Ultrasound-Assisted Extraction, Followed by Gas Chromatography-Mass Spectrometry for the Simultaneous Quantification of Ethinyl Estradiol and Drospirenone in Contraceptive Formulations.

Contraceptive tablets typically contain a combination of two synthetic versions of an estrogen and a progestogen, which work together to inhibit the ovulation process. An accurate and precise quantification of these components is essential for contraceptive producers. In this study, we have developed the first gas chromatography-mass spectrometry (GC-MS) method for the simultaneous quantification of 17α-ethinyl estradiol (EE) and drospirenone (DP) in contraceptive formulations. Under the final working conditions, analytes were extracted from the solid by ultrasound-assisted extraction (15 min) in methanol. The resulting suspension was diluted in ethyl acetate, subjected to centrifugation and, finally, the supernatant was directly injected into the GC-MS system. No derivatization reagents were utilized. To correct for instrumental variations, calibration was performed using the internal standard method, with cholesterol as the internal standard. A good linearity was achieved throughout the calibration range for both EE (3-12 µg mL-1) and DP (300-1200 µg mL-1), with R2 values exceeding 0.99. Trueness, assessed in terms of percentages of recovery, was also found to be satisfactory for both analytes, with recovery rates of 106 ± 8% for EE and 93 ± 9% for DP. Furthermore, intra-day and inter-day precision studies yielded relative standard deviation values below 6% for both analytes. In terms of sensitivity, the instrumental limits of detection were 0.25 µg mL-1 for EE and 6.6 µg mL-1 for DP, and the instrumental limits of quantification 0.82 µg mL-1 for EE and 22 µg mL-1 for DP. The method was successfully applied to the analysis of contraceptive tablets from three different pharmaceutical companies. No differences were observed between the measured and the declared amount of active principle per tablet, demonstrating the applicability of the procedure. In addition, a stability study conducted on both the standards and sample extracts demonstrated that they can be stored at room temperature for a minimum period of seven days.

Wastewater-Based Epidemiology as a New Tool for Estimating Population Exposure to Phthalate Plasticizers.

This study proposes the monitoring of phthalate metabolites in wastewater as a nonintrusive and economic alternative to urine analysis for estimating human exposure to phthalates. To this end, a solid-phase extraction-liquid chromatography-tandem mass spectrometry method was developed, allowing for the determination of eight phthalate metabolites in wastewater (limits of quantification between 0.5 and 32 ng L-1). The analysis of samples from the NW region of Spain showed that these substances occur in raw wastewater up to ca. 1.6 µg L-1 and in treated wastewater up to ca. 1 µg L-1. Concentrations in raw wastewater were converted into levels of exposure to six phthalate diesters. For two of them, these levels were always below the daily exposure thresholds recommended by the U.S. Environmental Protection Agency and the European Food Safety Authority. For the other four, however, estimates of exposure surpassed such a threshold (especially the toddler threshold) in some cases, highlighting the significance of the exposure to phthalates in children. Finally, concentrations in wastewater were also used to estimate metabolite concentrations in urine, providing a reasonable concordance between our results and the data obtained in two previous biomonitoring studies.

Health economic evaluation of Human Papillomavirus vaccines in women from Venezuela by a lifetime Markov cohort model.

BACKGROUND: Cervical cancer (CC) and genital warts (GW) are a significant public health issue in Venezuela. Our objective was to assess the cost-effectiveness of the two available vaccines, bivalent and quadrivalent, against Human Papillomavirus (HPV) in Venezuelan girls in order to inform decision-makers. METHODS: A previously published Markov cohort model, informed by the best available evidence, was adapted to the Venezuelan context to evaluate the effects of vaccination on health and healthcare costs from the perspective of the healthcare payer in an 11-year-old girls cohort of 264,489. Costs and quality-adjusted life years (QALYs) were discounted at 5%. Eight scenarios were analyzed to depict the cost-effectiveness under alternative vaccine prices, exchange rates and dosing schemes. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Compared to screening only, the bivalent and quadrivalent vaccines were cost-saving in all scenarios, avoiding 2,310 and 2,143 deaths, 4,781 and 4,431 CCs up to 18,459 GW for the quadrivalent vaccine and gaining 4,486 and 4,395 discounted QALYs respectively. For both vaccines, the main determinants of variations in the incremental costs-effectiveness ratio after running deterministic and probabilistic sensitivity analyses were transition probabilities, vaccine and cancer-treatment costs and HPV 16 and 18 distribution in CC cases. When comparing vaccines, none of them was consistently more cost-effective than the other. In sensitivity analyses, for these comparisons, the main determinants were GW incidence, the level of cross-protection and, for some scenarios, vaccines costs. CONCLUSIONS: Immunization with the bivalent or quadrivalent HPV vaccines showed to be cost-saving or cost-effective in Venezuela, falling below the threshold of one Gross Domestic Product (GDP) per capita (104,404 VEF) per QALY gained. Deterministic and probabilistic sensitivity analyses confirmed the robustness of these results.

