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Article ; Online: Incidence of serious infections in patients with ANCA-associated vasculitis receiving immunosuppressive therapy

Athanasios Vassilopoulos / Stephanos Vassilopoulos / Markos Kalligeros / Fadi Shehadeh / Eleftherios Mylonakis

Frontiers in Medicine, Vol

A systematic review and meta-analysis

2023 Volume 10

Abstract: IntroductionRituximab 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 ... ...

Abstract	IntroductionRituximab 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.MethodsWe 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).ResultsFrom 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.DiscussionThe 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 ...
Keywords	ANCA-associated vasculitis ; azathioprine ; cyclophosphamide ; maintenance ; methotrexate ; mycophenolate mofetil ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: How Comorbidities Affect Hospitalization from Influenza in the Pediatric Population

Sophia C. Mylonakis / Evangelia K. Mylona / Markos Kalligeros / Fadi Shehadeh / Philip A. Chan / Eleftherios Mylonakis

International Journal of Environmental Research and Public Health, Vol 19, Iss 2811, p

2022 Volume 2811

Abstract: Influenza is a contagious respiratory illness and can lead to hospitalization and even death. Understanding how comorbidities affect the severity of influenza can help clinical management. The aim of this study is to offer more information about ... ...

Abstract	Influenza is a contagious respiratory illness and can lead to hospitalization and even death. Understanding how comorbidities affect the severity of influenza can help clinical management. The aim of this study is to offer more information about comorbidities that might be associated with the severity of influenza in children. We used a statewide network in Rhode Island, USA, to extract data for laboratory-confirmed influenza cases among children 19 years old or younger. We identified 1169 lab-confirmed influenza cases. The most common comorbidities were asthma (17.1%), neurodevelopmental disorders (10.3%), gastrointestinal disorders (7.6%), atopic dermatitis (7%), and endocrine and metabolic diseases (6.8%). Interestingly, 80.8% (63 out of 78) of children who had an influenza-related hospital admission had at least one comorbidity, and among hospitalized children with influenza, the most common comorbidities were neurological diseases (28.2%, 22/78), gastrointestinal disorders (25.6%, 20/78), endocrine and metabolic diseases (24.4%, 19/78), and neurodevelopmental disorders (23.1%, 18/78). Children with endocrine or metabolic diseases were 8.23 times more likely to be admitted to the hospital, and children with neurological disorders were 6.35 times more likely to be admitted (OR: 8.23, 95% CI: 4.42–15.32 and OR: 6.35, 95% CI: 3.60–11.24, respectively). In summary, we identified specific comorbidities associated with influenza hospitalization and length of hospital stay, and these groups should be prioritized for public health interventions.
Keywords	influenza ; children ; diabetes ; length of stay ; metabolic diseases ; Medicine ; R
Subject code	360
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Risk Factors for Hospital Readmission for Clostridioides difficile Infection

Gregorio Benitez / Fadi Shehadeh / Markos Kalligeros / Evangelia K. Mylona / Quynh-Lam Tran / Ioannis M. Zacharioudakis / Eleftherios Mylonakis

Pathogens, Vol 11, Iss 555, p

A Statewide Retrospective Cohort Study

2022 Volume 555

Abstract: 1) Background: Clostridioides difficile infection (CDI) is associated with a high recurrence rate, and a significant proportion of patients with CDI are readmitted following discharge. We aimed to identify the risk factors for CDI-related readmission ... ...

