Efficacy of adjunctive inhaled colistin and tobramycin for ventilator-associated pneumonia: systematic review and meta-analysis.

INTRODUCTION: Ventilator-associated pneumonia (VAP) presents a significant challenge in intensive care units (ICUs). Nebulized antibiotics, particularly colistin and tobramycin, are commonly prescribed for VAP patients. However, the appropriateness of using inhaled antibiotics for VAP remains a subject of debate among experts. This study aims to provide updated insights on the efficacy of adjunctive inhaled colistin and tobramycin through a comprehensive systematic review and meta-analysis. METHODS: A thorough search was conducted in MEDLINE, EMBASE, LILACS, COCHRANE Central, and clinical trials databases ( www. CLINICALTRIALS: gov ) from inception to June 2023. Randomized controlled trials (RCTs) meeting specific inclusion criteria were selected for analysis. These criteria included mechanically ventilated patients diagnosed with VAP, intervention with inhaled Colistin and Tobramycin compared to intravenous antibiotics, and reported outcomes such as clinical cure, microbiological eradication, mortality, or adverse events. RESULTS: The initial search yielded 106 records, from which only seven RCTs fulfilled the predefined inclusion criteria. The meta-analysis revealed a higher likelihood of achieving both clinical and microbiological cure in the groups receiving tobramycin or colistin compared to the control group. The relative risk (RR) for clinical cure was 1.23 (95% CI: 1.04, 1.45), and for microbiological cure, it was 1.64 (95% CI: 1.31, 2.06). However, there were no significant differences in mortality or the probability of adverse events between the groups. CONCLUSION: Adjunctive inhaled tobramycin or colistin may have a positive impact on the clinical and microbiological cure rates of VAP. However, the overall quality of evidence is low, indicating a high level of uncertainty. These findings underscore the need for further rigorous and well-designed studies to enhance the quality of evidence and provide more robust guidance for clinical decision-making in the management of VAP.

Cost-utility analysis of prenatal supplementation with long-chain n-3 fatty acids to reduce the incidence of wheezing and asthma in neonates.

INTRODUCTION: Recent evidence indicates that Maternal Supplementation with Long-Chain n-3 Fatty Acids During Pregnancy Substantially Mitigates Offspring's Asthma. Adding information regarding its cost-utility will undoubtedly allow its adoption, or not, in clinical practice guidelines. This research aimed to determine the cost-utility of LCPUFA supplementation in the third trimester of pregnancy to reduce the risk of wheezing and asthma in infants in Colombia. METHODS: A Markov model was formulated to estimate the cost and quality-adjusted life-years (QALYs) attributed to individuals with severe asthma in Colombia, with a time horizon of five years and a cycle length of two weeks. Probabilistic sensitivity analysis and a value of information (VOI) analysis were conducted to evaluate the uncertainties in the case base. Cost-utility was assessed at a willingness-to-pay (WTP) value of US$5180. All costs were adjusted to 2021 with a 5% annual discounting rate for cost and QALYs. RESULTS: The mean incremental cost of LCPUFA supplementation versus no supplementation was US-43.65. The mean incremental benefit of LCPUFA supplementation versus no supplementation was 0.074 QALY. The incremental cost-utility ratio was estimated at US$590.68 per QALY. The outcomes derived from our primary analysis remained robust when subjected to variations in all underlying assumptions and parameter values. CONCLUSION: Supplementation strategy supplementation with long-chain n-3 fatty acids during pregnancy is cost-effective in reducing the risk of developing asthma during childhood in Colombia.

Cost effectiveness of omalizumab for severe asthma in Colombia.

