scholarly journals Voriconazole versus Itraconazole for the Initial and Step-Down Treatment of Histoplasmosis: A Retrospective Cohort

2020 ◽  
Author(s):  
Michael Joshua Hendrix ◽  
Lindsey Larson ◽  
Adriana M Rauseo ◽  
Sasinuch Rutjanawech ◽  
Alexander D Franklin ◽  
...  
Keyword(s):  
Retrospective Cohort ◽  
Proportional Hazards ◽  
Histoplasma Capsulatum ◽  
Case Reports ◽  
Case Series ◽  
Clinical Information ◽  
Cox Proportional Hazards ◽  
Heaviside Function ◽  
Step Down

Abstract Background Itraconazole is the preferred azole for histoplasmosis in the current Infectious Diseases Society of America guidelines. Voriconazole is increasingly used as treatment for histoplasmosis; it has in-vitro activity against Histoplasma capsulatum and has shown success in case reports and small case series but may have a lower barrier to resistance. No comparative studies have been published. Methods We constructed a single-center retrospective cohort of adult patients diagnosed with histoplasmosis from 2002 to 2017. Individual charts were reviewed to gather clinical information including demographics, clinical features, immune status, treatments, and mortality. Patients were categorized based on initial choice of azole, either as initial treatment or as step-down therapy from amphotericin B. Initial therapies with other azoles were excluded. Mortality was compared using a multivariable Cox proportional hazards with Heaviside function at 42 days. Results We identified 261 cases of histoplasmosis from 2002 to 2017. After excluding patients not treated with itraconazole or voriconazole, 194 patients remained. 175 (90%) patients received itraconazole and 19 (10%) received voriconazole. There were no significant demographic differences between patient populations receiving either azole as their initial azole treatment. Death at 180 days occurred in 41 patients (23.4%) in the itraconazole group and 6 patients (31.6%) in the voriconazole group. Patients on voriconazole had a statistically significant increase in mortality during the first 42 days after initiation of treatment when compared to patients receiving itraconazole (HR 4.30 [95% CI 1.3-13.9, p 0.015]) when controlled for other risk factors. Conclusion Voriconazole in histoplasmosis was associated with increased mortality in the first 42 days compared to itraconazole.

scholarly journals Impact of Pathological Stratification on the Clinical Outcomes of Advanced Well-Differentiated/Dedifferentiated Liposarcoma Treated with Trabectedin

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1453
Author(s):  
Chiara Fabbroni ◽  
Giovanni Fucà ◽  
Francesca Ligorio ◽  
Elena Fumagalli ◽  
Marta Barisella ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Case Series ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Low Grade ◽  
High Grade ◽  
Retrospective Case ◽  
Well Differentiated ◽  
The Impact

Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94; adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.

Evidence-based management of epistaxis in hereditary haemorrhagic telangiectasia

2015 ◽  
Vol 129 (5) ◽  
pp. 410-415 ◽  
Author(s):  
I Syed ◽  
V S Sunkaraneni
Keyword(s):  
Assessment Tool ◽  
Case Reports ◽  
Treatment Algorithm ◽  
Case Series ◽  
Team Approach ◽  
Hereditary Haemorrhagic Telangiectasia ◽  
Questionnaire Studies ◽  
Randomised Controlled ◽  
Specific Management

