Chronic Systemic Corticosteroid Research Articles

The effect of fixation type on periprosthetic fractures in high-risk patients who have osteoporosis undergoing total joint arthroplasty

IntroductionMinimizing the burden of periprosthetic fractures (PFF) following total joint arthroplasty (TJA) with regard to morbidity and mortality remains an outcome of interest. Patient and surgical risk factors, including osteoporosis and fixation type, have not truly been optimized in patients undergoing TJA as a means to reduce the risk of PFF. As such, we examined: (1) What percentage of patients who underwent THA and total knee arthroplasty (TKA) met the criteria for osteoporosis screening? (2) How did the 5-year rate of PFF and fragility fracture differ in the high-risk and low-risk groups for osteoporosis between the cemented and cementless cohorts? (3) What percentage of the aforementioned patients received a dual x-ray absorptiometry (DEXA) scan before THA or TKA? MethodsWe queried an all-payer, national database from April 1, 2016 to December 31, 2021, to identify high-risk and low-risk patients who underwent TJA with a cementless or cemented fixation. High-risk patients met at least one of the following criteria: men at least 70 years old, women at least 65 years old, or patients at least 60 years old who have the following: tobacco use, alcohol abuse, body mass index <18.5, prior fragility fracture, chronic systemic corticosteroids, or genetic condition affecting sex hormones or bone mineral density. Exclusion criteria were a diagnosis of malignancy, high-energy events (motor vehicle collision), those who underwent TJA indicated for fracture, patients less than 50 years old, those who had a prior diagnosis of or treatment for osteoporosis, and a minimum follow-up of less than 2 years. ResultsThere were 384,783 patients (67.1 %) who underwent cementless TKA and 67,774 patients (11.8 %) who underwent cementless TKA who were considered high risk. Additionally, there were 62,505 patients (10.9 %) who underwent cemented THA and 58,667 patients (10.2 %) who underwent cementless THA and were considered high risk. The cementless cohort had a 5-year periprosthetic fracture risk following TKA of 7.8 % (95 % CI, 5.56 to 10.98) in comparison to 4.30 % in the cemented cohort (85 % CI, 3.98 to 4.65), P < 0.0001. The high-risk cementless cohort had a 5-year periprosthetic fracture risk following THA of 7.9 % (95 % confidence interval (CI), 6.87 to 9.19) in comparison to 7.78 % in the cemented cohort (85 % CI, 6.77 to 8.94), P < 0.0001. ConclusionThere is an increased risk of PFF at 5 years following TKA in patients at high risk for osteoporosis undergoing cementless fixation in comparison to cemented fixation. There is an increased risk of PFF at 5 years following THA in patients at high risk for osteoporosis for both cementless fixation and cemented fixation, but no clinically meaningful difference between the two groups. Addressing the shortcomings of the underutilization of bone density scans and better selecting appropriate patients for TJA based on bone quality and fracture risk can help expedite the process of improving the current state of practice.

Non-infectious skin manifestations in patients with Chronic Granulomatous Disease: A report of 4 cases

BackgroundChronic granulomatous disease (CGD) is a monogenic inborn error of immunity caused by defects in the phagocytic NADPH oxidase complex. These defects lead to an increased risk of severe infection, autoimmunity, widespread granuloma formation and dysregulated inflammation. In individuals with CGD, immune dysregulation and autoimmune manifestations may impact almost every organ system with atypical dermatologic findings frequently reported. Case PresentationsHere we describe four cases of inflammatory skin lesions in patients with genetically confirmed CGD. Patient A is a 4-year-old male who presented with diffuse alopecia totalis preceded by a widespread skin eruption composed of polycyclic, annular, erythematous plaques and prominent facial erythema and edema. Whole exome sequencing was obtained due to concern for ectodermal dysplasia, which identified a variant in CYBB (CYBB c.901G>T; pVal301Phe). Patient B is a 4-year-old male with X-CGD (CYBB c.1016 C > A, p.Pro339His) who developed annular to polycyclic indurated red plaques on his face and arms. Patient C is a 19-year-old female with autosomal recessive CGD (NCF1 c.75_76delGT) and persistent hidradenitis suppurativa-like lesions in the axilla, inguinal areas, and popliteal fossa. Patient D is a 12-year-old female with autosomal recessive CGD (p47phox deficiency) and psoriasiform dermatitis of the scalp.Patient A had persistence of lesions that required chronic systemic corticosteroids and methotrexate. He underwent hematopoietic stem cell transplantation using a matched sibling donor with improvement in his dermatitis. Skin lesions in patient B resolved with the use of topical corticosteroids. Patient C improved with a combination of isotretinoin therapy and both intralesional and systemic corticosteroid treatment. Patient D had improvement in her psoriasiform dermatitis with topical corticosteroid solution and salicylic acid shampoo. ConclusionsThis case series expands our understanding of cutaneous non-infectious eruptions that can occur in patients with both X-linked and autosomal recessive forms of CGD. Each of these cases illustrates a unique clinical history, histologic findings and treatment plan in patients who developed cutaneous lesions secondary to immune dysregulation in the context of CGD. This series provides additional insights that may assist providers in identifying and managing non-infectious dermatologic manifestations of CGD.