Abstract	(1) Background: Clostridioides difficile infection (CDI) is associated with a high recurrence rate, and a significant proportion of patients with CDI are readmitted following discharge. We aimed to identify the risk factors for CDI-related readmission within 90 days following an index hospital stay for CDI. (2) Methods: We analyzed the electronic medical data of admitted patients in our health system over a two-year period. A multivariate logistic regression model, supplemented with bias-corrected and accelerated confidence intervals (BCa-CI), was implemented to assess the risk factors. (3) Results: A total of 1253 adult CDI index cases were included in the analysis. The readmission rate for CDI within 90 days of discharge was 11% (140/1253). The risk factors for CDI-related readmission were fluoroquinolone exposure within 90 days before the day of index CDI diagnosis (aOR: 1.58, 95% CI: 1.05–2.37), higher Elixhauser comorbidity score (aOR: 1.05, 95% CI: 1.02–1.07), and being discharged home (aOR: 1.64, 95% CI: 1.06–2.54). In contrast, a longer length of index stay (aOR: 0.97, 95% BCa-CI: 0.95–0.99) was associated with reduced odds of readmission for CDI. (4) Conclusion: More than 1 out of 10 patients were readmitted for CDI following an index hospital stay for CDI. Patients with recent previous fluoroquinolone exposure, greater overall comorbidity burden, and those discharged home are at higher risk of readmission for CDI.
Keywords	Clostridioides difficile ; risk factors ; readmission ; fluoroquinolone ; comorbidity ; discharge ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cost-effectiveness of molecular diagnostic assays for the therapy of severe sepsis and septic shock in the emergency department.

Ioannis M Zacharioudakis / Fainareti N Zervou / Fadi Shehadeh / Eleftherios Mylonakis

PLoS ONE, Vol 14, Iss 5, p e

2019 Volume 0217508

Abstract: Objectives Sepsis presents a major burden to the emergency department (ED). Because empiric inappropriate antimicrobial therapy (IAAT) is associated with increased mortality, rapid molecular assays may decrease IAAT and improve outcomes. We evaluated the ...

Abstract	Objectives Sepsis presents a major burden to the emergency department (ED). Because empiric inappropriate antimicrobial therapy (IAAT) is associated with increased mortality, rapid molecular assays may decrease IAAT and improve outcomes. We evaluated the cost-effectiveness of molecular testing as an adjunct to blood cultures in patients with severe sepsis or septic shock evaluated in the ED. Methods We developed a decision analysis model with primary outcome the incremental cost-effectiveness ratio expressed in terms of deaths averted. Costs were dependent on the assay price and the patients' length of stay (LOS). Three base-case scenarios regarding the difference in LOS between patients receiving appropriate (AAT) and IAAT were described. Sensitivity analyses regarding the assay cost and sensitivity, and its ability to guide changes from IAAT to AAT were performed. Results Under baseline assumptions, molecular testing was cost-saving when the LOS differed by 4 days between patients receiving IAAT and AAT (ICER -$7,302/death averted). Our results remained robust in sensitivity analyses for assay sensitivity≥52%, panel efficiency≥39%, and assay cost≤$270. In the extreme case that the LOS of patients receiving AAT and IAAT was the same, the ICER remained≤$20,000/death averted for every studied sensitivity (i.e. 0.5-0.95), panel efficiency≥34%, and assay cost≤$313. For 2 days difference in LOS, the bundle approach was dominant when the assay cost was≤$135 and the panel efficiency was≥77%. Conclusions The incorporation of molecular tests in the management of sepsis in the ED has the potential to improve outcomes and be cost-effective for a wide range of clinical scenarios.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical Outcomes of Adult Patients Hospitalized with COVID-19 after Vaccination

Markos Kalligeros / Fadi Shehadeh / Evangelia K. Mylona / Matthew Kaczynski / Saisanjana Kalagara / Eleftheria Atalla / Maria Tsikala Vafea / Eleftherios Mylonakis

Tropical Medicine and Infectious Disease, Vol 6, Iss 175, p

2021 Volume 175

Abstract: Vaccination remains the most effective way to prevent COVID-19. The aim of the present study was to assess the incidence of COVID-19 hospitalizations after vaccination, as well as the effect of prior vaccination on hospitalization outcomes among patients ...

