Evaluating implementation of a hospital-based cancer registry to improve childhood cancer care in low- and middle-income countries.

PURPOSE: Cancer is a leading cause of global childhood mortality, affecting 400,000 children annually. While treatable with modern therapies, children living in low- and middle-income countries (LMICs) have limited access to care and lower survival rates. Hospital-based cancer registries (HBCRs) collect detailed patient information to critically evaluate and evolve care. The St. Jude Global Childhood Cancer Analytics Resource and Epidemiological Surveillance System (SJCARES) is a cloud-based HBCR network facilitating quality data collection of pediatric cancer. Wide variation in the success of implementation has warranted further research into the implementation approach, to create a sustainable and adaptable HBCR in LMICs. METHODS: Seven of 89 sites using the SJCARES registry were selected, stratified by global region and stage of implementation. Semi-structured interviews were conducted with key groups (clinicians, administrators, data clerks) using an interview guide developed from the Consolidation Framework for Implementation Research (CFIR). Interviews were conducted via a video-telephone software program and transcribed by a transcription service. Transcripts were thematically coded using rapid qualitative analysis. RESULTS: A total of 18 participants (11 clinicians, 4 administrators, 3 data clerks) were interviewed. Several barrier themes were identified, including: difficulty integrating the registry into existing workflow; lack of resources; lack of government or administrative support; and damaged, misplaced, or illegible medical records. Facilitator themes were identified, including: internal support for the registry; clear and extensive training; and dedicated support staff. CONCLUSION: Interviewed participants identified key barriers and facilitators to the implementation of the SJCARES registry across multiple phases. We plan to use these results to develop targeted implementation strategies including a readiness assessment tool to help guide more successful implementation of the SJCARES registry and other HBCRs in LMICs.

Preliminary evidence of high prevalence of cerebral microbleeds in astronauts with spaceflight experience.

Long-duration spaceflight poses a variety of health risks to astronauts, largely resulting from extended exposure to microgravity and radiation. Here, we assessed the prevalence and incidence of cerebral microbleeds in sixteen astronauts before and after a typical 6-month mission on board the International Space Station Cerebral microbleeds are microhemorrhages in the brain, which are typically interpreted as early evidence of small vessel disease and have been associated with cognitive impairment. We identified evidence of higher-than-expected microbleed prevalence in astronauts with prior spaceflight experience. However, we did not identify a statistically significant increase in microbleed burden up to 7 months after spaceflight. Altogether, these preliminary findings suggest that spaceflight exposure may increase microbleed burden, but this influence may be indirect or occur over time courses that exceed 1 year. For health monitoring purposes, it may be valuable to acquire neuroimaging data that are able to detect the occurrence of microbleeds in astronauts following their spaceflight missions.

American College of Gastroenterology Guidelines: Management of Acute Pancreatitis.

Acute pancreatitis (AP), defined as acute inflammation of the pancreas, is one of the most common diseases of the gastrointestinal tract leading to hospital admission in the United States. It is important for clinicians to appreciate that AP is heterogenous, progressing differently among patients and is often unpredictable. While most patients experience symptoms lasting a few days, almost one-fifth of patients will go on to experience complications, including pancreatic necrosis and/or organ failure, at times requiring prolonged hospitalization, intensive care, and radiologic, surgical, and/or endoscopic intervention. Early management is essential to identify and treat patients with AP to prevent complications. Patients with biliary pancreatitis typically will require surgery to prevent recurrent disease and may need early endoscopic retrograde cholangiopancreatography if the disease is complicated by cholangitis. Nutrition plays an important role in treating patients with AP. The safety of early refeeding and importance in preventing complications from AP are addressed. This guideline will provide an evidence-based practical approach to the management of patients with AP.

Marathon pancreatitis: a case of acute pancreatitis caused by distance running.