AbstractBackground:There are currently no guidelines in the UK for the specific management of hereditary haemorrhagic telangiectasia related epistaxis. The authors aimed to review the literature and provide an algorithm for the management of hereditary haemorrhagic telangiectasia related epistaxis.Method:The Medline and Embase databases were interrogated on 15 November 2013 using the search items ‘hereditary haemorrhagic telangiectasia’ (title), ‘epistaxis’ (title) and ‘treatment’ (title and abstract), and limiting the search to articles published in English.Results:A total of 46 publications were identified, comprising 1 systematic review, 2 randomised, controlled trials, 27 case series, 9 case reports, 4 questionnaire studies and 3in vitrostudies.Conclusion:There is a lack of high-level evidence for the use of many of the available treatments for the specific management of epistaxis in hereditary haemorrhagic telangiectasia. Current management should be based on a multidisciplinary team approach involving both a hereditary haemorrhagic telangiectasia physician and an ENT surgeon, especially when systemic therapy is being considered. The suggested treatment algorithm considers that the severity of epistaxis merits intervention at different levels of the treatment ladder. The patient should be assessed using a reproducible validated assessment tool, for example an epistaxis severity score, to guide treatment. More research is required, particularly in the investigation of topical agents targeting the development and fragility of telangiectasiae in hereditary haemorrhagic telangiectasia.

scholarly journals Creatinine-to-body weight ratio is a predictor of incident diabetes: a population-based retrospective cohort study

2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Jiacheng He
Keyword(s):  
Body Weight ◽  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Proportional Hazards ◽  
Weight Ratio ◽  
Threshold Effect ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Incident Type

Abstract Purpose Creatinine to body weight (Cre/BW) ratio is considered the independent risk factor for incident type 2 diabetes mellitus (T2DM), but research on this relationship is limited. The relationship between the Cre/BW ratio and T2DM among Chinse individuals is still ambiguous. This study aimed to evaluate the correlation between the Cre/BW ratio and the risk of T2DM in the Chinese population. Methods This is a retrospective cohort study from a prospectively collected database. We included a total of 200,658 adults free of T2DM at baseline. The risk of incident T2DM according to Cre/BW ratio was estimated using multivariable Cox proportional hazards models, and a two-piece wise linear regression model was developed to find out the threshold effect. Results With a median follow-up of 3.13 ± 0.94 years, a total of 4001 (1.99%) participants developed T2DM. Overall, there was an L-shaped relation of Cre/BW ratio with the risk of incident T2DM (P for non-linearity < 0.001). When the Cre/BW ratio (× 100) was less than 0.86, the risk of T2DM decreased significantly as the Cre/BW ratio increased [0.01 (0.00, 0.10), P < 0.001]. When the Cre/BW ratio (× 100) was between 0.86 and 1.36, the reduction in the risk of developing T2DM was not as significant as before [0.22 (0.12, 0.38), P < 0.001]. In contrast, when the Cre/BW ratio (× 100) was greater than 1.36, the reduction in T2DM incidence became significantly flatter than before [0.73 (0.29,1.8), P = 0.49]. Conclusion There was an L-shaped relation of Cre/BW ratio with incidence of T2DM in general Chinese adults. A negative curvilinear association between Cre/BW ratio and incident T2DM was present, with a saturation effect predicted at 0.86 and 1.36 of Cre/BW ratio (× 100).

scholarly journals Associations between SARS-CoV-2 variants and risk of COVID-19 hospitalization among confirmed cases in Washington State: a retrospective cohort study

2021 ◽  
Author(s):  
Miguel I. Paredes ◽  
Stephanie Lunn ◽  
Michael Famulare ◽  
Lauren A. Frisbie ◽  
Ian Painter ◽  
...  
Keyword(s):  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Sentinel Surveillance ◽  
Cox Proportional Hazards Model ◽  
Ancestral Lineage ◽  
Significant Difference

Background: The COVID–19 pandemic is now dominated by variant lineages; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the risk of hospitalization following infection with nine variants of concern or interest (VOC/VOI). Methods: Our study includes individuals with positive SARS–CoV–2 RT PCR in the Washington Disease Reporting System and with available viral genome data, from December 1, 2020 to July 30, 2021. The main analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for the risk of hospitalization following infection with a VOC/VOI, adjusting for age, sex, and vaccination status. Findings: Of the 27,814 cases, 23,170 (83.3%) were sequenced through sentinel surveillance, of which 726 (3.1%) were hospitalized due to COVID–19. Higher hospitalization risk was found for infections with Gamma (HR 3.17, 95% CI 2.15–4.67), Beta (HR: 2.97, 95% CI 1.65–5.35), Delta (HR: 2.30, 95% CI 1.69–3.15), and Alpha (HR 1.59, 95% CI 1.26–1.99) compared to infections with an ancestral lineage. Following VOC infection, unvaccinated patients show a similar higher hospitalization risk, while vaccinated patients show no significant difference in risk, both when compared to unvaccinated, ancestral lineage cases. Interpretation: Infection with a VOC results in a higher hospitalization risk, with an active vaccination attenuating that risk. Our findings support promoting hospital preparedness, vaccination, and robust genomic surveillance.

Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study

2020 ◽  
Author(s):  
I Karaiskos ◽  
G L Daikos ◽  
A Gkoufa ◽  
G Adamis ◽  
A Stefos ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Active Agent ◽  
Bloodstream Infections ◽  
National Registry ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Fatal Disease

Abstract Background Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required. Objectives To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs). Methods A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity. Results One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival. Conclusions Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.

scholarly journals 373. Immune Reconstitution Inflammatory Syndrome in Patients with HIV/AIDS and Histoplasmosis: A Case Series

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S195-S195 ◽  
Author(s):  
Afroditi Boulougoura ◽  
Elizabeth Laidlaw ◽  
Gregg Roby ◽  
Yolanda Mejia ◽  
Alice Pau ◽  
...  
Keyword(s):  
Small Bowel ◽  
Small Bowel Obstruction ◽  
Bowel Obstruction ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Histoplasma Capsulatum ◽  
Case Reports ◽  
Case Series ◽  
The United States ◽  
Inflammatory Syndrome

Abstract Background Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV infection is the unexpected clinical deterioration due to worsening (paradoxical) or uncovering (unmasking) of an infection or malignancy upon initiation of antiretroviral therapy (ART). Histoplasma capsulatum (H. capsulatum) is the most common endemic mycosis in patients with AIDS, usually manifesting as disseminated disease at CD4 counts < 150 cells/μl. In the ART era, histoplasmosis IRIS has been described in case reports, but there has been a limited description regarding clinical presentations and pathogenesis in the United States. Methods ART-naive HIV+ patients with a CD4+ T-cell count < 100 cells/µL enrolled in prospective studies at the National Institutes of Health (NIH) (NCT00286767, NCT02147405) were evaluated to identify those with histoplasmosis and followed after ART initiation to identify those who would eventually develop IRIS. Results From a total of 271 patients, we identified 9 patients with histoplasmosis. The median age, CD4+ count and HIV VL of these 9 patients was 36 years, 40 cells/mm3 and 193,184 copies/mL, respectively. Two patients developed IRIS only to histoplasmosis (1 unmasking and 1 paradoxical), 2 patients developed IRIS to both histoplasmosis and nontuberculous mycobacteria (NTM) and 3 patients developed IRIS to other infections (1 VZV, and 2 NTM). The manifestations of histoplasmosis IRIS in our cohort ranged from worsening lymphadenopathy to small bowel obstruction and worsening pulmonary symptoms. Conclusion Histoplasma-related IRIS can present with worsening lymphadenopathy, small bowel obstruction, and worsening pulmonary symptoms. The emergence of IRIS appears to be very common in people with HIV and disseminated histoplasmosis but the underlying trigger may be histoplasma, other co-infections or both. Disclosures All authors: No reported disclosures.

scholarly journals Risk of depressive disorders after tobacco smoking cessation: a retrospective cohort study in Fukuoka, Japan

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e025124 ◽  
Author(s):  
Takako Fujita ◽  
Akira Babazono ◽  
Yumi Harano ◽  
Peng Jiang
Keyword(s):  
Smoking Cessation ◽  
Cohort Study ◽  
Survival Analysis ◽  
Retrospective Cohort ◽  
Depressive Disorders ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Proportional Hazards Models ◽  
Cox Proportional Hazards Models ◽  
Significant Difference

