Outcomes of Appropriate Empiric Combination versus Monotherapy for Pseudomonas aeruginosa Bacteremia

ABSTRACTPseudomonas aeruginosabacteremia is associated with high hospital mortality. Empirical combination therapy is commonly used to increase the likelihood of appropriate therapy, but the benefits of employing >1 active agent have yet to be established. The purpose of this study was to compare outcomes of patients receiving appropriate empirical combination versus monotherapy forP. aeruginosabacteremia. This was a retrospective, multicenter, cohort study of hospitalized adult patients withP. aeruginosabacteremia from 2002 to 2011. The primary endpoint (30-day mortality) was assessed using multivariate logistic regression, adjusting for underlying confounding variables. Secondary endpoints of hospital mortality and time to mortality were assessed by Fisher's exact test and the Cox proportional hazards model, respectively. A total of 384 patients were analyzed. Thirty-day mortality was higher for patients receiving inappropriate therapy than for those receiving appropriate empirical therapy (43.8% versus 21.5%;P= 0.03). However, there were no statistical differences in 30-day mortality following appropriate empirical combination versus monotherapy after adjusting for baseline APACHE II scores and lengths of hospital stay prior to the onset of bacteremia (P= 0.55). Observed hospital mortality was 36.6% for patients administered combination therapy, compared with 28.7% for monotherapy patients (P= 0.17). After adjusting for baseline APACHE II scores, the relationship between time to mortality and combination therapy was not statistically significant (P= 0.59). Overall, no significant differences were observed for 30-day mortality, hospital mortality, and time to mortality between combination and monotherapy forP. aeruginosabacteremia. Empirical combination therapy did not appear to offer an additional benefit, as long as the isolate was susceptible to at least one antimicrobial agent.

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

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa503 ◽

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.

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Impact of Carbapenem Resistance and Receipt of Active Antimicrobial Therapy on Clinical Outcomes of Acinetobacter baumannii Bloodstream Infections

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01728-10 ◽

2011 ◽

Vol 55 (10) ◽

pp. 4844-4849 ◽

Cited By ~ 55

Author(s):

John S. Esterly ◽

Milena Griffith ◽

Chao Qi ◽

Michael Malczynski ◽

Michael J. Postelnick ◽

...

Keyword(s):

Hospital Mortality ◽

Acinetobacter Baumannii ◽

Antimicrobial Therapy ◽

Active Agent ◽

Carbapenem Resistance ◽

Bloodstream Infections ◽

Chronically Ill ◽

Cox Proportional Hazards Model ◽

Bivariate Analysis ◽

Content Type

ABSTRACTNosocomialAcinetobacter baumanniibloodstream infections occur with significant prevalence and mortality. The relationship between carbapenem resistance inA. baumanniiand patient outcomes remains unclear. A retrospective cohort study was conducted on patients withA. baumanniibacteremia. Outcomes, controlling for confounders, were compared for carbapenem-nonresistantA. baumannii(CNRAB) and carbapenem-resistantA. baumannii(CRAB). The primary outcome studied was all-cause hospital mortality, and the secondary endpoints evaluated were time to mortality, time to negative cultures, and length of stay postinfection for survivors. A total of 79 patients, 37 infected with CRAB and 42 with CNRAB, were studied. Hospital mortality was greater in the CRAB group as determined based on bivariate analysis (P< 0.01); however, this effect was nullified when controlling for relevant confounders with logistic regression and a Cox proportional-hazards model (P= 0.71 and 0.75, respectively). Values for time to mortality and time to negative cultures did not differ between the groups. The median number of days of stay postinfection for survivors was greater for the CRAB group than the CNRAB group (14 versus 6.5;P< 0.01). Patients who received active antimicrobial therapy were less likely to die (93.5% versus 74.2%;P= 0.02), regardless of carbapenem susceptibility classifications, and this result was robust in the multivariate model (P= 0.02). Trends existed for improved outcomes in patients receiving an active beta-lactam, and patients fared worse if they had received a polymyxin as an active agent. Patients with CRAB bloodstream infections were more chronically ill and had more comorbidities. Inactive therapy was more important than carbapenem susceptibility with respect to outcomes, was a strong predictor of death, and is potentially modifiable.

