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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. Graphical abstract: [Figure not available: see fulltext.]

ObjectiveSeveral 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).DesignWe 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.ResultsClinical 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 (pConclusionPain-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 numberThe study was registered with ClinicalTrials.gov (NCT03434392).

A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities in pancreatic pain. The event was held on July 21, 2021, and structured into 4 sessions: (1) pathophysiology; (2) biomarkers, mediators, and pharmacology of pain; (3) pain assessment; and (4) pain treatment challenges and opportunities. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation. Common themes included the need to better understand the underlying mechanisms of pain in pancreatic diseases, the relationship of visceral neural pathways and central pain centers, the role of behavioral factors and disorders on the perception of pain, and differences in pain perception and processes in children when compared with adults. In addition, the role of genetic risk factors for pain and the mechanisms and role of placebos in pain treatment were discussed. Methods of pain assessment including quantitative sensory testing were examined, as well as the process of central sensitization of pain. Finally, newer approaches to pain management including cognitive behavioral therapy, nerve stimulation, experimental (nonopioid) drugs, and cannabinoid compounds were covered.

To determine factors affecting mortality, and long-term patency of portal vein, in patients with pancreatic-portal vein fistula (PPVF). Consecutive cases of PPVF at the University of Pittsburgh Medical Center from 2008 to 2020 were retrospectively identified. Clinical history, imaging studies, management strategies, complications, and long-term outcomes were analyzed. Fourteen patients, representing the largest PPVF cohort reported to date (mean age 58.6 years, 64.3% women, median follow-up 10 months [1–98 months]) were identified. Underlying chronic pancreatitis was seen in 9 (64.3%) patients, while 5 (35.7%) developed PPVF with first attack of acute pancreatitis. PPVF involved proximal main portal vein (MPV) in 10 (78.6%) patients. Of the 5 patients (35.7%) who died, all had occlusive (n=4) or near-occlusive (n=1) PPVF-associated filling defect (FD) in the MPV. Conversely, 7 of 9 survivors (87.5%) had subocclusive FD and patent MPV. In patients with sepsis (n=5), 1 underwent surgical necrosectomy and survived, while 3 of 4 (75%) patients without debridement died. Occlusive/near-occlusive PPVF-associated MPV FD, and sepsis, are associated with high mortality rates, while subocclusive MPV FD is associated with survival and long-term MPV patency. PPVF is a potentially life-threatening, and possibly under-diagnosed, entity that warrants early clinical suspicion for timely diagnosis, to facilitate optimal management.

Purpose of review Management of abdominal pain in patients with chronic pancreatitis is often suboptimal. We review recent data on the epidemiology and new approaches for managing pain in chronic pancreatitis. Recent findings Chronic pancreatitis duration does not appear to affect the pain experience. Pain pattern in chronic pancreatitis patients frequently changes and is not related to traditional patient and disease-related factors. Psychologic comorbidities, i.e. anxiety and depression, are frequent in patients with chronic pancreatitis, and are associated with more severe pain and pain interference. Adjunctive treatments, such as cognitive behavioral therapy, may positively influence pain management in chronic pancreatitis. Total pancreatectomy with islet autotransplantation (TPIAT) is an increasingly adopted treatment option in painful chronic pancreatitis. Ongoing multicenter studies will help define optimal candidates, predictors of successful pain remission and diabetes outcomes after TPIAT. Pancreatic quantitative sensory testing, a promising technique to interrogate nociception and sensory response, holds promise to identify patients with central sensitization. Initial studies show feasibility to stratify patients into defined pain profiles, and future studies will explore if these can help in prognostication of pain therapy. Summary Several lines of investigations currently under evaluation are likely to have a positive impact on the management of pain in chronic pancreatitis.

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.

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.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.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.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.

Background Immunoglobulin G subclass 4 (IgG4) is hypothesized to play an immunomodulatory role, downregulating humoral immune responses. The role of this anti-inflammatory molecule in inflammatory bowel disease (IBD) has not been fully characterized. We sought to define alterations in serum IgG4 in patients with IBD and their association with multiyear disease severity. Methods We analyzed metadata derived from curated electronic health records from consented patients with IBD prospectively followed at a tertiary center over a 10-year time period. Patients with IBD with IgG4 serum levels available formed the study population. Demographics and multiyear clinical data were collected and analyzed. We stratified patients with IBD with low, normal, or high serum IgG4 levels. Results We found IgG4 characterized in 1193 patients with IBD and low IgG4 levels in 233 patients (20%) and elevated IgG4 levels in 61 patients (5%). An IgG4 deficiency did not significantly correlate with other antibody deficiencies. In a multiple Poisson regression analysis, low IgG4 was associated with more years on biologic agents (P = 0.002) and steroids (P = 0.049) and more hospital admissions (P < 0.001), clinic visits (P = 0.010), outpatient antibiotic prescriptions (P < 0.001), and CD-related surgeries (P = 0.011) during the study period after controlling for certain confounders. Elevated IgG4 was only associated with primary sclerosing cholangitis (P = 0.011). A cohort of patients with IgG4-deficient severe IBD received intravenous Ig replacement therapy, which benefited and was continued in 10 out of 11 individuals. Conclusions An IgG4 subclass deficiency, distinct from other antibody deficiencies, occurred commonly in a referral IBD population and was associated with multiple markers of disease severity. This is the first association of IgG4 subclass deficiency with an inflammatory disease process. Further work is needed to define the mechanistic role of IgG4 deficiency in this severe IBD subgroup.

