Disease-Modifying Antirheumatic Drug Use and Its Effect on Long-term Opioid Use in Patients With Rheumatoid Arthritis.

BACKGROUND/OBJECTIVES: The prevalence of chronic pain is high in patients with rheumatoid arthritis (RA), increasing the risk for opioid use. The objective of this study was to assess disease-modifying antirheumatic drug (DMARD) use and its effect on long-term opioid use in patients with RA. METHODS: This cohort study included Medicare beneficiaries with diagnosis of RA who received at least 30-day consecutive prescription of opioids in 2017 (n = 23,608). The patients were grouped into non-DMARD and DMARD users, who were further subdivided into regimens set forth by the American College of Rheumatology. The outcome measured was long-term opioid use in 2018 defined as at least 90-day consecutive prescription of opioids. Dose and duration of opioid use were also assessed. A multivariable model identifying factors associated with non-DMARD use was also performed. RESULTS: Compared with non-DMARD users, the odds of long-term opioid use were significantly lower among DMARD users (odds ratio, 0.89; 95% confidence interval, 0.83-0.95). All regimens except non-tumor necrosis factor biologic + methotrexate were associated with lower odds of long-term opioid use relative to non-DMARD users. The mean total morphine milligram equivalent, morphine milligram equivalent per day, and total days of opioid use were lower among DMARD users compared with non-DMARD users. Older age, male sex, Black race, psychiatric and medical comorbidities, and not being seen by a rheumatologist were significantly associated with non-DMARD use. CONCLUSION: Disease-modifying antirheumatic drug use was associated with lower odds of long-term opioid use among RA patients with baseline opioid prescription. Factors associated with non-DMARD use represent a window of opportunity for intervention to improve pain-related quality of life in patients living with RA.

Co-prescribing of Central Nervous System-Active Medications for COPD Patients: Impact on Emergency Room Visits and Hospitalization.

BACKGROUND: Anxiety and chronic pain are common comorbidities in patients with chronic obstructive pulmonary disease (COPD), which are frequently managed with benzodiazepines (BZDs) and opioids, respectively. OBJECTIVE: The purpose of this study was to determine whether different combinations of opioids, BZD, and their substitutes-gabapentinoids (GABA) and selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs)-are associated with lower risk of acute respiratory events in COPD patients with co-occurring chronic pain and anxiety. METHODS: This retrospective cohort study used a nationally representative sample of Medicare beneficiaries with COPD, chronic pain, and anxiety. Patients were grouped based on drug combination (opioid + BZD/Z-hypnotics, opioid + GABA, opioid + SSRI/SNRI, BZD/Z-hypnotics + GABA, BZD/Z-hypnotics + SSRI/SNRI, GABA + SSRI/SNRI, or ≥3 drugs). The primary outcome was emergency room (ER) visit or hospitalization due to acute respiratory events assessed up to 180 days following initiation of drug combination. Overdose secondary to central nervous system (CNS)-related drugs was also assessed up to 180 days following initiation of drug combination. RESULTS: The drug combination opioid + GABA was associated with decreased risk for ER visit (hazard ratio [HR] = 0.73; 95% CI = 0.61-0.87) and hospitalization (HR = 0.69; 95% CI = 0.55-0.85). Opioid + SSRI/SNRI also showed decreased risk for ER visit (HR = 0.84; 95% CI = 0.71-0.99). There was no significant difference in risk for CNS-related drug overdose among different drug combinations compared with opioid + BZD/Z-hypnotics. CONCLUSION AND RELEVANCE: Opioids in combination with GABA and SSRI/SNRI demonstrate relatively lower risk for acute respiratory events among patients with COPD and comorbid chronic pain and anxiety. The findings emphasize the need for multimodal management in this vulnerable population.

