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Item Associations of opioid prescription dose and discontinuation with risk of substance-related morbidity in long-term opioid therapy(Wolters Kluwer, 2022) Quinn, Patrick D.; Chang, Zheng; Bair, Matthew J.; Rickert, Martin E.; Gibbons, Robert D.; Kroenke, Kurt; D’Onofrio, Brian M.; Medicine, School of MedicineEfforts to reduce opioid-related harms have decreased opioid prescription but have provoked concerns about unintended consequences, particularly for long-term opioid therapy (LtOT) recipients. Research is needed to address the knowledge gap regarding how risk of substance-related morbidity changes across LtOT and its discontinuation. This study used nationwide commercial insurance claims data and a within-individual design to examine associations of LtOT dose and discontinuation with substance-related morbidity. We identified 194,839 adolescents and adults who initiated opioid prescription in 2010 to 2018 and subsequently received LtOT. The cohort was followed for a median of 965 days (interquartile range, 525-1550), of which a median of 176 days (119-332) were covered by opioid prescription. During follow-up, there were 17,582 acute substance-related morbidity events, defined as claims for emergency visits, inpatient hospitalizations, and ambulance transportation with substance use disorder or overdose diagnoses. Relative to initial treatment, risk was greater within individual during subsequent periods of >60 to 120 (adjusted odds ratio [OR], 1.29; 95% CI, 1.12 to 1.49) and >120 (OR, 1.48; 95% CI, 1.24-1.76) daily morphine milligram equivalents. Risk was also greater during days 1 to 30 after discontinuations than during initial treatment (OR, 1.19; 95% CI, 1.05-1.35). However, it was no greater than during the 30 days before discontinuations, indicating that the risk may not be wholly attributable to discontinuation itself. Results were supported by a negative control pharmacotherapy analysis and additional sensitivity analyses. They suggest that LtOT recipients may experience increased substance-related morbidity risk during treatment subsequent to initial opioid prescription, particularly in periods involving higher doses.Item Comorbid Depression and Psychosis in Parkinson's Disease: A Report of 62,783 Hospitalizations in the United States(Cureus, 2019-07-24) Imran, Sundus; Patel, Rikinkumar S.; Onyeaka, Henry K.; Tahir, Muhammad; Madireddy, Sowmya; Mainali, Pranita; Hossain, Sadaf; Rashid, Wahida; Queeneth, Uwandu; Ahmad, Naveed; Neurology, School of MedicineBackground Depression and psychosis are common comorbidities that significantly affects the quality of life and disease outcomes in Parkinson's disease (PD) patients. Objective The aim of this study was to analyze and discern the differences in the hospitalization outcomes, comorbidities, and utilization of deep brain stimulation (DBS) in PD patients with comorbid depression and comorbid psychosis. Methods We used the Nationwide Inpatient Sample (2010-2014) and identified PD as a primary diagnosis (N = 62,783), and depression (N = 11,358) and psychosis (N = 2,475) as co-diagnosis using the International Classification of Diseases, Ninth Revision (ICD-9) codes. Pearson's chi-square test and independent-sample t-test were used for categorical data and continuous data, respectively. Results White male, older age, and comorbid psychosis were significantly associated with higher odds of having major severity of illness in PD inpatients. The mean length of stay (LOS) was higher in PD patients with psychosis compared to PD with depression (7.32 days vs. 4.23 days; P < 0.001), though the mean total charges of hospitalization were lower in psychosis ($31,240 vs. $38,581; P < 0.001). Utilization of DBS was lower in PD patients with psychosis versus with depression (3.9% vs. 24.3%; P < 0.001). Conclusion Psychiatric comorbidities are prevalent in PD patients and are associated with more disease severity, impaired quality of life, and increased use of healthcare resources (higher LOS and cost). They should be considered an integral part of the disease, and a multidisciplinary approach