Comparative Safety of Biologic Agents in Patients With Inflammatory Bowel Disease With Active or Recent Malignancy: A Multi-Center Cohort Study.

BACKGROUND & AIMS: Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer. METHODS: We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis. Primary outcomes were progression-free survival (cohort A) or recurrence-free survival (cohort B). Safety was compared using inverse probability of treatment weighting with propensity scores. RESULTS: In cohort A, of 125 patients (483.8 person-years of follow-up evaluation) with active cancer (age, 54 ± 15 y, 75% solid-organ malignancy), 10 of 55 (incidence rate [IR] per 100 py, 4.4) and 9 of 40 (IR, 10.4) patients treated with TNFα antagonists and non-TNF biologics had cancer progression, respectively. There was no difference in the risk of progression-free survival between TNFα antagonists vs non-TNF biologics (hazard ratio, 0.76; 95% CI, 0.25-2.30). In cohort B, of 170 patients (513 person-years of follow-up evaluation) with recent prior cancer (age, 53 ± 15 y, 84% solid-organ malignancy; duration of remission, 19 ± 19 mo), 8 of 78 (IR, 3.4) and 5 of 66 (IR 3.7) patients treated with TNFα antagonists and non-TNF biologics had cancer recurrence, respectively. The risk of recurrence-free survival was similar between both groups (hazard ratio, 0.94; 95% CI, 0.24-3.77). CONCLUSIONS: In patients with IBD with active or recent cancer, TNFα antagonists and non-TNF biologics have comparable safety. The choice of biologic should be dictated by IBD disease severity in collaboration with an oncologist.

Baseline Cannabinoid Use Is Associated with Increased Sedation Requirements for Outpatient Endoscopy.

Background and Aims: Given the underlying properties of cannabinoids, we aimed to assess associations between cannabinoid use and sedation requirements for esophagogastroduodenoscopy (EGD) and colonoscopy. Methods: A prospective cohort study was conducted at three endoscopy units. Adult outpatients undergoing EGD or colonoscopy with endoscopist-directed conscious sedation (EDCS) were given questionnaires on cannabinoid use and relevant parameters. Outcomes included intraprocedural midazolam, fentanyl, and diphenhydramine use, procedural tolerability, and adverse events. Multivariable logistic regression was performed to yield adjusted odds ratios (AORs) of outcomes. Results: A total of 419 patients were included. Baseline cannabinoid use was associated with high midazolam use, defined as ≥5 mg, during EGD (AOR 2.89, 95% confidence interval, CI: 1.19-7.50), but not during colonoscopy (AOR 0.89, 95% CI 0.41-1.91). Baseline cannabinoid use was associated with the administration of any diphenhydramine during EGD (AOR 3.04, 95% CI: 1.29-7.30) with a similar nonsignificant trend for colonoscopy (AOR 2.36, 95% CI: 0.81-7.04). Baseline cannabinoid use was associated with increased odds of requiring high total sedation, defined as any of midazolam ≥5 mg, fentanyl ≥100 mcg, or any diphenhydramine during EGD (AOR 3.72, 95% CI: 1.35-11.68). Cannabinoid use was not independently associated with fentanyl use, intraprocedural awareness, discomfort, or adverse events. Conclusions: Baseline cannabinoid use was associated with higher sedation use during endoscopy with EDCS, particularly with midazolam and diphenhydramine. Given increasingly widespread cannabinoid use, endoscopists should be equipped with optimal sedation strategies for this population. As part of the informed consent process, cannabis users should be counseled that they may require higher sedation doses to achieve the same effect.

Factors Associated with the Development of Gastrointestinal Symptoms in Patients Hospitalized with Covid-19.

BACKGROUND AND AIMS: The most common symptoms of Covid-19 are respiratory; however, gastrointestinal symptoms are present in up to 50% of patients. We aimed to determine characteristics associated with the development of gastrointestinal symptoms in patients with Covid-19. METHODS: A case-control study of adults hospitalized for Covid-19 was conducted across a geographically diverse alliance of 36 US and Canadian medical centers. Data were manually abstracted from electronic health records and analyzed using regression analyses to determine characteristics associated with any gastrointestinal symptoms and diarrhea specifically. RESULTS: Of 1406 patients, 540 (38%) reported at least one gastrointestinal symptom and 346 (25%) reported diarrhea. Older patients (≥ 80 years) had significantly lower rates of any gastrointestinal symptoms and diarrhea (vs. patients 18-79 years, OR 0.41, p < 0.01 and OR 0.43 p = 0.01, respectively), while those with IBS (OR 7.70, p = 0.02 and OR 6.72, p < 0.01, respectively) and on immunosuppressive therapy (OR = 1.56, p = 0.02) had higher rates of any gastrointestinal symptom and diarrhea. Patients with constitutional symptoms exhibited significantly higher rates (OR 1.91, p < 0.01), while those with pulmonary disease alone had lower rates of gastrointestinal symptoms (OR 0.23, p = 0.01). A significant interaction between constitutional symptoms and pre-existing pulmonary conditions was observed. CONCLUSIONS: Several patient- and disease-specific characteristics associate with gastrointestinal symptoms in patients with Covid-19. Knowledge of these may provide insights into associated pathophysiologic mechanisms, and help health care professionals provide targeted attention to reduce morbidity related to Covid-19.

