Relapses and Serious Infections in Patients with Neuromyelitis Optica Spectrum Disorder Treated with Rituximab: A Swedish Single-Center Study.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare immune-mediated relapsing-remitting disease of the central nervous system. The usage of rituximab, as relapse-preventive therapy, in NMOSD is common. We performed a single-center retrospective cohort study to assess the risk of relapses and severe infectious events (SIEs) in rituximab-treated NMOSD patients. This study included 24 aquaporin-4 IgG+ (AQP4+), 8 myelin-oligodendrocyte-protein IgG+ (MOG+), and 10 double-seronegative NMOSD patients. Relapses were observed in 50% of all patients during a mean treatment time of 4.0 (range: 0.5-8.25) years. The incidence risk ratio (IRR) of relapse was three times higher in MOG+ compared to AQP4+ patients (IRR: 3.0, 95% confidence interval (CI); 1.2-7.7). SIEs occurred in 40% of all patients during follow-up. AQP4+ patients conferred an increased risk of SIEs compared to MOG+ patients (IRR; 5.3, 95% CI; 1.2-24.3). Incomplete CD19+ B-lymphocyte suppression was not correlated with relapse risk (hazard ratio; 1.9, 95% CI; 0.7-5.2), and there was no correlation between IgG-levels and SIE risk (odds ratio; 2.0, 95% CI; 0.8-4.8). In conclusion, considerable risks of both relapses and SIEs were observed in NMOSD patients exposed to rituximab, which underlines the need for close clinical vigilance of disease activity and infections during treatment.

Serious Infections in Offspring Exposed in Utero to Vedolizumab.

Controlling IBD during pregnancy is important for maternal and fetal outcomes. We created a cohort of children born to mothers with IBD, comparing the risk of infections in those exposed to vedolizumab vs unexposed. We detected no increased risk.

Clinical prediction models for serious infections in children: external validation in ambulatory care.

BACKGROUND: Early distinction between mild and serious infections (SI) is challenging in children in ambulatory care. Clinical prediction models (CPMs), developed to aid physicians in clinical decision-making, require broad external validation before clinical use. We aimed to externally validate four CPMs, developed in emergency departments, in ambulatory care. METHODS: We applied the CPMs in a prospective cohort of acutely ill children presenting to general practices, outpatient paediatric practices or emergency departments in Flanders, Belgium. For two multinomial regression models, Feverkidstool and Craig model, discriminative ability and calibration were assessed, and a model update was performed by re-estimation of coefficients with correction for overfitting. For two risk scores, the SBI score and PAWS, the diagnostic test accuracy was assessed. RESULTS: A total of 8211 children were included, comprising 498 SI and 276 serious bacterial infections (SBI). Feverkidstool had a C-statistic of 0.80 (95% confidence interval 0.77-0.84) with good calibration for pneumonia and 0.74 (0.70-0.79) with poor calibration for other SBI. The Craig model had a C-statistic of 0.80 (0.77-0.83) for pneumonia, 0.75 (0.70-0.80) for complicated urinary tract infections and 0.63 (0.39-0.88) for bacteraemia, with poor calibration. The model update resulted in improved C-statistics for all outcomes and good overall calibration for Feverkidstool and the Craig model. SBI score and PAWS performed extremely weak with sensitivities of 0.12 (0.09-0.15) and 0.32 (0.28-0.37). CONCLUSIONS: Feverkidstool and the Craig model show good discriminative ability for predicting SBI and a potential for early recognition of SBI, confirming good external validity in a low prevalence setting of SBI. The SBI score and PAWS showed poor diagnostic performance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02024282. Registered on 31 December 2013.

Comparing the risk of serious infections in patients with and without MS: A German claims data analysis.