Abstract	Vaccination remains the most effective way to prevent COVID-19. The aim of the present study was to assess the incidence of COVID-19 hospitalizations after vaccination, as well as the effect of prior vaccination on hospitalization outcomes among patients with COVID-19. We analyzed and compared all consecutive patients, with or without prior vaccination, who were admitted to our hospital network due to COVID-19 from January to April 2021. Our primary outcome was to identify and describe cases of COVID-19 hospitalized after vaccination. We also utilized a multivariate logistic regression model to investigate the association of previous vaccination with hospitalization outcomes. We identified 915 consecutive patients hospitalized due to COVID-19 with 91/915 (10%) previously vaccinated with at least one dose of a COVID-19 vaccine. Utilizing our multivariate logistic regression model, we found that prior vaccination, regardless of the number of doses or days since vaccination, was associated with decreased mortality (aOR 0.44, 95% CI: 0.20–0.98) when compared to unvaccinated individuals. Our study showed that COVID-19 related hospitalization after vaccination may occur to a small percentage of patients, mainly those who are partially vaccinated. However, our findings underline that prior vaccination, even when partial, is associated with a decreased risk of death. Ongoing vaccination efforts should remain an absolute priority.
Keywords	COVID-19 ; SARS-COV-2 ; vaccination ; breakthrough infections ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Association of Community Factors with Hospital-onset Clostridioides (Clostridium) difficile Infection

Ioannis M. Zacharioudakis / Fainareti N. Zervou / Fadi Shehadeh / Evangelia K. Mylona / Eleftherios Mylonakis

EClinicalMedicine, Vol 8, Iss , Pp 12-

A Population Based U.S.-wide Study

2019 Volume 19

Abstract: Background: Clostridioides (Clostridium) difficile ranks first among the pathogens of hospital-acquired infections with hospital-based preventive strategies being only partially successful in containing its spread. Methods: We performed a spatial ... ...

Abstract	Background: Clostridioides (Clostridium) difficile ranks first among the pathogens of hospital-acquired infections with hospital-based preventive strategies being only partially successful in containing its spread. Methods: We performed a spatial statistical analysis to examine the association between population characteristics and parameters of community healthcare practice and delivery with hospital-onset Clostridioides (Clostridium) difficile infection (HO-CDI), using data from the Medicare Hospital Compare, Medicare Provider Utilization Part D, and other databases. Among the areas with the highest HO-CDI rates (“hot spots”), we conducted a geographically weighted regression (GWR) to quantify the effect of the decrease in the modifiable risk factors on the HO-CDI rate. Findings: Percentage of population > 85 years old, community claims of antimicrobial agents and acid suppressants, and density of hospitals and nursing homes within the hospital service areas (HSAs) had a statistically significant association with the HO-CDI incidence (p < 0.001). The model including the community claims of antimicrobial agents and number of hospital centers per HSA km2 was associated with 10% (R2 = 0.10, p < 0.001) of the observed variation in HO-CDI rate. The hot spots were organized into 5 Combined Statistical areas that crossed state borders. The association of the antimicrobial claims and HO-CDI rate was as high as 71% in the Boston–Worcester–Providence area (R2 = 0.71, SD 0.19), with a 10% decrease in the rate of antimicrobial claims having the potential to lead to up to 23.1% decrease in the HO-CDI incidence in this area. Interpretation: These results outline the association of HO-CDI with community practice and characteristics of the healthcare delivery system and support the need to further study the effect of community and nursing home-based antimicrobial and acid suppressant stewardship programs in the rate of HO-CDI in geographic areas that may cross state lines. Keywords: Clostridium difficile, ...
Keywords	Medicine (General) ; R5-920
Subject code	360
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Efficacy and safety of sofosbuvir in the treatment of hep C among patients on hemodialysis

Fadi Shehadeh / Markos Kalligeros / Katrina Byrd / Douglas Shemin / Eleftherios Mylonakis / Paul Martin / Erika M. C. D’Agata

Scientific Reports, Vol 10, Iss 1, Pp 1-

a systematic review and meta-analysis

2020 Volume 10

Abstract: Abstract Hepatitis C virus (HCV) infection among maintenance hemodialysis patients is implicated in increased morbidity and mortality compared to uninfected patients. Sofosbuvir (SOF)-based regimens may not be optimal among patients requiring ... ...