Background & Aims: Quantitative sensory testing (QST) has been previously used to study pain in chronic pancreatitis (CP) but included methods that are not suitable for clinical purposes. The aims of this study were to determine if pancreatic QST (P-QST) can differentiate patients into distinct pain phenotypes and to determine the association of these with their clinical pain and psychiatric comorbidities. Methods: A multicenter cross-sectional study was conducted where patients completed validated questionnaires assessing quality of life (QoL), depression and anxiety scores as well as clinical pain symptoms followed by P-QST which included a cold pressor test, repetitive pinprick stimuli and pressure stimulation of the upper abdominal (T10) and control dermatomes. P-QST categorized patients into pain phenotypes based on a previously established nomogram. QoL, clinical pain and psychiatric assessment scores were compared across these groups. Results: A total of 179 patients were enrolled with a mean age of 54.1±13.6 years among whom 59% were males and 42% had an alcoholic etiology. P-QST showed no hyperalgesia in 91 (51%), segmental hyperalgesia in 50 (28%) and widespread hyperalgesia in 38 (21%) patients. Patients with widespread hyperalgesia had significantly higher pain intensity scores (P =.03) and rates of constant pain (P =.002) as well as decreased QoL (P

Background/objectives While pain is the predominant symptom of chronic pancreatitis (CP), a subset of patients may experience a painless course. This systematic review aimed to determine the prevalence of primary painless CP. Methods MEDLINE (PubMed), EMBASE and Web of Science Core Collection databases were searched for published studies through September 15, 2020 that included at least 10 consecutive patients with CP and which reported the number with painless CP. The presence of a history of recurrent acute pancreatitis (RAP), exocrine pancreatic insufficiency (EPI), diabetes mellitus (DM) and pancreatic adenocarcinoma (PA) in the painless CP patients was also recorded. A random effects model was used to determine pooled prevalence estimates with 95% confidence intervals (95% CI). Results Among the 5057 studies identified and screened, 42 full-text articles were included in the final analysis. There were a total of 14,277 patients with CP among whom 1569 had painless CP. The pooled prevalence of painless CP was 12% (95% CI 10–15%). Among a subset of studies that reported on calcifications (n = 11), DM (n = 12), EPI (n = 8) and history of RAP (n = 14), the pooled prevalence estimates were 96% (95% CI 73–100%), 51% (95% CI 32–70%), and 47% (95% CI 15–81%), respectively. Alcohol, idiopathic/genetic and other etiologies were attributed to be the cause of painless CP in 32.4%, 56.9% and 8.9% patients, respectively. Conclusion Approximately one in ten patients with CP have primary painless disease with the majority being attributable to an idiopathic/genetic etiology. Further research is needed to determine the optimal management of these patients.

OBJECTIVES: Abdominal pain is the primary symptom of chronic pancreatitis (CP), but pain is difficult to assess, and objective methods for pain assessment are lacking. The characterization of the sensory component of pain as a surrogate for nociception can be achieved by sensory testing using standardized stimuli. Herein, we describe the rationale for and development of an international consortium to better understand and characterize CP pain.METHODS: A collaboration was initially formed between the University of Aalborg, Johns Hopkins University, and the University of Pittsburgh. This group refined the protocol for pancreatic quantitative sensory testing (P-QST) and then expanded the collaboration with plans for incorporating P-QST into prospective studies.RESULTS: The collaboration has successfully developed a P-QST nomogram. Chronic pancreatitis patients identified with P-QST as having widespread hyperalgesia had higher pain intensity scores, higher prevalence of constant pain, and decreased quality of life. Psychiatric comorbidities were independent of pain phenotypes. Multiple studies are underway to validate these findings and evaluate their utility in clinical trials.CONCLUSIONS: Development of the P-QST Consortium will facilitate collaborative efforts to use P-QST as a means for evaluation and characterization of pain in CP patients, and optimize methods to guide individualized pain management approaches.

A paucity of research regarding the psychosocial outcomes after TPIAT exists.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.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).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).

