Multivariate Sensitivity Analyses Research Articles

Out-of-Hospital Cervical Ripening With a Synthetic Hygroscopic Cervical Dilator May Reduce Hospital Costs and Cesarean Sections in the United States-A Cost-Consequence Analysis.

Objective: Out-of-hospital (outpatient) cervical ripening prior to induction of labor (IOL) is discussed for its potential to decrease the burden on hospital resources. We assessed the cost and clinical outcomes of adopting an outpatient strategy with a synthetic hygroscopic cervical dilator, which is indicated for use in preinduction cervical ripening.Methods: We developed a cost-consequence model from the hospital perspective with a time period from IOL to post-delivery discharge. A hypothetical cohort of women to undergo IOL at term with an unfavorable cervix (all risk levels) were assessed. As the standard of care (referred to as IP-only) all women were ripened as inpatients using the vaginal PGE2 insert or the single-balloon catheter. In the comparison (OP-select), 50.9% of low-risk women (41.4% of the study population) received outpatient cervical ripening using a synthetic hygroscopic cervical dilator and the remaining women were ripened as inpatients as in the standard of care. Model inputs were sourced from a structured literature review of peer-reviewed articles in PubMed. Testing of 2,000 feasible scenarios (probabilistic multivariate sensitivity analysis) ascertained the robustness of results. Outcomes are reported as the average over all women assessed, comparing OP-select to IP-only.Results: Implementing OP-select resulted in hospital savings of US$689 per delivery, with women spending 1.48 h less time in the labor and delivery unit and 0.91 h less in the postpartum recovery unit. The cesarean-section rate was decreased by 3.78 percentage points (23.28% decreased to 19.50%). In sensitivity testing, hospital costs and cesarean-section rate were reduced in 91% of all instances.Conclusion: Our model analysis projects that outpatient cervical ripening has the potential to reduce hospital costs, hospital stay, and the cesarean section rate. It may potentially allow for better infection-prevention control during the ongoing COVID-19 pandemic and to free up resources such that more women might be offered elective IOL at 39 weeks.

PMH48 Antidepressants and Health-Related Quality of Life (HRQOL) for Patients with Depression: Analysis of Medical Expenditure Panel Survey

Despite the empirical literature demonstrating the efficacy of antidepressant medications for treatment of depression disorder, these medications’ effect on patients’ overall well-being and health-related quality of life (HRQoL) remains controversial. This study investigates the effect of antidepressant medication use on patient-reported HRQoL for patients who have depression. A retrospective cohort study was conducted using data from the Medical Expenditures Panel Survey. Adult patients (≥18 years) with depression. The Multum drug database was used to identify patients on antidepressant medications. Subjects with complete data for the two-year follow-up in 11 consecutive cohorts (panels 10-20) were included. The HRQoL is measured using the SF-12 health survey and reported as physical and mental component summaries (PCS and MCS). The difference in differences (D-I-D) analysis was used to assess the significance of the mean difference of change on the PCS and MCS from baseline to follow-up between the two cohorts. A univariate D-I-D analyses were carried on for the combined panels and for each panel individually. Then, the robustness of the results was assessed in multivariate sensitivity analyses, controlling for the effect of significant demographical variables. On average, 17.5 million adults were diagnosed with depression disorder each year during the period 2005–2016. The majority were female (67.9%), a larger proportion of whom received antidepressant medications (60.5% vs. 51.5% of males). Although use of antidepressants was associated with some improvement on the MCS, D-I-D univariate analysis revealed no significant difference between the two cohorts in PCS (–0.35 vs. –0.34, p=0.9595) or MCS (1.28 vs. 1.13, p=0.6405). Moreover, these results were mostly consistent in the individual panels analyses, and the multivariate D-I-D analyses ensured the robustness of these results. The impact of using antidepressant medications on HRQoL were not statistically significant. These findings suggest the need for better intervention strategy for patients with depression.

An integrated approach for modeling uncertainty in human health risk assessment.

