assessment of FFAs is difficult and time-consuming, and little is known about relative levels of FFAs between patients with different severities of AP and controls. This study's aims were to assess early circulating levels of FFAs, (both saturated and unsaturated) in patients with AP vs. controls, and associations between FFA levels and AP severity. Serum samples from patients with AP were collected at enrollment ( day 1 of hospital stay); serum samples were also collected from controls. FFAs including palmitic, palmitoleic, stearic, oleic, and linoleic acid were extracted and quantitated using gas chromatography separation. Severity of AP was determined by Revised Atlanta Classification. Differences in FFA levels and percentages of total FFAs were assessed between patients with AP and controls and patients with AP of different severity grades. A total of 93 patients with AP (48 female, 52%) and 29 controls (20 female, 69%) were enrolled. Of the patients with AP, 74 had mild/moderate and 19 had severe AP. Serum levels of all FFAs except stearic acid were significantly higher in patients with AP compared with controls. A strong and independent association between elevated palmitoleic acid levels and severe AP was found. Serum unsaturated FFA levels, specifically palmitoleic acid, appear to correlate with severe AP. These findings have potential clinical implications for targeted AP therapies. NEW & NOTEWORTHY Drivers of the inflammatory response in acute pancreatitis remain incompletely understood. Unsaturated fatty acids, specifically palmitoleic, appear to have an association with more severe acute pancreatitis. This finding presents a new clinical understanding of fatty acid toxicity and highlights a potential future target for treatment in severe acute pancreatitis.

Background and Aims: Pancreatic enzyme replacement therapy (PERT) is most commonly used to treat exocrine insufficiency related to pancreatic diseases, but can be used for non-pancreatic digestive conditions (NPDC). We aimed to determine the prevalence of PERT use and describe prescription patterns in individuals with NPDC., Methods: A nationally representative claims database of 48.6 million enrollees was used to identify individuals who received PERT prescription(s) in the absence of any pancreas-related diagnosis. Data on demographics, enrolment, comorbidities, exocrine function testing, treatment and potential indications for PERT were retrieved, and compared with individuals who received PERT for primary diagnosis of chronic pancreatitis (CP)., Results: A total of 29,234 individuals (64.1% female, mean age 52.4 ± 16.5 years) received PERT for NPDC. The overall estimated US population prevalence rate for PERT use for NDPC was 60.2/100,000 persons. Rates increased significantly with age and were higher in women in all age groups except 1-20 years old. When compared with CP, individuals with NPDC receiving PERT were more likely to be older (52.4 vs. 50.1 years), female (64.1% vs. 51.0%), have lower prevalence of alcoholism (3.6% vs. 25.0%), tobacco abuse (8.4% vs. 30.1%), and received PERT for shorter mean duration (5.3 vs. 8.2 months) (all p < 0.001). Median dose of PERT in individuals with NPDC was 2880 lipase units/day., Conclusions: Although proportionally low, a sizable population receives PERT for NPDC. PERT for NPDC is usually prescribed at a low dose and for shorter duration, suggesting it is used mostly as a trial for or until resolution of symptoms., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Malakoplakia is a rare granulomatous tumor-like inflammatory condition, most frequently involving the genitourinary system and occurring in immunosuppressed patients. The gastrointestinal tract is the second most common site, where it is usually seen involving the colon. We report a case of malakoplakia presenting as a pancreatic mass. Imaging showed soft tissue along the pancreatic tail/greater curvature concerning for infiltrating tumor, but endoscopic ultrasound with biopsy showed malakoplakia. Our case discusses malakoplakia at an uncommon site, which was appropriately treated with antibiotics., (© 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

High-entropy order-disorder phase transitions can be used for efficient and eco-friendly barocaloric solid-state cooling. Here the barocaloric effect is reported in an archetypal plastic crystal, adamantane. Adamantane has a colossal isothermally reversible entropy change of 106 J K -1 kg -1 . Extremely low hysteresis means that this can be accessed at pressure differences less than 200 bar. Configurational entropy can only account for about 40% of the total entropy change; the remainder is due to vibrational effects. Using neutron spectroscopy and supercell lattice dynamics calculations, it is found that this vibrational entropy change is mainly caused by softening in the high-entropy phase of acoustic modes that correspond to molecular rotations. We attribute this difference in the dynamics to the contrast between an 'interlocked' state in the low-entropy phase and sphere-like behaviour in the high-entropy phase. Although adamantane is a simple van der Waals solid with near-spherical molecules, this approach can be leveraged for the design of more complex barocaloric molecular crystals. Moreover, this study shows that supercell lattice dynamics calculations can accurately map the effect of orientational disorder on the phonon spectrum, paving the way for studying the vibrational entropy, thermal conductivity, and other thermodynamic effects in more complex materials.