Marathon running or other forms of strenuous exercise have been reported as a rare cause of acute pancreatitis. Theories as to the mechanism of acute pancreatitis include microvascular ischaemia due to dehydration or repetitive trauma to the pancreas. We report a case of a healthy woman in her 30s who developed abdominal pain, nausea and vomiting after a 32 km marathon training run. She was found to have elevated lipase and inflammation of the pancreatic tail with associated pericolic and pelvic free fluid on CT scan. Workup including abdominal ultrasound and magnetic resonance cholangiopancreatography (MRCP) did not reveal biliary or pancreatic duct pathology. She improved with conservative management. These findings support the hypothesis of exercise-induced pancreatitis from long-distance running.

Fluid resuscitation in acute pancreatitis.

PURPOSE OF REVIEW: The purpose of the review is to critically evaluate the evidence from the literature to establish the current perspective on fluid resuscitation (FR) in acute pancreatitis (AP). We will review the rationale, type of fluid, rate of administration, total volume, duration, monitoring, ideal outcomes to be studied in clinical trials and recommendations for future studies. RECENT FINDINGS: FR remains the key component of supportive therapy in AP. The paradigm has shifted from administration of aggressive fluid resuscitation towards more moderate FR strategies. Lactated Ringer's remains the preferred fluid for resuscitation. There remain critical gaps in knowledge regarding the end point(s) to indicate adequate resuscitation, and accurate assessments of fluid sequestration and intravascular volume deficit in AP. SUMMARY: There is insufficient evidence to state that goal-directed therapy, using any of the parameters to guide fluid administration, reduces the risk of persistent organ failure, infected pancreatic necrosis, or mortality in AP, as well as the most appropriate method for the same.

CRISPR-Cas9 Long-Read Sequencing for Mapping Transgenes in the Mouse Genome.

Microinjected transgenes, both large and small, are known to insert randomly into the mouse genome. Traditional methods of mapping a transgene are challenging, thus complicating breeding strategies and accurate interpretation of phenotypes, particularly when a transgene disrupts critical coding or noncoding sequences. As the vast majority of transgenic mouse lines remain unmapped, we developed CRISPR-Cas9 Long-Read Sequencing (CRISPR-LRS) to ascertain transgene integration loci. This novel approach mapped a wide size range of transgenes and uncovered more complex transgene-induced host genome re-arrangements than previously appreciated. CRISPR-LRS offers a facile, informative approach to establish robust breeding practices and will enable researchers to study a gene without confounding genetic issues. Finally, CRISPR-LRS will find utility in rapidly and accurately interrogating gene/genome editing fidelity in experimental and clinical settings.

In-person radiologist to review the trauma panscan: a high-fidelity simulation training program for radiology trainees at an academic level 1 trauma center.

BACKGROUND: Radiology trainees were uncomfortable going to the CT scanner to review trauma panscans and interacting with trauma surgeons. OBJECTIVE: This study aims to determine if radiology residents can be trained to accurately identify injuries requiring immediate surgical attention at the CT scanner. METHODS: A high-fidelity simulation model was created to provide an immersive training experience. Between February 2015 and April 2017, 62 class 1 trauma panscans were read at the CT scanner by 11 PGY-3 radiology residents. Findings made at the scanner were compared to resident preliminary and attending radiology reports and correlated with clinical outcomes. Timestamps were recorded and analyzed. Surveys were administered to assess the impact of training on radiology residents' self-confidence and to assess trauma surgeons' preference for radiology at the scanner. Significance level was set at p < 0.05. RESULTS: The mean time to provide results at the CT scanner was 11.1 min. Mean time for the preliminary report for CT head and cervical spine was 24.4 ± 9.8 min, and for the CT chest, abdomen, and pelvis was 16.3 ± 6.9 min. 53 traumatic findings on 62 panscans were identified at the scanner and confirmed at preliminary and final reports, for a concordance rate of 85%, compared to 72% for the control group. Radiology residents agreed or strongly agreed the training prepared them for trauma panscan reporting. Trauma surgeons shifted in favor of radiology presence at the scanner. CONCLUSION: Radiology residents can be trained to accurately and rapidly identify injuries requiring immediate surgical attention at the CT scanner. CLINICAL IMPACT: These findings support the value-added of an in-person radiologist at the CT scanner for whole-body trauma panscans to facilitate timely detection of life-threatening injuries and improve professional relations between radiologists and trauma surgeons.