Background Weight bias is a pervasive problem for adolescents in school contexts. Despite evidence of negative attitudes towards students who are overweight, comparatively little research has examined whether teachers provide biased assessments of student work. Aims The purpose of this study was to experimentally test whether middle and high school teachers unfairly assess students who are overweight and perceive them to be less competent. Sample Participants included 133 teachers from first-ring suburban middle and high schools (Mteaching experience = 16 years; 38% male). Methods Teachers evaluated the quality of a bogus student essay assignment accompanied by photographs that portrayed the student as either not overweight or overweight. Weight bias was assessed by having teachers grade the essay and provide perceptions of student sufficiency (perceived effort, need for tutoring, and overall success in school). Opinions about bias in grading for other teachers and self were also assessed. Results Essays for students who were overweight were judged to be similar in structural quality, but were assigned lower grades compared to their healthy weight counterparts. Further, teachers estimated that students who were overweight put forth more effort, needed more remedial assistance, and had lower overall grades in school. Teachers' beliefs about grading bias showed low levels of supposed bias among other teachers and a significantly lesser degree for themselves. Conclusions This study confirms prior research on anti-fat attitudes and provides new evidence of biased attitudes in school settings.

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.

Background: Diabetic neuropathy is characterized by the paradoxical co-existence of hypo- and hyperalgesia to sensory stimuli. The literature shows consistently sensory differences between healthy and participants with diabetes. We hypothesized that due to differences in pathophysiology, advanced quantitative sensory testing (QST) might reveal sensory discrepancies between type 1 (T1D) and type 2 diabetes (T2D). Furthermore, we investigated whether vibration detection thresholds (VDT) were associated with sensory response.Method: Fifty-six adults with T1D [43 years (28–58)], 99 adults with T2D [65 years (57–71)], and 122 healthy individuals [51 years (34–64)] were included. VDT, pressure pain detection thresholds (pPDT) and tolerance (pPTT), tonic cold pain (hand-immersion in iced water), and central pain mechanisms (temporal summation and conditioned pain modulation) were tested and compared between T1D and T2D. VDT was categorized into normal (< 18 V), intermediary (18–25 V), or high (> 25 V).Results: In comparison to healthy, analysis adjusted for age, BMI, and gender revealed hypoalgesia to tibial (pPDT): p = 0.01, hyperalgesia to tonic cold pain: p < 0.01, and diminished temporal summation (arm: p < 0.01; abdomen: p < 0.01). In comparison to participants with T2D, participants with T1D were hypoalgesic to tibial pPDT: p < 0.01 and pPTT: p < 0.01, and lower VDT: p = 0.02. VDT was not associated with QST responses.Conclusion: Participants with T1D were more hypoalgesic to bone pPDT and pPTT independent of lower VDT, indicating neuronal health toward normalization. Improved understanding of differentiated sensory profiles in T1D and T2D may identify improved clinical endpoints in future trials.

Objectives We describe the methodology of Post-Acute Pancreatitis Pancreatic Exocrine Insufficiency (PAPPEI), a prospective, observational, multicenter cohort study. The objectives of PAPPEI are to estimate the incidence rate of post-acute pancreatitis (AP) pancreatic exocrine insufficiency (PEI), define factors that determine the development of post-AP PEI, and evaluate the impact of post-AP PEI on nutritional status and quality of life. Methods Enrollment started in June 2017 in 3 expert academic centers in the United States. Data were collected during hospitalization (baseline) at 3 and 12 months after enrollment. Fecal elastase-1 was used to assess PEI. Study questionnaires are completed by patient interview and review of electronic medical records. Blood is obtained to evaluate vitamin deficiencies and nutritional markers. Results As of August 2020, 77 subjects have completed the baseline evaluation. The median age was 58 years (interquartile range, 39-67 years), 38% were male, and 90% were white. The etiology of AP was biliary in 39 subjects (51%), and 51 subjects (66%) had mild AP. Three- and 12-month follow-up data have been collected in 29 and 13 subjects, respectively. Conclusion The PAPPEI study aims to expand our understanding of post-AP PEI incidence, including its impact on nutritional status and quality of life.

Background Ethiopia has set the ambitious national targets of eliminating soil-transmitted helminths (STH) and schistosomiasis (SCH) as public health problems by 2020, and breaking their transmission by 2025. This systematic review was performed to provide insight into the progress made by the national STH and SCH control programme purposed with reaching these targets. Methods Studies published on STH and SCH in Ethiopia were searched for using Web of Science, PubMed, Scopus, and the resulting references of selected studies. Prevalence and intensity were analysed, stratified by region, age, and diagnostics. Results A total of 231 papers published between 2000 and 2020 were included. Over the past two decades, Trichuris trichiura (TT) infection has shown the most statistically significant decrease (93%, p Schistosoma mansoni (SM) (69%, p Ascaris lumbricoides (AL) (67%, p Schistosoma haematobium (83%, p = 0.038) infections. Geographically, parasite burden has only consistently shown a significant reduction in the Southern Nations, Nationalities and Peoples’ Region of Ethiopia, where AL, TT, hookworm and SM significantly decreased by 80% (p = 0.006), 95% (p = 0.005), 98% (p = 0.009) and 87% (p = 0.031), respectively. Prevalence of STH was highest among adults across all species, contrary to typical age-infection profiles for TT and AL that peak among school-aged children. Expanding treatment to the whole community would target reservoirs of adult and preschool-aged infection within the community, assisting Ethiopia in reaching their national transmission break targets. There was substantial heterogeneity in diagnostic methods used across studies, the majority of which predominantly used single-slide Kato–Katz. This low slide frequency provides poor diagnostic sensitivity, particularly in low endemic settings. Conclusion The prevalence of STH and SCH in Ethiopia has decreased over time due to the strategic use of anthelmintics. Both standardising and increasing the sensitivity of the diagnostics used, alongside the ubiquitous use of parasite intensity with prevalence, would enable a more accurate and comparable understanding of Ethiopia’s epidemiological progress. Further work is needed on community-wide surveillance in order to understand the burden and subsequent need for treatment among those outside of the standard school-based control program. Graphical Abstract

