A Clinicopathological Appraisal of Duodenal Neuroendocrine Tumors at a Racially Diverse Safety Net Hospital.

INTRODUCTION: Significant knowledge gaps exist regarding clinicopathological profiling as well as treatment, surveillance, and survival of duodenal neuroendocrine tumors (dNETs). METHODS: We clinicopathologically characterized and identified racial differences among patients with dNETs at a large safety net hospital. Tumor grades were updated based on the World Health Organization 2019 NET classification, and overall survival was determined. RESULTS: We identified 17 dNETs and found no differences in clinicopathologic characteristics across racial groups. Pathological diagnosis was upgraded in 35% of dNETs, and age >65 years significantly shortened overall survival. DISCUSSION: Larger-scale studies are needed to determine the significance of these findings.

Disorders of the Pancreas.

The pancreas is a vital intra-abdominal organ with dual exocrine and endocrine function. This article provides an overview of several common pancreatic pathologies including pancreatitis, pancreatic cysts, and pancreatic cancer with a focus on clinical presentation as well as initial diagnosis and management.

Irritable Bowel Syndrome and the Gut Microbiome: A Comprehensive Review.

Irritable Bowel Syndrome (IBS) is a functional disorder of the gastrointestinal tract characterized by abdominal pain and altered bowel habits. It has a prevalence of 10 to 25% in the United States and has a high disease burden, as evidenced by reduced quality of life, decreased work productivity and increased healthcare utilization and costs. IBS has been associated with several intra-intestinal and extra-intestinal conditions, including psychiatric comorbidities. Although the pathophysiology of IBS has not been fully elucidated, it involves dysregulation of communication between the brain and gut (brain-gut axis) which is associated with alterations in intestinal motility, gut permeability, visceral hypersensitivity and gut microbiota composition. The purpose of this article is to review the role the gut microbiota plays in the pathophysiology of IBS, understand factors that affect the gut microbiome and explore the microbiome as a target of treatment.

A Monte Carlo Simulation to Estimate the Additional Cost Associated With Adverse Medication Events Leading to Intraoperative Hypotension and/or Hypertension in the United States.

OBJECTIVES: Intraoperative hypertension and hypotension are common and often related to adverse medication events (AMEs). The study objective is to estimate the annual additional fully allocated costs to the U.S. healthcare system related to AMEs associated with clinically significant intraoperative hypertension and hypotension. METHODS: Using anesthesia-trained observers in randomly selected operating rooms, we estimated the rates of clinically significant intraoperative hypotension and hypertension. We conducted systematic literature reviews to estimate incidence and additional costs of acute kidney injury (AKI), acute myocardial injury, and stroke after intraoperative hypotension and hypertension. We used Monte Carlo simulation to estimate annual costs to the U.S. healthcare system. RESULTS: Intraoperative hypotension (mean arterial pressure <55 mm Hg for >6 minutes) occurred in 11 of 277 operations (3.97%), hypotension (>30% drop from baseline mean arterial pressure in patients with coronary artery disease) in 9 operations (3.25%) and hypertension in 14 operations (5.05%). After hypotension, incremental incidence of AKI was 1.46% (additional cost $17,289/case), acute myocardial injury was 0.75% ($21,340/case), and stroke was 0.05% ($19,903/case). After hypertension, incremental stroke incidence was 4.76% ($28,320/case). Annually in the United States, we estimated 11,513 cases of AKI, 5914 of acute myocardial injury, 345 of stroke after intraoperative hypotension, and 47,774 cases of stroke after intraoperative hypertension, costing the U.S. $1.7 billion (90% confidence interval, $1.4-$2.0 billion), of which $923 million (90% confidence interval, $763-$1101 million) is preventable. CONCLUSIONS: Adverse medication events related to blood pressure are frequent, costly, and can cause considerable patient harm. Cost estimates for these events may provide a means of prioritizing safety improvements to reduce cost of care and improve patient outcomes.

Development of a Perioperative Medication-Related Clinical Decision Support Tool to Prevent Medication Errors: An Analysis of User Feedback.