A human health risk assessment (HHRA) will not remain simple and straightforward when it involves multiple uncertain input variables. Uncertainties in HHRA result from the unavailability and subjectivity of input variables. Though several studies have performed HHRA, the quantification of uncertainty in HHRA under a situation of data scarcity and the simultaneous application of random and non-random input variables have rarely been reported. The present study proposes an integrated hybrid health risk modeling framework involving the concurrent treatment of random and non-random input variables and estimating the uncertainties linked to the input variables in HHRA. The proposed framework presents the flexibility to classify the input variables into fuzzy and probabilistic categories, based on their data availability and provenience nature. The framework is demonstrated over the Turbhe sanitary landfill in Navi Mumbai, India, where the fate and transport of heavy metals in leachate are investigated through LandSim modeling. The present study considers the LandSim-simulated heavy metal concentration and body weight as a random variable and water intake, exposure duration, frequency, bioavailability, and average time as fuzzy variables. Further, the uncertainties in the non-carcinogenic human health risk have been quantified using Monte Carlo simulations, followed by a comprehensive multivariate sensitivity analysis of the proposed framework. High health risk at Turbhe is estimated for the male and female population. This study presents the first effort to quantify the non-carcinogenic human health risks from leachate-contaminated groundwater considering the health risk input variables as non-deterministic. The proposed framework is generic and applicable to any landfill site and will remain unaltered when integrated health risk assessment and uncertainty assessment are performed for the landfill.

Considering Criteria for Active Phase Labor Management of Nulliparous Women: A Cost-Effectiveness Analysis.

The aim of the study is to evaluate differences in maternal and neonatal outcomes based on updated criteria for defining active labor at 6 cm of cervical dilation and to determine if these recommendations are cost-effective. A decision-analytic model was built using TreeAge Pro 2020 software. We included maternal outcomes of mode of delivery, endometritis, postpartum hemorrhage requiring transfusion, and death. Neonatal outcomes included rates of shoulder dystocia and permanent brachial plexus injury. Costs and quality-adjusted life years (QALYs) were included from the maternal and infant perspectives. We used a willingness-to-pay threshold of $100,000 per QALY and all model inputs were subjected to sensitivity analysis. In a theoretical cohort of 1.4 million women, a threshold of 6 cm to define active labor resulted in 373,668 fewer cesarean deliveries, 33,181 fewer cases of endometritis, 143 fewer postpartum hemorrhages requiring transfusions, and seven fewer maternal deaths when compared with a threshold of 4 cm. However, there were higher rates of adverse neonatal outcomes, including 484 more cases of shoulder dystocia and 17 more instances of permanent brachial plexus injury. Using 6 cm as the threshold resulted in lower costs and greater effectiveness, making it a dominant strategy. Multivariate sensitivity analysis demonstrated the model was robust over a wide range of assumptions. In this model, considering 6 cm of cervical dilation as the threshold for the active phase of labor compared with 4 cm was a cost-effective strategy to prevent primary cesarean deliveries, lower costs, and improve maternal outcomes, despite associated increased adverse neonatal outcomes. · Cervical dilation of 6 cm should be considered the threshold for the active phase of labor. This is a change from the prior definition of 4 cm.. · We built a theoretical model to compare outcomes and costs associated with the new active phase definition of 6 cm.. · Using a 6-cm threshold is a cost-effective strategy for decreasing primary cesarean deliveries..

Prevención de CLABSI por el uso de tapón desinfectante 3M Curos®: metanálisis y evaluación económica

Background. Healthcare-associated infections are a relevant health-public issue because of their economic and social impact; thus, they represent a challenge for the health institutions and the personnel in charge of fighting the infections. Particularly, central venous catheter-associated infections require a long-period administration of antibiotics, which increases the catheter blockade. That may derive in replacing the catheter, more extended hospital stays, and a higher sepsis risk. Objective. To analyze the efficacy of the disinfectant cap (3M Curos®), compared to the traditional disinfection method of the needle-free connectors, catheters or disinfectant ports. Material and Methods. A systematic review, meta-analysis, and cost-effectiveness study were performed to determine the effectiveness of the disinfectant cap in order to define the efficiency compared to the traditional disinfection method. Univariate, multivariate, and probabilistic sensitivity analyses were performed to reduce uncertainty. Results. The disinfectant cap had an infection ratio of 1.54 infections per 1,000 catheters / day vs. traditional desinfection methods, which had a ratio of 4.84 infections per 1,000 catheters / day. Those results led to find a cost difference of $21,819.39 USD for 3M Curos® and $67,165.26 USD for traditional methods. Conclusions. The disinfectant cap proves to be a more efficient alternative for pediatric health in Mexico.