to managing this disease is crucial to improve the health-related quality of life of PD patients.Item Critical Illness Cholangiopathy in COVID-19 Long-haulers(Elsevier, 2022) Saleem, Nasir; Li, Betty H.; Vuppalanchi, Raj; Gawrieh, Samer; Gromski, Mark A.; Medicine, School of MedicineItem In-Hospital Mortality and Morbidity in Cancer Patients with COVID-19: A Nationwide Analysis from the United States(MDPI, 2022-12-30) Abuhelwa, Ziad; Alsughayer, Anas; Abuhelwa, Ahmad Y.; Beran, Azizullah; Sayeh, Wasef; Khokher, Waleed; Sajdeya, Omar; Khuder, Sadik; Assaly, Ragheb; Medicine, School of MedicineBackground: Coronavirus disease 2019 (COVID-19) caused significant mortality and mortality worldwide. There is limited information describing the outcomes of COVID-19 in cancer patients. Methods: We utilized the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS) 2020 database to collect information on cancer patients hospitalized for COVID-19 in the United States. Using the International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) coding system, adult (≥18 years) patients with COVID-19 were identified. Adjusted analyses were performed to assess for mortality, morbidity, and resource utilization among cancer patients. Results: A total of 1,050,045 patients were included. Of them, 27,760 had underlying cancer. Cancer patients were older and had more comorbidities. The all-cause in-hospital mortality rate in cancer patients was 17.58% vs. 11% in non-cancer. After adjusted logistic regression, cancer patients had a 21% increase in the odds of all-cause in-hospital mortality compared with those without cancer (adjusted odds ratio (aOR) 1.21, 95%CI 1.12−1.31, p-value < 0.001). Additionally, an increased odds in acute respiratory failure rate was found (aOR 1.14, 95%CI 1.06−1.22, p-value < 0.001). However, no significant differences were found in the odds of septic shock, acute respiratory distress syndrome, and mechanical ventilation between the two groups. Additionally, no significant differences in the mean length of hospital stay and the total hospitalization charges between cancer and non-cancer patients. Conclusion: Cancer patients hospitalized for COVID-19 had increased odds of all-cause in hospital mortality and acute respiratory failure compared with non-cancer patients.Item Non-Transfusion-Dependent Thalassemia: An Update on Complications and Management(MDPI, 2018-01-08) Sleiman, Joseph; Tarhini, Ali; Bou-Fakhredin, Rayan; Saliba, Antoine N.; Cappellini, Maria Domenica; Taher, Ali T.; Medicine, School of MedicinePatients with non-transfusion-dependent thalassemia (NTDT) experience many clinical complications despite their independence from frequent transfusions. Morbidities in NTDT stem from the interaction of multiple pathophysiological factors: ineffective erythropoiesis, iron overload (IOL), and hypercoagulability. Ineffective erythropoiesis and hemolysis are associated with chronic hypoxia and a hypercoagulable state. The latter are linked to a high prevalence of thromboembolic and cerebrovascular events, as well as leg ulcers and pulmonary hypertension. IOL in NTDT patients is a cumulative process that can lead to several iron-related morbidities in the liver (liver fibrosis), kidneys, endocrine glands (endocrinopathies), and vascular system (vascular disease). This review sheds light on the pathophysiology underlying morbidities associated with NTDT and summarizes the mainstays of treatment and some of the possible future therapeutic interventions.Item Potential role of intermittent fasting on decreasing cardiovascular disease in human immunodeficiency virus patients receiving antiretroviral therapy(Baishideng Publishing Group, 2021-11-20) Gnoni, Martin; Beas, Renato; Raghuram, Anupama; Díaz-Pardavé, Celeste; Riva-Moscoso, Adrian; Príncipe-Meneses, Fortunato S.; Vásquez-Garagatti, Raúl; Medicine, School of MedicineCardiovascular disease (CVD) has become one of the commonest causes of comorbidity and mortality among People living with human immunodeficiency virus (HIV) (PLWH) on antiretroviral therapy (ART). Nearly 50% of PLWH are likely to have an increased risk of developing