OBJECTIVES: Medication use in the perioperative setting presents many patient safety challenges that may be improved with electronic clinical decision support (CDS). The objective of this paper is to describe the development and analysis of user feedback for a robust, real-time medication-related CDS application designed to provide patient-specific dosing information and alerts to warn of medication errors in the operating room (OR). METHODS: We designed a novel perioperative medication-related CDS application in four phases: (1) identification of need, (2) alert algorithm development, (3) system design, and (4) user interface design. We conducted group and individual design feedback sessions with front-line clinician leaders and subject matter experts to gather feedback about user requirements for alert content and system usability. Participants were clinicians who provide anesthesia (attending anesthesiologists, nurse anesthetists, and house staff), OR pharmacists, and nurses. RESULTS: We performed two group and eight individual design feedback sessions, with a total of 35 participants. We identified 20 feedback themes, corresponding to 19 system changes. Key requirements for user acceptance were: Use hard stops only when necessary; provide as much information as feasible about the rationale behind alerts and patient/clinical context; and allow users to edit fields such as units, time, and baseline values (e.g., baseline blood pressure). CONCLUSION: We incorporated user-centered design principles to build a perioperative medication-related CDS application that uses real-time patient data to provide patient-specific dosing information and alerts. Emphasis on early user involvement to elicit user requirements, workflow considerations, and preferences during application development can result in time and money efficiencies and a safer and more usable system.

Global PRoMiSe (Perioperative Recommendations for Medication Safety): protocol for a mixed-methods study.

INTRODUCTION: Medication errors (MEs), which occur commonly in the perioperative period, have the potential to cause patient harm or death. Many published recommendations exist for preventing perioperative MEs; however, many of these recommendations conflict and are often not applicable to middle-income and low-income countries. The goal of this study is to develop and disseminate consensus-based recommendations for perioperative medication safety that are tailored to country income level. METHODS AND ANALYSIS: The primary site of this mixed-methods study is Massachusetts General Hospital/Harvard Medical School. Participants include a minimum of 108 international medication safety experts, 27 from each of the World Bank's four country income groups (high, upper-middle, lower-middle and low-income). Using the Delphi method, participants will rate the appropriateness of candidate medication safety recommendations by completing online surveys using RedCAP. We will use Condorcet ranking methods to prioritise the final recommendations for each country income group. We will execute a comprehensive dissemination strategy for the recommendations across each country income group. Finally, we will conduct semistructured interviews with our participants to evaluate the initial adoption and implementation of the recommendations in each country income group. ETHICS AND DISSEMINATION: This study was approved by the Human Research Committee/Institutional Review Board at Partners Healthcare (2019P003567). Findings will be published in peer-reviewed journals and presented at local and international conferences. TRIAL REGISTRATION NUMBER: NCT04240301.

Glucose and lipid metabolism, bone density, and body composition in individuals with Williams syndrome.

OBJECTIVE: We assessed body composition, bone mineral density (BMD), glucose and lipids in Williams syndrome (WS), a rare microdeletion disorder. DESIGN: Individuals with WS had outpatient assessment at Massachusetts General Hospital. Controls were selected from the National Health and Nutrition Examination Survey (NHANES 2005-2006). PATIENTS: A total of 22 individuals with WS, each matched by age, sex and race to four NHANES controls. MEASUREMENTS: Blood sampling, oral glucose tolerance test, dual-energy X-ray absorptiometry scan. RESULTS: WS and control groups were 59% female and 29 ± 8 years old. Compared to controls, individuals with WS were shorter but had similar body weight, with more fat and less lean mass. Per cent body fat was higher in WS even after adjusting for BMI (+2.1% [95% CI 0.4, 3.9%]). Four WS patients had abnormal lower extremity fat accumulation resembling lipedema. HbA1c (+0.5% [0.2, 0.7]) and 2-hour glucose (+68 mg/dL [44, 93]) were higher in WS vs controls, differences which persisted after adjusting for BMI. Fasting glucose was comparable between groups. LDL (-18 mg/dL [-35, -2]) and triglycerides (-45 mg/dL [-87, -2]) were significantly lower in WS. Whole-body BMD was significantly lower (-0.15 g/cm2 [-0.20, -0.11]) in WS, and this remained true controlling for height (-0.06 g/cm2 [-0.11, -0.02]). Vitamin D was <30 ng/mL in 81% of those with WS. CONCLUSIONS: On average, adults with WS have increased fat, decreased lean mass, impaired glucose homeostasis and reduced BMD. Clinical efforts to build muscle and bone mass, and to ensure vitamin D sufficiency, are warranted. Genotype-phenotype research efforts are also warranted.