BACKGROUND: Research suggests that serious infections (SIs), comorbidities, and advanced disability represent key drivers of early death in people with Multiple Sclerosis (pwMS). Nevertheless, further research is warranted to better characterize and quantify the risk of SI among pwMS compared to the general population. METHODS: Our study consisted of a retrospective analysis of claims data provided by a German statutory health insurance fund, AOK PLUS, covering 3.4 million individuals in Saxony and Thuringia from 01/01/2015-31/12/2019. A propensity score (PS) matching method was used to compare the incidence of SIs among people with and without MS. PwMS were required to have ≥1 inpatient or ≥2 confirmed outpatient diagnoses of MS (ICD-10 G35) from a neurologist from 01/01/2016-31/12/2018, while people from the general population could not have any inpatient/outpatient codes for MS during the entire study period. The index date was defined as the first observed MS diagnosis or, in the case of the non-MS cohort, a randomly assigned date within the inclusion period. For both cohorts a PS was assigned, corresponding with their probabilistic likelihood of having MS based on observable factors including patient characteristics, comorbidities, medication use and other variables. People with and without MS were matched using a 1:1 nearest neighbor strategy. An exhaustive list of ICD-10 codes was created in association with 11 main SI categories. SIs were those recorded as the main diagnosis during an inpatient stay. ICD-10 codes from the 11 main categories were sorted into smaller classification units, used to distinguish between infections. A 60-day threshold for measuring new cases was defined to account for the potential risk of re-infection. Patients were observed until the end of the study period (31/12/2019) or death. Cumulative incidence, incidence rates (IRs) and IR ratios (IRRs) were reported during follow-up and at 1-, 2- and 3-years post-index. RESULTS: A total of 4250 and 2,098,626 patients were included in the unmatched cohorts of people with and without MS. Ultimately, one match was identified for all 4,250 pwMS, corresponding with a final population of 8,500 patients. On average, patients were 52.0/52.2 years in the matched MS/non-MS cohorts; the gender breakdown was 72% female. Overall, IRs of SIs per 100 patient years (PY) were higher in pwMS than in those without MS (1 year: 7.6 vs. 4.3; 2 years: 7.1 vs. 3.8; 3 years: 6.9 vs. 3.9). During follow-up, the most common infection types in pwMS were of a bacterial/parasitic origin (2.3 per 100 PY), followed by respiratory (2.0) and genitourinary (1.9) infections. Respiratory infections were most common in patients without MS (1.5 per 100 PY). Differences in the IRs of SIs were statistically significant (p<0.01) at each measurement window, with IRRs ranging from 1.7-1.9. PwMS had a higher risk of hospitalized genitourinary infections (IRR: 3.3-3.8) and bacterial/parasitic infections (2.0-2.3). CONCLUSIONS: The incidence of SIs is much higher in pwMS, than comparators from the general population in Germany. Differences in hospitalized infection rates were largely driven by higher levels of bacterial/parasitic and genitourinary infections in the MS population.

Incidence of serious infections in patients with ANCA-associated vasculitis receiving immunosuppressive therapy: A systematic review and meta-analysis.

Introduction: Rituximab and azathioprine are used to induce or maintain remission in patients with ANCA-associated vasculitis (AAV). We evaluated the incidence of serious infections and infection-related deaths in patients with AAV treated with rituximab and azathioprine, during the maintenance of remission period. Methods: We searched PubMed and EMBASE for randomized clinical trials (RCTs) and observational studies evaluating immunosuppressive agents in patients with AAV. We defined serious or severe infections according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The study was registered on PROSPERO (CRD42022366269). Results: From 1,265 abstracts, we identified 21 studies (7 RCTs and 14 observational), with relevant data. We included data from 1,284 and 2,938 individuals for assessment in our primary and secondary outcomes, respectively. The overall cumulative incidence of serious infections was 15.99% (CI 95%: 6.95-27.53%) during the total follow-up period (induction and maintenance) and 7.62% (CI 95%: 4.43-11.43%) during the maintenance period. Additionally, we found a 0.49% overall case fatality rate (CI 95%: 0.02-1.37%) and a 0.09% infection-related mortality rate (CI 95%: 0.00-0.51%) during maintenance treatment. Notably, we found a 14.61% (CI 95%: 10.19-19.61%) cumulative incidence of serious infections among patients who received rituximab and a 5.93% (CI 95%: 1.19-13.26%) cumulative incidence of serious infections among patients who received azathioprine during maintenance. Moreover, the cumulative incidence of serious infections during the total follow-up period (induction and maintenance) was 20.81% (CI 95%:4.56-43.70%) for the combination of cyclophosphamide and azathioprine and 14.12% (CI 95%: 5.20-26.00%) for rituximab. Discussion: The cumulative incidence of serious infections during total follow-up and maintenance was within expected limits, while fatal infections during maintenance treatment were uncommon. Additionally, treatment with rituximab for both induction and maintenance did not exceed the anticipated by previous studies incidence of serious infections. Clinical practice and long-term follow up data are needed to corroborate these findings. Systematic review registration: Identifier: PROSPERO (CRD42022366269).