Challenges in severe asthma: Do we need new drugs or new biomarkers?

Severe asthma is a complex, heterogenous airway condition. There have been significant advances in severe asthma management in the past decade using monoclonal antibody therapies that target the inflammatory component of the disease. Patient selection has been paramount for the success of these biologicals, leading to significant interest in biomarkers to guide treatment. Some severe asthmatics remain suboptimally controlled despite trials of biologicals and many of these patients still require chronic systemic corticosteroids. New therapeutics are currently in development to address this unmet need. However, whether these patients could be better treated by using novel biomarkers that inform selection among currently available biologics, and that objectively measure disease control is unclear. In this review, we examine the currently used biomarkers that guide severe asthma management and emerging biomarkers that may improve asthma therapy in the future.

Chronic systemic corticosteroid therapy influences the development of pulp necrosis and experimental apical periodontitis, exacerbating the inflammatory process and bone resorption in rats.

The main aim of the study was to evaluate the inflammatory response and development of apical periodontitis in rats chronically treated with glucocorticoids. Male Wistar rats (Rattus novergicus) were randomly divided into two groups: the experimental group, which was treated with prednisone (5mg/kg/day) and a control group, which was administered saline solution for 30days before induction of apical periodontitis, continuing until the day of euthanasia days 0, 7, 14 and 28 after injury induction. The mandibles were subjected to histological evaluation to determine the size of the lesion, was also performed for the presence and absence of pulp necrosis, bone resorption and micro abscesses, and histomorphometric analyses were performed based on the number of polymorphonuclear cells and mononuclear cells. Histochemical analysis was also performed to assess the percentage of collagen fibres and their typification, in addition to immunohistochemistry for the inflammatory markers interleukin IL-1β, IL-6, TNF-α and TRAP. Despite after 7days, there was no differences between groups, a significant increase in the root pulp necrosis (p=.001), micro-abscesses (p=.026) and the size of the apical lesion on the 14th day of treatment with prednisone (p=.008). On the same day, there was also an increase in the number of polymorphonuclear cells (p=.042) and cells immunostained for IL-1β (p=.006), IL-6 (p<.001) and TRAP (p=.002) in animals treated with prednisone. The numbers of mononuclear cells also increase in 28days (p=.025) and TNF-α ± increases in the prednisone group on the 7th day (p=.041). The prednisone group also showed a decrease in collagen after 14 (both type I [p=.041] and type III [p=.046]) and 28 type III (p=.002) days after the coronary opening. The glucocorticoids modified the development of experimental apical periodontitis induced in rats, causing an early increase in periapical bone resorption and pulp necrosis. These effects are associated with alterations in cytokine levels, in the inflammatory response and in collagen deposition, in the 14th day after injury induction.

Influence of chronic use of corticosteroids and calcineurin inhibitors on COVID-19 clinical outcomes: analysis of a nationwide registry

ObjectivesThe aim of this study was to analyze whether subgroups of immunosuppressive (IS) medications conferred different outcomes in COVID-19.MethodsThe study involved a multicenter retrospective cohort of consecutive immunosuppressed patients (ISPs) hospitalized with COVID-19 from March to July, 2020. The primary outcome was in-hospital mortality. A propensity score-matched (PSM) model comparing ISP and non-ISP was planned, as well as specific PSM models comparing individual IS medications associated with mortality.ResultsOut of 16 647 patients, 868 (5.2%) were on chronic IS therapy prior to admission and were considered ISPs. In the PSM model, ISPs had greater in-hospital mortality (OR 1.25, 95% CI 0.99–1.62), which was related to a worse outcome associated with chronic corticoids (OR 1.89, 95% CI 1.43–2.49). Other IS drugs had no repercussions with regard to mortality risk (including calcineurin inhibitors (CNI); OR 1.19, 95% CI 0.65–2.20). In the pre-planned specific PSM model involving patients on chronic IS treatment before admission, corticosteroids were associated with an increased risk of mortality (OR 2.34, 95% CI 1.43–3.82).ConclusionsChronic IS therapies comprise a heterogeneous group of drugs with different risk profiles for severe COVID-19 and death. Chronic systemic corticosteroid therapy is associated with increased mortality. On the contrary, CNI and other IS treatments prior to admission do not seem to convey different outcomes.