Immunogenicity and Safety of SARS-CoV-2 Vaccination in Patients With Rheumatic Diseases: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analysis examining the immunogenicity and safety of SARS-CoV-2 vaccination in patients with RD. METHODS: We systematically searched PubMed/MEDLINE and Scopus to identify observational studies that examined the immunogenicity and safety of SARS-CoV-2 vaccination in RD patients. Information on disease, immunosuppressant, vaccine type, and proportion of patients with serologic response was obtained from each study. RESULTS: There were 25 eligible studies. The pooled rate of seroconversion was 0.79 (95% confidence interval [CI], 0.72-0.86). Compared with control subjects, the odds of seroconversion were significantly lower (odds ratio, 0.11; 95% CI, 0.05-0.24). Users of rituximab showed the lowest rate of seroconversion (0.39; 95% CI, 0.29-0.51) followed by mycophenolate (0.56; 95% CI, 0.40-71). On the other hand, users of interleukin 17 (0.94; 95% CI, 0.78-0.98) and tumor necrosis factor inhibitors (0.94; 95% CI, 0.84-0.98) showed high seroconversion rate. Regarding safety of COVID-19 vaccine, approximately 2% of patients reported severe adverse events and 7% reported diseases flares following the first or second dose. CONCLUSION: Vaccination against SARS-CoV-2 appears to be safe. Most RD patients developed humoral immune response following vaccination. However, the odds of seroconversion were significantly lower in RD patients compared with controls. This is likely driven by certain immunosuppressants including rituximab and mycophenolate. Future studies need to identify strategies to improve vaccine response in these patients.

Pharmacologic venous thromboembolism prophylaxis is not associated with post sphincterotomy bleeding after endoscopic retrograde cholangiopancreatography.

BACKGROUND/AIM: Endoscopic sphincterotomy is considered high risk for post-procedure bleeding. Sphincterotomy in patients on therapeutic anticoagulation is avoided given increased bleeding risk. There is minimal data on the risk of post-sphincterotomy bleeding (PSB) among those on prophylactic anticoagulation for venous thromboembolism (VTE) prophylaxis. METHODS: We performed a retrospective case control study of all inpatient endoscopic retrograde cholangiopancreatographies (ERCPs) with a sphincterotomy at our institution between July 2016 to February 2020. Cases were divided into two groups based on administration of peri­procedural pharmacologic VTE prophylaxis. The outcomes were the rates of PSB and VTE within 30-days of the ERCP. RESULTS: A total of 369 inpatient ERCPs with a sphincterotomy were identified. 151 cases received peri­procedural pharmacologic VTE prophylaxis and 218 did not. The mean Padua score and American Society of Anesthesiologists physical status classification were significantly greater in the prophylaxis group. PSB was statistically similar between both groups (3.3% vs. 5.5%, p=.32). VTE was statistically similar (0.7% vs. 0.5%, p=.79). Multivariate analysis did not reveal an association between PSB and peri­procedural pharmacologic VTE prophylaxis. CONCLUSION: Peri-procedural pharmacologic VTE prophylaxis is not associated with increased rates of PSB. These findings suggest that pharmacologic VTE prophylaxis can be safely continued in those undergoing an endoscopic sphincterotomy.

Cognitive impairment in elderly patients with rheumatic disease and the effect of disease-modifying anti-rheumatic drugs.

Recent development of biologic disease-modifying anti-rheumatic drugs (DMARDs) has led to better control of disease activity among patients with chronic rheumatological diseases. Many patients with rheumatic disease are living longer, adding to the growing elderly population. Rheumatic diseases, most notably rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), are known to increase the risk of cognitive impairment. Systemic inflammation associated with chronic rheumatological diseases has been postulated to be key driver of cognitive decline. Recent development of classic and biologic DMARDs have led to better control of disease activity among patients with rheumatic conditions. It is proposed that strict control of systemic inflammation will significantly lower the risk of cognitive impairment among patients with rheumatic disease. The impact of classic DMARDs on cognitive function appears to be variable. On the other hand, biologic DMARDs, specifically antitumor necrosis factor (TNF) drugs (i.e., etanercept), have been shown to significantly lower the risk of dementia. Experimental studies on IL-1, IL-6, and B and T cell blockade are promising. However, clinical data is limited. Preclinical studies on targeted therapies, specifically JAK/STAT inhibitors, also show promising results. Additional studies are necessary to better understand the impact of these newer biologic agents on cognitive function in elderly patients with rheumatic disease. Key points • Patients with chronic rheumatic conditions are beginning to live longer, adding to the elderly population. • Patients with chronic rheumatologic disease are at increased risk of cognitive impairment compared to the general population. • Recent development of biologic (i.e., TNF, IL-1, IL-6) and targeted drugs (i.e., Janus kinase inhibitors) have led to better control of disease activity. • Current evidence suggests that TNF inhibitors may have beneficial effects on cognitive function. However, evidence on newer biologic and targeted therapies is limited.