Generation and Comparative Analysis of an Itga8-CreER T2 Mouse with Preferential Activity in Vascular Smooth Muscle Cells.

All current smooth muscle cell (SMC) Cre mice similarly recombine floxed alleles in vascular and visceral SMCs. Here, we present an Itga8-CreER T2 knock-in mouse and compare its activity with a Myh11-CreER T2 mouse. Both Cre drivers demonstrate equivalent recombination in vascular SMCs. However, Myh11-CreER T2 mice, but not Itga8-CreER T2 mice, display high activity in visceral SMC-containing tissues such as intestine, show early tamoxifen-independent activity, and produce high levels of CreERT2 protein. Whereas Myh11-CreER T2 -mediated knockout of serum response factor (Srf) causes a lethal intestinal phenotype precluding analysis of the vasculature, loss of Srf with Itga8-CreER T2 (Srf Itga8 ) yields viable mice with no evidence of intestinal pathology. Male and female Srf Itga8 mice exhibit vascular contractile incompetence, and angiotensin II causes elevated blood pressure in wild type, but not Srf Itga8 , male mice. These findings establish the Itga8-CreER T2 mouse as an alternative to existing SMC Cre mice for unfettered phenotyping of vascular SMCs following selective gene loss.

Characteristics of 30-Day All-Cause Hospital Readmissions Among Patients with Acute Pancreatitis and Substance Use.

BACKGROUND/OBJECTIVES: Previous studies on healthcare resource utilization and 30-day readmission risks among patients with acute pancreatitis (AP) have focused upon opioid and alcohol use. The data on other substance types are lacking. In this study we aim to estimate the 30-day readmission rates, predictors of readmission, impact of readmission on patient outcomes and resulting economic burden among patients with AP and substance use in the USA. METHODS: This was a retrospective cohort study, based upon data from 2017 National Readmission Database of adult patients with AP and substance use (alcohol in combination, opioid, cannabis, cocaine, sedatives, other stimulants, other hallucinogens, other psychoactive, inhalant and miscellaneous). We estimated the 30-day readmission rates and predictors of 30-day readmission. RESULTS: Among 25,795 eligible patients, most were male, belonged to the lower income quartile, resided in the urban facility and had a Charlson comorbidity score of 0 or 1. The use of a combination of substances was the most common in 17,265 (66.9%) patients followed by only opioids in 4691 (18.2%) patients and only marijuana in 3839 (14.9%) patients. A total of 14.6% patients were readmitted within 30 days after discharge for non-elective causes with the highest risk of readmission within the 1st week after discharge with 5.2% readmissions. Among top ten causes of readmission, most of the principal diagnosis were related to AP in 53.1%. Compared to index admission, readmitted patients had significantly higher rates of acute cardiac failure, shock, and higher in-hospital mortality rate. Overall, readmission attributed to an additional 17,801 days of hospitalization resulting in a total of $150 million in hospitalization charges and $36 million in hospitalization costs in 2017. On multivariate analysis, chronic pancreatitis, self-discharge against medical advice, treatment at the highest volume centers, higher Charlson comorbidity index, increasing length of stay and severe disease were associated with higher odds of readmission while female gender and private insurance were associated with lower odds. CONCLUSION: Readmission was associated with higher morbidity and in-hospital mortality among patients with AP and substance use and resulted in a significant monetary burden on the US healthcare system. Several factors identified in this study may be useful for categorizing patients at higher risk of readmission warranting special attention during discharge planning.