Introduction The Geshiyaro project aims to break transmission of soil-transmitted helminths and schistosomiasis in the Wolaita Zone of Ethiopia through a combination of two interventions: behavior change communication (BCC) for increased water, sanitation and hygiene (WaSH) infrastructure use alongside preventive chemotherapy (PC) using albendazole (ALB) and praziquantel (PZQ), targeted to reach 90% treatment coverage. Coverage evaluation surveys (CES) were conducted post-treatment, and the resultant survey coverage was compared to reported administrative coverage. This provided a secondary confirmation of the Geshiyaro project coverages, and is used to monitor the success of each Mass Drug Administration (MDA) round. Methods A community-based cross-sectional study was conducted in 13 woredas (districts) of the Wolaita Zone. All eligible individuals from the selected households were invited for an interview. The study design, sample size, analysis and report writing were conducted according to the World Health Organization (WHO) CES guidelines for PC. Results The study interviewed a total of 3,568 households and 18,875 individuals across 13 woredas in the Wolaita Zone. Overall, the survey coverage across all studied woredas was 81.5% (95% CI; 80.9–82.0%) for both ALB and PZQ. Reported administrative coverage across all studied woredas was higher than survey coverage, 92.7% and 91.2% for ALB and PZQ, respectively. A significant portion of individuals (17.6%) were not offered PC. The predominant reason for not achieving the target coverage of 90% was beneficiary absenteeism during MDA (6.6% ALB, 6.8% PZQ), followed by drug distributors failing to reach all households (4.7% ALB, 4.8% PZQ), and beneficiaries not informed of the program (1.3% ALB, 1.7% PZQ). Conclusion Programmatic actions will need to be taken during the next MDA campaign to achieve the targeted Geshiyaro project coverage threshold across data collection and program engagement. Adequate training and supervision on recording and reporting administrative coverage should be provided, alongside improved social mobilization of treated communities to increase participation, and strengthened institutional partnerships and communication.

BACKGROUND AND AIM: The primary aim was to validate the Pancreatitis Activity Scoring System (PASS) in a multicenter prospectively ascertained acute pancreatitis (AP) cohort. Second, we investigated the association of early PASS trajectories with disease severity and length of hospital stay (LOS). METHODS: Data were prospectively collected through the APPRENTICE consortium (2015-2018). AP severity was categorized based on revised Atlanta classification. Delta PASS (ΔPASS) was calculated by subtracting activity score from baseline value. PASS trajectories were compared between severity subsets. Subsequently, the cohort was subdivided into three LOS subgroups as short (S-LOS): 2-3 days; intermediate (I-LOS): 3-7 days; and long (L-LOS): ≥7 days. The generalized estimating equations model was implemented to compare PASS trajectories. RESULTS: There were 434 subjects analyzed including 322 (74%) mild, 86 (20%) moderately severe, and 26 (6%) severe AP. Severe AP subjects had the highest activity levels and the slowest rate of decline in activity (P = 0.039). Focusing on mild AP, L-LOS subjects (34%) had 28 points per day slower decline; whereas, S-LOS group (13%) showed 34 points per day sharper decrease compared with I-LOS (53%; P

Pain burn-out during the course of chronic pancreatitis (CP), proposed in the 1980s, remains controversial, and has clinical implications. We aimed to describe the natural course of pain in a well-characterized cohort.We constructed the clinical course of 279 C P patients enrolled from 2000 to 2014 in the North American Pancreatitis Studies from UPMC by retrospectively reviewing their medical records (median observation period, 12.4 years). We assessed abdominal pain at different time points, characterized pain pattern (Type A [short-lived pain episodes] or B [persistent pain and/or clusters of recurrent severe pain]) and recorded information on relevant covariates.Pain at any time, at the end of follow-up, Type A pain pattern or B pain pattern was reported by 89.6%, 46.6%, 34% and 66% patients, respectively. In multivariable analyses, disease duration (time from first diagnosis of pancreatitis to end of observation) did not associate with pain - at last clinical contact (OR, 1.0, 95% CI 0.96-1.03), at NAPS2 enrollment (OR 1.02, 95% CI 0.96-1.07) or Type B pain pattern (OR 1.01, 95% CI 0.97-1.04). Patients needing endoscopic or surgical therapy (97.8 vs. 75.2%, p 0.001) and those with alcohol etiology (94.7 vs. 84.9%, p = 0.007) had a higher prevalence of pain. In multivariable analyses, invasive therapy associated with Type B pain and pain at last clinical contact.Only a subset of CP patients achieve durable pain relief. There is urgent need to develop new strategies to evaluate and manage pain, and to identify predictors of response to pain therapies for CP.