Predictors of hospitalization due to infection in rituximab-treated MS patients.

BACKGROUND: Rituximab is extensively used off-label to treat multiple sclerosis (MS), and long-term vigilance for adverse events is needed. This study was conducted to determine frequencies and predictors of hematological adverse events, including hypogammaglobulinemia, severe lymphopenia, neutropenia, and infections leading to hospitalization. METHODS: This retrospective cohort study included all patients with MS initiating rituximab treatment at Haukeland University Hospital between January 1st, 2017, and July 1st, 2021. Patients were followed by clinical monitoring and repeated blood sampling every six months. Clinical outcomes and laboratory results were retrieved from the Norwegian MS Registry and Biobank and the patient administrative system at Haukeland University Hospital. RESULTS: Five hundred and fifty-six patients were included, 515 with relapsing-remitting MS (RRMS) and 41 with progressive MS. Overall, 33 patients (5.9%) experienced 56 episodes of infections requiring hospital admission. Sixty patients (10.8%) had confirmed hypogammaglobulinemia, 17 (3.1%) had confirmed severe lymphopenia, and 10 (1.8%) had confirmed severe neutropenia. Predictors of infection requiring hospital admission were progressive MS (adjusted OR (aOR): 4.81; 95%CI: 1.25-18.48), duration of treatment with rituximab (aOR: 1.52; 95%CI: 1.11-2.09) and confirmed severe lymphopenia (aOR: 13.58; 95%CI: 3.41-54.06) and neutropenia (aOR: 13.40; 95%CI: 2.93-61.25). Of the hematological abnormalities, only hypogammaglobulinemia was associated with treatment duration (aOR: 1.35; 95%CI: 1.09-1.69). CONCLUSION: The risk of hospitalization due to infection is associated with time on rituximab treatment, in patients with lympho- or neutropenia, and in patients with primary progressive MS. We observed a time-dependent decline in IgG values, in contrast to neutrophil and lymphocyte count, suggesting a cumulative dose-dependent response. These predictors can assist clinicians in assessing and monitoring MS patients receiving rituximab.

Efficacy and Safety of Interferon-Gamma in Chronic Granulomatous Disease: a Systematic Review and Meta-analysis.

BACKGROUND: Chronic granulomatous disease (CGD) is a primary immunodeficiency with increased susceptibility to several bacteria, fungi, and mycobacteria, caused by defective or null superoxide production by the NADPH oxidase enzymatic complex. Accepted treatment consists mainly of antimicrobial prophylaxis. The role of human recombinant subcutaneous interferon-gamma (IFNγ) is less clear since the available evidence on its efficacy derives mainly from a single clinical trial that has been challenged. OBJECTIVE: We aimed to assess the efficacy and safety of IFNγ as an added treatment for CGD when compared to antimicrobial prophylaxis alone. METHODS: A literature search was conducted using MeSH terms "Chronic granulomatous disease" AND ("interferon gamma" OR "interferon-gamma"), as well as antibiotics, placebo, no therapy, clinical trial, and trial, on MEDLINE, EMBASE, LILACS, WHOs, CENTRAL, KOREAMED, The Cochrane Library, clinicaltrials.gov, and abstracts from meetings, from 1976 to July 2022. We included clinical trials (CT) and prospective follow-up studies and registered the number of serious infections (requiring hospitalization and IV antibiotics) and deaths, adverse events, and autoimmune complications, in patients treated for CGD with antimicrobial prophylaxis plus IFN-γ, versus antimicrobial prophylaxis alone. We assessed the quality of the studies using risk of bias and STROBE. We performed a meta-analysis by calculating both Peto's odds ratio (OR) and risk reduction (RR) through the Mantel-Haenszel method with a fixed-effect model, using Review Manager 5.4, and we reported the number needed to treat (NNT). RESULTS: We identified 54 matches from databases and 4 from other sources. We excluded 12 duplicates, 7 titles, and 9 abstracts for relevance, after which we had 30 eligible studies. Twenty-four were then excluded after reading the full text. Six papers were included: one randomized CT and 5 follow-up studies. In total, 324 patients with Chronic granulomatous disease were followed for 319 months under treatment with antibiotic prophylaxis plus interferon-gamma or placebo (or antibiotic prophylaxis alone), reported between the years 1991 and 2016. Three of the studies included a control group, allowing for the aggregate analysis of efficacy (prevention of serious infections). The aggregate OR was 0.49, with a 95% confidence interval of 0.19 to 1.23. The risk ratio for serious infection was 0.56 (95%CI 0.35-0.90) under IFN-γ. The meta-analysis thus favors interferon-gamma for a risk reduction of serious infection. DISCUSSION: The results from this meta-analysis support the use of IFN-γ in the treatment of patients with CGD. However, we found insufficient clinical evidence and believe more clinical trials are needed to better assess the efficacy and long-term safety of IFN-γ.