Sympatico-vagal balance is essential for regulating cardiac electrophysiology and plays an important role in arrhythmogenic conditions. Various noninvasive methods, including electrocardiography (ECG), have been used for clinical assessment of the sympatico-vagal balance. This study aimed to use a custom-designed wearable device to record ECG and ECG-based cardiac function biomarkers to assess sympatico-vagal balance during tonic pain in healthy controls. Nineteen healthy volunteers were included for the ECG measurements using the custom-designed amplifier based on the Texas Instruments ADS1299. The ECG-based biomarkers of the sympatico-vagal balance, (including heart rate variability, deceleration capacity of the heart rate, and periodic repolarization dynamic), were calculated and compared between resting and pain conditions (tonic pain). The custom-designed device provided technically satisfactory ECG recordings. During exposure to tonic pain, the periodic repolarization dynamics increased significantly ( p = 0.02), indicating enhancement of sympathetic nervous activity. This study showed that custom-designed wearable devices can potentially be useful in healthcare as a new telemetry technology. The ECG-based novel biomarkers, including periodic repolarization dynamic and deceleration capacity of heart rate, can be used to identify the cold pressor-induced activation of sympathetic and parasympathetic systems, making it useful for future studies on pain-evoked biomarkers.

Abstract: Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N = 681) with CP, 80% experienced abdominal pain within the year before enrollment. Subjects who experienced pain in the week before enrollment (N = 391) completed PROMIS Neuropathic and Nociceptive Pain Quality instruments which were then used to classify them by pain type: 40% had nociceptive, 5% had neuropathic-like, and 32% had both types of pain. The prevalence of having both types of pain was higher among women and subjects with diabetes mellitus, whereas nociceptive-only pain was more prevalent among men and those with pancreatic duct stricture. Other factors, including pain medication use and healthcare utilization, did not differ between groups based on pain type. Subjects in the Both group had significantly worse health and QoL scores relative to those with nociceptive-only pain, suggesting that using psychosocial pain surveys may be useful for understanding pain subtypes in patients with CP. Additional research is needed to identify biochemical and biophysical signatures that may associate with and predict responses to mechanism-specific interventions., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Purpose: The need for incorporation of quantitative imaging biomarkers of pancreatic parenchymal and ductal structures has been highlighted in recent proposals for new scoring systems in chronic pancreatitis (CP). To quantify inter- and intra-observer variability in CT-based measurements of ductal- and gland diameters in CP patients., Materials and Methods: Prospectively acquired pancreatic CT examinations from 50 CP patients were reviewed by 12 radiologists and four pancreatologists from 10 institutions. Assessment entailed measuring maximum diameter in the axial plane of four structures: (1) pancreatic head (PDhead), (2) pancreatic body (PDbody), (3) main pancreatic duct in the pancreatic head (MPDhead), and (4) body (MPDbody). Agreement was assessed by the 95% limits of agreement with the mean (LOAM), representing how much a single measurement for a specific subject may plausibly deviate from the mean of all measurements on the specific subject. Bland-Altman limits of agreement (LoA) were generated for intra-observer pairs., Results: The 16 observers completed 6400 caliper placements comprising a first and second measurement session. The widest inter-observer LOAM was seen with PDhead (± 9.1 mm), followed by PDbody (± 5.1 mm), MPDhead (± 3.2 mm), and MPDbody (± 2.6 mm), whereas the mean intra-observer LoA width was ± 7.3, ± 5.1, ± 3.7, and ± 2.4 mm, respectively., Conclusion: Substantial intra- and inter-observer variability was observed in pancreatic two-point measurements. This was especially pronounced for parenchymal and duct diameters of the pancreatic head. These findings challenge the implementation of two-point measurements as the foundation for quantitative imaging scoring systems in CP., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Several factors have been suggested to mediate pain in patients with chronic pancreatitis. However, it is unknown whether these factors are overlapping and if they have cumulative effects on patient-reported outcomes (PROs)., Design: We performed a multicentre cross-sectional study of 201 prospectively enrolled subjects with definitive chronic pancreatitis. All subjects underwent evaluation for pancreatic duct obstruction, abnormalities in pain processing using quantitative sensory testing, and screening for psychological distress (anxiety, depression and pain catastrophising) based on validated questionnaires. Abnormality was defined by normal reference values. PROs included pain symptom severity (Brief Pain Inventory short form) and quality of life (EORTC-QLQ-C30 questionnaire). Associations between pain-related factors and PROs were investigated by linear