We used reported behavioural data from cisgender men who have sex with men and transgender women (MSM/TGW) in Bangalore, mainly collected from 'hot-spot' locations that attract MSM/TGW, to illustrate a technique to deal with potential issues with the representativeness of this sample. A deterministic dynamic model of HIV transmission was developed, incorporating three subgroups of MSM/TGW, grouped according to their reported predominant sexual role (insertive, receptive or versatile). Using mathematical modelling and data triangulation for 'balancing' numbers of partners and role preferences, we compared three different approaches to determine if our technique could be useful for inferring characteristics of a more 'hidden' insertive MSM subpopulation, and explored their potential importance for the HIV epidemic. Projections for 2009 across all three approaches suggest that HIV prevalence among insertive MSM was likely to be less than half that recorded in the surveys (4.5-6.5% versus 13.1%), but that the relative size of this subgroup was over four times larger (61-69% of all MSM/TGW versus 15%). We infer that the insertive MSM accounted for 10-20% of all prevalent HIV infections among urban males aged 15-49. Mathematical modelling can be used with data on 'visible' MSM/TGW to provide insights into the characteristics of 'hidden' MSM. A greater understanding of the sexual behaviour of all MSM/TGW is important for effective HIV programming. More broadly, a hidden subgroup with a lower infectious disease prevalence than more visible subgroups, has the potential to contain more infections, if the hidden subgroup is considerably larger in size.

INTRODUCTION: Studies evaluating the natural history of exocrine pancreatic dysfunction (EPD) after acute pancreatitis (AP) are sparse. This study aims to assess incidence and predictors of weight loss and gastrointestinal (GI) symptoms suggestive of EPD 12 months after an AP episode. METHODS: Patients enrolled in the Pancreatitis-associated Risk of Organ Failure Study at the time of an AP episode were included. Weight and GI symptom data were prospectively collected by self-report at enrollment and at 3- and 12-month (windows 2–7 and 8–20) telephone follow-ups. Multivariable logistic regression was used to assess factors associated with ≥10% total body weight loss (EPD surrogate) at 12 months. A generalized estimating equation was used to measure each factor's population effect (in pounds) over 12 months after AP. RESULTS: Follow-up at 12 months in 186 patients (median age = 54 years, 46% men, 45% biliary, 65% first AP attack) revealed weight loss ≥10% from baseline, occurring in 44 patients (24%). Risk of weight loss increased with higher baseline body mass index, previous diagnosis of diabetes mellitus, and worsening AP severity (all P < 0.010). GI symptoms were reported in 13/31 (42%) patients at 12 months. AP severity was independently associated with ≥10% weight loss at 12 months. Over 12 months, men lost more weight than women (average 9.5 lbs); patients with severe AP lost, on average, 14 lbs. DISCUSSION: Weight loss after AP occurs in one-quarter of patients and is associated with AP severity. EPD incidence after AP is likely underappreciated. Further work is needed to assess EPD and potential for pancreatic enzyme supplementation.