Clinical evolution of a severe asthmatics group in the use of immunobiological therapy in a Brazilian Public Hospital.

A small portion of the asthmatic population (3.6%) has severe asthma (SA), presenting high morbimortality rates and demanding more financial resources than other asthmatic populations. The use of immunobiological therapy is an effective tool in controlling symptoms, decreasing the number of exacerbations, and reducing the use of systemic corticosteroids in these patients. In Brazil, epidemiological data regarding this asthmatic population using immunobiologicals and their evolution are scarce. This is an observational, analytical, cross-sectional, and retrospective study. The sample consisted of adult patients with SA in follow-up at the pulmonology service of the Complexo Hospital de Clínicas of the Federal University of Paraná, from January 2011 to August 2019. The analyzed variables were as follows: the number of exacerbations that required hospitalization in the previous year, forced expiratory volume in one second (FEV1), and asthma control test (ACT) scores before and after the start of immunobiological therapy. We studied 20 patients with SA using omalizumab or mepolizumab. We observed an increase in the mean ACT score of 4.8 points, a nonsignificant reduction in the number of exacerbations that required hospitalization, and a slight improvement in the FEV1. Regarding the patients using chronic systemic corticosteroid therapy, 14.2% (n=1) of patients had the medication discontinued and 57% (n=4) of patients had the dose reduced by half. The use of omalizumab and mepolizumab as additional therapy in SA provided a significant improvement in the ACT and allowed the dose reduction of systemic corticosteroids, without significant improvement in FEV1 and in the frequency of severe exacerbations.

COVID-19 risk and outcomes in adult asthmatic patients treated with biologics or systemic corticosteroids: Nationwide real-world evidence

BackgroundManaging severe asthma during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging, particularly due to safety concerns regarding the use of systemic corticosteroids and biologics.ObjectivesWe sought to determine the association between biologics or systemic corticosteroids use and PCR positivity for SARS-CoV-2 and coronavirus disease 2019 (COVID-19) outcomes among asthmatic patients.MethodsWe used the computerized database of Clalit Health Services, the largest health care provider in Israel, to identify all asthmatic adult patients who underwent PCR testing for SARS-CoV-2, between March 1, 2020, and December 7, 2020. A cohort approach was used to assess the association between biologics use and steroids treatment and COVID-19 severity and 90-day mortality.ResultsOverall, 8,242 of 80,602 tested asthmatic patients had positive PCR testing result for SARS-CoV-2. Both biologics and systemic corticosteroids were not associated with increased risk of SARS-CoV-2 infection. Multivariate analyses revealed that biologics were not associated with a significantly increased risk of moderate to severe COVID-19, nor with the composite end point of moderate to severe COVID-19 or all-cause mortality within 90 days. Chronic systemic corticosteroid use was associated with significantly increased risk of all tested outcome. Recent (within the previous 120 days) systemic corticosteroid use, but not former use, was significantly associated with increased risk of both moderate to severe COVID-19 and the composite of moderate to severe COVID-19 or all-cause mortality.ConclusionsBiologics approved for asthma and systemic corticosteroids are not associated with increased risk of SARS-CoV-2 infection. In contrast, systemic corticosteroids are an independent risk factor for worst COVID-19 severity and all-cause mortality. Our findings underscore the risk of recent or current exposure to systemic corticosteroids in asthmatic patients infected with SARS-CoV-2.

Tezepelumab as an Emerging Therapeutic Option for the Treatment of Severe Asthma: Evidence to Date.