Point-of-care C-reactive protein test results in acute infections in children in primary care: an observational study.

BACKGROUND: Acute infections are a common reason for children to consult primary care. Serious infections are rare but differentiating them from self-limiting illnesses remains challenging. This can lead to inappropriate antibiotic prescribing. Point-of-care C-reactive protein testing is used to guide antibiotic prescribing in adults. However, in children its use remains unclear. The purpose of this study was to assess point-of-care CRP test levels with respect to patients' characteristics, care setting, preliminary diagnosis, and management. METHODS: A prospective observational study was performed in children with an acute infection presenting to ambulatory care in Belgium. RESULTS: In this study 8280 cases were analysed, of which 6552 had a point-of-care CRP value available. A total of 276 physicians participated. The median patient age was 1.98 years (IQR 0.97 to 4.17), 37% of children presented to a general practitioner, 33% to a paediatric out-patient clinic, and 30% to the emergency department. A total of 131 different preliminary diagnoses were found, with acute upper airway infection as the most frequent. In 6% (n = 513) patients were diagnosed with a serious infection. The most common serious infection was pneumonia. Antibiotics were prescribed in 28% (n = 2030) of all episodes. The median CRP over all infectious episodes was 10 mg/L (IQR < 5-29). Children below 5 years of age and those presenting to a paediatrician had a higher median CRP. Median CRP in patients with serious infections was 21 mg/L (IQR 6 to 63.5). Pneumonia had a median CRP of 48 mg/L (IQR 13-113). In the episodes with antibiotics prescription, median CRP level was 29 mg/L (IQR 10-58) compared to 7 mg/L (IQR < 5-19) when they were not prescribed. CONCLUSION: A low POC CRP as a standalone tool did not seem to be sufficient to rule out serious infections, but its potential in assessing serious infections could increase when integrated in a clinical decision rule. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02024282 (registered on 31/12/2013).

Description and outcomes of patients with substance use disorder with serious bacterial infections who had a multidisciplinary care conference.