ObjectiveWe sought to examine the effect of smoking cessation on subsequent development of depressive disorders.DesignThis was a retrospective cohort study.MethodsWe used administrative claim and health check data from fiscal years 2010 to 2014, obtained from the largest health insurance association in Fukuoka, Japan. Study participants were between 30 and 69 years old. The end-point outcome was incidence of depressive disorders. Survival analysis and Cox proportional hazards models were conducted. The evaluated potential confounders were sex, age, standard monthly income and psychiatric medical history.ResultsThe final number of participants was 87 255, with 7841 in the smoking cessation group and 79 414 in the smoking group. The result of survival analysis showed no significant difference in depressive disorders between the two groups. The results of Cox proportional hazards models showed no significant difference by multivariate analysis between participants, including users of smoking cessation medication (HR 1.04, 95% Cl 0.89 to 1.22) and excluding medication use (HR 0.97, 95% Cl 0.82 to 1.15).ConclusionsThe present study showed that there were no significant differences with respect to having depressive disorders between smoking cessation and smoking groups. We also showed that smoking cessation was not related to incidence of depressive disorders among participants, including and excluding users of smoking cessation medication, after adjusting for potential confounders. Although the results have some limitations because of the nature of the study design, our findings will provide helpful information to smokers, health professionals and policy makers for improving smoking cessation.

Patient gender bias on the diagnosis of idiopathic pulmonary fibrosis

Thorax ◽  
2020 ◽  
Vol 75 (5) ◽  
pp. 407-412 ◽  
Author(s):  
Deborah Assayag ◽  
Julie Morisset ◽  
Kerri A Johannson ◽  
Athol U Wells ◽  
Simon L F Walsh
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Proportional Hazards ◽  
Usual Interstitial Pneumonia ◽  
Clinical Information ◽  
Cox Proportional Hazards ◽  
Diagnostic Confidence ◽  
Patient Gender ◽  
And Gender ◽  
Gender Influences

BackgroundPatient sex has clinical and prognostic implications in idiopathic pulmonary fibrosis (IPF). It is not known if sex-related and gender-related discrepancies exist when establishing a diagnosis of IPF. The aim was to determine how patient gender influences the diagnosis of IPF and the physician’s diagnostic confidence.MethodsThis study was performed using clinical cases compiled from a single centre, then scored by respiratory physicians for a prior study. Using clinical information, physicians were asked to provide up to five diagnoses, together with their diagnostic confidence. Logistic regression was used to assess the odds of receiving a diagnosis of IPF based on patient gender. Prognostic discrimination between IPF and non-IPF was used to assess diagnostic accuracy with Cox proportional hazards modelling.ResultsSixty cases were scored by 404 physicians. IPF was diagnosed more frequently in men compared with women (37.8% vs 10.6%; p<0.0001), and with greater mean diagnostic confidence (p<0.001). The odds of a male patient receiving an IPF diagnosis was greater than that of female patients, after adjusting for confounders (OR=3.05, 95% CI: 2.81 to 3.31), especially if the scan was not definite for the usual interstitial pneumonia pattern. Mortality was higher in women (HR=2.21, 95% CI: 2.02 to 2.41) than in men with an IPF diagnosis (HR=1.26, 95% CI: 1.20 to 1.33), suggesting that men were more often misclassified as having IPF.ConclusionPatient gender influences diagnosis of IPF: women may be underdiagnosed and men overdiagnosed with IPF.