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Genetic and nongenetic factors for contralateral progression of unilateral moyamoya disease: the first report from the SUPRA Japan Study Group

Journal of Neurosurgery ◽

10.3171/2021.3.jns203913 ◽

2021 ◽

pp. 1-10

Author(s):

Yohei Mineharu ◽

Yasushi Takagi ◽

Akio Koizumi ◽

Takaaki Morimoto ◽

Takeshi Funaki ◽

...

Keyword(s):

Risk Factors ◽

Moyamoya Disease ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Regression ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Multicenter Cohort Study ◽

Cox Regression Analysis ◽

Unilateral Moyamoya Disease

OBJECTIVE Although many studies have analyzed risk factors for contralateral progression in unilateral moyamoya disease, they have not been fully elucidated. The aim of this study was to examine whether genetic factors as well as nongenetic factors are involved in the contralateral progression. METHODS The authors performed a multicenter cohort study in which 93 cases with unilateral moyamoya disease were retrospectively reviewed. The demographic features, RNF213 R4810K mutation, lifestyle factors such as smoking and drinking, past medical history, and angiographic findings were analyzed. A Cox proportional hazards model was used to find risk factors for contralateral progression. RESULTS Contralateral progression was observed in 24.7% of cases during a mean follow-up period of 72.2 months. Clinical characteristics were not significantly different between 63 patients with the R4810K mutation and those without it. Cox regression analysis showed that the R4810K mutation (hazard ratio [HR] 4.64, p = 0.044), childhood onset (HR 7.21, p < 0.001), male sex (HR 2.85, p = 0.023), and daily alcohol drinking (HR 4.25, p = 0.034) were independent risk factors for contralateral progression. CONCLUSIONS These results indicate that both genetic and nongenetic factors are associated with contralateral progression of unilateral moyamoya disease. The findings would serve to help us better understand the pathophysiology of moyamoya disease and to manage patients more appropriately.

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Correlation of tumor mutation with efficacy in patients with gastric cancer who received nivolumab and ramucirumab combination therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.413 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 413-413 ◽

Cited By ~ 1

Author(s):

Izuma Nakayama ◽

Hirokazu Shoji ◽

Hiroki Hara ◽

Taito Esaki ◽

Nozomu Machida ◽

...

Keyword(s):

Gastric Cancer ◽

Combination Therapy ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Tissue Sample ◽

Objective Response ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Cox Proportional Hazards Model ◽

Mutation Load

413 Background: Nivolumab (Nivo) plus ramucirumab (Ram) showed promising efficacy in the second-line chemotherapy for advanced gastric cancer (AGC) in NIVORAM study with the 44% of objective response rate (ORR) and 38.6% of 6-month progression free survival (PFS) rate. We investigated the correlation of tumor mutation load and efficacy. Methods: Patients received Nivo (3mg/kg, Q2W) in combination with Ram (8mg/kg, Q2W) until unacceptable toxicity or disease progression. Tissue samples were collected before the treatment, and analyzed for tumor mutation load using Oncomine Tumor Mutation Load Assay. Efficacy included ORR, overall survival (OS), PFS and duration of response. OS and PFS curves were estimated using the Kaplan-Meier method. Hazard ratio (HR) was estimated using the Cox proportional hazards model. Results: By the data cut off of December 15, 2018, the median follow duration on therapy was 13.7 month. Thirty AGC pts who obtained tissue sample were analyzed. Median tumor mutation load (TML) was 6.755 mutation/Mb (range 0.84-19.67). Higher TML (cut-off median) related to better tendency of efficacy with ORR (40.0% vs 20.0%), PFS (5.32 vs 2.33 months) and OS (18.1 vs 10.6 months). 6-month PFS rate was better in TML higher group (48%) compared to TML lower group (18%). In multivariate analysis, higher TML showed 2.030 of hazard ratio (95% CI; 0.849-4.855, p-0.112) for PFS, and 1.915 (95% CI; 0.578-6.343, p=0.287) for OS. Conclusions: The patients with higher tumor mutation load have a better tendency for OS and PFS, among AGC patients who received Nivo and Ram combination therapy. Clinical trial information: NCT02999295.