Wastewater-Based Epidemiology To Monitor Synthetic Cathinones Use in Different European Countries.

Synthetic cathinones are among the most consumed new psychoactive substances (NPS), but their increasing number and interchangeable market make it difficult to estimate the real size of their consumption. Wastewater-based epidemiology (WBE) through the analysis of metabolic residues of these substances in urban wastewater can provide this information. This study applied WBE for the first time to investigate the presence of 17 synthetic cathinones in four European countries. A method based on solid-phase extraction and liquid chromatography coupled to tandem mass spectrometry was developed, validated, and used to quantify the target analytes. Seven substances were found, with mephedrone and methcathinone being the most frequently detected and none of the analytes being found in Norway. Population-normalized loads were used to evaluate the pattern of use, which indicated a higher consumption in the U.K., followed by Spain and Italy, in line with the European prevalence data from population surveys. In the U.K., where an entire week was investigated, an increase of the loads was found during the weekend, indicating a preferential use in recreational contexts. This study demonstrated that WBE can be a useful additional tool to monitor the use of NPS in a population.

Screening new psychoactive substances in urban wastewater using high resolution mass spectrometry.

Analysis of drug residues in urban wastewater could complement epidemiological studies in detecting the use of new psychoactive substances (NPS), a continuously changing group of drugs hard to monitor by classical methods. We initially selected 52 NPS potentially used in Italy based on seizure data and consumption alerts provided by the Antidrug Police Department and the National Early Warning System. Using a linear ion trap-Orbitrap high resolution mass spectrometer, we designed a suspect screening and a target method approach and compared them for the analysis of 24 h wastewater samples collected at the treatment plant influents of four Italian cities. This highlighted the main limitations of these two approaches, so we could propose requirements for future research. A library of MS/MS spectra of 16 synthetic cathinones and 19 synthetic cannabinoids, for which analytical standards were acquired, was built at different collision energies and is available on request. The stability of synthetic cannabinoids was studied in analytical standards and wastewater, identifying the best analytical conditions for future studies. To the best of our knowledge, these are the first stability data on NPS. Few suspects were identified in Italian wastewater samples, in accordance with recent epidemiological data reporting a very low prevalence of use of NPS in Italy. This study outlines an analytical approach for NPS identification and measurement in urban wastewater and for estimating their use in the population.

Sentinel node in breast cancer as an indicator of quality in medical care: Evaluation of statistics in Colombia.

BACKGROUND: Sentinel lymph node biopsy in breast cancer is considered the standard of staging in cases of clinically negative lymph nodes. Its omission in favor of axillary dissection generates significant morbidity. OBJECTIVE: To determine the total number of sentinel node biopsy procedures in breast cancer in Colombia from 2017 through 2020, model and analyze them as if they were performed only in stage I breast cancer patients, and integrate their results into the concepts of quality of medical care. METHODS: Search in a database of the Ministry of Health and Social Protection of Colombia with sentinel lymph node biopsy codes, and filters of breast cancer and year. Their results are contrasted with the number of cases in stage I of breast cancer. RESULTS: Breast cancer TNM staging was reported in 22154 cases, 3648 stage I. In the same time frame, the number of sentinel lymph node biopsies for breast cancer in Colombia was 1045, 28.64% of the total cases reported in stage I. CONCLUSIONS: Colombia is far from complying with the standard indicator of sentinel lymph node biopsy. It is recommended to concentrate breast cancer cases in hospitals that provide the conditions for its performance.

Safety of surgery: quality assessment of meta-analyses on the WHO checklist.