Pre-hospital antiplatelet medication use on COVID-19 disease severity.

OBJECTIVE: To evaluate the association between pre-hospitalization antiplatelet medication use and COVID-19 disease severity. DESIGN: Retrospective cohort study. SETTING: Inpatient units at The Mount Sinai Hospital. PATIENTS: Adults age ≥18 admitted between March 1, 2020 and April 9, 2020 with confirmed COVID-19 infection with at least 28 days follow-up. MEASUREMENTS: We captured baseline demographic, pre-hospitalization antiplatelet medication use, and clinical encounter data for all patients who met inclusion criteria. The primary endpoint was peak score on a 6-point modified ordinal scale (MOS), which is based on World Health Organization blueprint R&S groups, used to grade severity of illness through clinical outcomes of interest. Scores indicate the following: 1 - COVID-19 infection not requiring hospitalization, 2 - requiring hospitalization but not supplemental oxygen, 3 - hospitalization requiring supplemental oxygen, 4 - hospitalization requiring high-flow nasal cannula (HFNC) or non-invasive positive pressure ventilation (NIPPV), 5 - hospitalization requiring intubation or extracorporeal membrane oxygenation (ECMO), 6 - death. Multivariable adjusted partial proportional odds model (PPOM) was performed to examine the association between pre-hospitalization antiplatelet medication use and likelihood of each MOS score. MAIN RESULTS: Of 762 people admitted with COVID-19, 239 (31.4%) used antiplatelet medications pre-hospitalization while 523 (68.6%) did not. Antiplatelet users were older and had more co-morbidities at baseline. Before adjusting for covariates, patients who used antiplatelet medications pre-hospitalization were more likely than non-users to have peak MOS score 6 (death, OR 1.75, 95% CI 1.21-2.52), peak MOS score ≥5 (intubation/ECMO or death, OR 1.4, 95% CI 1.00-1.98) and peak MOS score ≥4 (HFNC, NIPPV, intubation/ECMO or death, OR 1.40, 95% CI 1.01-1.94). On multivariable adjusted PPOM analysis controlling for 13 covariates, there were no longer any significant differences in peak MOS scores between users and non-users. CONCLUSIONS: After adjusting for covariates, pre-hospital antiplatelet use was not associated with COVID-19 severity in hospitalized patients.

Initiation of Somatostatin analogues for neuroendocrine tumor patients: a cost-effectiveness analysis.

BACKGROUND & AIMS: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous neoplasms. Although some have a relatively benign and indolent natural history, others can be aggressive and ultimately fatal. Somatostatin analogues (SSAs) improve both quality of life and survival for these patients once they develop metastatic disease. However, these drugs are costly and their cost-effectiveness is not known. METHODS: A decision-analytic model was developed and analyzed to compare two treatment strategies for patients with Stage IV GEP-NETs. The first strategy had all patients start SSA immediately while the second strategy waited, reserving SSA initiation until the patient showed signs of progression. Sensitivity analysis was performed to explore model parameter uncertainty. RESULTS: Our model of patients age 60 with metastatic GEP-NETs suggests empiric initiation of SSA led to an increase 0.62 unadjusted life-years and incremental increase in quality-adjusted life years (QALYs) of 0.44. The incremental costs were $388,966 per QALY and not cost-effective at a willingness-to-pay threshold of $100,000. Death was attributed to GEP-NETs for 94.1% of patients in the SSA arm vs. 94.9% of patients in the DELAY SSA arm. Sensitivity analysis found that the model was most sensitive to costs of SSAs. Using probabilistic sensitivity analysis, the SSA strategy was only cost-effective 1.4% of the time at a WTP threshold of $100,000 per QALY. CONCLUSIONS: Our modeling study finds it is not cost-effective to initiate SSAs at time of presentation for patients with metastatic GEP-NETs. Further clinical studies are needed to identify the optimal timing to initiate these drugs.