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Association between the findings of metachronous secondary primary malignancies and the number of Lugol-voiding lesions

Diseases of the Esophagus ◽

10.1093/dote/doz110 ◽

2020 ◽

Vol 33 (9) ◽

Author(s):

Chikatoshi Katada ◽

Tetsuji Yokoyama ◽

Tomonori Yano ◽

Ichiro Oda ◽

Yuichi Shimizu ◽

...

Keyword(s):

Cumulative Incidence ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Strong Predictor ◽

Progressive Increase ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Esophageal Mucosa ◽

Multicenter Cohort Study ◽

Hazards Model

Summary This study was designed to evaluate the relation between dysplastic squamous epithelium in the esophageal mucosa and the development of metachronous secondary primary malignancies (mSPM) other than esophagus after endoscopic resection (ER) in patients with early esophageal squamous cell carcinoma (SCC). We studied 330 patients with early esophageal SCC who underwent ER as a post hoc analysis of a prospective multicenter cohort study (UMIN Clinical Trials Registry ID UMIN000001676). Lugol-voiding lesions (LVL) were graded into 3 categories (A = no lesion; B = 1 to 9 lesions; C ≥ 10 lesions). The following variables were studied: (i) the incidences of mSPM other than esophagus; (ii) the standardized incidence ratios (SIRs) of mSPM; (iii) the cumulative incidence and total number of mSPM other than esophagus; and (iv) predictors of mSPM other than esophagus on analysis with a multivariate Cox proportional-hazards model. After a median follow-up of 46.6 months, mSPM other than esophagus was diagnosed in a total of 73 patients (90 lesions). Among the 106 patients in group C, 37 patients had mSPM (51 lesions), including head and neck cancer in 14 patients (24 lesions) and gastric cancer in 12 patients (16 lesions). The SIR of mSPM was 3.61 in this study subjects. An increase in the LVL grade (A to B to C) was associated with a progressive increase in the cumulative incidence rate of mSPM other than esophagus (P = 0.017 for A vs. C, P = 0.023 for B vs. C). An increase in the LVL grade (A to B to C) was also associated with a progressive increase in the total number of mSPM other than esophagus per 100 person-years (primary events, relative risk [RR] = 1.66 and 3.24 for grades B and C, respectively, vs. A, P = 0.002 for trend; all events, RR = 1.81 and 4.66 for grades B and C, respectively, vs. A, P < 0.0001 for trend). LVL grade C was a strong predictor of mSPM other than esophagus (RR = 3.41 for A vs. C). LVL grade may be a useful predictor of the risk of mSPM other than esophagus after ER in patients with early esophageal SCC.

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Serum sodium on admission affects postoperative in-hospital mortality in acute aortic dissection patients

PLoS ONE ◽

10.1371/journal.pone.0261168 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0261168

Author(s):

Pengfei Huang ◽

Hongyan Wang ◽

Dong Ma ◽

Yongbo Zhao ◽

Xiao Liu ◽

...