Cost minimization analysis of two chemotherapy regimens in the treatment of colorectal cancer in a public reimbursement hospital in Brazil

Objective: To conduct a pharmacoeconomic evaluation between XELOX and mFOLFOX6 in the adjuvant and metastatic treatment of colorectal cancer from the perspective of a public reimbursement hospital. Methods: The cost minimization analysis was conducted for patients who started treatment in 2013 and 2014. The micro-costing technique was used to verify expenditures on drugs, materials, laboratory and imaging tests, ambulatory and daily hospitalization, human and administrative resources and determine the individual cost of each alternative, per patient. To evaluate the robustness of the economic analysis, multivariate sensitivity analysis was performed in six different scenarios. Results: There was an average cost for XELOX of U$ 4,637.14 in adjuvant and U$ 3,831.48 for palliative treatment, and a cost for mFOLFOX6 of U$ 5,474.89 in adjuvant and U$ 4,432.95 in palliative treatment. Sensitivity analysis maintained the dominance of XELOX. Material and drug costs accounted for about 85% of the total cost of XELOX; for mFOLFOX6 this cost was around 36%. On the other hand, the cost of hospitalization and placement of a catheter occured exclusively for mFOLFOX6, which also presented a higher cost with human resources. Conclusion: From the perspective of the hospital, XELOX proved to be the least costly alternative on the treatment of colorectal cancer.

An evaluation on the association of vancomycin trough concentration with mortality in critically ill patients: A multicenter retrospective study.

To determine the impact of initial vancomycin trough concentration (VTC) on mortality in adult patients in the intensive care unit (ICU) undergoing vancomycin therapy. During their first ICU stay, patients with initial VTC records after vancomycin treatment were recruited from the eICU Collaborative Research Database to this multicenter retrospective cohort study, and classified into four groups according to VTC: less than 10, 10–15, 15–20, and greater than 20 mg/L. Multivariable logistic regression and sensitivity analyses were performed to explore the association of VTC, as a continuous and categorical variable, with mortality. This study enrolled 7220 patients from 335 different ICUs at 208 hospitals. Multivariable logistic regression models indicated that VTC was positively correlated with ICU (odds ratio [OR], 1.028, 95% confidence interval [CI], 1.019–1.037) and hospital (OR 1.028, 95% CI, 1.020–1.036) mortalities. Moreover, compared with VTC less than 10 mg/L, VTCs of 10–15, 15–20, and greater than 20 mg/L were associated with a higher risk of ICU mortality (OR, 1.330, 95% CI, 1.070–1.653; OR, 1.596, 95% CI, 1.265–2.015; abd OR, 1.875, 95% CI, 1.491–2.357, respectively), and VTCs of 15–20 and greater than 20 mg/L were also correlated with increased hospital mortality (OR, 1.482, 95% CI, 1.225–1.793; and OR, 1.831, 95% CI, 1.517–2.210, respectively). Similar results persisted in patients with different Acute Physiology and Chronic Health Evaluation Ⅳ scores, creatinine clearance levels, ages, and body mass indexes. Our findings indicated a potential relationship of initial VTC with ICU and hospital mortalities in patients in the ICU. However, due to the retrospective nature of this study, future prospective studies or randomized controlled trials are needed to validate those results.

A model for estimating the carbon footprint of maritime transportation of Liquefied Natural Gas under uncertainty

The demand for Liquefied Natural Gas (LNG) in the global markets has changed significantly. As a result, industries have been forced to consider investing significantly in supply chains to achieve an efficient distribution of LNG for cost efficiency and carbon footprint reduction. To minimize the contribution of LNG maritime transportation to global climate change, there is a need to quantify the carbon footprints systematically. In this research, we developed a novel and practical model for estimating the carbon footprint for LNG maritime transport. Using the MATLAB program, an uncertainty-based carbon footprint accounting framework is created. The Monte Carlo simulation model is built to conduct a carbon footprint analysis while the main input parameters were changed within a reliable range. Later, a multivariate sensitivity analysis is performed using the Risk Solver software to estimate the most significant parameters on the net carbon footprints. The sensitivity analysis results showed that that steam process day and steaming fuel consumption are found to be the most sensitive parameters for the overall carbon footprint for both Laden and Ballast trips. Furthermore, it was found that the Q-Max vessel produces more carbon emissions when compared to the Q-Flex, although both are traveling the same distance and are using the same fuel type. The type of fuel is also significantly affecting the emission values due to the relevant carbon content in the fuel. Like the case of the two conventional vessels, the one that is running with the only LNG is found to have fewer emissions when compared to the one run with dual-mode.

