Tu1904 The Impact of Gender on Age-Specific Risks and Benefits of Combination Therapy With Infliximab and Azathioprine Versus Infliximab Alone: A Markov Model

Abstract Background It is well established that single pill combination (SPC) therapies have the potential to improve patient adherence versus multi-pill regimens, thereby improving blood pressure control and clinical outcomes in populations with hypertension. Purpose To develop a microsimulation model, capturing different treatment pathways, to project the impact on clinical outcomes of using single pill combination therapies for the management of hypertension in five countries (Italy, Russia, China, South Korea and Mexico). Methods The model was designed to project health outcomes between 2020 and 2030 for populations with hypertension managed according to four different treatment pathways: current treatment practices [CTP], single drug with dosage titration first then sequential addition of other agents [start low and go slow, SLGS], free choice combination with multiple pills [FCC] and combination therapy in the form of a single pill [SPC]. Model inputs were derived from Global Burden of Disease 2017 dataset, including demographics, health status/risk factors, transition probabilities and treatment attributes/healthcare utilization, and the model incorporated real-world challenges to healthcare delivery such as access to care, SBP measurement error, adherence and therapeutic inertia. Simulated outcomes of mortality, incidence of chronic kidney disease (CKD), stroke and ischemic heart disease (IHD), and disability-adjusted life years (DALYs) due to these conditions were estimated for population of 1,000,000 simulated patients for each treatment pathway and country. Results SPC therapy was projected to improve health outcomes over SLGS, FCC and CTP over 10 years in all five countries. SPC was forecast to reduce mortality by 5.4% (Italy), 4.9% (Russia), 4.5% (China), 2.3% (South Korea) and 3.6% (Mexico) versus CTP and showed greater projected reductions in mortality than SLGS and FCC. DALYs were projected to be reduced with SPC therapy by between 5.7% (Italy) and 2.2% (South Korea) compared with CTP and reductions in the incidence of clinical events were also projected with SPC therapy, with decreases in the range of 11.5% (Italy) to 4.9% (South Korea) versus CTP. Conclusions Ten-year projections of clinical outcomes associated with different anti-hypertensive treatment pathways in five countries indicated that both combination therapies (FCC and SPC) are likely to reduce the disease burden of hypertension compared with conventional management approaches, with SPC showing the greatest overall benefits due to improved adherence. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi, Gentilly, France

Download Full-text

Efficacy and safety of aliskiren combination therapy: a protocol for an umbrella review

BMJ Open ◽

10.1136/bmjopen-2020-043807 ◽

2021 ◽

Vol 11 (3) ◽

pp. e043807

Author(s):

Jiantong Shen ◽

Wenming Feng ◽

Yike Wang ◽

Qiyuan Zhao ◽

Billong Laura Flavorta ◽

...

Keyword(s):

Combination Therapy ◽

Systematic Reviews ◽

Cochrane Library ◽

Umbrella Review ◽

Quality Of Reporting ◽

Ethical Approval ◽

Registration Number ◽

Third Person ◽

Meta Analyses ◽

The Impact

IntroductionEfficacy of aliskiren combination therapy with other antihypertensive has been evaluated in the treatment of patients with hypertension in recent systematic reviews. However, most previous reviews only focused on one single health outcome or one setting, none of them made a full summary that assessed the impact of aliskiren combination treatment comprehensively. As such, this umbrella review based on systematic reviews and meta-analyses is aimed to synthesise the evidences on efficacy, safety and tolerability of aliskiren-based therapy for hypertension and related comorbid patients.Methods and analysisA comprehensive search of PubMed, EMBASE, Cochrane Library, CNKI published from inception to August 2020 will be conducted. The selected articles are systematic reviews which evaluated efficacy, safety and tolerability of aliskiren combination therapy. Two reviewers will screen eligible articles, extract data and evaluate quality independently. Any disputes will be resolved by discussion or the arbitration of a third person. The quality of reporting evidence will be assessed using the Assessment of Multiple Systematic Reviews V.2 tool tool. We will take a mixed-methods approach to synthesising the review literatures, reporting summary of findings tables and iteratively mapping the results.Ethics and disseminationEthical approval is not required for the study, as we would only collect data from available published materials. This umbrella review will be also submitted to a peer-reviewed journal for publication after completion.PROSPERO registration numberCRD42020192131.

Download Full-text

Landscape pattern and economic factors’ effect on prediction accuracy of cellular automata-Markov chain model on county scale

Open Geosciences ◽

10.1515/geo-2020-0162 ◽

2020 ◽

Vol 12 (1) ◽

pp. 626-636

Author(s):

Wang Song ◽

Zhao Yunlin ◽

Xu Zhenggang ◽

Yang Guiyan ◽

Huang Tian ◽

...