trend analyses, multiple regression models and mediation analyses., Results: Clinical evaluation suggestive of pancreatic duct obstruction was observed in 29%, abnormal pain processing in 23%, anxiety in 47%, depression in 39% and pain catastrophising in 28%; each of these factors was associated with severity of at least one PRO. Two or more factors were present in 51% of subjects. With an increasing number of factors, there was an increase in pain severity scores (p<0.001) and pain interference scores (p<0.001), and a reduction in quality of life (p<0.001). All factors had independent and direct effects on PROs, with the strongest effect size observed for psychological distress., Conclusion: Pain-related factors in chronic pancreatitis are often present in an overlapping manner and have a cumulative detrimental effect on PROs. These findings support a multidisciplinary strategy for pain management., Trial Registration Number: The study was registered with ClinicalTrials.gov (NCT03434392)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Geshiyaro project is a 5-year intervention to assess the impact of community- and school-based water, sanitation, and hygiene (WaSH) interventions on reducing infection with soil-transmitted helminths (STH) and schistosome parasites in combination with deworming in Wolayita zone, Ethiopia., Methods: A population-based, cross-sectional census and parasitological mapping activity was conducted between 2018 and 2019. Individuals in the census were identified using either a registered study ID card or biometric fingerprint to enable linkage of their household WaSH data with baseline STH and schistosome prevalence for risk analysis., Results: Prevalence of STH was 15.5% for any STH species, 9.47% for Ascaris lumbricoides, 1.78% for Trichuris trichiura, and 7.24% for hookworm. Intestinal schistosomiasis (Schistosoma mansoni) infection prevalence was 0.85% by Kato Katz, 21.6% by POC-CCA trace positive (Tr +), and 13.3% trace negative (Tr-). Microhaematuria was 2.77%, with 0.13% of people examined with S. haematobium eggs detected by urine filtration. At the household level, increased (> 30 min) time taken to collect drinking water, sharing a latrine, and lack of handwashing facilities were all associated with a greater risk of A. lumbricoides, hookworm, and S. mansoni infection. Not disposing of infant stool at the household and clothes washing/recreational freshwater contact were significantly associated with higher risk of schistosomiasis infection. Aggregating WaSH data at the community level showed odds of A. lumbricoides, hookworm, and T. trichiura infection were significantly lower as both community sanitation coverage and access to improved drinking water improved., Conclusions: The principal finding of this study is that lack of access to WaSH, such as improved drinking water and shared toilet and hand-washing facilities, were linked to an increased risk of infection with STH and schistosome parasites. These associations are difficult to establish at an individual household level because of wide variability in access between houses but are detectable when coverage is aggregated at the community level. Maintenance of WaSH facilities as well as increased access within the whole community is important in influencing the community-wide prevalence of infection with STH and schistosome parasites., (© 2022. The Author(s).)

Mass drug administration (MDA), targeted at school-aged children (SAC) is recommended by the World Health Organization for the control of morbidity induced by soil-transmitted helminth (STH) infection in endemic countries. However, MDA does not prevent reinfection between treatment rounds, and research suggests that only treating SAC will not be sufficient to interrupt transmission of STH. In countries with endemic infection, such as Ethiopia, the coverage, community-groups targeted, and rates of reinfection will determine how effective MDA is in suppressing transmission in the long-term. In this paper, individually-linked longitudinal data from three epidemiological STH surveys conducted between November 2018 and November 2020 in the Wolaita region of Ethiopia are analysed to determine how STH prevalence and intensity changes according to individual level treatment data collected over two rounds of MDA. This study demonstrates that while community-wide MDA successfully reduces overall infection intensity across the villages treated, the observed levels of non-compliance to treatment by individuals acts to maintain levels of parasite abundance whereby transmission interruption is not possible at to, despite reasonable levels of MDA coverage in the communities studied (ranging from 65% to 84% of the village populations). This quantifies with substantial data the often-postulated difference between coverage (accepting treatment) and compliance (swallowing of treatment), the latter impacting the former to a previously unquantified level. The paper highlights the need to focus treatment to partially treated, or never treated groups of individuals within existing community wide MDA control activities to interrupt the transmission of STH, and to reduce the basic reproductive number, R0, of the parasites to less than unity in value., Competing Interests: The authors have declared no competing interests exist.

