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  • 1
    In: Open Forum Infectious Diseases, Oxford University Press (OUP)
    Abstract: Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitors (BTKi) for treatment of chronic lymphoid malignancies such as chronic lymphocytic leukemia (CLL), but precise estimates are lacking. We aim to characterize the prevalence of IFIs among patients with CLL, for whom BTKi are now the first line recommended therapy. Methods We queried TriNetX, a global research network database, to identify adult patients with CLL using the ICD-10 codes (C91.1) and laboratory results. We performed a case-control propensity score-matched analysis to determine IFIs events by BTKi use. We adjusted for age, sex, ethnicity, and clinical risk factors associated with an increased risk of IFIs. Results Among 5,358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi vs. 3.5% among patients with CLL not on a BTKi at five years. Approximately 1% of patients with CLL developed an IFI while on a BTKi within this period. Our adjusted IFI event analysis found an elevated rate of Pneumocytis jirovecii pneumonia (PJP) (0.5% vs. 0.3%, p = 0.02) and invasive candidiasis (3.5% vs 2.7%, p = 0.012) with the use of a BTKi. The number needed to harm for patients taking a BTKi was 120 and 358 for invasive candidiasis and PJP, respectively. Conclusions We found an adjusted elevated rate of PJP and invasive candidiasis with BTKi use. The rates are however low with a high number needed to harm. Additional studies stratifying other IFIs with specific BTKi are required to identify at-risk patients and preventive, cost-effective interventions.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2012
    In:  Transactions of the Royal Society of Tropical Medicine and Hygiene Vol. 106, No. 9 ( 2012-9), p. 521-527
    In: Transactions of the Royal Society of Tropical Medicine and Hygiene, Oxford University Press (OUP), Vol. 106, No. 9 ( 2012-9), p. 521-527
    Type of Medium: Online Resource
    ISSN: 0035-9203
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2012
    detail.hit.zdb_id: 2135136-3
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  • 3
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. 11 ( 2019-11-01)
    Abstract: Cryptococcus gattii represents an emerging fungal pathogen of immunocompromised and immunocompetent hosts in the United States. To our knowledge, this is the first case of posttransplant immune reconstitution syndrome due to C. gattii meningoencephalitis successfully treated with corticosteroids. We also report successful maintenance phase treatment with isavuconazole, a novel triazole, following fluconazole-induced prolonged QT syndrome.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 4
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2018
    In:  Clinical Infectious Diseases Vol. 66, No. 8 ( 2018-04-03), p. 1314-1315
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 66, No. 8 ( 2018-04-03), p. 1314-1315
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2002229-3
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  • 5
    In: Clinical Infectious Diseases, Oxford University Press (OUP), ( 2023-09-06)
    Abstract: Glucocorticoids are widespread anti-inflammatory medications used in medical practice. The immunosuppressive effects of systemic glucocorticoids and increased susceptibility to infections are widely appreciated. However, the dose-dependent model frequently used may not accurately predict the risk of infection in all patients treated with long-term glucocorticoids. In this review, we examine the risks of opportunistic infections (OIs) in patients requiring glucocorticoid therapy by evaluating the influence of the glucocorticoid dose, duration, and potency, combined with biological and host clinical factors and concomitant immunosuppressive therapy. We propose strategies to prevent OIs, which involve screening, antimicrobial prophylaxis, and immunizations. While this review focuses on patients with autoimmune, inflammatory, or neoplastic diseases, the potential risks and preventative strategies are likely applicable to other populations. Clinicians should actively assess the benefit–harm ratios of systemic glucocorticoids and implement preventive efforts to decrease their associated infections complications.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 6
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2016