Asthma is a complex heterogeneous disease defined by chronic inflammation of the airways. Patients present with wheezing, chest tightness, cough and shortness of breath. Bronchial hyperresponsiveness and variable expiratory airflow limitation are hallmark features. About 3.6–6.1% of patients, despite receiving high-dose inhaled corticosteroids (ICS) and a second controller medication, report persistent symptoms referred to as severe asthma. Uncontrolled severe asthma is associated with increased mortality, morbidity, diminished quality of life and increased health expenditures. The development of modern biological therapy has revolutionized severe asthma treatment. By targeting specific chemokines, asthma control has drastically improved, resulting in better quality of life, less emergency department visits and inpatient admissions, and decreased chronic systemic corticosteroid utilization. Despite these advances, there remains a subset of asthma patients who remain symptomatic with poor quality of life and heavy utilization of the healthcare system. Recently attention has been given to pharmaceutical therapy directed at receptors and cytokines on the epithelial layer of the lung referred to as “alarmins”. Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like receptor family found on the epithelial layer of the lung that releases a cytokine cascade inducing eosinophilic inflammation, mucus production and airflow obstruction in asthmatics. Tezepelumab is the first investigational monoclonal antibody that inhibits TSLP. Proof of concept study and phase IIb studies demonstrated reduced asthma exacerbations, improvement in quality of life, less decline in FEV1 and decrease in biochemical inflammatory markers in comparison to placebo. It is presently undergoing three phase III studies and an additional phase II study.

Risk Factors for Invasive Pulmonary Aspergillosis in Critically Ill Patients With Coronavirus Disease 2019-Induced Acute Respiratory Distress Syndrome.

Severe coronavirus disease 2019 pneumonia can lead to acute respiratory distress syndrome. Recently, several publications reported on coronavirus disease 2019-associated pulmonary aspergillosis. However, risk factors remain unclear. We retrospectively collected all the cases of coronavirus disease 2019 acute respiratory distress syndrome patients (n = 46) admitted to our 34-bed ICU between March 24, 2020, and May 25, 2020, and identified six patients that met the diagnosis of invasive pulmonary aspergillosis according to previously established definitions. This population exhibited higher severity scores at admission and less hospital discharge compared with noninvasive pulmonary aspergillosis patients. Chronic obstructive pulmonary disease, malnutrition, and systemic corticosteroid use were identified as risk factors for invasive pulmonary aspergillosis in coronavirus disease 2019-induced acute respiratory distress syndrome patients. Coronavirus disease 2019-associated pulmonary aspergillosis may be a serious concern regarding corticosteroids use to control the inflammatory response of coronavirus disease 2019-induced acute respiratory distress syndrome.

Outcomes of Transcatheter Aortic Valve Implantation in Patients Receiving Chronic Systemic Corticosteroid Treatment

The aim of this study was to describe the effects of chronic systemic corticosteroid treatment (SCT) on early and late outcomes after transcatheter aortic valve implantation (TAVI). From October 2006 to November 2018, 1,299 patients underwent TAVI in our institution. Among them, 48 (3.7%) received chronic SCT at the time of procedure (SCT group). They were more frequently women (p = 0.08) and needed more often dialysis (p = 0.002). All other baseline characteristics were similar between both groups. At 30 days, there was no difference on mortality. However, after adjustment, the SCT group had more major vascular complications: 16.7% versus 7.4%, hazard ratio (HR) 2.52 (95% confidence interval [CI] 1.14 to 5.9, p = 0.023), major or life-threatening bleedings: 22.9% versus 12.4%, HR 2.02 (95% CI 1.00 to 4.08, p = 0.05), and tamponades: 8.3% versus 2.4%, HR 4.05 (95% CI 1.35 to 12.15, p <0.001) than the non-SCT group. One-year all-cause mortality was significantly higher in the SCT than in the non-SCT group (37.5% vs 12.5%, p <0.0001). Multivariate analysis confirmed that SCT use was an independent predictor of 1-year mortality (HR 2.29, 95% CI 1.16 to 4.50, p = 0.017). In conclusion, chronic use of SCT significantly increases the rates of early vascular complications, major or life-threatening bleedings and tamponade and is an independent predictor of 1-year all-cause mortality after TAVI.

Pulmonary Embolism in Acute Asthma Exacerbation: Clinical Characteristics, Prediction Model and Hospital Outcomes.

Little is known about the characteristics and impact of acute pulmonary embolism (PE) during episodes of asthma exacerbation. We aimed to characterize patients diagnosed with acute PE in the setting of asthma exacerbation, develop a prediction model to help identify future patients and assess the impact of acute PE on hospital outcomes. We included 758 patients who were treated for asthma exacerbation and underwent a computed tomographic pulmonary angiography (CTA) during the same encounter at a university-based hospital between June 2011 and October 2018. We compared clinical characteristics of patients with and without acute PE and developed a machine learning prediction model to classify the PE status based on the clinical variables. We used multivariable regression analysis to evaluate the impact of acute PE on hospital outcomes. Twenty percent of the asthma exacerbation patients who underwent CTA had an acute PE. Factors associated with acute PE included previous history of PE, high CHA2DS2-VASc score, hyperlipidemia, history of deep vein thrombosis, malignancy, chronic systemic corticosteroids use, high body mass index and atrial fibrillation. Using these factors, we developed a random forest machine learning prediction model which had an 88% accuracy in classifying the acute PE status of the patients (area under the receiver operating characteristic curve = 0.899; 95% confidence interval: 0.885-0.913). Acute PE in asthma exacerbation was associated with longer hospital stay and intensive care unit stay. It is important to consider acute PE, a potentially life-threatening event, in the setting of asthma exacerbation especially when other risk factors are present.