Abstract	Abstract Hepatitis C virus (HCV) infection among maintenance hemodialysis patients is implicated in increased morbidity and mortality compared to uninfected patients. Sofosbuvir (SOF)-based regimens may not be optimal among patients requiring hemodialysis. Several studies, however, provide evidence that use of SOF among HCV-positive patients with renal impairment, is effective and safe. We searched Pubmed and Embase to identify studies reporting the efficacy and safety of SOF-based regimens for the treatment of HCV-positive patients on maintenance hemodialysis and performed a random effects meta-analysis. The overall pooled estimate of the efficacy of SOF-based therapy was 95% (95% CI 91–98%). The efficacy of the SOF-based regimen was 92% (95% CI 80–99%), 98% (95% CI 96–100%), and 100% (95% CI 95–100%) for the following doses: 400 mg on alternate days, 400 mg daily, and 200 mg daily, respectively. The most frequent adverse event was fatigue with a pooled prevalence of 16% (95% CI 5–29%), followed by anemia 15% (95% CI 3–31%), and nausea or vomiting 14% (95% CI 4–27%). Anemia was more prevalent in treatment regimens containing ribavirin (46%, 95% CI 33–59%) compared to ribavirin-free regimens (3%, 95% CI 0–9%). This study suggests that SOF-based regimens in the treatment of HCV infection among hemodialysis patients are both effective and safe.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Statin Use Is Associated with Decreased Risk of Invasive Mechanical Ventilation in COVID-19 Patients

Sophia L. Song / Sarah B. Hays / Constance E. Panton / Evangelia K. Mylona / Markos Kalligeros / Fadi Shehadeh / Eleftherios Mylonakis

Pathogens, Vol 9, Iss 759, p

A Preliminary Study

2020 Volume 759

Abstract: COVID-19 disproportionately affects patients with medical comorbidities such as cardiovascular disease (CVD). Patients with CVD are widely prescribed 3-hydroxy-3-methyl-glutayl-CoA (HMG-CoA) reductase inhibitors (statins), a class of lipid-lowering ... ...

Abstract	COVID-19 disproportionately affects patients with medical comorbidities such as cardiovascular disease (CVD). Patients with CVD are widely prescribed 3-hydroxy-3-methyl-glutayl-CoA (HMG-CoA) reductase inhibitors (statins), a class of lipid-lowering medications known for their pleiotropic anti-inflammatory and immunomodulatory effects. However, the relationship between statin use and COVID-19 outcomes is not fully understood. In this preliminary study, we explored the association between statin use and severe COVID-19 outcomes in hospitalized patients, including intensive care unit (ICU) admission, the need for invasive mechanical ventilation (IMV), and in-hospital death. We performed a retrospective cohort study of 249 patients hospitalized with COVID-19 from 3 March 2020 to 10 April 2020 in Rhode Island, USA. Patient demographics, past medical history, current medications, and hospital course were recorded and analyzed. A multivariate logistic regression analysis was conducted to examine associations. After adjusting for age, sex, race, cardiovascular disease, chronic pulmonary disease, diabetes, and obesity, statin use was significantly associated with decreased risk for IMV (adjusted Odds Ratio (aOR) = 0.45, 95% Confidence Interval (CI): 0.20–0.99). Our results support the continued use of statins among COVID-19 patients and could have implications for future prospective studies on the management of COVID-19.
Keywords	COVID-19 ; SARS-CoV2 ; ICU ; hospitalization ; HMG-CoA reductase inhibitors ; statins ; Medicine ; R ; covid19
Subject code	610
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical Presentation, Course, and Risk Factors Associated with Mortality in a Severe Outbreak of COVID-19 in Rhode Island, USA, April–June 2020

Eleftheria Atalla / Raina Zhang / Fadi Shehadeh / Evangelia K. Mylona / Maria Tsikala-Vafea / Saisanjana Kalagara / Laura Henseler / Philip A. Chan / Eleftherios Mylonakis

Pathogens, Vol 10, Iss 8, p

2021 Volume 8

Abstract: Long-term care facilities (LTCFs) have had a disproportionally high mortality rate due to COVID-19. We describe a rapidly escalating COVID-19 outbreak among 116 LTCF residents in Rhode Island, USA. Overall, 111 (95.6%) residents tested positive and, of ... ...