Association between somatostatin analogues and diabetes mellitus in gastroenteropancreatic neuroendocrine tumor patients: A Surveillance, Epidemiology, and End Results-Medicare analysis of 5235 patients.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are increasingly common malignancies and tend to have favorable long-term prognoses. Somatostatin analogues (SSA) are a first-line treatment for many NETs. Short-term experiments suggest an association between SSAs and hyperglycemia. However, it is unknown whether there is a relationship between SSAs and clinically significant hyperglycemia causing development of diabetes mellitus (DM), a chronic condition with significant morbidity and mortality. AIM: In this study, we aimed to compare risk of developing DM in patients treated with SSA vs no SSA treatment. METHODS AND RESULTS: Using the Surveillance, Epidemiology, and End Results (SEER) database and linked Medicare claims (1991-2016), we identified patients age 65+ with no prior DM diagnosis and a GEP-NET in the stomach, small intestine, appendix, colon, rectum, or pancreas. We used χ2 tests to compare SSA-treated and SSA-untreated patients and multivariable Cox regression to assess risk factors for developing DM. Among 8464 GEP-NET patients, 5235 patients had no prior DM and were included for analysis. Of these, 784 (15%) patients received SSAs. In multivariable analysis, the hazard ratio of developing DM with SSA treatment was 1.19, which was not statistically significant (95% CI 0.95-1.49). Significant risk factors for DM included black race, Hispanic ethnicity, prior pancreatic surgery, prior chemotherapy, tumor size >2 cm, pancreas tumors, and higher Charlson scores. CONCLUSION: DM was very common in GEP-NET patients, affecting 53% of our cohort. Despite prior studies suggesting an association between SSAs and hyperglycemia, our analysis found similar risk of DM in SSA-treated and SSA-untreated GEP-NET patients. Further studies are needed to better understand this relationship. As NET patients have increasingly prolonged survival, it is crucial to identify chronic conditions such as DM that these patients may be at elevated risk for.

Outcomes of COVID-19 Among Hospitalized Health Care Workers in North America.

Importance: Although health care workers (HCWs) are at higher risk of acquiring coronavirus disease 2019 (COVID-19), it is unclear whether they are at risk of poorer outcomes. Objective: To evaluate the association between HCW status and outcomes among patients hospitalized with COVID-19. Design, Setting, and Participants: This retrospective, observational cohort study included consecutive adult patients hospitalized with a diagnosis of laboratory-confirmed COVID-19 across 36 North American centers from April 15 to June 5, 2020. Data were collected from 1992 patients. Data were analyzed from September 10 to October 1, 2020. Exposures: Data on patient baseline characteristics, comorbidities, presenting symptoms, treatments, and outcomes were collected, including HCW status. Main Outcomes and Measures: The primary outcome was a requirement for mechanical ventilation or death. Multivariable logistic regression was performed to yield adjusted odds ratios (AORs) and 95% CIs for the association between HCW status and COVID-19-related outcomes in a 3:1 propensity score-matched cohort, adjusting for residual confounding after matching. Results: In total, 1790 patients were included, comprising 127 HCWs and 1663 non-HCWs. After 3:1 propensity score matching, 122 HCWs were matched to 366 non-HCWs. Women comprised 71 (58.2%) of matched HCWs and 214 (58.5%) of matched non-HCWs. Matched HCWs had a mean (SD) age of 52 (13) years, whereas matched non-HCWs had a mean (SD) age of 57 (17) years. In the matched cohort, the odds of the primary outcome, mechanical ventilation or death, were not significantly different for HCWs compared with non-HCWs (AOR, 0.60; 95% CI, 0.34-1.04). The HCWs were less likely to require admission to an intensive care unit (AOR, 0.56; 95% CI, 0.34-0.92) and were also less likely to require an admission of 7 days or longer (AOR, 0.53; 95% CI, 0.34-0.83). There were no differences between matched HCWs and non-HCWs in terms of mechanical ventilation (AOR, 0.66; 95% CI, 0.37-1.17), death (AOR, 0.47; 95% CI, 0.18-1.27), or vasopressor requirements (AOR, 0.68; 95% CI, 0.37-1.24). Conclusions and Relevance: In this propensity score-matched multicenter cohort study, HCW status was not associated with poorer outcomes among hospitalized patients with COVID-19 and, in fact, was associated with a shorter length of hospitalization and decreased likelihood of intensive care unit admission. Further research is needed to elucidate the proportion of HCW infections acquired in the workplace and to assess whether HCW type is associated with outcomes.

Digestive Manifestations in Patients Hospitalized With Coronavirus Disease 2019.

BACKGROUND & AIMS: The prevalence and significance of digestive manifestations in coronavirus disease 2019 (COVID-19) remain uncertain. We aimed to assess the prevalence, spectrum, severity, and significance of digestive manifestations in patients hospitalized with COVID-19. METHODS: Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were abstracted manually from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. RESULTS: A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least 1 gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were increased to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio, 0.93; 95% CI, 0.76-1.15) or liver test abnormalities on admission (odds ratio, 1.31; 95% CI, 0.80-2.12) were not associated independently with mechanical ventilation or death. CONCLUSIONS: Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common, but the majority were mild and their presence was not associated with a more severe clinical course.