Outcomes of transcatheter aortic-valve implantation in patients receiving chronic systemic corticosteroid treatment

The chronic use of systemic corticosteroid (CS) therapy is associated with greater tissue fragility. Data assessing the effects of this treatment on the results of transcatheter aortic-valve implantation (TAVI) are scarce. To describe the impact of chronic use of CS treatment on early and late outcomes after TAVI. All 1299 consecutive patients undergoing TAVI in our institution between October 2006 and November 2018 were included. Their mean age was 81 ± 10 years, 52.4% were male, their median EuroSCORE 2 was 4.7% (2.8–7.5). Among them, 48 (3.7%) received chronic systemic CS treatment at the time of the procedure and were compared to those without CS. Patients with chronic CS therapy tended to be women (60% vs. 47%, P = 0.078) and needed more frequently dialysis (12.5% vs. 2.6%, P = 0.002). All other baseline clinical and echocardiographic characteristics were similar between both groups. No differences were observed in 30-day mortality (6.2% vs. 4.3%, P = 0.46). However, after adjustment, patients in the CS group had more frequent major vascular complications (16.7% vs. 7.4%, hazard ratio (HR) 2.52, 95%Confidence Interval (CI) 1.14–5.9; P = 0.02), major or life-threatening bleedings (22.9% vs. 12.4%, HR 2.02, 95%CI 1.00–4.08; P = 0.05) and tamponades (8.3% vs. 2.4%, HR 4.05, 95%CI 1.35–12.15, P < 0.001) at 30 days than those in the non-CS group. At 1-year, all-cause mortality was significantly higher in CS group than in the non-CS group (37.5% vs. 12.6%, p-log rank < 0.0001). Multivariate analysis confirmed that chronic use of CS was an independent predictor of 1-year all-cause mortality (HR 2.29, 95%CI: 1.16–4.50, P = 0.017) ( Fig. 1 ). Chronic systemic CS treatment was associated with an increase in major or life-threatening bleedings, major vascular complications and tamponades at 30 days and was an independent predictor of 1-year all-cause mortality. This treatment should be taken into account in the risk stratification of TAVI candidates.

Immunologic Adverse Effects of Biologics for the Treatment of Atopy.

The use of biologic agents as therapies for atopic diseases such as asthma and atopic dermatitis has increased greatly in recent years. The biological agents used to treat atopic diseases are for the most part monoclonal antibodies that suppress the immune response and reduce inflammation by targeting particular cytokines or other molecules involved in Th1, Th2, or Th17 immune reactions. Various side effects and rare complications have been reported from these agents. In this review, we discuss mechanisms of various adverse effects for the biologic agents currently in use or in development for atopic and inflammatory diseases. Monoclonal antibodies targeting the Th1 and Th17 pathways have been associated with significant side effects, partially due to their ability to cause significant impairment in immune responses to pathogens because of the immunologic alterations that they produce. Biologicals targeting Th2-mediated inflammation have had fewer reported side effects, though many are new and emerging drugs whose adverse effects may remain to be fully elucidated with more use. Therefore, continued long-term safety monitoring is required. As with all therapies, the risks associated with side effects of biologics must be balanced against the benefits these drugs offer for treating atopic diseases. One of the most apparent benefits is the steroid-sparing effect of well-chosen biologic therapy used to treat severe atopic disease. In contrast with the quite favorable safety profile of currently available biologics that target the Th2-mediated immune response, chronic systemic corticosteroid use is associated with significant side effects, many of which impact the majority of patients who are placed on long-term steroid therapy.