Background and study aims  N95-filtering facepiece respirators (FFR) use is associated with physiological changes and symptoms due to impaired nasal airflow and increased breathing resistance. We prospectively studied the effect of using an external nasal dilator (END) in gastroenterology laboratory (gastrointestinal lab) staff using N95FFR. Patients and methods  N95FFR qualitative saccharine fit testing was performed on study participants with and without an END. Prospective data collection and comparisons included: 1) survey of perceived symptoms and difficulty of performing one day of gastrointestinal procedures with N95FFR and 1 day of gastrointestinal procedures with END plus N95FFR in random sequence; and 2) vitals and respiratory belt plethysmography in ten gastroenterologists performing simulated colonoscopy while wearing a surgical mask (SM), N95FFR plus SM, END plus N95FFR plus SM for 20 minutes each in random sequence and rapid succession. Results  Twenty-nine of 31 participants passed the N95FFR and the END plus N95FFR fit test. Twenty-two participants (12 physicians; 11 males; mean age 44.1 years, range 31-61) performed 1 day of gastrointestinal procedures with an N95FFR and 1 day of gastrointestinal procedures with an END plus N95FFR. Significantly less difficulty with nasal breathing and severity of symptoms including breathing difficulty, headache, fatigue and frustration, occurred while using an END plus N95FFR. Respiratory plethysmography peak-to-trough measurement showed an increase during the N95FFR stage compared to the END plus N95FFR stage and the SM stage. Conclusions  N95FFR related respiratory changes and symptom development may be mitigated by END use., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The perovskites are an intensely studied class of materials, with a breadth of possible compositions made even wider by the possibility of incorporating molecular ions. Here the context is discussed of a newly reported metal-free perovskite with the H 3 O + ion on the B site., (© Anthony E. Phillips 2022.)

Abstract: Recurrent acute pancreatitis and chronic pancreatitis represent high morbidity diseases, which are frequently associated with chronic abdominal pain, pancreatic insufficiencies, and reduced quality of life. Currently, there are no therapies to reverse or delay disease progression, and clinical trials are needed to investigate potential interventions that would address this important gap. This conference report provides details regarding information shared during a National Institute of Diabetes and Digestive and Kidney Diseases-sponsored workshop on Clinical Trials in Pancreatitis that sought to clearly delineate the current gaps and opportunities related to the design and conduct of patient-focused trials in recurrent acute pancreatitis and chronic pancreatitis. Key stakeholders including representatives from patient advocacy organizations, physician investigators (including clinical trialists), the US Food and Drug Administration, and the National Institutes of Health convened to discuss challenges and opportunities with particular emphasis on lessons learned from trials in participants with other painful conditions, as well as the value of incorporating the patient perspective throughout all stages of trials., Competing Interests: The following authors disclose potential conflicts of interest: P.A.H. (honoraria for consulting from Kangen Pharmaceuticals and Sagent Pharmaceuticals paid to his institution; honorarium for advisory board from Horizon Therapeutics USA, Inc, paid to his institution); G.A.C. (honoraria for consulting from Olympus Corporation of the Americas); I.G. (honoraria from Adynxx, Biogen, Eupraxia, Novaremed and GW Research); R.H.D. (past 5 years, research grants and contracts from the US Food and Drug Administration and the US National Institutes of Health and compensation forf serving on advisory boards or consulting on clinical trial methods from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, Beckley, Biogen, Biohaven, Biosplice, Boston Scientific, Braeburn, Cardialen, Celgene, Centrexion, Chiesi, Chromocell, Clexio, Collegium, Concert, Confo, Decibel, Editas, Eli Lilly, Endo, Ethismos (equity), Eupraxia, Exicure, Glenmark, Gloriana, Grace, Hope, Lotus, Mainstay, Merck, Mind Medicine (also equity), Neumentum, Neurana, NeuroBo, Novaremed, Novartis, OCT, OliPass, Pfizer, Q-State, Reckitt Benckiser, Regenacy (also equity), Sangamo, Sanifit, Scilex, Semnur, SIMR Biotech, Sinfonia, SK Biopharmaceuticals, Sollis, SPRIM, Teva, Theranexus, Toray, Vertex, Vizuri, and WCG); C.E.F. (research funding from Abbvie, consulting fees from Nestlé, and board member for National Pancreas Foundation); J.A.R. (consulting for Pediatrics Steering Committee, Pacira Pharmaceuticals); and D.C.W. (cofounder and chief scientific offer of Ariel Precision Medicine, consultant to Nestlé, Regeneron, and Ariel Precision Medicine). The rest of the authors declare no conflict of interest., (Copyright © 2022 “Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.”.)