CVD, including coronary heart disease, cerebrovascular disease, peripheral artery disease and aortic atherosclerosis. Aside from the common risk factors, HIV infection itself and side effects of antiretroviral therapy contribute to the pathophysiology of this entity. Potential non-pharmacological therapies are currently being tested worldwide for this purpose, including eating patterns such as Intermittent fasting (IF). IF is a widespread practice gaining high level of interest in the scientific community due to its potential benefits such as improvement in serum lipids and lipoproteins, blood pressure (BP), platelet-derived growth factor AB, systemic inflammation, and carotid artery intima-media thickness among others cardiovascular benefits. This review will focus on exploring the potential role of intermittent fasting as a non-pharmacological and cost-effective strategy in decreasing the burden of cardiovascular diseases among HIV patients on ART due to its intrinsic properties improving the main cardiovascular risk factors and modulating inflammatory pathways related to endothelial dysfunction, lipid peroxidation and aging. Intermittent fasting regimens need to be tested in clinical trials as an important, cost-effective, and revolutionary coadjutant of ART in the fight against the increased prevalence of cardiovascular disease in PLWH.Item Prevalence of cardiovascular and respiratory complications following trauma in patients with obesity(Elsevier, 2017-09) Bell, Teresa; Stokes, Samantha; Jenkins, Peter C.; Hatcher, LeRanna; Fecher, Alison M.; Surgery, School of MedicineBACKGROUND: It is generally accepted that obesity puts patients at an increased risk for cardiovascular and respiratory complications after surgical procedures. However, in the setting of trauma, there have been mixed findings in regards to whether obesity increases the risk for additional complications. OBJECTIVE: The aim of this study was to identify whether obese patients suffer an increased risk of cardiac and respiratory complications following traumatic injury. METHODS: A retrospective analysis of 275,393 patients was conducted using the 2012 National Trauma Data Bank. Hierarchical regression modeling was performed to determine the probability of experiencing a cardiac or respiratory complication. RESULTS: Patients with obesity were at a significantly higher risk of cardiac and respiratory complications compared to patients without obesity [OR: 1.81; CI: 1.72-1.91]. Prevalence of cardiovascular and respiratory complications for patients with obesity was 12.6% compared to 5.2% for non-obese patients. CONCLUSIONS: Obesity is predictive of an increased risk for cardiovascular and respiratory complications following trauma.Item SARS-CoV-2 Infections and ACE2: Clinical Outcomes Linked With Increased Morbidity and Mortality in Individuals With Diabetes(American Diabetes Association, 2020-07-15) Obukhov, Alexander G.; Stevens, Bruce R.; Prasad, Ram; Calzi, Sergio Li; Boulton, Michael E.; Raizada, Mohan K.; Oudit, Gavin Y.; Grant, Maria B.; Anatomy and Cell Biology, School of MedicineIndividuals with diabetes suffering from coronavirus disease 2019 (COVID-19) exhibit increased morbidity and mortality compared with individuals without diabetes. In this Perspective, we critically evaluate and argue that this is due to a dysregulated renin-angiotensin system (RAS). Previously, we have shown that loss of angiotensin-I converting enzyme 2 (ACE2) promotes the ACE/angiotensin-II (Ang-II)/angiotensin type 1 receptor (AT1R) axis, a deleterious arm of RAS, unleashing its detrimental effects in diabetes. As suggested by the recent reports regarding the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), upon entry into the host, this virus binds to the extracellular domain of ACE2 in nasal, lung, and gut epithelial cells through its spike glycoprotein subunit S1. We put forth the hypothesis that during this process, reduced ACE2 could result in clinical deterioration in COVID-19 patients with diabetes via aggravating Ang-II–dependent pathways and partly driving not only lung but also bone marrow and gastrointestinal pathology. In addition