Increased Mortality in Patients with Corticosteroid-Dependent Asthma: A Nationwide Population-Based Study

Background: Chronic systemic corticosteroid (CS) therapy is associated with an increased risk of mortality in patients with many chronic diseases. However, it has not been elucidated whether chronic, systemic CS therapy is associated with increased mortality in patients with asthma. The aim of this study was to determine effects of chronic, systemic CS therapy on long-term mortality in adult patients with asthma. Methods: A population-based matched cohort study of men and women aged 18 years or older with asthma was performed using Korean National Health Insurance Service database from 2005 to 2015. Hazard ratio (HR) with 95% confidence interval (CI) for all-cause mortality among patients in CS-dependent cohort (CS use > 6 months during baseline period) relative to those in CS-independent cohort (CS use < 6 months during baseline period) was evaluated. Findings: The baseline cohort included 466,941 patients with asthma, of whom 8,334 were CS-dependent and 456,607 were CS-independent. After 1:1 matching, 8,334 subjects with CS-independent asthma were identified. The HR of mortality associated with CS-dependent asthma relative to CS-independent asthma was 2·17 (95% CI, 2·04-2·31). In patients receiving low-dose CS, HR was 1·84 (95% CI, 1·69-2·00), and that for those receiving high-dose CS was 2·56 (95% CI, 2·35-2·80). Interpretation: In this real-world, clinical practice, observational study, chronic use of systemic CS was associated with increased risk of mortality in patients with asthma, with a significant dose-response relationship between systemic CS use and long-term mortality. Funding: Korea Ministry of Environment (MOE) as the Environmental Health Action Program (2016001360003). Declaration of Interest: All authors have no conflict of interest to disclose. Ethical Approval: This study was approved by Institutional R 340 eview Board of Hanyang University Hospital (IRB number: HYUH 2017-09-051). The requirement of informed consent from participants was waived because NHIS database was constructed after anonymization.

Severe Striae and Steroid Acne as Side Effects of Long-term Systemic Corticosteroid Treatment: A Case Report and Review of The Literature

Background: Systemic corticosteroids are often used in dermatology. The anti-inflammatory and immunosuppressive properties of corticosteroids make this agent as the first-line option in many disorders such as autoimmune and bullous diseases. However, there are also potential side effects and dermatologists who prescribe corticosteroids have to be aware of them. Case Summary: We report a 16-year-old girl with a history of taking oral methylprednisolone in the past 8 months who came with a acne-like eruption on the face, chest, and extremities as well as lines on the skin. Physical examination revealed monomorphic papules on the facial, thorax, and superior and inferior extremities region. Comedones were absent. Striae were found in the bilateral femur, abdomen, and mammary region. The patient was diagnosed with acneiform eruption and striae distensae rubra. Treatment using a combination of topical clindamycin and tretinoin showed clinical improvement of the acneiform eruption after three months of therapy. However, striae did not show improvement despite topical application of tretinoin and Centella asiatica extract. Conclusion: This case demonstrates the importance of understanding the cutaneous side effects that may result from chronic systemic corticosteroids administration as well as the evidence-based management.

Acute and chronic systemic corticosteroid–related complications in patients with severe asthma

Many patients with severe asthma require maintenance treatment with systemic corticosteroids (SCSs) to control daily symptoms and prevent serious acute exacerbations, but chronic SCS use is associated with complications. We sought to evaluate the risk of SCS-related complications by SCS exposure and quantify the associated health care costs and resource use in patients with severe asthma. We performed a longitudinal, open-cohort, observational study using health insurance claims data (1997-2013: Medicaid) from Florida, Iowa, Kansas, Missouri, Mississippi, and New Jersey. Eligible patients were 12 years old or older with 2 or more asthma diagnoses and had more than 6 months of continuous SCS use. An open-cohort approach was used to classify patients' follow-up into low, medium, and high SCS exposure (≤ 6, >6-12, and >12 mg/d, respectively). Multivariate generalized estimating equation models were used to estimate the adjusted risk of SCS-related complications for patients with medium and high exposure compared with patients with low exposure and quantify the resulting health care resource use and costs. The study included 3628 patients (mean age, 57.6 years; 68% female). Patients with medium and high SCS exposure had significantly higher risks of SCS-related complications, including infections and cardiovascular, metabolic, psychiatric, ocular, gastrointestinal, and bone-related complications (odds ratio, 1.23-2.12 by complication; P < .05 for all but one) versus those with low (reference group) SCS exposure. Medium and high SCS exposure were also associated with significantly more emergency department visits (incidence rate ratios, 1.31 [P = .0004] and 1.78 [P < .0001]) and inpatient visits (incidence rate ratios, 1.25 [P < .0001] and 1.59 [P < .0001]) versus low SCS exposure. A significant dose-response relationship was demonstrated between chronic SCS use and risk of SCS-related complications in patients with severe asthma. Effective SCS-sparing strategies might reduce the burden associated with SCS-related complications in patients with severe asthma.