Insulin-like growth factor 1 inversely relates to monocyte/macrophage activation markers in HIV.

OBJECTIVE: Monocyte/macrophage activation is increased among people with HIV, and may contribute to the heightened risk of atherosclerosis and neurocognitive dysfunction in this population. Insulin-like growth factor 1 (IGF-1) has been shown to attenuate the innate immune response in animal models of atherosclerosis and inflammatory bowel disease. We investigated, for the first time, relationships of circulating IGF-1 with monocyte/macrophage-specific indices among HIV-infected individuals and uninfected controls. DESIGN: Observational. METHODS: One hundred and thirty-one HIV-infected patients and 65 well matched controls without known cardiac disease or viral hepatitis were recruited previously. IGF-1, expressed as a z-score relative to the age-adjusted and sex-adjusted population mean, was related to log-transformed inflammatory markers within HIV and non-HIV groups. RESULTS: In HIV, IGF-1 inversely related to sCD163 (r = -0.28, P = 0.002), sCD14 (r = -0.29, P = 0.002), and high-sensitivity IL-6 (r = -0.27, P = 0.006). There was no association of IGF-1 with high-sensitivity CRP, MCP-1, IL-18, or LPS in HIV, or between IGF-1 and any inflammatory marker in controls. Relationships of IGF-1 with sCD163 and sCD14 remained significant in HIV after controlling for age, sex, smoking, BMI, visceral fat, statin use, viral load, and antiretroviral therapy. For every one-unit decline in IGF-1 z-score, sCD163 and sCD14 increased by 14% (95% CI, 0.23-29%) and 29% (95% CI, 1.4-63%), respectively. CONCLUSION: Low IGF-1 was robustly associated with high sCD163 and sCD14 in HIV. Prospective studies are needed to investigate augmentation of IGF-1 as a novel strategy to reduce monocyte/macrophage activation in this population.

Evaluation of Perioperative Medication Errors and Adverse Drug Events.

BACKGROUND: The purpose of this study is to assess the rates of perioperative medication errors (MEs) and adverse drug events (ADEs) as percentages of medication administrations, to evaluate their root causes, and to formulate targeted solutions to prevent them. METHODS: In this prospective observational study, anesthesia-trained study staff (anesthesiologists/nurse anesthetists) observed randomly selected operations at a 1,046-bed tertiary care academic medical center to identify MEs and ADEs over 8 months. Retrospective chart abstraction was performed to flag events that were missed by observation. All events subsequently underwent review by two independent reviewers. Primary outcomes were the incidence of MEs and ADEs. RESULTS: A total of 277 operations were observed with 3,671 medication administrations of which 193 (5.3%; 95% CI, 4.5 to 6.0) involved a ME and/or ADE. Of these, 153 (79.3%) were preventable and 40 (20.7%) were nonpreventable. The events included 153 (79.3%) errors and 91 (47.2%) ADEs. Although 32 (20.9%) of the errors had little potential for harm, 51 (33.3%) led to an observed ADE and an additional 70 (45.8%) had the potential for patient harm. Of the 153 errors, 99 (64.7%) were serious, 51 (33.3%) were significant, and 3 (2.0%) were life-threatening. CONCLUSIONS: One in 20 perioperative medication administrations included an ME and/or ADE. More than one third of the MEs led to observed ADEs, and the remaining two thirds had the potential for harm. These rates are markedly higher than those reported by retrospective surveys. Specific solutions exist that have the potential to decrease the incidence of perioperative MEs.