Background: Patients with substance use disorders (SUDs) and severe bacterial infections requiring prolonged antibiotic therapy represent a significant challenge to providers due to complexity of care coordination required to ensure safe and effective treatment. Our institution developed a patient-centered multidisciplinary discharge planning conference, OPTIONS-DC, to address this challenge. Methods: We conducted a retrospective review to evaluates parameters between patients who received an OPTIONS-DC and those who did not. Results: We identified 73 patients receiving an OPTIONS-DC and 100 who did not. More patients with an OPTIONS-DC were < 40 years of age (76.7% versus 61.0%, OR = 2.3, 95% CI = 1.1-4.7, p = 0.02), had positive HCV antibody testing (58.9% versus 41.0%, OR = 2.1, 95% CI = 1.1-3.8, p = 0.02), injection drug use (93.2% versus 79.0%, OR = 3.6 95% CI = 1.3-10.1, p = 0.01), used methamphetamines (84.9% versus 72.0%, OR = 2.2, 95% CI = 1.0-4.8, p = 0.04), and started inpatient SUD treatment (80.8% versus 63%, OR = 2.5, 95% CI = 1.2-5.0, p = 0.04) compared with those without a conference. The OPTIONS-DC group was more likely to be diagnosed with bacteremia (74.0% versus 57.0%, OR = 2.1, 95% CI = 1.1-4.1, p = 0.02), endocarditis (39.7% versus21.0%, OR = 2.5, 95% CI = 1.3-4.9, p = 0.03), vertebral osteomyelitis (45.2% versus 15.0%, OR = 4.7, 95% CI = 2.3-9.6, p < 0.01), and epidural abscess (35.6% versus 10.0%, OR = 5.0, 95% CI = 2.2-11.2, p < 0.01) and require 4 weeks or more of antibiotic treatment (97.3% versus 51.1%, OR = 34.1, 95% CI = 7.9-146.7, p = 0.01). Patients with an OPTIONS-DC were also more likely to be admitted between 2019 and 2020 than between 2018 and 2019 (OR = 4.1, 95% CI = 2.1-7.9, p < 0.01). Conclusion: Patients with an OPTIONS-DC tended to have more complicated infections and longer courses of antibiotic treatment. While further research on outcomes is needed, patients receiving an OPTIONS-DC were able to successfully complete antibiotic courses across a variety of settings.

Risk of serious infections in multiple sclerosis patients by disease course and disability status: Results from a Swedish register-based study.

Background and objectives: Serious infections are an emerging concern with increasing use of potent immunomodulation in multiple sclerosis (MS), but the extent to which MS disease features influence infectious susceptibility is poorly characterized. The objective of this study was to assess the associations of MS disease course and disability status with risk of serious infections. Methods: A cohort of 8660 MS patients was individually matched on age, sex and region of residence with 86,600 people without MS from the general population using national registers in Sweden. The study period was from 1996 to 2012, with follow-up until December 31, 2014. The main outcomes were infection as the underlying or contributory cause of death or infection-related hospital admission identified in the Cause of Death and Patient registers. MS disease course (relapsing-remitting or progressive disease) and Expanded Disability Status Scale (EDSS) score (six and over or below six) were extracted from the MS Register Hazard ratios (HRs) for any serious infection were estimated using flexible parametric models. Results: During a median follow-up of 9.6 years (interquartile range = 5.5-13.5 years), 1337 MS patients experienced a serious infection. Compared with individually matched people without MS, risk of serious infection was greater for progressive disease (HR = 3.80; 95% CI 3.52: 4.09) than relapsing-remitting disease (HR = 1.77; 95% CI: 1.62:1.93). A similar pattern of risk was seen for dichotomised EDSS score (HR = 4.26; 95% CI 3.87: 4.70 for EDSS 6.0-9.5 and HR = 1.30; 95% CI 1.1853: 1.43 for EDSS 0.0-5.5). Overall, associations with greater disability did not notably differ by immunomodulatory therapy use, but associations with lower disability were more pronounced in patients receiving these therapies. Conclusions: Disease course or EDSS score (which may be more readily available than MS course in some patients) should be considered in individual management and monitoring of MS patients, including assessing benefit-risk of therapies that influence general immune function.

The infection risks of JAK inhibition.

INTRODUCTION: Janus Kinase inhibitors (JAKi) have shown to be highly effective in the treatment of immune-mediated inflammatory diseases. As with all immunomodulatory therapies, careful assessment of any treatment-associated infection risk is essential to inform clinical decision-making. AREAS COVERED: We summarize current literature on infection rates among the licensed JAKi using published phase II/III trial results, post-licensing and registry data. EXPERT OPINION: licensed JAKi show increased risk of infection across the class compared to placebo, most commonly affecting respiratory and urinary tracts, nasopharynx and skin. This risk is dose-dependent. Risks are similar at licensed JAKi doses to that seen with biologic therapies. The risk is compounded by other risk factors for infection, such as age and steroid co-prescription. Herpes zoster reactivation is more common with JAKi compared to other targeted immune modulation, making screening for varicella exposure and vaccination in appropriate cohorts an advisable strategy. Crucially, these small risk increases must be balanced against the known harms (including infection) of uncontrolled autoimmune disease. JAKi are a safe and potentially transformative treatment when used for appropriately selected patients.