Intraocular pressure in chronic users of low-dose oral corticosteroids for connective tissue disease

ObjectiveTo investigate the mean intraocular pressure (IOP) of patients with connective tissue disease (CTD) on low-dose chronic systemic corticosteroid therapy and compare with control subjects. DesignCross-sectional comparative study. ParticipantsA total of 86 patients with CTD were grouped according to corticosteroid therapy. Group 1 (n = 27) was composed of patients with CTD receiving low-dose systemic corticosteroid therapy (<10 mg prednisone or its equivalent oral corticosteroid) for at least 6 months, and group 2 (n = 59) included patients with CTD without use of corticosteroid therapy. Group 3 (n = 20) was composed of healthy control subjects. MethodsAll patients underwent a complete ophthalmic evaluation by an experienced investigator and had their clinical records reviewed by another independent investigator. IOP was measured by Goldmann applanation tonometry. ResultsIn all 3 groups, the IOPs were within the normal range. The mean IOP was 13.1 ± 2.7 mm Hg (range 8–19 mm Hg) in the CTD corticosteroid group (group 1), 13.7 ± 2.7 mm Hg (range 9–22 mm Hg) in CTD group without corticosteroid therapy (group 2), and 13.1 ± 1.6 mm Hg (range 10–16 mm Hg) in the control group (group 3). No significant differences in IOP were observed among the 3 groups (p = 0.50). ConclusionsPatients under chronic treatment with low-dose systemic corticosteroid therapy for CTD presented with IOP within the normal range, not clinically significant different from the IOP of patients with CTD without any steroid therapy or from healthy control subjects.

Characterization of factors associated with systemic corticosteroid use in severe asthma: Data from the Severe Asthma Research Program

Inhaled corticosteroids (ICS) remain gold standard asthma therapy; however, some patients appear to require chronic systemic corticosteroids (SCSs) for optimal control. Although no previous studies have addressed factors predisposing a severe asthmatic patient to require SCSs, obesity, persistent inflammation and airway obstruction have all been associated with higher inhaled and SCS use.(1, 2) The study's purpose was to identify factors, which could increase the likelihood for chronic SCS use in adults with severe asthma (SA) from the Severe Asthma Research Program (SARP) to help identify high-risk patients. Biologic and clinical factors were compared between rigorously defined SA participants who used SCSs regularly verses those who did not. Logistic regression analysis identified the most predictive factors.

Unrelated Cord Blood Does Not Increase An Overall Risk Of Invasive Fungal Infections Compared To Unrelated Bone Marrow: A Single Center Retrospective Analysis For 749 Recipients