G CSF association with prolonged survival in HIV infected patients with disseminated Mycobacterium avium complex infection

1998 ◽  
Vol 9 (7) ◽  
pp. 394-399 ◽  
Author(s):  
Philip Keiser ◽  
Steven Rademacher ◽  
James Smith ◽  
Daniel Skiest
Keyword(s):  
Mycobacterium Avium ◽  
Mycobacterium Avium Complex ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cd4 Count ◽  
Risk Of Death ◽  
Hazards Model

Summary: Clarithromycin can ameliorate symptoms and improve survival in disseminated Mycobacterium avium complex DMAC infection. Optimal combina tions of this drug with other agents remain unknown. Granulocyte colony stimulating factor G CSF is a cytokine that can improve phagocytosis of M. avium complex in vitro . We aim to determine if G CSF administration is associated with improved survival in patients with DMAC in a retrospective, cohort study. Case records from 1991 to 1995 of 91 patients with DMAC at Parkland Memorial Hospital were reviewed for date of initial DMAC diagnosis, baseline CD4 count, race, sex, antiretroviral use, G CSF use, therapy for DMAC clarithromycin, ethambutol, ciprofloxacin and rifabutin and date of death. Of 91 cases identified, 25 were treated with G CSF and 66 never received this drug. Baseline characteristics were similar in each group including CD4 count 40 cells mm 3 vs 33 cells mm 3, P =0.68 , clarithromycin use 18 patients vs 52 patients, P =0.90 , and antiretroviral use 20 patients vs 42 patients, P =0.21 . Subjects treated with G CSF lived longer than those who did not receive this drug 355 days vs 211 days, P 0.01 . In the subgroup treated with clarithromycin, G CSF was also associated with increased survival 377 days vs 252 days, P 0.01 . Cox proportional hazards model showed a decreased risk of death in patients treated with G CSF RH=0.22, P 0.01 , clarithromycin RH=0.13, P 0.01 and ethambutol RH=0.51, P =0.02 . Ciprofloxacin and rifabutin use did not influence survival. These data support the use of clarithromycin and ethambutol in the treatment of DMAC. Addition of G CSF to a regimen of clarithromycin and ethambutol may increase survival in DMAC and should be studied prospectively.

Antiseptic Use in Orthopaedic Wounds

2020 ◽  
pp. 46-61
Author(s):  
Fahima A. Begum ◽  
Tiffanie-Marie Borg ◽  
Hamed Mazoochy ◽  
Nima Heidari
Keyword(s):  
Strong Evidence ◽  
Case Reports ◽  
Single Agent ◽  
Case Series ◽  
Human Studies ◽  
In Vivo Studies ◽  
Foot And Ankle ◽  
Skin Preparation ◽  
Systemic Complications

Objectives: The aim of this study is to review the available literature addressing the safety and efficacy of antiseptics in surgical wounds. The different antiseptic solutions, irrigation volumes, time scales and delivery methods have been compared so that evidence-based recommendations on antiseptic use in orthopaedic, foot and ankle surgical procedures can be proposed. Methods: A literature search was performed using the online databases Medline and EMBase to identify in-vitro and in-vivo studies pertaining to antiseptic use in an orthopaedic context. Terms including antiseptic, irrigation fluid, bacitracin, hydrogen peroxide, povidone-iodine and chlorhexidine were searched. Literature published in English from inception to July 2020 in which the full text was accessible was considered for inclusion. Cellular and animal studies were included on the basis that authors analysed antiseptic efficacy and/or toxic effect of antiseptic on cells present in orthopaedic wounds. Clinical studies that met the criteria for inclusion in this review assessed antiseptic use in a surgical context, with a focus on foot and ankle procedures.         These included case reports, case series, case control, prospective and retrospective studies as well as randomised controlled trials. Studies were categorised as in-vitro, animal and human studies. Twenty-three, eleven and forty-four studies were identified as in-vitro, animal and       human studies respectively. These have been summarised and presented herein in a narrative format. Results: There is strong evidence that skin preparation with antiseptics before orthopaedic procedures reduces the risk of post-operative infection. Conclusion: Routine prophylactic intra-operative antiseptic use should be performed with caution as they increase the risk of local and systemic complications. However, there is strong evidence supporting the use of antiseptics pre-operatively when preparing the skin. Determining the best antiseptic preparation remains a matter of debate since a single agent or solution is not effective against all organisms. Further research is therefore needed to assess the efficacy of antiseptics in prevention and treatment of infections.

Sign in / Sign up

Export Citation Format

Share Document