Timing of active phase labor arrest diagnosis in nulliparous women: a cost-effectiveness analysis

Background Recommendations from the American College of Obstetricians and Gynecologists for the safe prevention of primary cesarean deliveries propose that cesarean delivery for active phase arrest in the first stage of labor should be performed only if women fail to progress despite four hours of adequate uterine activity and no cervical change. This is a change in recommendation from a two-hour threshold. Objective To determine the economic and clinical implications of waiting four hours compared to two hours for cervical progression before diagnosing active phase labor arrest. Study Design We designed a cost-effectiveness analysis using TreeAge Pro 2020 software with model inputs derived from the literature. We used a theoretical cohort of 1.4 million women, the approximate number of nulliparous U.S. women reaching four centimeters in spontaneous labor. We compared maternal and neonatal outcomes and costs associated with defining active phase arrest after four hours of no cervical progression versus two hours. As a baseline assumption, active labor was defined at four centimeters. It was assumed that women with active phase arrest were delivered via cesarean delivery. In addition to cost and maternal quality-adjusted life years (QALY), outcomes included mode of delivery, endometritis, postpartum hemorrhage requiring transfusion, and maternal deaths. Neonatal outcomes included rates of shoulder dystocia and permanent brachial plexus injury. The willingness-to-pay threshold was set at $100,000/QALY. Results In a theoretical cohort of 1.4 million women, waiting four hours instead of two hours led to 322,253 fewer cesarean deliveries, 6 fewer maternal deaths, 123 fewer postpartum hemorrhages requiring transfusions, and 28,615 fewer episodes of endometritis. There were 418 more instances of neonatal shoulder dystocia and 14 more cases of permanent brachial plexus injuries with a four-hour threshold. A four-hour threshold leads to 56% more women having a vaginal delivery in our theoretical cohort. Results from our model show that waiting four hours versus two hours to diagnose active phase labor arrest led to increased total QALYs with increased costs, with an incremental cost effectiveness ratio (ICER) below our willingness-to-pay threshold of $100,000 per QALY. Thus, it was cost effective to wait for at least four hours in the diagnosis of active phase arrest. Multivariable sensitivity analysis demonstrated the model was robust over a wide range of assumptions. Conclusions Increasing the time threshold from two to four hours for diagnosing active phase labor arrest beyond four centimeters is a cost-effective strategy, resulting in fewer primary cesarean deliveries and improved maternal outcomes, despite a small increase in adverse neonatal outcomes.

Effect of limb oversizing on the risk of type Ib endoleak in patients after endovascular aortic repair

ObjectiveWe assessed the association between the degree of limb oversizing and the risk of type Ib endoleak (TIBEL) in different types of iliac landing zones after endovascular aortic aneurysm repair. MethodsWe performed a retrospective cohort study of patients who had undergone endovascular aortic aneurysm repair with bifurcated and limb endografts in an academic center. The main exposure was the degree of limb oversizing. The primary outcome was the occurrence of TIBELs. The secondary outcomes included limb occlusion, reintervention, and overall survival. Subgroup analyses stratified by ectatic and normal iliac landing zones were performed. Multivariate Cox regression analysis and sensitivity analyses using marginal structure model were conducted to adjust for potential confounders. ResultsA total of 750 patients with 1500 iliac limb endografts were included in our study (817 limbs with oversizing of ≤10% and 683 with oversizing >10%). The median 1-year freedom from TIBEL was 98.9% (interquartile range [IQR], 98.0%-99.8%) for limbs with oversizing of ≤10% and 99.6% (IQR, 99.0%-100%) for limbs with oversizing >10%. The median 3-year freedom from TIBEL was 95.6% (IQR, 93.1%-98.1%) and 98.2% (IQR, 96.5%-99.9%) for oversizing ≤10% and >10%, respectively. We found that limb oversizing >10% was associated with a significantly decreased risk of TIBEL (adjusted hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.19-0.76) in the overall population. After stratification by ectatic iliac landing zone, we found that limb oversizing >10% was associated with a significantly decreased risk of TIBEL in the ectatic iliac landing zones (adjusted HR, 0.38; 95% CI, 0.16-0.88). However, no significant difference was found in the limb endografts landing in normal iliac arteries (adjusted HR, 0.44; 95% CI, 0.13-1.45). In the subgroup of normal iliac arteries, we observed a significantly increased risk of limb occlusion in the limbs with distal oversizing >15% compared with the limbs with distal oversizing of ≤15% (adjusted HR, 4.66; 95% CI, 1.68-12.91). ConclusionsAdequate limb oversizing >10% was associated with a significantly decreased risk of TIBEL in limbs with ectatic iliac landing zones. However, no additional benefit was observed for oversizing >10% in limb grafts landing in normal iliac arteries. Furthermore, excessive limb oversizing (>15%) in normal iliac landing zones can be associated with an increased risk of limb occlusion.