Abstract: Acute pancreatitis (AP) is a disease characterized by an acute inflammatory phase followed by a convalescent phase. Diabetes mellitus (DM) was historically felt to be a transient phenomenon related to acute inflammation; however, it is increasingly recognized as an important late and chronic complication. There are several challenges that have prevented precisely determining the incidence rate of DM after AP and understanding the underlying mechanisms. The DREAM (Diabetes RElated to Acute Pancreatitis and its Mechanisms) Study is a prospective cohort study designed to address these and other knowledge gaps to provide the evidence needed to screen for, prevent, and treat DM after AP. In the following article, we summarize literature regarding the epidemiology of DM after AP and provide the rationale and an overview of the DREAM study., Competing Interests: E.A. is on the advisory board for Nestle. M.D.B. receives research support from Viacyte and Dexcom and is on advisory board for Insulet. K.M.D. receives research support from Sanofi, Viacyte, Abbott, and Dexcom; has consulting activities with Eli Lilly, Boehringer Ingelheim, Elsevier; and receives honoraria from UptoDate, Elsevier, Medscape, and Academy for Continued Healthcare Learning. C.E.F. receives research support from AbbVie and has consulting activities with Nestle. G.I.P. receives research support from AbbVie and has consulting activities with Nestle. C.S. is on the advisory board for Vertex Pharmaceuticals. F.G.S.T. receives research support from Dompé Pharmaceuticals and has consulting activities with Sanofi, Eli Lilly, and AstraZeneca. The other authors declare no conflict of interest., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

The vibrational properties of crystalline bulk materials are well described by Debye theory, which successfully predicts the quadratic ω 2 low-frequency scaling of the vibrational density of states. However, the analogous framework for nanoconfined materials with fewer degrees of freedom has been far less well explored. Using inelastic neutron scattering, we characterize the vibrational density of states of amorphous ice confined inside graphene oxide membranes and we observe a crossover from the Debye ω 2 scaling to an anomalous ω 3 behaviour upon reducing the confinement size L. Additionally, using molecular dynamics simulations, we confirm the experimental findings and prove that such a scaling appears in both crystalline and amorphous solids under slab-confinement. We theoretically demonstrate that this low-frequency ω 3 law results from the geometric constraints on the momentum phase space induced by confinement along one spatial direction. Finally, we predict that the Debye scaling reappears at a characteristic frequency ω ×  = vL/2π, with v the speed of sound of the material, and we confirm this quantitative estimate with simulations., (© 2022. The Author(s).)

The orientational disorder in crystalline sulfur hexafluoride, SF 6 , has been studied using a combination of neutron total scattering and the reverse Monte Carlo method. Analysis of the atomic configurations has shown the extent of the disorder through the evaluation of the S-F bond orientational distribution function, consistent with, but improving upon, the results of earlier neutron powder diffraction data. The correlations between orientations of neighbouring molecules have been studied through analysis of the distributions of F-F distances, showing that nearest-neighbour F-F close contacts are avoided, consistent with previous molecular dynamics simulation results. The results present a new case study of the application of neutron total scattering and the reverse Monte Carlo methods for the study of orientational disorder, where in this instance the disorder arises from orientational frustration rather than from a mismatch of molecular and site symmetries., (Creative Commons Attribution license.)

Background and Aims: Pain is the primary symptom of chronic pancreatitis (CP) and has been associated with abnormal pain processing and psychologic distress. Little is known about these phenomena in patients with painless disease. The aim of this study was to characterize patterns of pain processing and psychologic distress in patients with primary painless vs painful CP., Methods: This was a cross-sectional multicenter study of 235 patients with definitive CP. Patients were categorized based on current and past pain history; current pain (79%), no current (but prior) pain (11%), and painless CP (10%). Demographic information and clinical data including symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale were collected. All patients underwent quantitative sensory testing to assess patterns of pain processing., Results: A total of 235 patients (57% males, mean age 53.9 ± 14.0 years, 41% alcohol etiology) were included. Compared to patients with painless CP, enhanced pain sensitivity was observed in both patients with current pain (odds ratio [OR] 3.29; 95% confidence interval [CI] [1.11-9.77], P  = .032) and no current pain (OR 4.07; 95% CI [1.10-15.03], P  = .035). Patients with current pain also had increased depression prevalence compared to patients with painless CP (OR 6.15; 95% CI [1.28-29.41], P  = .023), while no difference was seen for patients with no current pain (OR 1.24; 95% CI [0.19-8.26], P  = .824)., Conclusion: Total absence of pain in CP is associated with normal pain processing and low prevalence of psychologic distress, whereas patients with prior pain experience appear to have persistent and enhanced pain sensitivity even in the absence of clinical pain and psychologic distress., (© 2022 The Authors.)