Keyword(s):

Land Use ◽

Markov Chain ◽

Cellular Automata ◽

Markov Model ◽

Prediction Accuracy ◽

Driving Mechanism ◽

Economic Factors ◽

Chain Model ◽

The Impact ◽

County Scale

AbstractUnderstanding and modeling of land use change is of great significance to environmental protection and land use planning. The cellular automata-Markov chain (CA-Markov) model is a powerful tool to predict the change of land use, and the prediction accuracy is limited by many factors. To explore the impact of land use and socio-economic factors on the prediction of CA-Markov model on county scale, this paper uses the CA-Markov model to simulate the land use of Anren County in 2016, based on the land use of 1996 and 2006. Then, the correlation between the land use, socio-economic data and the prediction accuracy was analyzed. The results show that Shannon’s evenness index and population density having an important impact on the accuracy of model predictions, negatively correlate with kappa coefficient. The research not only provides a reference for correct use of the model but also helps us to understand the driving mechanism of landscape changes.

Download Full-text

Shift Detection in Hydrological Regimes and Pluriannual Low-Frequency Streamflow Forecasting Using the Hidden Markov Model

Water ◽

10.3390/w12072058 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2058 ◽

Cited By ~ 2

Author(s):

Larissa Rolim ◽

Francisco de Souza Filho

Keyword(s):

Time Series ◽

Markov Model ◽

Hidden Markov Model ◽

Extreme Events ◽

Hidden Markov ◽

Low Frequency ◽

Streamflow Forecasting ◽

Hydrologic Time Series ◽

Low Frequency Variability ◽

The Impact

Improved water resource management relies on accurate analyses of the past dynamics of hydrological variables. The presence of low-frequency structures in hydrologic time series is an important feature. It can modify the probability of extreme events occurring in different time scales, which makes the risk associated with extreme events dynamic, changing from one decade to another. This article proposes a methodology capable of dynamically detecting and predicting low-frequency streamflow (16–32 years), which presented significance in the wavelet power spectrum. The Standardized Runoff Index (SRI), the Pruned Exact Linear Time (PELT) algorithm, the breaks for additive seasonal and trend (BFAST) method, and the hidden Markov model (HMM) were used to identify the shifts in low frequency. The HMM was also used to forecast the low frequency. As part of the results, the regime shifts detected by the BFAST approach are not entirely consistent with results from the other methods. A common shift occurs in the mid-1980s and can be attributed to the construction of the reservoir. Climate variability modulates the streamflow low-frequency variability, and anthropogenic activities and climate change can modify this modulation. The identification of shifts reveals the impact of low frequency in the streamflow time series, showing that the low-frequency variability conditions the flows of a given year.

Download Full-text

Calibrating the impact of dual RAAS blockade on the heart and the kidney - balancing risks and benefits

International Journal of Clinical Practice ◽

10.1111/ijcp.12803 ◽

2016 ◽

Vol 70 (7) ◽

pp. 537-553 ◽

Cited By ~ 5

Author(s):

O. J. Ziff ◽

A. Covic ◽

D. Goldsmith

Keyword(s):

Raas Blockade ◽

Risks And Benefits ◽

The Impact

Download Full-text

The Combination of Meropenem and Levofloxacin Is Synergistic with Respect to both Pseudomonas aeruginosa Kill Rate and Resistance Suppression

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00065-10 ◽

2010 ◽

Vol 54 (6) ◽

pp. 2646-2654 ◽

Cited By ~ 46

Author(s):

Arnold Louie ◽

Caroline Grasso ◽

Nadzeya Bahniuk ◽

Brian Van Scoy ◽

David L. Brown ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Combination Therapy ◽

Infection Model ◽

Combination Regimen ◽

Time Data ◽

Kaplan Meier ◽

Drug Concentrations ◽

Cell Kill ◽

The Impact

ABSTRACT New approaches are needed for the treatment of Pseudomonas aeruginosa infections. All available single agents are suboptimal, especially for resistance suppression. Classical β-lactam/aminoglycoside combinations are not used often enough at least in part because of concern for nephrotoxicity. We evaluated the combination of meropenem and levofloxacin against the P. aeruginosa PAO1 wild type and its isogenic MexAB pump-overexpressed mutant. The drugs were studied using an in vitro hollow-fiber pharmacodynamic infection model. There were 16 different regimens evaluated for both isolates. Both total population and resistant subpopulations were quantified. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS-MS). The impact of monotherapy versus that of combination therapy for attainment of a 3-log cell kill and for resistance suppression was examined using Kaplan-Meier analysis. Drug exposures were calculated by fitting the concentration-time data using the ADAPT II package of programs. For both isolates, monotherapy allowed resistance emergence with all but the largest exposure or with all exposures. In contrast, there was no resistance emergence with any combination regimen. Kaplan-Meier analysis showed significant differences in time to attainment of a 3-log cell kill as well as time to resistance emergence for monotherapy and combination therapy for both isolates, in favor of the combination regimens. Determination of the pharmacodynamic indices associated with resistance suppression demonstrated a 2- to 3-fold reduction with the use of combinations. Combination therapy with meropenem and levofloxacin provides a significantly faster time to attain a 3-log cell kill and significantly better resistance suppression than does either monotherapy. This combination should be evaluated in a clinical trial.