BACKGROUND: Omalizumab is a humanized monoclonal antibody that specifically binds to free human immunoglobulin E. The introduction of this drug raises concerns about economic impact in scenarios with constrained. This study aimed to estimate the cost utility of omalizumab in adults with severe asthma uncontrolled in Colombia. METHODS: We used a Markov state-transition model to estimate the cost and QALYs associated with omalizumab compared to standard of care; from a third payer perspective over a lifetime horizon. This model used local costs while utilities were derived from international literature. Cost and transition probabilities were obtained from a mixture of Colombian-specific and internationally published data. RESULTS: The mean incremental cost of omalizumab versus standard of care is US$3 481. The mean incremental benefit of omalizumab versus standard of care 0.094 QALY. The incremental expected cost per unit of benefit is estimated at US$36846 per QALY. There is only a probability of 0.032 that Omalizumab is more cost-effective than standard of care at a threshold of US$5180 per QALY. CONCLUSION: Omalizumab is not cost-effective in adults with severe asthma uncontrolled in Colombia. If the cost of Omalizumab is reduced by 83%, this treatment would be cost-effective in our country. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Economic evidence supports the cost savings of sputum eosinophil counts to guide the treatment of pediatrics patients with persistent asthma: implications for clinical practice guidelines in middle-income countries.

BACKGROUND: Tailoring asthma interventions based on biomarkers could substantially impact the high cost associated with asthma morbidity. For policymakers, the main concern is the economic impact of adopting this technology, especially in developing countries. This study evaluates the budget impact of asthma management using sputum eosinophil counts in Colombia patients between 4 and 18 years of age. METHODS: A budget impact analysis was performed to evaluate the potential financial impact of sputum eosinophil counts (EO). The study considered a 5-year time horizon and the Colombian National Health System perspective. The incremental budget impact was calculated by subtracting the cost of the new treatment, in which EO is reimbursed, from the cost of the conventional therapy without EO (management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma-related). Univariate one-way sensitivity analyses were performed. RESULTS: In the base-case analysis, the 5-year costs associated with EO and no-EO were estimated to be US$ 532.865.915 and US$ 540.765.560, respectively, indicating savings for Colombian National Health equal to US$ 7.899.645, if EO is adopted for the routine management of patients with persistent asthma. This result was robust in univariate sensitivity one-way analysis. CONCLUSION: EO was cost-saving in guiding the treatment of patients between 4 and 18 years of age with persistent asthma. Decision-makers in our country can use this evidence to improve clinical practice guidelines, and it should be replicated to validate their results in other middle-income countries.

Phosphodiesterase 5 Inhibitor for Pediatric Pulmonary Arterial Hypertension: A Cost-Utility Analysis.

OBJECTIVES: Despite the growing evidence of efficacy, scarce information exists regarding the cost of tadalafil to improve the functional classes of pediatric patients with pulmonary arterial hypertension. This study aims to determine the cost-utility of tadalafil compared sildenafil to treat pediatric patients with pulmonary arterial hypertension in Colombia. METHODS: A Markov model was developed to compare expected costs, outcomes, and quality-adjusted life-years of sildenafil and tadalafil in pediatric patients with pulmonary arterial hypertension. The model was analyzed probabilistically, and a value of information analysis was conducted to inform the value of conducting further research to reduce current uncertainties in the evidence base. Cost-effectiveness was evaluated at a willingness-to-pay value of US $5180. RESULTS: The mean incremental cost of tadalafil versus sildenafil is US $15 270. The 95% credible interval for the incremental cost ranges from US $28 033.65 to US $5940.86. The mean incremental benefit of tadalafil versus sildenafil is 1.00 quality-adjusted life-years (QALY). The 95% credible interval for the incremental benefit ranges from 1.88 to 0.31 QALY. The expected incremental cost per QALY is estimated at US $15 286. There is a probability less than 1% that tadalafil is more cost-effective than sildenafil at a threshold of US $5180 per QALY. Form the value of information analysis, the theoretical upper bound on the value of further research was US $9.298 for Colombia. CONCLUSION: Our economic evaluation shows that tadalafil is not cost-effective regarding sildenafil to treat pediatric patients with pulmonary arterial hypertension in Colombia. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines.