Background Inability to advance to an oral diet, or oral feeding intolerance, is a common complication in patients with acute pancreatitis associated with worse clinical outcomes. The factors related to oral feeding intolerance are not well studied. Objective We aimed to determine the incidence and risk factors of oral feeding intolerance in acute pancreatitis. Methods Patients were prospectively enrolled in the Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience, an international acute pancreatitis registry, between 2015 and 2018. Oral feeding intolerance was defined as worsening abdominal pain and/or vomiting after resumption of oral diet. The timing of the initial feeding attempt was stratified based on the day of hospitalization. Multivariable logistic regression was performed to assess for independent risk factors/predictors of oral feeding intolerance. Results Of 1233 acute pancreatitis patients included in the study, 160 (13%) experienced oral feeding intolerance. The incidence of oral feeding intolerance was similar irrespective of the timing of the initial feeding attempt relative to hospital admission day (p = 0.41). Patients with oral feeding intolerance were more likely to be younger (45 vs. 50 years of age), men (61% vs. 49%), and active alcohol users (44% vs. 36%). They also had higher blood urea nitrogen (20 vs. 15 mg/dl; p, Key Summary Current knowledge on this subject Oral feeding intolerance is a relatively common complication of acute pancreatitis.Oral feeding intolerance results in longer hospitalization and frequent readmissions. What is new in this study The incidence of oral feeding intolerance is similar irrespective of the timing of the initial feeding attempt.Oral feeding intolerance is independently associated with systemic inflammatory response syndrome at 48 h and nonbiliary etiology.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was created to conduct research that could inform programmatic decision-making related to schistosomiasis. SCORE included several large cluster randomized field studies involving mass drug administration (MDA) with praziquantel. The largest of these were studies of gaining or sustaining control of schistosomiasis, which were conducted in five African countries. To enhance relevance for routine practice, the MDA in these studies was coordinated by or closely aligned with national neglected tropical disease (NTD) control programs. The study protocol set minimum targets of at least 90% for coverage among children enrolled in schools and 75% for all school-age children. Over the 4 years of intervention, an estimated 3.5 million treatments were administered to study communities. By year 4, the median village coverage was at or above targets in all studies except that in Mozambique. However, there was often a wide variation behind these summary statistics, and all studies had several villages with very low or high coverage. In studies where coverage was estimated by comparing the number of people treated with the number eligible for treatment, denominator estimation was often problematic. The SCORE experiences in conducting these studies provide lessons for future efforts that attempt to implement strong research designs in real-world contexts. They also have potential applicability to country MDA campaigns against schistosomiasis and other NTDs, most of which are conducted with less logistical and financial support than was available for the SCORE study efforts.

This report summarizes the design and outcomes of randomized controlled operational research trials performed by the Bill & Melinda Gates Foundation–funded Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) from 2009 to 2019. Their goal was to define the effectiveness and test the limitations of current WHO-recommended schistosomiasis control protocols by performing large-scale pragmatic trials to compare the impact of different schedules and coverage regimens of praziquantel mass drug administration (MDA). Although there were limitations to study designs and performance, analysis of their primary outcomes confirmed that all tested regimens of praziquantel MDA significantly reduced local Schistosoma infection prevalence and intensity among school-age children. Secondary analysis suggested that outcomes in locations receiving four annual rounds of MDA were better than those in communities that had treatment holiday years, in which no praziquantel MDA was given. Statistical significance of differences was obscured by a wider-than-expected variation in community-level responses to MDA, defining a persistent hot spot obstacle to MDA success. No MDA schedule led to elimination of infection, even in those communities that started at low prevalence of infection, and it is likely that programs aiming for elimination of transmission will need to add supplemental interventions (e.g., snail control, improvement in water, sanitation and hygiene, and behavior change interventions) to achieve that next stage of control. Recommendations for future implementation research, including exploration of the value of earlier program impact assessment combined with intensification of intervention in hot spot locations, are discussed.

Background & aims The natural history of groove pancreatitis is incompletely characterized. Published literature suggests a high rate of surgery. We describe the short- and long-term outcomes in a cohort of patients with groove pancreatitis treated at our institution. Methods Medical records of patients hospitalized in the University of Pittsburgh Medical Center system from 2000 to 2014 and diagnosed with groove pancreatitis based on imaging were retrospectively reviewed. Clinical presentation and outcomes during index admission and follow-up were recorded. Results Forty-eight patients with groove pancreatitis were identified (mean age 53.2 years, 79% male). Seventy-one percent were alcohol abusers and an equal number were cigarette smokers. Prior histories of acute and chronic pancreatitis were noted in 30 (62.5%) and 21 (43.8%), respectively. Forty-four (91.7%) met criteria for acute pancreatitis during their index admission. Alcohol was the most common etiology (68.8%). No patient experienced organ failure. The most frequent imaging findings were fat stranding in the groove (83.3%), duodenal wall thickening (52.1%), and soft tissue mass/thickening in the groove (50%). Over a mean follow-up of 5.0 years, seven (14.6%) required a pancreas-related surgery. Patients had a high burden of pancreatitis-related readmissions (68.8%, 69.4/100 patient-years). Incident diabetes and chronic pancreatitis were diagnosed in 5 (13.9% of patients at risk) and 8 (29.6% of patients at risk) respectively. Conclusions Groove pancreatitis has a wide spectrum of severity; most patients have mild disease. These patients have a high burden of readmissions and progression to chronic pancreatitis. A small minority requires surgical intervention.

OBJECTIVES: Presentation of pancreatic adenocarcinoma (PC) as acute pancreatitis (AP), association of chronic pancreatitis (CP) with PC, and role of inflammation in PC carcinogenesis are well recognized. We hypothesized that inflammatory changes associated with remote history of AP (≥2 yrs prior to PC diagnosis) would result in earlier age of PC diagnosis. METHODS: We evaluated PC patients prospectively enrolled in the Pancreatic Adenocarcinoma Gene Environment Risk (PAGER) study at the University of Pittsburgh for history of pancreatitis and reviewed relevant medical records and imaging studies. Univariate and multivariable linear regression analyses evaluated the relationship between PC and remote history of AP. RESULTS: Among 790 patients with histologically confirmed PC, 114 (14.4%) had a history of pancreatitis (AP within 2 years of PC diagnosis in 69 [8.7%], remote history of AP in 28 [3.5%], CP in 4 [0.5%], and unknown duration of pancreatitis in 13 [1.6%]). After controlling for age, sex, body mass index, smoking, alcohol history and diabetic status at diagnosis, patients with a remote history of AP were diagnosed on average 4.7 years earlier with PC when compared to PC patients without history of AP (P < 0.035). CONCLUSION: Remote history of AP may accelerate carcinogenesis in PC.