Severity of COVID-19 infection in ACEI/ARB users in specialty hospitals: A retrospective cohort study

BackgroundThe uncertainty about COVID-19 outcomes in angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) users continues with contradictory findings. This study aimed to determine the effect of ACEI/ARB use in patients with severe COVID-19. MethodsThis retrospective cohort study was done in two Saudi public specialty hospitals designated as COVID-19 referral facilities. We included 354 patients with a confirmed diagnosis of COVID-19 between April and June 2020, of which 146 were ACEI/ARB users and 208 were non-ACEI/ARB users. Controlling for confounders, we conducted multivariate logistic regression and sensitivity analyses using propensity score matching (PSM) and Inverse propensity score weighting (IPSW) for high-risk patient subsets. ResultsCompared to non-ACEI/ARB users, ACEI/ARB users had an eight-fold higher risk of developing critical or severe COVID-19 (OR = 8.25, 95%CI = 3.32–20.53); a nearly 7-fold higher risk of intensive care unit (ICU) admission (OR = 6.76, 95%CI = 2.88–15.89) and a nearly 5-fold higher risk of requiring noninvasive ventilation (OR = 4.77,95%CI = 2.15–10.55). Patients with diabetes, hypertension, and/or renal disease had a five-fold higher risk of severe COVID-19 disease (OR = 5.40,95%CI = 2.0−14.54]. These results were confirmed in the PSM and IPSW analyses. ConclusionIn general, but especially among patients with hypertension, diabetes, and/or renal disease, ACEI/ARB use is associated with a significantly higher risk of severe or critical COVID-19 disease, and ICU care.

Cost-effectiveness analysis of multiple imaging modalities in diagnosis and follow-up of intermediate complex cystic renal lesions.

To compare health-economic aspects of multiple imaging modalities used to monitor renal cysts, the present study evaluates costs and outcomes of patients with Bosniak IIF and III renal cysts detected and followed-up by either contrast-enhanced computed tomography (ceCT), contrast-enhanced magnetic resonance imaging (ceMRI), or contrast-enhanced ultrasonography (CEUS). A simulation using Markov models was implemented and performed with 10 cycles of 1year each. Proportionate cohorts were allocated to Markov models by a decision tree processing specific incidences of malignancy and levels of diagnostic performance. Costs of imaging and surgical treatment were investigated using internal data of a European university hospital. Multivariate probabilistic sensitivity analysis was performed to confirm results considering input value uncertainties. Patient outcomes were measured in quality-adjusted life years (QALY), and costs as averages per patient including costs of imaging and surgical treatment. Compared to the 'gold standard' of ceCT, ceMRI was more effective but also more expensive, with a resulting incremental cost-effectiveness ratio (ICER) >€70000 (Euro) per QALY gained. CEUS was dominant compared to ceCT in both Bosniak IIF and III renal cysts in terms of QALYs and costs. Probabilistic sensitivity analysis confirmed these results in the majority of iterations. Both ceMRI and CEUS can be used as alternatives to ceCT in the diagnosis and follow-up of intermediately complex cystic renal lesions without compromising effectiveness, while CEUS is clearly cost-effective. The economic results apply to a large university hospital and must be adapted for smaller hospitals.