Vitamin A supplementation for the prevention of chronic lung disease in premature infants: A cost-utility analysis.

INTRODUCTION: Despite the growing evidence on efficacy, little is known regarding the efficiency of Vitamin A supplementation to decrease the probability of chronic lung disease (CLD) in preterm infants. This study aims to determine the cost-utility of Vitamin A to prevent CLD in preterm infants in Colombia. METHODS: A decision tree model was used to estimate the cost and quality-adjusted life-years (QALYs) of Vitamin A supplementation in preterm infants. Multiple sensitivity analyses were conducted to evaluate the robustness of the model. Cost-effectiveness was evaluated at a willingness-to-pay value of US$5180. RESULTS: Vitamin A was associated with lower costs and higher QALYs. The expected annual cost per patient with Vitamin A was US$1579 (95% CI US$1555-US$1585) and without Vitamin A was US$1913 (95% CI US$1891-US$1934). The QALYs per person estimated with Vitamin A was 0.66 (95% CI 0.66-0.67) and without Vitamin A was 0.61 (95% CI 0.60-0.61). This position of absolute dominance (Vitamin A has lower costs and higher QALYs than without Vitamin A) is unnecessary to estimate the incremental cost-effectiveness ratio. CONCLUSION: Our economic evaluation shows that Vitamin A is cost-effective to reduce the incidence rate of CLD in premature infants in Colombia. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines.

Fractional exhaled nitric oxide and eosinophil count in induced sputum to guide the management of children with asthma: a cost-utility analysis.

INTRODUCTION: Previous evidence has shown that fractional exhaled nitric oxide (FeNO) and eosinophil count in induced sputum (EO) are cost-effective relative to standard of care in guiding the management of children with persistent asthma. There is some doubt as if there are differences between these two biomarkers in terms of costs and benefits. Clarifying this doubt would allow prioritization of the design of clinical practice guidelines. The study aimed to compare in terms of costs and benefits these biomarkers in patients with asthma between 4 and 18 years of age. METHODS: A Markov model was used to estimate the cost-utility of asthma management using FeNO and EO in patients between 4 and 18 years of age. Transition probabilities, cost and utilities were estimated from previously published local studies, while relative risks were obtained from the systematic review of published randomized clinical trials. The analysis was carried out from a societal perspective. RESULTS: The expected annual cost per patient with EO was US $1376 (CI 95% US $1376-US $1377) and for FeNO was US $1934 (CI 95% US $1333-US $1334), with a difference of US $42.3 between these strategies. The Quality-adjusted life years (QALYs) per person estimated with EO was 0.95 (CI 95% 0.951-0.952) and for FeNO was 0.94 (CI 95% 0.930-0.940), with a difference of 0.01 between these strategies. The NMB with EO was US $4902 (CI 95% 4900-4904) and for FeNO was US $4841 (CI 95% 4839-4843). The incremental cost-effectiveness ratio of EO was $3566 per QALY gained regarding FeNO. CONCLUSION: Our study demonstrates that induced sputum-guided management is a strategy cost-effective over FeNO and standard asthma management in Colombia. This evidence should encourage the adoption of any of these techniques to objectively guide the management of children with asthma in routine clinical practice in low-resource settings.

Podotimod in pediatric recurrent respiratory tract infections: a cost-utility analysis.