Provider Differences in Monitoring and Management of Exocrine Pancreatic Insufficiency in Chronic Pancreatitis.

OBJECTIVES: Chronic pancreatitis (CP) is a common cause of exocrine pancreatic insufficiency (EPI). Regular monitoring and treatment are recommended to decrease morbidity. This study evaluates whether provider type impacts EPI monitoring and management in CP. METHODS: Fecal elastase 1 (FE-1) testing and pancreatic enzyme replacement therapy (PERT) utilization were retrospectively compared between primary care providers (PCPs), gastroenterologists and pancreas specialists using pairwise comparisons. Multivariate analysis was conducted to study the association between adequate PERT and age, sex, race, insurance status, provider type, and etiology. RESULTS: Among 256 patients, FE-1 was measured in 115 (44.9%) and of 143 (55.9%) patients who received PERT, 100 (69.9%) received adequate dosage. Fecal elastase 1 testing was performed in 7/57 (12.3%) by PCP, 11/38 (28.9%) by gastroenterologists, and 97/161 (60.2%) by pancreas specialists (P < 0.0001). Adequate PERT was prescribed in 7/24 (29.2%) patients by PCPs, 11/20 (55.0%) by gastroenterologists, and 82/99 (82.8%) by pancreas specialists (P < 0.0001). On multivariate analysis, pancreas specialists were significantly more likely to prescribe adequate PERT compared with PCP (odds ratio, 11.3; 95% confidence interval, 3.3-38.2; P < 0.001). CONCLUSIONS: Many patients with CP receive inadequate surveillance and EPI treatment. Pancreas specialists are more likely to surveil and treat EPI adequately.

Nutrition and Acute Pancreatitis.

Acute pancreatitis (AP) is an acute inflammatory process of the pancreas that is characterized by severe abdominal pain, elevated pancreatic enzymes, and pancreatic changes on abdominal imaging. AP is, by nature, an inflammatory process that leads to protein catabolism and an increased metabolic rate, highlighting the strong need for early nutritional support in the initial management of the disease process. The goal of nutritional support in acute pancreatitis is to correct the negative nitrogen balance to reduce inflammation and improve outcomes. Many trials and multiple systemic reviews and meta-analyses have examined the best modality, timing, and composition of nutritional support for acute pancreatitis. Early enteral nutrition has emerged as an important aspect of the clinical management of AP. This narrative review aimed to provide an overview of the clinical management of nutrition in acute pancreatitis based on the currently available data.

Does Provider Type Affect Bone Health Surveillance in Chronic Pancreatitis?

BACKGROUND: Bone density screening (DEXA) and vitamin D serum assay (Vit-D) are recommended in chronic pancreatitis, but adherence by providers is unknown. AIMS: Assess DEXA/Vit-D testing according to provider type. METHODS: A retrospective cohort study of chronic pancreatitis patients followed in a tertiary hospital (August 2017-2018) was conducted. Provider type was primary care (PCP), gastroenterologist, and pancreas specialist. Chi-square test and multivariable analysis were conducted to assess the relation between provider type and DEXA/Vit-D testing. Subset analyses were performed among patients with fecal elastase < 200 mcg/g. RESULTS: A total of 478 charts were reviewed, and 256 (53.6%) met diagnosis of chronic pancreatitis; 184 (71.9%) definite, 45 (17.6%) probable, and 27 (10.6%) borderline chronic pancreatitis. DEXA was tested in 112/256 (43%) patients; 16/57(28%) patients followed by PCP, 11/38 (28.9%) by gastroenterologists, and 85/161(52.2%) by pancreas specialists (p = 0.001). Vit-D was tested in 210/256 (82.0%) patients; 42/57(73.7%) followed by PCP, 29/38 (76.3%) by gastroenterologists, and 139/161(86.3%) by pancreas specialists (p = 0.06). Multivariate analysis assessing DEXA/Vit-D testing showed pancreas specialists were more likely to test compared to PCP (DEXA: OR 3.70, CI 1.77-7.74, p = 0.001. Vit-D: OR 3.24, CI 1.43-7.38, p = 0.005), but gastroenterologists were not. In patients with low fecal elastase, pancreas specialists were more likely to test DEXA (pancreas specialists: 62.1%, PCP: 40.0%, Gastroenterologists: 11.1%, p = 0.01) and all patients received Vit-D testing. CONCLUSIONS: Chronic pancreatitis patients often do not receive optimal preventive care. Pancreas specialists were more likely to perform DEXA and Vit-D testing compared to PCP and gastroenterologists. More physician education is needed.