Risk of Serious Infections With Vedolizumab Versus Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: The risk of serious infections associated with vedolizumab in patients with inflammatory bowel disease (IBD) is uncertain. We assessed the risk of serious infections associated with use of vedolizumab versus anti-TNF in patients with IBD, according to IBD subtype and previous exposure to anti-TNF. METHODS: Based on two U.S. nationwide commercial insurance databases and the French nationwide health insurance database, anti-TNF naïve and experienced patients diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) aged 18 years or older who initiated vedolizumab or an anti-TNF agent after 2010 were identified. Hazard ratios for serious infections comparing vedolizumab and anti-TNF were estimated in propensity score matched cohorts. RESULTS: Among 8768 vedolizumab and 26,656 anti-TNF initiators included after 1:4 variable ratio propensity score matching, 893 serious infections occurred during 37,725 person-years of follow-up. The risk of serious infections was not different between vedolizumab and anti-TNF in the overall IBD cohort (HR, 0.95; 95% CI, 0·79-1.13), while the risk was decreased for vedolizumab users in patients with UC (HR, 0.68; 95% CI, 0.50-0.93), but not CD (HR, 1.10; 95% CI, 0.87-1.38). In patients with UC, vedolizumab was consistently associated with lower risk of serious infections after exclusion of gastrointestinal infections (HR, 0.59; 95% CI, 0.39-0.90). CONCLUSIONS: While the risk of serious infections associated with vedolizumab was not different compared to anti-TNF in the overall group of patients with IBD, the risk varied according to IBD subtype, by decreasing in patients with UC, but not CD. These findings may help to clarify the optimal position of vedolizumab in the therapeutic management of IBD.

Serious Infections in Children Born to Mothers With Inflammatory Bowel Disease With In Utero Exposure to Thiopurines and Anti-Tumor Necrosis Factor.

BACKGROUND & AIMS: We aimed to compare the risk of serious infections in children with in utero exposure to thiopurines and/or anti-tumor necrosis factor (TNF) born to mothers with inflammatory bowel disease (IBD). METHODS: Using the French national health database, which covers 99% of the French population (around 66,000,000 people), we identified live births among women with IBD in France between 2010 and 2018. The risks of serious infections in children during the first 5 years of life were compared according to treatment exposures during pregnancy using propensity score-weighted marginal Cox models. RESULTS: A total of 26,561 children were included: 3392 were exposed to thiopurine monotherapy, 3399 to anti-TNF monotherapy, 816 to combination therapy, and 18,954 were not exposed to any of these drugs. The risks of serious infections during the first year of life among children exposed to thiopurine monotherapy (adjusted hazard ratio [aHR], 0.94; 95% confidence interval [CI], 0.83-1.07) and anti-TNF monotherapy (aHR, 1.10; 95% CI, 0.95-1.27) were similar to those of unexposed children; a higher risk was observed in children exposed to combination therapy (aHR, 1.36; 95% CI, 1.04-1.79). The highest increased risks were observed for nervous system infections and viral infections. The risk of serious infections during the second to fifth years of life was not associated with IBD treatments. CONCLUSIONS: In children born to mothers with IBD, in utero exposure to thiopurine and anti-TNF monotherapies do not increase the risk of serious infections during the first 5 years of life. Combination therapy is associated with an increased risk of serious infections during the first year of life.

Risk factors for serious infections in inpatients with systemic lupus erythematosus. / ç³»ç»Ÿæ€§çº¢æ–‘ç‹¼ç–®ä½é™¢æ‚£è€ åˆå¹¶ä¸¥é‡æ„ŸæŸ“çš„å±é™©å› ç´ .