Keyword(s):

Aortic Dissection ◽

Hospital Mortality ◽

Serum Sodium ◽

Proportional Hazards ◽

Acute Aortic Dissection ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hospital Death ◽

Hazards Model

Background Acute aortic dissection (AAD) is very fatal without surgical treatment. Higher serum sodium can increase in-hospital mortality of many diseases; however, the effect of serum sodium on postoperative in-hospital mortality in AAD patients remains unknown. Methods We collected a total of 415 AAD patients from January 2015 to December 2019. Patients were classified into four categories (Q1-Q4) according to the admission serum sodium quartile. The cox proportional hazards model evaluated the association between serum sodium and in-hospital mortality. All-cause in-hospital mortality was set as the endpoint. Results By adjusting many covariates, cox proportional hazards model revealed the in-hospital mortality risk of both Q3 and Q4 groups was 3.086 (1.242–7.671, P = 0.015) and 3.370 (1.384–8.204, P = 0.007) respectively, whereas the risk of Q2 group was not significantly increased. Univariate and multiple Cox analysis revealed that Stanford type A, serum glucose, α-hydroxybutyrate dehydrogenase and serum sodium were risk factors correlated with in-hospital death in AAD patients. Conclusion The study indicates that the admission serum sodium of AAD patients has a vital impact on postoperative hospital mortality.

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Exploring the determinants of liquidity with big data – market heterogeneity in German markets

Journal of Property Investment and Finance ◽

10.1108/jpif-01-2017-0006 ◽

2018 ◽

Vol 36 (1) ◽

pp. 3-18 ◽

Cited By ~ 4

Author(s):

Marcelo Cajias ◽

Philipp Freudenreich

Keyword(s):

Big Data ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

City Centre ◽

Content Type ◽

Rental Market ◽

Hazards Model ◽

German Cities

Purpose The purpose of this paper is to examine the market liquidity (time-on-market (TOM)) and its determinants, for rental dwellings in the largest seven German cities, with big data. Design/methodology/approach The determinants of TOM are estimated with the Cox proportional hazards model. Hedonic characteristics, as well as socioeconomic and spatial variables, are combined with different fixed effects and controls for non-linearity, so as to maximise the explanatory power of the model. Findings Higher asking rent and larger living space decrease the liquidity in all seven markets, while the age of a dwelling, the number of rooms and proximity to the city centre accelerate the letting process. For the other hedonic characteristics heterogeneous implications emerge. Practical implications The findings are of interest for institutional and private landlords, as well as governmental organisations in charge of housing and urban development. Originality/value This is the first paper to deal with the liquidity of rental dwellings in the seven most populated cities of Europe’s second largest rental market, by applying the Cox proportional hazards model with spatial gravity variables. Furthermore, the German rental market is of particular interest, as approximately 60 per cent of all rental dwellings are owned by private landlords and the German market is organised polycentrically.

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Money transfer between banks

International Journal of Bank Marketing ◽

10.1108/ijbm-04-2019-0131 ◽

2019 ◽

Vol 38 (2) ◽

pp. 283-295

Author(s):

Andrea Lippi ◽

Laura Barbieri ◽

Federica Poli

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Financial Advisors ◽

Data Set ◽

Financial Intermediary ◽

Content Type ◽

Financial Advisor ◽

Hazards Model

Purpose The purpose of this paper is to examine which individual traits of financial advisors influence portfolio transfer speed when a financial advisor recommends investors to migrate to a new financial intermediary. Design/methodology/approach With reference to the years 2014–2016, one of the three leading Italian tied-agent banks provided the authors with an exclusive and unique data set containing information regarding the financial advisors who had become tied agents, transferring their existing portfolios from their previous banks (traditional or tied-agent banks). The authors observed the ability of the migrant financial advisor in successfully transferring the entire portfolio declared within 12 months of observation. To investigate empirically which personal traits of financial advisors determine their success in the rapid transfer of clients’ portfolios to a new financial intermediary, the authors applied a Cox proportional hazards model. Findings The authors find that factors such as age, type of bank of origin and size of the managed financial portfolio positively affect the speed transfer. Practical implications The obtained results may be interesting for guiding recruiting policies of financial intermediaries. Social implications Regulators should closely examine the phenomenon analyzed in this paper to avoid conflict of interests. Originality/value The literature on this topic is scarce, mainly due to the lack of available data. This paper represents an original contribution to open a new field of research.