Provider type influences adherence to lifestyle changes in chronic pancreatitis.

BACKGROUND: /Objectives: Alcohol and smoking cessation are recommended in chronic pancreatitis. The aim of this study is to measure the rates of alcohol and smoking cessation counselling among providers and adherence to recommendations. METHODS: Retrospective cohort study of chronic pancreatitis patients at a tertiary hospital. Provider types were defined as primary care (PCP), gastroenterologist, or pancreas specialist. Pairwise comparisons and multivariable analysis were conducted to assess the relation between provider type and smoking/alcohol cessation. RESULTS: Of 256 patients with chronic pancreatitis, 142 (55.5%) consumed alcohol and 130 (91.5%) were advised to stop. Alcohol cessation was advised to 88.9, 96.0 and 92.5% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively. Sixty-one patients (46.9%) were compliant with the recommendation: 31.3, 44.0 and 54.1% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively (Pairwise comparisons PCP vs Pancreas: p = 0.03, others nonsignificant). In multivariable analysis, patients followed by pancreas specialists were more likely to adhere to alcohol cessation recommendation compared to those followed by PCP (OR = 4.31, CI 1.52-12.20, p = 0.006). Smoking cessation was advised to all the 127 current smokers (100%). Fifty-six (44.1%) were compliant with the recommendation: 24.1, 58.3 and 47.3% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively (Pairwise comparisons PCP vs Pancreas: p = 0.03, PCP vs. Gastroenterologist: p = 0.01, others nonsignificant). Multivariable analysis did not confirm this finding. CONCLUSIONS: The majority of providers counsel for alcohol/smoking cessation. Less than half the patients follow the recommendations. Patients followed by pancreas specialists were more likely to adhere to alcohol cessation recommendation.

Overview of Inositol and Inositol Phosphates on Chemoprevention of Colitis-Induced Carcinogenesis.

Chronic inflammation is one of the most common and well-recognized risk factors for human cancer, including colon cancer. Inflammatory bowel disease (IBD) is defined as a longstanding idiopathic chronic active inflammatory process in the colon, including ulcerative colitis and Crohn's disease. Importantly, patients with IBD have a significantly increased risk for the development of colorectal carcinoma. Dietary inositol and its phosphates, as well as phospholipid derivatives, are well known to benefit human health in diverse pathologies including cancer prevention. Inositol phosphates including InsP3, InsP6, and other pyrophosphates, play important roles in cellular metabolic and signal transduction pathways involved in the control of cell proliferation, differentiation, RNA export, DNA repair, energy transduction, ATP regeneration, and numerous others. In the review, we highlight the biologic function and health effects of inositol and its phosphates including the nature and sources of these molecules, potential nutritional deficiencies, their biologic metabolism and function, and finally, their role in the prevention of colitis-induced carcinogenesis.

Hypertriglyceridemia and acute pancreatitis.