BACKGROUND: Multiple pathogenic genetic variants are associated with pancreatitis in patients of European (EA) and Asian ancestries, but studies on patients of African ancestry (AA) are lacking. We evaluated the prevalence of known genetic variations in African-American subjects in the US. METHODS: We studied prospectively enrolled controls (n = 238) and patients with chronic (CP) (n = 232) or recurrent acute pancreatitis (RAP) (n = 45) in the NAPS2 studies from 2000–2014 of self-identified AA. Demographic and phenotypic information was obtained from structured questionnaires. Ancestry and admixture were evaluated by principal component analysis (PCA). Genotyping was performed for pathogenic genetic variants in PRSS1, SPINK1, CFTR and CTRC. Prevalence of disease-associated variants in NAPS2 subjects of AA and EA was compared. RESULTS: When compared with CP subjects of EA (n = 862), prevalence of established pathogenic genetic variants was infrequent in AA patients with CP, overall (29 vs. 8.19%, OR 4.60, 95% CI 2.74–7.74, p < 0.001), and after stratification by alcohol etiology (p < 0.001). On PCA, AA cases were more heterogeneous but distinct from EA subjects; no difference was observed between AA subjects with and without CP-associated variants. Of 19 A A patients with CP who had pathogenic genetic variants, 2 had variants in PRSS1 (R122H, R122C), 4 in SPINK1 (all N34S heterozygotes), 12 in CFTR (2 CFTR(sev), 9 CFTR(BD), 1 compound heterozygote with CFTR(sev) and CFTR(BD)), and 1 in CTRC (R254W). CONCLUSION: Pathogenic genetic variants reported in EA patients are significantly less common in AA patients. Further studies are needed to determine the complex risk factors for AA subjects with pancreatitis.

This report summarizes the design and outcomes of randomized controlled operational research trials performed by the Bill & Melinda Gates Foundation-funded Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) from 2009 to 2019. Their goal was to define the effectiveness and test the limitations of current WHO-recommended schistosomiasis control protocols by performing large-scale pragmatic trials to compare the impact of different schedules and coverage regimens of praziquantel mass drug administration (MDA). Although there were limitations to study designs and performance, analysis of their primary outcomes confirmed that all tested regimens of praziquantel MDA significantly reduced local Schistosoma infection prevalence and intensity among school-age children. Secondary analysis suggested that outcomes in locations receiving four annual rounds of MDA were better than those in communities that had treatment holiday years, in which no praziquantel MDA was given. Statistical significance of differences was obscured by a wider-than-expected variation in community-level responses to MDA, defining a persistent hot spot obstacle to MDA success. No MDA schedule led to elimination of infection, even in those communities that started at low prevalence of infection, and it is likely that programs aiming for elimination of transmission will need to add supplemental interventions (e.g., snail control, improvement in water, sanitation and hygiene, and behavior change interventions) to achieve that next stage of control. Recommendations for future implementation research, including exploration of the value of earlier program impact assessment combined with intensification of intervention in hot spot locations, are discussed.

Background and aims: Pain is the primary symptom of chronic pancreatitis (CP), but methods for sensory testing and pain characterization have not previously been validated for clinical use. We present a clinically feasible method for the assessment and characterization of pain mechanisms in patients with CP based on quantitative sensory testing (QST). Methods: This was a cross-sectional, multicenter study of 122 control subjects without pancreatic disease and another 60 patients with painful CP. All subjects underwent standardized QST assessments including a cold pressor test, a conditioned pain modulation paradigm, repetitive pin-prick stimuli (temporal summation) and pressure stimulation of the upper abdominal (pancreatic) and control dermatomes. The effects of age and gender on QST assessment parameters were investigated and normative reference values based on quartile regression were derived and implemented in algorithms to categorize patients according to their patterns of central pain processing (normal vs. segmental sensitization vs. widespread sensitization). Results: Absolute pressure thresholds were subject to clinically relevant gender effects (all p < 0.001), while the remainder of QST parameters were unaffected by age and gender. The algorithm with the best discriminatory capacity showed good separation between patients and controls (p < 0.001); 50% of patients had normal central pain processing, 23% had evidence of segmental sensitization and 27% had evidence of widespread sensitization. Conclusion: We show normative reference values for a clinically feasible method for assessment and characterization of pain mechanisms in patients with CP. Application of this method streamlines the evaluation of pancreatic pain and may be used to inform treatment. Clinicaltrials.gov id: NCT03434392.