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The impact of corporate venture capital involvement in syndicates

Management Decision ◽

10.1108/md-01-2017-0024 ◽

2019 ◽

Vol 57 (1) ◽

pp. 131-151 ◽

Cited By ~ 4

Author(s):

Shinhyung Kang

Keyword(s):

Venture Capital ◽

Initial Public Offering ◽

Proportional Hazards Model ◽

Negative Relationship ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Corporate Venture Capital ◽

Content Type ◽

Corporate Venture ◽

The Impact

Purpose Prior literature indicates that syndication enhances the likelihood of ventures’ successful exits; however, it has neglected the differences among venture capital (VC) investor types. In fact, there are various types of VC investors with distinctive objectives. Therefore, by focusing on ventures backed by corporate venture capital (CVC) and independent venture capital (IVC) investors, the purpose of this paper is to investigate how the relative influence among a heterogeneous group of VC investors in a syndicate affects the likelihood of the venture’s successful exit. Design/methodology/approach A sample of 1,121 US ventures that received funding from both CVC and IVC investors during 2001 and 2013 are collected. Then, a Cox proportional hazards model is applied to analyze the likelihood of a successful exit (i.e. initial public offering or acquisition). Findings The relative reputation of CVC investors vis-à-vis their IVC co-investors in a syndicate is negatively associated with the likelihood of the venture’s successful exit. This negative relationship is exacerbated when CVC investors are geographically close to the focal venture, and it is weakened when CVC investors syndicate with IVC investors that they have collaborated in the past. Originality/value First, this paper advances VC syndication literature by demonstrating that syndication does not positively affect the likelihood of a venture’s successful exit unless key syndicate members seek to pursue going public or acquisition strategy. Second, this paper also reveals when CVC is beneficial from the ventures’ perspective. CVC participation facilitates ventures’ successful exits as long as reputable IVC investors are present in the syndicate. Third, this study contributes to the multiple agency perspective by showing that formal governance mechanisms affect ventures’ conduct and performance as well as informal sources of power.

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Effects of founder CEO duality and board size on foreign IPOs’ survival in US markets

Corporate Governance ◽

10.1108/cg-04-2021-0151 ◽

2022 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Sang-Youn Lee ◽

Eun-Jeong Ko

Keyword(s):

Initial Public Offerings ◽

Proportional Hazards Model ◽

Negative Impact ◽

Negative Relationship ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Foreign Firms ◽

Board Size ◽

Ceo Duality ◽

Content Type

Purpose This study aims to investigate how three critical governance decisions by foreign firms impacted their survivability post-initial public offerings (IPO): the choice of CEO (founder vs non-founder); the power the founder CEO wields relative to the board in terms of CEO duality; and board size. Design/methodology/approach This study uses data from 86 foreign firms that completed IPOs in the US market between 2000 and 2008 and adopts a Cox proportional hazards model to examine how the founder, founder CEO duality and board size influence foreign firm delisting post-IPO. Findings A founder CEO or a founder CEO with duality (i.e. when a founder CEO is also chair of the board of directors) does not support a foreign firm’s survival post-IPO. Expectedly, board size has a negative impact on post-IPO firm survivability; however, founder CEO duality positively moderates this negative relationship. Therefore, founder CEO duality plays a positive indirect role in the context of post-IPO firms with large boards. Originality/value First, while the benefits of CEO duality have been empirically ambiguous, this study clarifies how founder CEO duality manifests its positive impacts in foreign listings. Second, by focusing on board cognition, this study confirms the negative impact of large boards, but highlights that this can be mitigated by governance leadership structure. Finally, despite organizational life-cycle theorists’ advocacy of the replacement of founder CEOs with professional CEOs in sizable ventures, this study shows the benefits of their retention when the board is large.

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