Quantifying the potential value of antigen-detection rapid diagnostic tests for COVID-19: a modelling analysis

BackgroundTesting plays a critical role in treatment and prevention responses to the COVID-19 pandemic. Compared to nucleic acid tests (NATs), antigen-detection rapid diagnostic tests (Ag-RDTs) can be more accessible, but typically have lower sensitivity and specificity. By quantifying these trade-offs, we aimed to inform decisions about when an Ag-RDT would offer greater public health value than reliance on NAT.MethodsFollowing an expert consultation, we selected two use cases for analysis: rapid identification of people with COVID-19 amongst patients admitted with respiratory symptoms in a ‘hospital’ setting and early identification and isolation of people with mildly symptomatic COVID-19 in a ‘community’ setting. Using decision analysis, we evaluated the health system cost and health impact (deaths averted and infectious days isolated) of an Ag-RDT-led strategy, compared to a strategy based on NAT and clinical judgement. We adopted a broad range of values for ‘contextual’ parameters relevant to a range of settings, including the availability of NAT and the performance of clinical judgement. We performed a multivariate sensitivity analysis to all of these parameters.ResultsIn a hospital setting, an Ag-RDT-led strategy would avert more deaths than a NAT-based strategy, and at lower cost per death averted, when the sensitivity of clinical judgement is less than 90%, and when NAT results are available in time to inform clinical decision-making for less than 85% of patients. The use of an Ag-RDT is robustly supported in community settings, where it would avert more transmission at lower cost than relying on NAT alone, under a wide range of assumptions.ConclusionsDespite their imperfect sensitivity and specificity, Ag-RDTs have the potential to be simultaneously more impactful, and have a lower cost per death and infectious person-days averted, than current approaches to COVID-19 diagnostic testing.

A framework for incorporating 3D hyperelastic vascular wall models in 1D blood flow simulations

We present a novel framework for investigating the role of vascular structure on arterial haemodynamics in large vessels, with a special focus on the human common carotid artery (CCA). The analysis is carried out by adopting a three-dimensional (3D) derived, fibre-reinforced, hyperelastic structural model, which is coupled with an axisymmetric, reduced order model describing blood flow. The vessel transmural pressure and lumen area are related via a Holzapfel–Ogden type of law, and the residual stresses along the thickness and length of the vessel are also accounted for. After a structural characterization of the adopted hyperelastic model, we investigate the link underlying the vascular wall response and blood-flow dynamics by comparing the proposed framework results against a popular tube law. The comparison shows that the behaviour of the model can be captured by the simpler linear surrogate only if a representative value of compliance is applied. Sobol’s multi-variable sensitivity analysis is then carried out in order to identify the extent to which the structural parameters have an impact on the CCA haemodynamics. In this case, the local pulse wave velocity (PWV) is used as index for representing the arterial transmission capacity of blood pressure waveforms. The sensitivity analysis suggests that some geometrical factors, such as the stress-free inner radius and opening angle, play a major role on the system’s haemodynamics. Subsequently, we quantified the differences in haemodynamic variables obtained from different virtual CCAs, tube laws and flow conditions. Although each artery presents a distinct vascular response, the differences obtained across different flow regimes are not significant. As expected, the linear tube law is unable to accurately capture all the haemodynamic features characterizing the current model. The findings from the sensitivity analysis are further confirmed by investigating the axial stretching effect on the CCA fluid dynamics. This factor does not seem to alter the pressure and flow waveforms. On the contrary, it is shown that, for an axially stretched vessel, the vascular wall exhibits an attenuation in absolute distension and an increase in circumferential stress, corroborating the findings of previous studies. This analysis shows that the new model offers a good balance between computational complexity and physics captured, making it an ideal framework for studies aiming to investigate the profound link between vascular mechanobiology and blood flow.

Multivariate sensitivity analysis and derivative-based global sensitivity measures with dependent variables

In this paper, we propose a new methodology for better assessing the single, overall and interactions contributions of dependent and/or correlated variables over the whole model outputs. Our methodology relies on our ability to extract a model that characterizes the dependency structures of any random vector. Such dependency model is then coupled with the initial model to perform uncertainty quantification, variance-based sensitivity analysis and derivative-based global sensitivity measures. Our methodology allows for defining the main-effect and total sensitivity indices of input(s) with the former index less than the latter. We provide derivative-based upper bounds of total indices, which can be used for screening dependent variables. We also extend Morris’ methods to cope with dependent variables. For proposing such indices, we distinguish the case of the multivariate and/or functional outputs.