Objectives: To assess the quality of the meta-analyses that review the WHO surgical safety checklist. Methods: A systematic review of meta-analysis studies was undertaken using the search terms "World Health Organization Surgical Safety Checklist" in PubMed, Embase, and Lilacs databases. The selected meta-analyses were rated using the AMSTAR 2 assessment tool. Results: In the three meta-analyses evaluated, the checklist was associated with a decrease in the rates of complications and mortality. Overall confidence in the results of the evaluated meta-analysis was critically low. Conclusions: The meta-analysis coincides with obtaining lower complications and mortality rates with the WHO surgical safety checklist. However, the studies included in the meta-analyses were mostly observational, with potential biases, and according to the AMSTAR 2 tool, the overall confidence in the results of the evaluated studies was critically low.

In-situ acetylation followed by liquid-liquid extraction and gas chromatography - mass spectrometry for the determination of bromophenols in urine.

A novel and simple method combining in-situ acetylation, liquid-liquid extraction and gas chromatography-mass spectrometry (GC-MS) has been developed for the quantification of 10 bromophenols in urine, used as biomarkers of exposure to polybrominated diphenyl ethers. The analytical process involves an enzymatic hydrolysis of the bromophenol glucuronide fraction followed by an aqueous derivatization of the phenol group with acetic anhydride. A subsequent liquid-liquid extraction of the sample with hexane allows the injection of the organic layer, using a programmed temperature vaporizer, into a gas chromatograph coupled to a single quadrupole mass spectrometer. Quantification is performed by the standard addition method. Limits of detection are in the pg mL-1 range. Trueness, assessed in terms of percentages of recovery, varies between 100 % and 118 % in synthetic urine and between 79 % and 117 % in human urine. Precision, assessed at two different levels, 0.25 ng mL-1 and 2.5 ng mL-1, shows values of relative standard deviation below 14 % both in intra- and inter-day studies for both matrices. The method has been applied to the analysis of seven urine samples, measuring concentrations higher than the LOQ in three of them. These levels are in agreement with others found in literature, but they have been obtained by applying a much simpler and faster protocol. In addition, the replacement of silylating reagents by acetic anhydride, to derivatize the phenol moiety, provides a greener alternative to other GC-MS procedures published up to date.

Mortality from Breast Cancer in Women under 50 Years of Age in Colombia.

OBJECTIVE: To calculate and analyze the mortality rates from breast cancer in women under 50 years of age in Colombia and to compare them with those of other countries in the region. METHODS: Based on data from the registry of deaths in 2018 and the results of the National Population and Housing Census of Colombia for the same year, specific mortality rates in women with breast cancer, specific mortality according to age group, standardized by age, proportional mortality, potential years of life lost, and years of life expectancy lost in women under 50 years of age who died from breast cancer were calculated. The mortality rate of regional countries was consulted on the Global Cancer Observatory webpage. RESULTS: In the group from 20 to 49 years, the specific mortality rate was higher in the age range from 45 to 49 years, with a rate of 23.42 × 100,000, a value that was above the specific mortality rate due to breast cancer in women in Colombia, 15.17 × 100.000. In the age range of 45 to 49 years, the potential years of life lost were 42.16. Of the 0.275 years of life expectancy lost by the population due to this neoplasia, women under 50 years of age represented 0.091 (33%). Colombia is the fifth in the rank of mortality in Latin American countries in this age group. CONCLUSION: Breast cancer in patients from 30 to 59 years is the number one cause for the decrease in life expectancy of women in Colombia. Women under 50 years of age represent one third of this decrease. This neoplasm is also the leading cause of mortality in women younger than 50 years in South America.

Comparative analyses of holder pasteurization vs. HTST pasteurization for donor milk: a cost-minimization study applicable to human milk banks.