Hypertriglyceridemia is the third most common cause of acute pancreatitis. It typically occurs in patients with an underlying disorder of lipoprotein metabolism and in the presence of a secondary condition such as uncontrolled diabetes, alcohol abuse, or medication use. The presentation of hypertriglyceridemia-induced pancreatitis is similar to that of acute pancreatitis due to other causes; however, patients with hypertriglyceridemia-induced pancreatitis are more likely to have severe disease courses and have a higher likelihood of persistent organ failure. The initial treatment of hypertriglyceridemia-induced pancreatitis is also similar to acute pancreatitis from other causes and consists of aggressive fluid resuscitation, pain control, and nutritional support. Hypertriglyceridemia is specifically treated with apheresis or insulin therapy when necessary. The prompt recognition of hypertriglyceridemia in the setting of acute pancreatitis is essential in both the initial and long-term management of this disease and are essential to prevent recurrent acute pancreatitis. The review seeks to highlight the etiology, pathogenesis, and clinical course of hypertriglyceridemia-induced acute pancreatitis.

Opiate Prescriptions at Discharge Are Not Associated with Early Readmissions in Acute Pancreatitis.

BACKGROUND: Early readmissions in acute pancreatitis (AP) are common. The impact of opiate prescriptions on readmissions is unknown. AIMS: To determine whether the prescription of opiates at hospital discharge and the dose prescribed are associated with early readmissions in AP. METHODS: Direct admissions from the Emergency Department (ED) for AP from September 1, 2013, to August 31, 2016 were identified. Opiate prescription was defined as a new prescription at discharge in an opiate-naïve patient. Early readmission was ED visit or hospitalization within 30 days for an AP-related reason. Multivariable logistic regression was performed, adjusted for age, Charlson Comorbidity Index, pancreatic necrosis, baseline opiate use, non-opiate analgesics, and pain score at discharge. RESULTS: A total of 318 AP patients were identified; the overall early readmission rate was 18%. One hundred and twenty-one (38%) were prescribed opiates at discharge, and 22% had an early readmission. One hundred and ninety-seven (62%) were not prescribed opiates, and 16% had an early readmission. Median opiate dose was 48 mg (24-h morphine equivalents). On multivariable analysis, neither the prescription of opiates (OR 1.2, 95% CI 0.6-2.4, p = 0.55) nor the dose of opiates (OR 0.99, 95% CI 0.99-1.00, p = 0.39) was associated with early readmission. In subset analysis of patients discharged with an opiate prescription, those on opiates at baseline were significantly more likely to have an early readmission (OR 4.19, 95% CI 1.04-16.94, p = 0.04). CONCLUSIONS: In AP patients, neither prescription of opiates at discharge nor prescribed dose was associated with early readmission. Patients on opiates at baseline discharged with an opiate prescription were more likely to have an early readmission.

Are Opioid-Naive Patients With Acute Pancreatitis Given Opioid Prescriptions at Discharge?

OBJECTIVES: Opioids are commonly used in the management of acute pancreatitis (AP). Inpatient opioid exposure is known to increase the risk of chronic opioid use after discharge. Prescription patterns for opioids at discharge for AP are unknown. METHODS: Medical records of adult AP patients who presented to the emergency department from September 1, 2013, to August 31, 2016, were reviewed. Opioid prescription at discharge was defined as a prescription for opioids in a patient who was opioid naive at admission. Multivariable logistic regression was performed to identify predictors of opioid prescription at discharge. RESULTS: A total of 259 opioid-naive AP patients were identified. Of these, 108 (41.6%) of 259 were discharged with an opioid prescription and 61 (56.5%) of 108 had discharge pain scores of 3 or lower. Two hundred twenty-two (85.7%) received opioids during admission and 105 (47.3%) of 222 were discharged with an opioid prescription. On multivariable analysis, predictors of discharge opioid prescription included inpatient use of opioids, female sex, and discharge pain score greater than 3. CONCLUSIONS: In opioid-naive AP patients, 41.6% were discharged from the hospital with a new prescription for opioids, even though a significant proportion had pain scores of 3 or lower. Guidelines are needed for opioid prescriptions at discharge for AP.