Застосування левосимендану порівняно з добутаміном за необхідності інотропної підтримки в пацієнтів з гострою декомпенсованою хронічною серцевою недостатністю тяжкого ступеня

The aim – to conduct clinical effectiveness, meta-analysis of 30 and 120-days mortality data, pharmacoeconomic evaluation of levosimendan treatment compared with dobutamine in patients with severe acute decompensated chronic heart failure (ADCHF) who require inotropic support.Materials and methods. The PubMed and Cochrane databases were searched for direct randomized clinical trials of levosimendan treatment compared with dobutamine in patients with ADCHF. The clinical efficacy of levosimendan and dobutamine was analyzed. Pharmacoeconomic analysis was carried out using the cost-effectiveness method with an assessment of the incremental cost-effectiveness ratio. A decision tree model of levosimendan or dobutamine treatments was constructed. The efficacy endpoints and impact on the budget were analyzed in terms of long-term effectiveness of levosimendan and dobutamine use. Discounted was conducted with rate of 3 %. Sensitivity analysis was carried out in terms of price changing of drugs, the cost of drugs in mg, the likelihood of re-hospitalization of the patient in a 3-year horizon and survival in the long term.Results and discussion. Analysis of clinical data and meta-analysis of randomized clinical trials found that mortality rates with levosimendan and dobutamine in the 30-day period were 9.6 % and 13.8 %, RR 0.71 (95 % CI 0.53–0.95) and in the 120-day period – 13.5 % and 25.2 %, RR 0.54 (95 % CI 0.32–0.92), respectively. The total cost of the course of treatment, taking into account the price of the drug, medical devices, staff services, diagnostic procedures and treatment of adverse reactions when using levosimendan, was 34 003.02 UAH per patient and 18 787.28 UAH when treated with dobutamine. The weighted average hospital stay was 6.4 days in case of levosimendan treatment and 7.5 days of dobutamine treatment. Extrapolation of the data from clinical trials to the 3-year survival rate of patients allowed us to determine an additional indicator of efficacy – the number of life years saved with levosimendan – 2.64 and 2.37 with dobutamine treatment. A cost-effectiveness analysis found that levosimendan is more efficient but more expensive technology compare to dobutamine. The incremental cost-effectiveness ratio for the additional life year saved of a patient with severe CHF is 43,473.55 UAH, which is 6 times less than the likely threshold of willingness to pay in Ukraine.Conclusions. The multivariate sensitivity analysis detected the model sustainability to the most crucial parameters of the model – drug price; the cost of drugs associated with their actual use in mg, the possibility of re-hospitalization of the patient in a 3-year horizon, and long-term survival, which is associated with the time horizon of the model. The total cost of a cohort of patients with ADCHF in Ukraine when using scenario 1 (100 % distribution of costs for dobutamine treatment) over 5 years is 268 188 351.94 UAH, when using scenario 2 (100 % distribution for treatment with levosimendan) total budget costs will be in amount of 485 393 073.09 UAH, if scenario 3 is applied (gradual 5 % transition in the treatment of patients with ADCHF with dobutamine for treatment with levosimendan within 5 years), the total budget costs will amount to 289 916 431.92 UAH.

C-reactive Protein and Risk of OSA in Four US Cohorts

Individuals with OSA have elevated levels of inflammatory markers, but no prospective study has examined the role of inflammation in the development of OSA. Is C-reactive protein (CRP) prospectively associated with risk of developing OSA? We followed 1,882 women from the Nurses' Health Study (NHS) (2002-2012), 3,854 women from Nurses' Health Study II (NHSII) (1995-2013), 3,075 men from the Health Professionals Follow-up Study (HPFS) (1996-2012), and 1,919 women and men from the Multi-Ethnic Study of Atherosclerosis (MESA) (2000-2012) who did not have diagnosed OSA at baseline and for whom CRP levels were available. In NHS/NHSII/HPFS, physician-diagnosed OSA was self-reported. In MESA, at-home polysomnography was performed and OSA was identified as an apnea-hypopnea index≥ 30. Logistic regression was used to estimate the OR for OSA risk according to baseline CRP level, adjusted for multiple inflammation-related factors. After multivariable adjustment not including BMI, the pooled OR for OSA risk per doubling of baseline CRP level was 1.24 (95%CI, 1.18-1.30). Additional adjustment for BMI substantially attenuated the association (pooled OR, 1.07; 95%CI, 1.01-1.12). The fully adjusted association was consistently stronger in individuals< 55 vs≥ 55 years of age (P interaction= .01), in individuals with BMI< 25 vs≥ 25kg/m2 (P interaction= .02), and in pre- vspostmenopausal women (P interaction= .002). CRP was more strongly associated with risk of OSA associated with excessive daytime sleepiness, high airway collapsibility, and low arousal threshold (P heterogeneity< .05). Higher CRP was prospectively associated with increased OSA risk, particularly among younger individuals, underweight/normal-weight individuals, or premenopausal women. The differential associations by OSA phenotype/endotype suggest possible mechanisms through which inflammation operates to modulate OSA risk. Given our reliance on a single CRP level measured a decade before OSA assessment, future studies with repeated CRP measurements are warranted to confirm these prospective associations.