Dietary inflammatory potential in relation to the gut microbiome: results from a cross-sectional study.

Diet has direct and indirect effects on health through inflammation and the gut microbiome. We investigated total dietary inflammatory potential via the literature-derived index (Dietary Inflammatory Index (DII®)) with gut microbiota diversity, composition and function. In cancer-free patient volunteers initially approached at colonoscopy and healthy volunteers recruited from the medical centre community, we assessed 16S ribosomal DNA in all subjects who provided dietary assessments and stool samples (n 101) and the gut metagenome in a subset of patients with residual fasting blood samples (n 34). Associations of energy-adjusted DII scores with microbial diversity and composition were examined using linear regression, permutational multivariate ANOVA and linear discriminant analysis. Spearman correlation was used to evaluate associations of species and pathways with DII and circulating inflammatory markers. Across DII levels, α- and ß-diversity did not significantly differ; however, Ruminococcus torques, Eubacterium nodatum, Acidaminococcus intestini and Clostridium leptum were more abundant in the most pro-inflammatory diet group, while Akkermansia muciniphila was enriched in the most anti-inflammatory diet group. With adjustment for age and BMI, R. torques, E. nodatum and A. intestini remained significantly associated with a more pro-inflammatory diet. In the metagenomic and fasting blood subset, A. intestini was correlated with circulating plasminogen activator inhibitor-1, a pro-inflammatory marker (rho = 0·40), but no associations remained significant upon correction for multiple testing. An index reflecting overall inflammatory potential of the diet was associated with specific microbes, but not overall diversity of the gut microbiome in our study. Findings from this preliminary study warrant further research in larger samples and prospective cohorts.

Renal Safety of Intravenous Gadolinium-enhanced MRI in Patients Following Liver Transplantation.

BACKGROUND: Intravenous contrast-enhanced imaging is invaluable in diagnosing pathology following liver transplantation. Given the potential risk of contrast nephropathy associated with iodinated computed tomography contrast, alternate contrast modalities need to be examined, especially in the setting of renal insufficiency. The purpose of this study was to examine the renal safety of MRI with gadolinium following liver transplantation. METHODS: The study involved a retrospective analysis of 549 cases of abdominal MRI with low-dose gadobenate dimeglumine in liver transplant recipients at a single center. For each case, serum creatinine values before and after the MRI were compared. In addition, cases were analyzed for the development of nephrogenic systemic fibrosis. RESULTS: Pre-MRI creatinine values ranged from 0.32 to 6.57 mg/dL (median, 1.28 g/dL), with 191 cases having values ≥1.5 mg/dL (median, 1.86 g/dL). A comparison of the pre- and post-MRI creatinine values showed no significant difference, including those patients with pre-MRI values ≥1.5 mg/dL (mean change of -0.04 [95% confidence interval, -0.07 to -0.01; P = 0.004]). No cases of nephrogenic systemic fibrosis were noted. CONCLUSIONS: Our findings suggest that, irrespective of baseline renal function, MRI with gadobenate dimeglumine is a nonnephrotoxic imaging modality in liver transplant recipients. Importantly, this intravenous contrast-enhanced imaging modality can be considered in those posttransplant patients who have a contraindication to computed tomography contrast due to renal insufficiency.

Right Ventricular Outflow Obstruction Due to Metastatic Neuroendocrine Tumor.

Neuroendocrine tumors (NETs) are rare malignant tumors that arise from neuroendocrine cells of the gastrointestinal tract and often metastasize to the liver, lung, and bone. Cardiac metastasis of NETs is uncommon. We report a patient with a past medical history of a neuroendocrine tumor of the left femur presenting with signs and symptoms of new onset heart failure. Transthoracic echocardiogram and cardiac magnetic resonance showed a large mass within the right ventricle causing right ventricular outflow obstruction. A positron emission tomographic/computed tomographic scan (PET-CT) revealed increased uptake of fluorodeoxyglucose (FDG) activity within the right ventricle consistent with metastasis. Cardiac biopsy of the right ventricular mass revealed metastatic nonfunctioning neuroendocrine tumor. In view of the fact that it was a tumor that caused the right ventricular obstruction, the patient was started on chemotherapy with improvement of symptoms. This case highlights that in patients with a history of neuroendocrine tumor presenting with heart failure, cardiac metastasis should be included in the differential.