Abstract	Long-term care facilities (LTCFs) have had a disproportionally high mortality rate due to COVID-19. We describe a rapidly escalating COVID-19 outbreak among 116 LTCF residents in Rhode Island, USA. Overall, 111 (95.6%) residents tested positive and, of these, 48 (43.2%) died. The most common comorbidities were hypertension (84.7%) and cardiovascular disease (84.7%). A small percentage (9%) of residents were asymptomatic, while 33.3% of residents were pre-symptomatic, with progression to symptoms within a median of three days following the positive test. While typical symptoms of fever (80.2%) and cough (43.2%) were prevalent, shortness of breath (14.4%) was rarely found despite common hypoxemia (95.5%). The majority of patients demonstrated atypical symptoms with the most common being loss of appetite (61.3%), lethargy (42.3%), diarrhea (37.8%), and fatigue (32.4%). Many residents had increased agitation (38.7%) and anxiety (5.4%), potentially due to the restriction measures or the underlying mental illness. The fever curve was characterized by an intermittent low-grade fever, often the first presenting symptom. Mortality was associated with a disease course beginning with a loss of appetite and lethargy, as well as one more often involving fever greater than 38 °C, loss of appetite, altered mental status, diarrhea, and respiratory distress. Interestingly, no differences in age or comorbidities were noted between survivors and non-survivors. Taking demographic factors into account, treatment with anticoagulation was still associated with reduced mortality (adjusted OR 0.16; 95% C.I. 0.06–0.39; p < 0.001). Overall, the clinical features of the disease in this population can be subtle and the symptoms are commonly atypical. However, clinical decline among those who did not survive was often rapid with patients expiring within 10 days from disease detection. Further studies are needed to better explain the variability in clinical course of COVID-19 among LTCF residents, specifically the factors affecting ...
Keywords	COVID-19 ; LTCF ; nursing homes ; pandemic ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: ESBL-producing Enterobacteriaceae Colonization in Long-Term Care Facilities (LTCFs): A Systematic Review and Metaâanalysis

Flokas, Myrto Eleni / Michail Alevizakos / Fadi Shehadeh / Nikolaos Andreatos / Eleftherios Mylonakis

International Journal of Antimicrobial Agents. 2017,

2017

Abstract: To estimate the colonization rate by extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-PE) among residents of Long Term Care facilities (LTCFs) and to identify pertinent risk factors.A systematic search of PubMed and EMBASE databases ... ...

Abstract	To estimate the colonization rate by extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-PE) among residents of Long Term Care facilities (LTCFs) and to identify pertinent risk factors.A systematic search of PubMed and EMBASE databases for studies published up to May, 2016 that provided raw data for gastrointestinal colonization by ESBL-PE among LTCF residents.Twenty three studies reporting data on 9,775 screened subjects met our inclusion criteria. The prevalence of ESBL-PE among LTCF residents was 18% (95% CI 12, 24). Risk factors for colonization included recent antibiotic use (within 6 months) [OR=2.06, (95%CI 1.79, 2.38)], previous hospitalization (within 2.5 years) [OR=1.5, (95% CI 1.05, 2.15)], history of invasive procedures [OR=2.79, (95% CI 1.66, 4.7)], previous ESBL-PE colonization or infection [OR=6.77, (95% CI 1.33, 34.62)], history of urinary tract infection [OR=2.66, (95% CI 1.76, 4.01)] and urinary catheter use [OR=2.55, (95% CI 1.29, 5.04)].Almost one in five LTCF residents is colonized with ESBL-PE, and colonized residents are more likely to have a history of recent antibiotic use or healthcare facility utilization. Strict adherence to antimicrobial stewardship in LTCFs is needed to address these high resistance rates.
Keywords	Enterobacteriaceae ; antibiotics ; beta-lactamase ; catheters ; databases ; gastrointestinal system ; long term care ; meta-analysis ; risk factors ; systematic review ; urinary tract diseases
Language	English
Size	p. .
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	1093977-5
ISSN	1872-7913 ; 0924-8579
ISSN (online)	1872-7913
ISSN	0924-8579
DOI	10.1016/j.ijantimicag.2017.08.003
Database	NAL-Catalogue (AGRICOLA)

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