Download Full-text

Candida parapsilosis Candidemia Resistance Patterns and Treatment Outcomes: An Opportunity for Antifungal Stewardship

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.037 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S86-S86

Author(s):

Gary Fong ◽

Kim Ngo ◽

Hannah Russo ◽

Nicholas Beyda

Keyword(s):

Combination Therapy ◽

Treatment Outcomes ◽

Candida Parapsilosis ◽

Medical Center ◽

Antifungal Susceptibility ◽

Antifungal Stewardship ◽

Resistance Patterns ◽

Fluconazole Therapy ◽

The Impact ◽

Research Grant

Abstract Background Candida parapsilosis has emerged as an important fungal pathogen with mortality rates up to 30%. Recent studies show no difference in treatment outcomes for patients treated both empirically and definitively with either echinocandins or fluconazole. However, the impact of antifungal susceptibility testing and opportunities for antifungal stewardship are less clear in this patient population. The purpose of this study was to assess antifungal susceptibility rates, treatment patterns, and outcomes among patients with C. parapsilosis candidemia. Methods This was a single-center, retrospective cohort review of adult patients with a positive blood culture for C. parapsilosis hospitalized at Baylor St. Luke’s Medical Center, between 2006 and 2016. Patients with mixed or breakthrough candidemia were excluded as well as patients who expired within 3 days of candidemia onset. Results Eighty patients with C. parapsilosis candidemia were identified of which 48 met inclusion criteria. Nine patients had infections caused by fluconazole non-susceptible isolates (19%). The most common empiric treatment choice was an echinocandin (33/48, 69%), followed by fluconazole (9/48, 19%), and combination therapy (6/48, 13%). Of the 39 patients with fluconazole susceptible isolates, only 17 were treated with fluconazole definitively (44%). Among patients who received empiric echinocandin vs. fluconazole therapy, there was no difference in 14-day mortality (9% vs. 11%, P = 1.00) or in-hospital mortality (12% vs. 11%, P = 1.00). Empiric combination therapy was the only independent risk factor for treatment failure (OR, 13.8; 95% CI, 1.4–138.3; P = 0.03). Conclusion Treatment outcomes for patients receiving echinocandins were similar for those receiving fluconazole. At our institution, the increased incidence of fluconazole non-susceptible isolates warrants the use of echinocandins empirically. Patients were more likely to remain on echinocandin therapy even when fluconazole susceptible isolates were identified. This study reinforces the guideline suggestion that neither echinocandins nor fluconazole treatment leads to superior outcomes, but also identifies a cohort of patients in need of antifungal stewardship. Disclosures N. Beyda, Astellas: Grant Investigator and Scientific Advisor, Research grant

Download Full-text

Methylmercury Exposure and Developmental Outcomes in Tohoku Study of Child Development at 18 Months of Age

Toxics ◽

10.3390/toxics6030049 ◽

2018 ◽

Vol 6 (3) ◽

pp. 49 ◽

Cited By ~ 8

Author(s):

Nozomi Tatsuta ◽

Kunihiko Nakai ◽

Mineshi Sakamoto ◽

Katsuyuki Murata ◽

Hiroshi Satoh

Keyword(s):

Child Development ◽

Urban Area ◽

Prenatal Exposure ◽

Coastal Area ◽

Psychomotor Development ◽

Birth Cohort Study ◽

Risks And Benefits ◽

Methylmercury Exposure ◽

Low Levels ◽

The Impact

Seafood is an important component in a healthy diet and may contain methylmercury or other contaminants. It is important to recognize the risks and benefits of consuming seafood. A longitudinal prospective birth cohort study has been conducted to clarify the effects of neurotoxicants on child development—the Tohoku Study of Child Development (TSCD) in Japan. TSCD comprises two cohorts; a polychlorinated biphenyls (PCB) cohort (urban area) and a methylmercury cohort (coastal area). Our previous results from the coastal area showed prenatal methylmercury exposure affected psychomotor development in 18-month-olds, and boys appear to be more vulnerable to the exposure than girls. In this report, we have added the urban area cohort and we reanalyzed the impact of prenatal exposure to methylmercury, which gave the same results as before. These findings suggest prenatal exposure to low levels methylmercury may have adverse effects on child development, especially in boys.

Download Full-text