OBJECTIVES: To investigate the risk factors for serious infections among hospitalized systemic lupus erythematosus (SLE) patients, and to provide the advice for preventing serious infections in SLE patients. METHODS: Information of SLE patients hospitalized from March 2017 to February 2019 at the Department of Rheumatology and Immunology, Xiangya Hospital, Central South University was obtained. The patients were assigned into a serious infection group and a non-serious infection group. The risk factors for serious infections among SLE inpatients were identified by comparison between the 2 groups and multivariate logistic regression analysis. RESULTS: There were 463 SLE inpatients in total, and 144 were in the serious infection group and 319 in the non-serious infection group. Multivariate logistic regression analysis showed that age ≥54.50 years old (OR=4.958, P<0.001), cardiovascular involvement (OR=6.287, P<0.001), hematologic involvement (OR=2.643, P=0.003), serum albumin <20 g/L (OR=2.340, P=0.036), C-reaction protein (CRP)/erythrocyte sedimentation rate (ESR)≥0.12 (OR=2.430, P=0.002), glucocorticoid dose ≥8.75 mg/d prednisone-equivalent (OR=2.465, P=0.002), and the combined use of immunosuppressive agents (OR=2.847, P=0.037) were the risk factors for serious infections in SLE inpatients. CONCLUSIONS: SLE patients with older age, cardiovascular involvement, hematologic involvement, low serum albumin are prone to suffering serious infections. Increased CRP/ESR ratio indicates serious infections in SLE inpatients. High-dose glucocorticoid and the combined use of immunosuppressive agents can increase the risk of serious infections in SLE inpatients.

Optimizing Immunization Strategies in Patients with IBD.

Recent advances in the treatment of inflammatory bowel disease (IBD) include the use of immune modifiers and monoclonal antibodies, such as tumor necrosis factor (TNF) alpha inhibitors, anti-integrin agents, janus kinase inhibitors, and interleukin-12/23 inhibitors. These agents achieve higher rates of clinical remission and mucosal healing than conventional therapy. However, these therapies increase the risk of infections, including some vaccine-preventable diseases. Infections are one of the most common adverse event of immunosuppressive therapy. Thus, providers should optimize immunization strategies to reduce the risk of vaccine-preventable infections in patients with IBD. There are several newly licensed vaccines recommended for adults by the US Advisory Committee on Immunization Practices. This review will focus on how gastroenterology providers can implement the adult immunization schedule approved by ACIP for patients with IBD.

Long-term Infective Endocarditis Mortality Associated With Injection Opioid Use in the United States: A Modeling Study.

BACKGROUND: The expansion of the US opioid epidemic has led to significant increases in infections, such as infective endocarditis (IE), which is tied to injection behaviors. We aimed to estimate the population-level IE mortality rate among people who inject opioids and compare the risk of IE death against the risks of death from other causes. METHODS: We developed a microsimulation model of the natural history of injection opioid use. We defined injection behavior profiles by both injection frequency and injection techniques. We accounted for competing risks of death and populated the model with primary and published data. We modeled cohorts of 1 million individuals with different injection behavior profiles until age 60 years. We combined model-generated estimates with published data to project the total expected number of IE deaths in the United States by 2030. RESULTS: The probabilities of death from IE by age 60 years for 20-, 30-, and 40-year-old men with high-frequency use with higher infection risk techniques compared to lower risk techniques for IE were 53.8% versus 3.7%, 51.4% versus 3.1%, and 44.5% versus 2.2%, respectively. The predicted population-level attributable fraction of 10-year mortality from IE among all risk groups was 20%. We estimated that approximately 257 800 people are expected to die from IE by 2030. CONCLUSIONS: The expected burden of IE among people who inject opioids in the United States is large. Adopting a harm reduction approach, including through expansion of syringe service programs, to address injection behaviors could have a major impact on decreasing the mortality rate associated with the opioid epidemic.

Hospitalized Infections in People With Osteoarthritis: A National US Study.