BACKGROUND: High-temperature short-time (HTST) pasteurization (72-75 °C, 15 s) is an alternative treatment to traditional Holder pasteurization (HoP) (62ºC, 30 min) for donor milk. HTST pasteurization guarantees the milk's microbiological safety and retains more of its biologically and nutritionally active compounds, but the cost of implementing this technology for a human milk bank is unknown. METHODS: A cost-minimization study was carried out on the facilities of a regional human milk bank in a public hospital. Total production costs (fixed plus variables) were quantified using HTST pasteurization and HoP in three hypothetical scenarios: (1) costs of the first 10 L of pasteurized milk in a newly opened milk bank; (2) costs of the first 10 L of pasteurized milk in an active milk bank; and (3) costs using the maximum production capacity of both technologies in the first two years of operation. The following costs were analyzed: health care professionals, equipment and software, external services, and consumables. RESULTS: In scenario 1, the total production costs were € 228,097.00 for the HTST method versus € 154,064.00 for the HoP method. In scenario 2, these costs were similar (€ 6,594.00 for HTST pasteurization versus € 5,912.00 for HoP). The cost of healthcare professionals was reduced by more than half when pasteurization was carried out by the HTST method versus the Holder method (€ 84.00 and € 191.00, respectively). In scenario 3, the unit cost of milk pasteurized by the HTST method decreased from the first to the second year by 43.5%, while for the HoP method, it decreased by 30%. CONCLUSIONS: HTST pasteurization requires a high initial investment in equipment; however, it provides a significant minimization of production costs in the long term, pasteurizes large quantities of donor milk per working day and achieves a more efficient management of the time of the health care professionals in charge of the bank's operation compared to HoP.

Use of a guard column coupled to mass spectrometry as a fast semi-quantitative methodology for the determination of plasticizer metabolites in urine.

For the first time, a very simple and fast method combining the use of a guard column coupled to tandem mass spectrometry (guard column-MS/MS) has been proposed for the determination of plasticizer metabolites in urine. Briefly, samples (1.0 mL) were submitted to enzymatic hydrolysis for 10 min, filtered, diluted 1/10 v/v with ultrapure water and directly injected into the system. A fast run of only 2 min (3 min including the injection cycle) allowed the determination of 19 analytes. Enzymatic hydrolysis, filtering material, and guard column-MS/MS conditions were optimized. Intra-day precision at the low-level concentration (expressed as relative standard deviation, %RSD) obtained from the analysis of synthetic urine samples varied between 11 and 20%. Limits of quantification ranged from 2.8 to 60 ng/mL. Trueness values, calculated as apparent recoveries, ranged from 70 to 135%. To correct for matrix effects, analyte concentrations in real urine were quantified by the standard addition method. To confirm the results obtained by guard column-MS/MS, an ultra(high)-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was also applied (total chromatographic run time 17 min, including column re-equilibration). Concentrations measured with both methods were in good agreement. Hence, we propose the use of guard column-MS/MS to analyse a large number samples in a very short time (semi-quantification), and apply the chromatographic analysis only to those samples with levels close to/higher than the concentrations equivalent to the safe maximum daily intakes of the parent compounds (confirmation). This double strategy (semi-quantification by guard column-MS/MS and confirmation-when needed-by UHPLC-MS/MS) implies important savings in time and money.

Assessing the impact of a major electronic music festival on the consumption patterns of illicit and licit psychoactive substances in a Mediterranean city using wastewater analysis.

The consumption patterns of five categories of psychoactive substances (PS), including "conventional" illicit drugs, new psychoactive substances (NPS), therapeutic opioids, alcohol and nicotine, were studied in the city of Split, Croatia, using wastewater-based epidemiology (WBE), with an emphasis on the impact of a large electronic music festival. The study involved the analysis of 57 urinary biomarkers of PS in raw municipal wastewater samples collected in three characteristic periods, including the festival week in the peak-tourist season (July) and reference weeks in the peak-tourist season (August) and the off-tourist season (November). Such a large number of biomarkers allowed the recognition of distinct patterns of PS use associated with the festival, but also revealed some subtle differences between summer and autumn seasons. The festival week was characterized by markedly increased use of illicit stimulants (MDMA: 30-fold increase; cocaine and amphetamine: 1.7-fold increase) and alcohol (1.7-fold increase), while consumption of other common illicit drugs (cannabis and heroin), major therapeutic opioids (morphine, codeine and tramadol) and nicotine remained rather constant. Interestingly, NPS and methamphetamine clearly contributed to the festival PS signature in wastewater, but their prevalence was rather low compared to that of common illicit drugs. Estimates of cocaine and cannabis use were largely consistent with prevalence data from national surveys, whereas differences were found for typical amphetamine-type recreational drugs, particularly MDMA, and for heroin. The WBE data suggest that the largest proportion of morphine came from heroin consumption and that the percentage of heroin users seeking treatment in Split is probably rather low. The prevalence of smoking calculated in this study (30.6 %) was consistent with national survey data for 2015 (27.5-31.5 %), while the average alcohol consumption per capita >15 years (5.2 L) was lower than sales statistics suggest (8.9 L).