INTRODUCTION: Despite the growing evidence on efficacy, few economic evaluations have evaluated the cost-utility of Pidotimod (PDT) supplementation to decrease the probability of recurrent respiratory tract infections in children. This study aimed to determine the cost-utility of PDT to reduce the incidence rate of recurrent respiratory tract infections in children. METHODS: A decision tree model was used to estimate the cost and quality-adjusted life-years (QALYs) of PDT in a patient aged 1-6 with a history of recurrent respiratory tract infections. Multiple sensitivity analyses were conducted to evaluate the robustness of the model. Cost-effectiveness was evaluated at a willingness-to-pay (WTP) value of US$5180. RESULTS: The base-case analysis showed that compared with placebo, PDT was associated with lower costs and higher QALYs. The expected annual cost per patient with PDT was US$797 (CI 95% US$794- US$801) and with placebo was US$1175 (CI 95% US$1169- US$1181). The QALYs per person estimated with PDT was 0.95 (CI 95% 0.94-0.95) and with placebo was 0.94 (CI 95% 0.94-0.94). The NMB with PDT was US$ 4121 (CI 95% 4114-4127) and with placebo was US$ 3710 (CI 95% 3700-3720). This position of absolute dominance (PDT has lower costs and higher QALYs than placebo) of PDT it is unnecessary to estimate the incremental cost-effectiveness ratio. CONCLUSION: In conclusion our study shows that PDT is a cost-effective strategy to reduce the incidence rate of recurrent respiratory tract infections in children. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines.

Cost-effectiveness of procalcitonin for detection of serious bacterial infections in children presenting with fever without source.

INTRODUCTION: Procalcitonin (PCT) offers better specificity than C-reactive protein (CRP) to detect SBI. However, their cost limited their use and routine application. The objective of this work is to determine the cost-effectiveness of PCT against CPR or Rochester scale in infants between 1 and 3 months from the perspective of the third payer in Colombia. METHODS: A Monte Carlo simulation was performed with a hypothetical cohort of 10,000 patients with fever without focus (FWS) between 1 to 3 months, to estimate the number of cases correctly diagnosed for each test and the associated costs with each test. RESULTS: The test with the highest number of correctly diagnosed cases was PCT 79%, followed by C-reactive protein 75%, and the Rochester scale 68%. The test with the lowest cost per patient was PCT $645 (95% CI US$646-US$645) followed by C-reactive protein U$ 653 (95% CI US$655-$645) and Rochester scale US$804 (95% CI US$807-US$804). This position of dominance of PCT eliminated the need to calculate an incremental cost effectiveness ratio. CONCLUSIONS: PCT is the most cost-effective strategy for the detection of IBS in infants with FWS. These results should be interpreted within the clinical context of the patient and not as a single method for therapeutic decision-making.

Cost Utility of Intermittent Inhaled Corticosteroids in Preschoolers with Viral-Triggered Wheeze.

Background: Evidence has demonstrated that adding intermittent inhaled corticosteroids (ICS) to treatment with short-acting b2-agonists (SABAs) in children 5 years of age and younger who experience intermittent viral-induced wheezing (VIW) reduces the risk of severe exacerbations. However, there is concern about whether the extra benefit offered by this drug outweighs the additional cost. This study aimed to evaluate the cost-effectiveness of intermittent ICS in children 5 years of age and younger who experience intermittent VIW. Methods: We constructed a probabilistic Markov model to estimate the cost and quality-adjusted life-years (QALYs) of intermittent ICS compared with SABA reliever therapy in preschoolers with viral-triggered wheezing in Colombia. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $5,180. Results: In an analysis of the Markov cohort model, we estimated a gain of 0.2 QALYs per patient per year on intermittent ICS compared with SABA and a reduction of cost per patient of USD $37 per year. This position of dominance negated the need to calculate an incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analyses, our base case results were robust to variations of all assumptions and parameters. Conclusion: Adding intermittent ICS to treatment with SABAs in children 5 years of age and younger who experience intermittent VIW was found to be cost effective. These results could improve the use of health care resources, especially in settings with limited economic resources.

Cost­effectiveness of tiotropium versus omalizumab for uncontrolled allergic asthma.