    In:  Clinical Infectious Diseases Vol. 62, No. 3 ( 2016-02-01), p. 407-408
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 62, No. 3 ( 2016-02-01), p. 407-408
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
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  • 7
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Corticosteroids increase the risk of Pneumocystis jirovecii pneumonia (PJP). It is unknown how much corticosteroid dose exposure would modify the risk of PJP in different populations. We aim to develop a PJP risk calculator based on the previous dose of corticosteroids and modulated by additional clinical factors. Methods A multicenter retrospective case-control study was performed on patients tested for PJP within the UCHealth system from 2000 to 2021. We developed a model for estimating PJP risk based on previous prednisone equivalent daily dose (PEDD) and adjustable for additional clinical variables. PJP was fit to a generalized additive model (GAM), with a spline for prednisone dose and additive covariates for demographics and risk factors. We used a multicenter federated network to calibrate the model to estimate the PJP prevalence among hospitalized patients with hypoxic respiratory failure. Results We had a complete sample of 199 patients, 104 cases with PJP, and 95 controls. Patients with HIV (OR: 19 CI: 6.3-60.8, p & lt; 0.0001), diabetes (OR: 4.1 CI: 1.2-14.8, p & lt; 0.0288), and autoimmune disease (OR: 5.2 CI: 1.4-19.2, p & lt; 0.0139) were more likely to have PJP. Patients with preexisting lung disease (OR: 0.3 CI: 0.1-0.6, p & lt; 0.0041) and on PJP prophylaxis (OR: 0.06 CI: 0.02-0.2, p & lt; 0.0001) were less likely to have PJP. 36.8% of controls and 49% of cases were on steroids with a mean PEDD of 15 mg/day and 20.4 mg/day, respectively. We found a prevalence of PJP of 0.126% among hospitalized patients with hypoxic respiratory failure. The developed model can estimate the PJP risk based on a previous PEDD in 32 different clinical combinations: e.g., a PEDD of 20 mg/day would give a calculated annual PJP risk of approximately 1.74% (95% CI: [0.39, 7.42]) if a patient has autoimmune disease only but 6.29% (95% CI: [1.34, 24.91] ) if a patient has HIV only (Figure 1). Figure 1.Predicted probability of PJP based on previous prednisone dose among hospitalized patients with hypoxic respiratory failure for three different clinical scenarios Conclusion Previous corticosteroid dose alone is inadequate to inform of an increased risk of PJP. A multivariable calculator incorporating the absence or presence of additional traditional risk factors could optimally stratify the PJP risk. Future directions include validating the findings in external cohorts and modeling PJP risk in the ambulatory setting to inform the need for PJP prophylaxis. Disclosures All Authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 8
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Diabetes mellitus type 2 (DM2) is a common medical condition that increases the risk of bacterial infections, and is often present in patients with cryptococcosis. The role of DM2 as an independent risk factor for cryptococcosis is debatable. We aim to better characterize the natural history of cryptococcosis in patients with DM2 as their only comorbidity. Methods We utilized TrinetX, a federal national network, to identify HIV-negative patients who had cryptococcosis without known risk factors. Demographic characteristics and outcomes were compared between patients with DM2 and those without DM2, who tested positive or had ICD based diagnoses of Cryptococcus infection within five years of diagnosis of DM2. Results Sixty patients with DM2 (as the sole risk factor) and 707 patients without DM2 had cryptococcosis. Patients with DM2 and cryptococcosis were older (61 ± 13.6 years vs. 55.8 ± 16.2 years, p=0.0219), and more likely to be Hispanic or Latino (18% vs. 9%, p=0.023). They had higher rates of hypertension (77% vs 44%, p & lt; 0.0001), cystic fibrosis (18% vs 1%, p & lt; 0.0001), tuberculosis (18% vs 1%, p & lt; 0.0001), and chronic kidney disease (33% vs 18%, p=0.0026). The mean HbA1c among patients with DM2 who developed cryptococcosis was 8.16 (SD 2.62). The most common sites of cryptococcus infection were pulmonary (56% vs 55%, p=0.8930) and cerebral (36% vs 40%, p=0.5589), in both groups. The two groups had similar mortality (20% vs 25.47%, p=0.3676) (Figure 1), and hospitalization rates (20% vs 31.3%, p=0.08). The overall annual cryptococcosis risk among HIV-negative patients with DM2 without any additional risk factors was 0.001%. Conclusion Cryptococcosis occurs rarely in HIV-negative patients with DM2 and without additional risk factors. Hispanic or Latino ethnicity, uncontrolled hyperglycemia, and chronic kidney disease may increase the risk of cryptococcosis among patients with DM2. Cryptococcosis in patients whose only comorbidity is DM2 have as high of mortality as that seen with more established comorbitidies. Disclosures All Authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 9