Background Invasive fungal infections (IFIs) are of great concern after allogeneic hematopoietic stem cell transplantation (HSCT), the risk of which is considered to be particularly prominent among cord blood transplantation (CBT) recipients. Patients and Methods We retrospectively analysed the records of 749 adult patients who underwent CBT or unrelated bone marrow transplantation (uBMT) for the first time at the Toranomon Hospital between 2002 and 2012, and who had neither prior history nor suspicious findings of IFIs. As prophylaxis for IFIs, fluconazole (FLCZ) or itraconazole (ITCZ) capsules were conventionally used until around 2006, which were then changed to newer mold-active agents including ITCZ oral solution, voriconazole or micafungin after their approval in Japan, the choice of which was subjected to physician's discretion. Results Engraftment achieved in 418 CBT patients and 198 uBMT patients with a significantly longer neutropenic period in CBT patients (median 20 days vs 18 days, P&lt;0.001), whereas 37 patients underwent re-transplantation and 96 died before engraftment. The incidences of grade II-IV acute graft-versus-host disease (GVHD) and extensive chronic GVHD were significantly less frequent after CBT compared to uBMT (40% vs 54% and 17% vs 46%, both P&lt;0.001). Systemic corticosteroids at ≥0.5mg/kg/day was given in fewer CBT patients compared to uBMT patients (59% vs 66%, P=0.07). The median durations of immunosuppressants and antifungal prophylaxis were significantly shorter in CBT patients compared to uBMT patients (118 days vs 302 days and 315 days vs 491 days, both P&lt;0.001). As prophylaxis for IFIs, 194 CBT patients and 91 uBMT patients received FLCZ/ITCZ capsules, while 341 CBT patients and 123 uBMT patients received newer mold-active agents. Seventy-nine patients (57 in CBT and 22 in uBMT) developed IFIs with a cumulative incidence of 12.2%, at a median of 27 (1-1646) days after HSCT. About 60% of the patients developed IFIs by day 50 and the percentage reached more than 90% until 1 year. The median onset was significantly earlier in CBT patients compared to uBMT patients (day 19 vs day 61, P=0.007). The cumulative incidence of IFIs was significantly higher in CBT patients compared to uBMT patients during 50 days after HSCT (7.9% vs 3.8%, P=0.04), but became significantly lower thereafter until 1 year (2.7% vs 6.9%, P=0.02), and an overall incidence was almost similar between the 2 groups (12.6% vs 11.6%, P=0.58) (Figure 1). Four patients had 2 infectious episodes caused by different fungal species, and a total of 83 infectious episodes were documented. Eighty-one cases were breakthrough infection during antifungal prophylaxis (FLCZ/ITCZ capsules in 28, and newer mold-active agents in 53). Invasive aspergillosis (IA) was the most common, accounting for 67.9% (proven in 11, probable in 46), followed by invasive candidiasis (IC), (19.3%; candidemia in 15, encephalitis in 1). Although the incidences of IA and IC were comparable between CBT and uBMT patients, relatively rare type of IFIs caused by Trichosporon (4 cases), Mucor (2 cases) and Rodotorula (1 case) exclusively occurred in CBT patients, except one case of Fusarium infection in a patient who relapsed after uBMT. Grade II-IV acute GVHD, extensive chronic GVHD and systemic corticosteroids at ≥0.5mg/kg/day were identified as significant risk factors of IFIs for both groups (HR 1.89, P=0.01, HR 4.16, P=0.006, and HR 1.83, P=0.02). However, the impact of all these were not apparent in CBT patients (HR 1.59, P=0.16, HR 2.18, P=0.29 and HR 1.48, P=0.22), in contrast with the powerful impact in uBMT patients (HR 2.51, P=0.049, HR 10.23, P=0.03 and HR 2.87, P=0.03). Although the cessation of antifungal prophylaxis significantly increased the risk of IFIs in uBMT patients (HR 5.95, P=0.01), it showed no impact in CBT patients (HR 0.87, P=0.89). IFIs were main causes of death in 21 patients, which significantly affected non-relapse mortality in both CBT and uBMT patients (HR 3.93 and HR 6.08, both P&lt;0.001). Conclusion Unrelated cord blood did not increase an overall incidence of IFIs, because higher risk in the early post-transplant period was counterbalanced by the dramatically decreased risk due to lower frequencies of GVHD and its treatment in the later period. Particular attention might be required to the early-onset IFIs due to fungi other than Aspergillus or Candida species, in order to further decrease the risk of IFIs after CBT. Disclosures: No relevant conflicts of interest to declare.

Demographic, Physiologic and Radiographic Characteristics of COPD Patients Taking Chronic Systemic Corticosteroids

Long-term therapy with systemic corticosteroids is not recommended in the treatment of chronic obstructive pulmonary disease (COPD). However, experience demonstrates that some patients receive low dose therapy. Our objective was to describe the demographic, physiologic and radiologic characteristics of COPD patients treated with chronic systemic corticosteroids. We analyzed COPD subjects with GOLD I-IV disease in the COPDGene® study. Subjects were divided into 2 groups based on whether they reported using chronic oral steroids or not; 1264 subjects were included. Fifty-eight (4.5%) reported chronic systemic corticosteroid use. There were no differences in age, race, co-morbid conditions (other than asthma), or body mass index between the groups. There was a greater proportion of GOLD III (41% vs. 26%) and IV (41% vs. 13%) subjects in the group using chronic systemic corticosteroids. This group used more respiratory medications, required more oxygen (2.31 ± 0.21 vs. 0.59 ± 0.05 L/min; p < 0.0001), and walked less distance (245.4 ± 17.4 vs. 367.2 ± 3.9 meters; p < 0.0001). They reported more total (1.7 ± 0.16 vs. 0.62 ± 0.03; p < 0.0001) and severe exacerbations per year (0.41 ± 0.05 vs. 0.18 ± 0.01; p < 0.0001). BODE (5.0 ± 0.3 vs. 2.6 ± 0.1; p < 0.0001), MMRC (3.31 ± 0.19 vs. 1.90 ± 0.04; p < 0.0001) and SGRQ scores (54.9 ± 2.9 vs 53.3 ± 0.6; p < 0.0001) were higher. They also had a higher percentage of emphysema (22.4 ± 1.9 vs. 14.0 ± 0.4;%, p = <0.0001) on CT scan. COPD patients that report using chronic systemic corticosteroids have more severe clinical, physiologic, and radiographic disease.