We report results from a study of the crystal and magnetic structures of strontium-doped BiFeO 3 using neutron powder diffraction and the Rietveld method. Measurements were obtained over a wide range of temperatures from 300-800 K for compositions between 10%-16% replacement of bismuth by strontium. The results show a clear variation of the two main structural deformations-symmetry-breaking rotations of the FeO 6 octahedra and polar ionic displacements that give ferroelectricity-with chemical composition, but relatively little variation with temperature. On the other hand, the antiferromagnetic order shows a variation with temperature and a second-order phase transition consistent with the classical Heisenberg model. There is, however, very little variation in the behaviour of the antiferromagnetism with chemical composition, and hence with the degree of the structural symmetry-breaking distortions. We therefore conclude that there is no significant coupling between antiferromagnetism and ferroelectricity in Sr-doped BiFeO 3 and, by extension, in pure BiFeO 3 ., (Creative Commons Attribution license.)

Background & Aims: Pain is the foremost complication to chronic pancreatitis (CP), but no validated questionnaires for assessment exist. The COMPAT questionnaire includes all relevant pain dimensions in CP, but a short form is needed to make it usable in clinical practice., Methods: The full COMPAT questionnaire was completed by 91 patients and systematically reduced to 6 questions. Pain severity and analgesic use were merged, leaving 5 pain dimensions. The pain dimension ratings were normalized to a 0-100 scale, and the weighted total score was calculated, where 3 dimensions were weighted double. Reliability of the short form was tested in a test-retest study in 76 patients, and concurrent validity tested against the Brief Pain Inventory and Izbicki pain questionnaire. Convergent validity was verified using confirmatory factor analysis, and criterion validity tested against quality-of-life and hospitalization rates., Results: The COMPAT-SF questionnaire consisted of the following pain dimensions: a) pain severity, b) pain pattern, c) factors provoking pain, d) widespread pain, and e) a qualitative pain-describing dimension. Quality of life correlated with the total score and all pain dimensions (P <.05). The total score, pain severity, pain pattern, and factors provoking pain were correlated with hospitalization rates (P <.05). The total score correlated with the Izbicki and Brief Pain Inventory scores (P <.0001). The reliability of the questionnaire in patients in a stable phase was good with an interclass correlation coefficient of 0.89., Conclusion: The COMPAT-SF questionnaire includes the most relevant aspects of pain in CP and is a feasible, reliable, and valid pain assessment instrument recommended to be used in future trials., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A paucity of research regarding the psychosocial outcomes after TPIAT exists., Methods: Adults (>18 years), adolescents (13-18 years), and children (5-12 years) with their parents were administered questionnaires at the time of evaluation for TPIAT and 1-year postsurgery to assess psychosocial outcomes., Results: A total of 13 adults (6 male, 46%; mean age 35.2 years) and 9 children/adolescents (4 female, 44.4%; mean age 11.78 years) with CP were included in the study. A total of 69.2% of the adults and 66.7% of the children and adolescents were insulin dependent at 1-year postsurgery. In adults, improvements on the SF-36 pain (p = .001) and general health (p = .045) subscales were generally observed 1-year postsurgery. Adult patients who underwent robotic-assisted surgery compared to open surgery specifically reported better general health on the SF-36 (p < .05) at 1 year. For children and adolescents, reductions in average pain in the last week (p < .05), pain interference (p < .001), and fatigue were observed (p < .05) at 1-year postsurgery. For the entire sample, using repeated measures ANOVA and covarying for age, significant differences were found 1-year postsurgery in average pain in the last week (p = .034) and pain interference with the following categories: general activity (p < .001), walking (p = .04), normal work (p = .003), sleep (p = .002), and enjoyment in life (p = .007)., Conclusions: While few transplant centers offer this treatment, the improvement in quality of life suggests this may be a viable treatment option for those with CP complicated by intractable pain. (IRB Approval PRO 19080302)., (© 2021 Wiley Periodicals LLC.)