to systemic RAS, the pathophysiological response of the local RAS within the intestinal epithelium involves mechanisms distinct from that of RAS in the lung; however, both lung and gut are impacted by diabetes-induced bone marrow dysfunction. Careful targeting of the systemic and tissue RAS may optimize clinical outcomes in subjects with diabetes infected with SARS-CoV-2.Item Specialized care improves outcomes for patients with cirrhosis who require general surgical operations(Public Library of Science, 2019-10-16) Kays, Joshua K.; Milgrom, Daniel P.; Butler, James R.; Liang, Tiffany W.; Valsangkar, Nakul P.; Wojcik, Brandon; Frye, C. Corbin; Maluccio, Mary A.; Kubal, Chandrashekhar A.; Koniaris, Leonidas G.; Surgery, School of MedicineBACKGROUND: General surgical operations on patients with cirrhosis have historically been associated with high morbidity and mortality rates. This study examines a contemporary series of patients with cirrhosis undergoing general surgical procedures. METHODS: A retrospective evaluation of 358 cirrhotic patients undergoing general surgical operations at a single institution between 2004-2015 was performed. Thirty- and 90-day mortality along with complications and subsequent transplantation rates were examined. RESULTS: 358 cirrhotic patients were identified. The majority were Child-Turcotte-Pugh class (CTP) A (55.9%) followed by class B (32.4%) and class C (11.7%). Mean MELD score differed significantly between the groups (8.7 vs. 12.1 vs. 20.1; p<0.001). The most common operations were herniorrhaphy (29.9%), cholecystectomy (19.3%), and liver resection (14.5%). The majority of cases were performed semi-electively (68.4%), however, within the CTP C patients most cases were performed emergently (73.8%). Thirty and 90-day mortality for all patients were 5% and 6%, respectively. Mortality rates increased from CTP A to CTP C (30 day: 3.0% vs. 5.2% vs. 14.3%; p = 0.01; 90 day: 4.5% vs. 6.9% vs. 16.7%; p = 0.016). Additionally, 30-day mortality (12.8% vs. 2.3%; p<0.001), 90 day mortality (16.0% vs. 3.4%; p<0.001) were higher for emergent compared to elective cases. A total of 13 (3.6%) patients underwent transplantation ≤ 90 days from surgery. No elective cases resulted in an urgent transplantation. CONCLUSION: Performing general surgical operations on cirrhotic patients carries a significant morbidity and mortality. This contemporary series from a specialized liver center demonstrates improved outcomes compared to historical series. These data strongly support early referral of cirrhotic patients needing general surgical operation to centers with liver expertise to minimize morbidity and mortality.Item Successful Modified Therapy in a Patient With Probable Infection-Associated Hemophagocytic Lymphohistiocytosis(Hindawi, 2019) Kay, Carl L.; Rendo, Matthew J.; Gonzales, Paul; Beganovic, Sead G.; Czader, Magdalena; Medicine, School of MedicineHemophagocytic lymphohistiocytosis (HLH) is a rare, hyperinflammatory syndrome characterized by clinical signs and symptoms of extreme inflammation. In adults, HLH is typically a complication of infections, autoimmune diseases, and malignancies. While the disease is often fatal, classic management of HLH revolves around early diagnosis and initiation of protocolized therapy. We present a case of a previously healthy 56-year-old female who developed distributive shock requiring intubation, vasopressors, and continuous venovenous hemofiltration. In the setting of multiple infectious syndromes, severe cytopenias, and rising direct hyperbilirubinemia, her diagnosis of HLH was confirmed. Therapy was initiated with dexamethasone and two doses of reduced-intensity etoposide based on the patient's clinical course. Over the next few weeks, she continued to improve on dexamethasone monotherapy and has maintained remission up to the present with complete resolution of her cytopenias and return of baseline renal function. Our case highlights the variability in the management of probable infection-associated HLH (IHLH) with a good patient outcome. We demonstrate the potential to treat IHLH with partial protocols and minimal chemotherapeutics.