Visceral adipose tissue plays a critical role in numerous diseases. Although imaging studies often show adipose involvement in abdominal diseases, their outcomes may vary from being a mild self-limited illness to one with systemic inflammation and organ failure. We therefore compared the pattern of visceral adipose injury during acute pancreatitis and acute diverticulitis to determine its role in organ failure. Acute pancreatitis-associated adipose tissue had ongoing lipolysis in the absence of adipocyte triglyceride lipase (ATGL). Pancreatic lipase injected into mouse visceral adipose tissue hydrolyzed adipose triglyceride and generated excess nonesterified fatty acids (NEFAs), which caused organ failure in the absence of acute pancreatitis. Pancreatic triglyceride lipase (PNLIP) increased in adipose tissue during pancreatitis and entered adipocytes by multiple mechanisms, hydrolyzing adipose triglyceride and generating excess NEFAs. During pancreatitis, obese PNLIP-knockout mice, unlike obese adipocyte-specific ATGL knockouts, had lower visceral adipose tissue lipolysis, milder inflammation, less severe organ failure, and improved survival. PNLIP-knockout mice, unlike ATGL knockouts, were protected from adipocyte-induced pancreatic acinar injury without affecting NEFA signaling or acute pancreatitis induction. Therefore, during pancreatitis, unlike diverticulitis, PNLIP leaking into visceral adipose tissue can cause excessive visceral adipose tissue lipolysis independently of adipocyte-autonomous ATGL, and thereby worsen organ failure.

Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). The results of previous studies evaluating aggressive hydration with lactated Ringer solution for reducing the incidence of post-ERCP pancreatitis (PEP) are inconsistent.We performed a meta-analysis to determine whether aggressive hydration with lactated Ringer solution reduced PEP.Randomized controlled trials (RCTs) comparing aggressive hydration with standard hydration with the same lactated Ringer solution for prophylaxis of PEP were searched in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL databases. ClinicalTrial.gov and International Standard Randomised Controlled Trial Number registry were also searched for unpublished studies. A meta-analysis was conducted in accordance with the Cochrane Handbook for Systemic Reviews of Intervention.A total of 7 RCTs with 1047 participants were included into this meta-analysis. Meta-analysis showed that aggressive hydration reduced the incidence of PEP as compared with standard hydration [odds ratio (OR), 0.47; 95% confidence interval (CI), 0.30-0.72; P=0.0006]. Aggressive hydration also reduced the incidence of post-ERCP hyperamylasemia as compared with standard hydration (OR, 0.38; 95% CI, 0.25-0.59; P0.00001). No difference of adverse effects was found between aggressive hydration and standard hydration (OR, 0.48; 95% CI, 0.15-1.57; P=0.23). Sensitivity analyses showed that neither alternative effect measures nor statistical models regarding heterogeneity affected the conclusions of this meta-analysis. Sensitivity analyses also showed that omitting 1 study from analysis did not change the conclusion of this meta-analysis.On the basis of this meta-analysis of RCTs, aggressive hydration with lactated Ringer solution is an effective and safe therapy for prophylaxis of PEP.

Background and Aims During the severe acute respiratory syndrome coronavirus 2 pandemic, N95 filtering facepiece respirator (FFR) use was required while performing aerosol-generating procedures. We studied the physiologic effects of N95 FFR use in a cohort of gastroenterologists performing simulated colonoscopies. Methods Data collection and comparisons included (1) symptoms and change in vital signs in 12 gastroenterologists performing simulated colonoscopy for 60 minutes while wearing a surgical mask (SM) and faceshield (FS); N95 FFR, SM, and FS; and powered air-purifying respirator (PAPR) and (2) respiratory belt plethysmography and continuous electrocardiographic frequency-based heart rate (HR) variability indices including very low frequency power (measures intracardiac sympathetic tone) and low frequency to high frequency ratios (intracardiac sympathetic to vagal ratio) in 11 gastroenterologists performing simulated colonoscopy while wearing an SM (15 minutes), N95 FFR and SM (60 minutes), and SM (15 minutes) in rapid sequence. Results Ten of 12 gastroenterologists (83%) reported symptoms with N95 FFR use, most commonly breathing difficulty, frustration, fatigue, and headache. Nine of these gastroenterologists (75%) had associated significant HR elevation. Respiratory peak to trough measurement showed a significant increase (F(2) = 7.543, P = .004) during the N95 FFR stage, which resolved after removal of the N95 FFR. Although not statistically different, all gastroenterologists showed a decrease in sympathetic to vagal ratios and an increase in intracardiac sympathetic effects in the N95 FFR stage. PAPR use was better tolerated but was associated with headache and elevated HR in 4 gastroenterologists (33%). Conclusions N95 FFR use by gastroenterologists is associated with development of acute physiologic changes and symptoms.