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. 6 ( 2021-06-01)
    Abstract: Cryptococcus species are ubiquitous in the environment with a global distribution. While causing disease predominantly in immunocompromised hosts such as those with advanced HIV, HIV-uninfected patients are increasingly recognized as being affected. The most common forms of infection are cryptococcal pneumonia and meningitis. HIV-uninfected patients and extrapulmonary infections have worse outcomes, likely due to delayed diagnosis and treatment. Cryptococcus infections involving chylothorax or chyloabdomen have rarely been reported in humans. We describe a case of fulminant disseminated cryptococcosis with fungemia, peritonitis, and empyema in a patient with chronic chylothorax treated with an indwelling pleurovenous shunt. Key autopsy findings included cryptococcal organisms identified on calcified lymphadenopathy, pleural adhesions, and pericardium. We discuss the importance of identifying patients with nontraditional risks factors for cryptococcal disease, such as lymphopenia and hypogammaglobulinemia, and the potential implications of pleurovenous catheters in Cryptococcus dissemination.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 10
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  Open Forum Infectious Diseases Vol. 8, No. Supplement_1 ( 2021-12-04), p. S271-S271
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S271-S271
    Abstract: Chronic comorbidities increase the risk of poor outcomes in patients with COVID-19. However, there are insufficient data to determine whether control of chronic comorbidities influences outcomes. The purpose of this study was to determine whether pharmacologic treatment for common comorbidities influences in-hospital mortality. Methods This multicenter, retrospective study included adult patients with diabetes, hypertension, and/or dyslipidemia who were hospitalized with COVID-19 in Southwest GA, U.S. Patients were divided into two groups based on treatment status, where treated was defined as documentation in the electronic medical record of outpatient pharmacologic therapy indicated for that specific comorbidity while untreated was defined as no record of pharmacologic therapy for one or more comorbidity. The primary outcome was to compare in-hospital mortality between treated and untreated COVID-19 patients. Secondary outcomes included comparing length of hospital stay, development of thrombotic events, requirement for vasopressors, mechanical ventilation, and transfer to the ICU between groups. Results A total of 360 patients were included with a median age of 66 years (IQR 56-75). The majority were African American (83%) and female (61%) with a median Charlson Comorbidity Index of 4 (IQR 2-6). Hypertension, diabetes, and dyslipidemia were present in 91%, 55%, and 45% of patients, respectively, of which 76% (n=274) were treated. Mortality was similar between treated and untreated patients (25% vs 20%, p=0.304). Average length of stay was 9.5 days (SD 8.7) in treated patients compared to 10.6 days (SD 9.1) in untreated patients (p=0.302). No differences were observed in the rates of thrombosis (3% vs 4%, p=0.765), receipt of vasopressors (23% vs 21%, p=0.741), mechanical ventilation (31% vs 27%, p=0.450), or transfer to the ICU (27% vs 14%, p=0.112). Conclusion Hospitalized COVID-19 patients being treated for hypertension, diabetes, and/or dyslipidemia have similar rates of complications and mortality compared to untreated patients. Further research is needed to determine whether degree of control of chronic comorbidities impacts COVID-19 outcomes. Disclosures All Authors: No reported disclosures
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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