OBJECTIVE: To study the incidence, time trends, and outcomes of serious infections in people with osteoarthritis (OA). METHODS: We used 1998-2016 US National Inpatient Sample (NIS) data. Using recommended weights, we examined the epidemiology of 5 types of serious infections requiring hospitalization in people with OA (opportunistic infections [OIs], skin and soft tissue infections [SSTIs], urinary tract infections [UTIs], pneumonia, and sepsis/bacteremia). We performed multivariable-adjusted logistic regression analyses to analyze factors associated with healthcare utilization (hospital charges, length of hospital stay, discharge to nonhome setting), and in-hospital mortality. RESULTS: Of all serious infection hospitalizations, 46,708,154 were without OA and 3,258,416 had OA. People with OA were 16.4 years older, more likely to be female (52% vs 65%), White (59% vs 70%), have a Deyo-Charlson Comorbidity Index (DCCI) ≥ 2 (42% vs 51%), receive Medicare (54% vs 80%), and less likely to receive care at an urban teaching hospital (45% vs 39%). Serious infection rates per 100,000 NIS hospitalizations increased from the study period of 1998-2000 to 2015-2016: OI (from 4.5 to 7.2); SSTI (from 48.4 to 145.9); UTI (from 8.4 to 104.6); pneumonia (from 164.0 to 224.3); and sepsis (from 39.4 to 436.3). In multivariable-adjusted analyses, older age, higher DCCI, sepsis, northeast region, urban hospital, and medium or large hospital bed size were significantly associated with higher healthcare utilization outcomes and in-hospital mortality; Medicaid insurance, non-White race, and female sex were significantly associated with higher healthcare utilization. CONCLUSION: Serious infection rates have increased in people with OA. Association of demographic, clinic, and hospital variables with serious infection outcomes identifies potential targets for future interventions.

Elevation of cytomegalovirus antigenemia predicts serious infection and death in patients receiving immunosuppressive therapies for autoimmune diseases.

AIM: We examined the relationship between cytomegalovirus (CMV) reactivation and serious infections. METHOD: We conducted a single-center retrospective chart review study with 43 autoimmune disease patients experiencing CMV reactivation. We investigated the risk factors for serious infections among the patients using logistic regression analysis. RESULTS: We identified that the maximum count of CMV antigenemia during the course of infection (CMV Ag MAX) was significantly associated with serious infection by multivariate analysis (adjusted odds ratio: 1.509; 95% confidence interval: 1.071-2.125). The receiver operating characteristic curve of CMV Ag MAX count showed a predictive value for serious infections (76.9% in sensitivity and 93.3% in specificity) and death (83.3% in sensitivity and 91.9% in specificity), and the cut-off count of serious infections and death was 6 and 10 per 105 white blood cell count, respectively. CONCLUSION: We suggest that the counts of CMV Ag MAX can reflect the extent of compromise in the immune system, and can be a predictive marker for serious infections and death.

Serious infections in people with systemic sclerosis: a national US study.

OBJECTIVE: To study incidence, time trends, and outcomes of serious infections in systemic sclerosis (SSc). METHODS: We used the 1998-2016 US National Inpatient Sample data. We examined the epidemiology, time trends, and outcomes of five serious infections (opportunistic infections (OI), skin and soft tissue infections (SSTI), urinary tract infection (UTI), pneumonia, and sepsis/bacteremia) in hospitalized people with SSc. We performed multivariable-adjusted logistic regression analyses to analyze independent association of factors with healthcare utilization (hospital charges, length of hospital stay, discharge to non-home setting) and in-hospital mortality. RESULTS: There were 49,904,955 hospitalizations with serious infections in people without SSc and 61,615 in those with SSc. During 1998-2016, the most common serious infections in SSc were pneumonia (45%), sepsis (32%), SSTI (19%), UTI (3%), and OI (3%). In 2013-2014, sepsis surpassed pneumonia as the most common serious infection; by 2015-2016, sepsis was 1.8 times more common than pneumonia. Over the study period, hospital charges increased, while length of hospital stay and in-hospital mortality decreased, overall and for each serious infection. Multivariable-adjusted analyses showed that sepsis, age ≥ 80 years, and Deyo-Charlson score ≥ 2 were associated with significantly higher odds of healthcare utilization and in-hospital mortality, and Medicare or Medicaid insurance payer, Northeast location, urban teaching or non-teaching hospital, and medium or large hospital bed size with significantly higher odds of healthcare utilization. CONCLUSIONS: Outcomes in people with SSc hospitalized with serious infections have improved over time, except higher hospital charges. Identification of factors associated with higher healthcare utilization and in-hospital mortality allows for developing interventions to improve outcomes.