Evidence-based benchmarks for use of cancer surgery in high-income countries: a population-based analysis.

Estimating a population-level benchmark rate for use of surgery in the management of cancer helps to identify treatment gaps, estimate the survival impact of such gaps, and benchmark the workforce and other resources, including budgets, required to meet service needs. A population-based benchmark for use of surgery in high-income settings to inform policy makers and service provision has not been developed but was recommended by the Lancet Oncology Commission on Global Cancer Surgery. We aimed to develop and validate a cancer surgery benchmarking model. We examined the latest clinical guidelines from high-income countries (Australia, the UK, the EU, the USA, and Canada) and mapped surgical treatment pathways for 30 malignant cancer sites (19 individual sites and 11 grouped as other cancers) that were notifiable in Australia in 2014, broadly reflecting contemporary high-income models of care. The optimal use of surgery was considered as an indication for surgery where surgery is the treatment of choice for a given clinical scenario. Population-based epidemiological data, such as cancer stage, tumour characteristics, and fitness for surgery, were derived from Australia and other similar high-income settings for 2017. The probabilities across the clinical pathways of each cancer were multiplied and added together to estimate the population-level benchmark rates of cancer surgery, and further validated with the comparisons of observed rates of cancer surgery in the South Western Sydney Local Health District in 2006-12. Univariable and multivariable sensitivity analyses were done to explore uncertainty around model inputs, with mean (95% CI) benchmark surgery rates estimated on the basis of 10 000 Monte Carlo simulations. Surgical treatment was indicated in 58% (95% CI 57-59) of newly diagnosed patients with cancer in Australia in 2014 at least once during the course of their treatment, but varied by site from 23% (17-27) for prostate cancer to 99% (96-99) for testicular cancer. Observed cancer surgery rates in South Western Sydney were comparable to the benchmarks for most cancers, but were higher for some cancers, such as prostate (absolute increase of 29%) and lower for others, such as lung (-14%). The model provides a new template for high-income and emerging economies to rationally plan and assess their cancer surgery provision. There are differences in modelled versus observed surgery rates for some cancers, requiring more in-depth analysis of the observed differences. University of New South Wales Scientia Scholarship, UK Research and Innovation-Global Challenges Research Fund.

Association between cumulative exposure to different lipid parameters and risk of newly developed carotid plaque

Background and purposeBoth the magnitude and cumulative exposure of atherogenic lipoproteins have an impact on the atherosclerosis risk, and the exploration focus has shifted from one single lipoprotein assessment to...

Association between the weekday on which coronary artery bypass graft surgery is performed and the 30-day mortality: A nationwide cohort study in South Korea.

Postoperative mortality associated with elective coronary artery bypass graft (CABG) surgery may reportedly increase as the weekday of surgery approaches the weekend. We aimed to investigate the potential effect of the weekday of CABG surgery on the 30-day mortality. This population-based cohort study analyzed data obtained from the South Korea national health insurance service database. The cohort included all adult patients diagnosed with ischemic heart disease (International Classification of Diseases-10 codes I20*-I25*) who underwent isolated and elective CABG surgery from January 2012 to December 2017. Of the 13,556 patients included in the analysis, 595 (4.4%) died within 30 days after CABG surgery. In a multivariable Cox model, the 30-day mortality of patients who underwent CABG surgery later in the week (Wednesday-Friday) was not significantly associated with the weekday of surgery as similar to those who underwent surgery early in the week (Monday-Tuesday)(hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 0.97-1.34; p = .109). Multivariable sensitivity analysis revealed that CABG surgery on Friday was associated with a 1.40-fold higher hazard of 30-day mortality (HR: 1.40; 95% CI: 1.09-1.80; p = .008) than CABG surgery on Monday. This South Korean population-based cohort study revealed that relative to surgery early in the week (Monday-Tuesday), CABG surgery later in the week (Wednesday-Friday) was not associated with higher 30-day mortality. However, using surgery on Monday as a reference, CABG surgery on Friday was associated with higher 30-day mortality. Future studies must confirm these findings.