OBJECTIVE: In patients with uncontrolled asthma, despite management with high doses of inhaled corticosteroids, the additional use of omalizumab and tiotropium is recommended. Omalizumab is an expensive medication and doubts arise as to whether the benefit of this drug outweighs the additional expense of the drug. The purpose of this study was to assess the cost-effectiveness of tiotropium versus omalizumab as add-on therapies to ICS + LABA for patients with uncontrolled allergic asthma. METHODS: A probabilistic Markov model was created to estimate the cost and quality-adjusted life years (QALYs) of patients with uncontrolled allergic asthma in Colombia. Total costs and QALYs of three interventions including standard therapy (ICS + LABA), add-on therapy with tiotropium, and add-on therapy with omalizumab, were calculated over a 10-year time horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000. RESULTS: The model showed that tiotropium was associated with lower cost than standard therapy and omalizumab (US$5590 vs. US$5693 vs. U$18,154 average annual cost per patient), and higher QALYs (11.8 vs. 11.3 vs. 11.9) average per patient), showing dominance respect to standard therapy. The probability that tiotropium provides a more cost-effective use of resources compared with standard therapy exceeds 99% for willingness-to-pay threshold. CONCLUSION: Add-on therapy with tiotropium was a cost-effective alternative to omalizumab and standard therapy for uncontrolled allergic asthma. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Cost-utility of as-needed combination low-dose budesonide-formoterol in adolescents mild asthma.

BACKGROUND: Previously evidence has demonstrated that as-needed combination low-dose budesonide-formoterol reduced the risk of severe exacerbations compared with short-acting ß2-agonist (SABA) reliever therapy in an adolescent with mild asthma. Concerns as if the extra benefit offered by this drug outweighs the additional cost. This study aimed to evaluate the cost-effectiveness of as-needed combination low-dose budesonide-formoterol compared with short-acting ß2-agonist (SABA) reliever therapy in adolescents with mild asthma in Colombia. METHODS: A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with mild asthma in Colombia. Total costs and QALYs of low-dose budesonide-formoterol compared with short-acting ß2-agonist (SABA) were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000. RESULTS: The model suggests a potential gain of 0.03 QALYs and per patient per year on low-dose budesonide-formoterol. The cost difference per person was US$-4 per patient per year in favor of budesonide- formoterol. The position of dominance negates the need to calculate an incremental cost-effectiveness ratio. In the one-way and probabilistic sensitivity analyses, our base-case results were robust to variations of all assumptions and parameters. CONCLUSION: In conclusion, low-dose budesonide-formoterol as a reliever was found to be cost-effective when added to usual care in adolescents with mild asthma. This evidence should promote economic evaluations in developed and developing countries for the inclusion of new drugs in health insurance plans.

Importance of respiratory syncytial virus as a predictor of hospital length of stay in bronchiolitis.

Introduction: Bronchiolitis is the leading cause of hospitalization in children. Estimate potentially preventable variables that impact the length of hospital stay are a priority to reduce the costs associated with this disease. This study aims to identify clinical variables associated with length of hospital stay of bronchiolitis in children in a tropical middle-income country Methods: We conducted a retrospective cohort study in 417 infants with bronchiolitis in tertiary centers in Colombia. All medical records of all patients admitted to the emergency department were reviewed. To identify factors independently associated we use negative binomial regression model, to estimate incidence rate ratios (IRR) and adjust for potential confounding variables Results: The median of the length of hospital stay was 3.68 days, with a range of 0.74 days to 29 days, 138 (33.17%) of patients have a hospital stay of 5 or more days. After modeling and controlling for potential confounders age <6 months, comorbidities (CHD or neurological), BPD,  chest indrawing, RSV isolation, and C-reactive protein were independent predictors of LOS Conclusions: Our results show that in infants with bronchiolitis, RSV isolation, age <6 months, comorbidities (CHD or neurological), BPD,  chest indrawing, and C-reactive protein were independent predictors of LOS. As a potentially modifiable risk factor, efforts to reduce the probability of RSV infection can reduce the high medical cost associates with prolonged LOS in bronchiolitis.