Screening and selective quantification of illicit drugs in wastewater by mixed-mode solid-phase extraction and quadrupole-time-of-flight liquid chromatography-mass spectrometry.

For the first time, a mixed-mode solid-phase extraction with fractionation of basic analytes from neutral and acidic species during cartridge elution and liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS) was combined for the quantitative determination of 24 illicit drugs and metabolites in urban sewage samples. The effects of several sample preparation and instrumental parameters in the sensitivity and selectivity of the quantitative method are thoroughly discussed. Under final working conditions, recoveries above 63% and 82% were attained for all species in raw and treated sewage, respectively; whereas, the limits of quantification of the method, defined for a signal-to-noise of 10 (S/N = 10), ranged from 2 to 50 ng L(-1). Sequential elution of mixed-mode cartridges allowed a significant reduction of matrix effects observed during electrospray ionization of basic drugs versus those measured for hydrophilic balance reversed-phase sorbents and the same mixed-mode polymer without fractionated elution. Analysis of raw wastewater samples confirmed the ubiquity of cocaine (COC), benzoylecgonine (BE), and 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol (THCCOOH) in this matrix. The capability of the above methodology to identify new illicit drugs and/or metabolites in sewage samples is also discussed. With this aim, a two step strategy is proposed. First, high-resolution MS chromatograms, acquired throughout each chromatographic run, are automatically searched against an in-house built database, a reduced list of candidate drugs is generated, and the corresponding extracted ion chromatograms are obtained. In a further LC run, the tandem mass spectrometry (MS/MS) spectra of unknown peaks are acquired using different collision energies and compared with those existing in public libraries, or interpreted, to assign the unknown peak to one of the previously selected candidates.

Transformation of cocaine during water chlorination.

The stability of cocaine and its two main human metabolites, benzoylecgonine and ecgonine methyl ester, in chlorine-containing waters has been investigated by direct injection of different reaction time aliquots in a liquid chromatograph (LC) coupled to a quadrupole-time-of-flight mass spectrometer (QTOF-MS). Factors potentially affecting cocaine degradation (the only compound showing a significant decrease in the preliminary study) were evaluated in detail by means of a Box-Behnken experimental design. Sample pH resulted to be the most important variable, increasing both the rate of chlorination-mediated reactions and the ester hydrolysis process. From these reactions, and due to the high mass accuracy measurements obtained with the QTOF system, four by-products could be positively identified: benzoylecgonine, norcocaine, norbenzoylecgonine and N-formylnorcocaine. Finally, their formation and cocaine degradation yields were assessed under chlorination experiments with two real surface water samples. In one of them, showing a low anthropogenic impact, benzoylecgonine and norcocaine were notably generated even after only 1 h of reaction, whereas at higher contact times also norbenzoylecgonine and N-formylnorcocaine could be determined with a lower yield. On the other hand, the second sample, with a higher organic matter content, consumed rapidly the chlorine, so that only benzoylecgonine was produced. These findings point out the convenience of monitoring the described transformation products, in addition to the precursor illicit drug, during drinking water production, taking into account that cocaine traces might be present in water catchments and particularly in areas with high population densities.

Inter-observer agreement in the diagnosis of breast atypical ductal hyperplasia: A systematic review.

OBJECTIVE: To review the concordance between pathologists in the diagnosis of atypical ductal hyperplasia of the breast. METHODS: Systematic review of articles registered in the PubMed database with the terms "pathologists" and "atypical ductal hyperplasia", "atypical ductal hyperplasia" and "interobserver variability", in Embase with "interobserver agreement in atypical ductal hyperplasia" and Lilacs with the terms in Spanish "patólogos" and "hiperplasia ductal atípica", without the use of filters, between 03/16/2022 and 03/26/2022 searching for articles that assess inter-observer agreement in the diagnosis of atypical ductal hyperplasia by using the kappa statistic. Review articles, conference proceedings, and commentaries were excluded. RESULTS: With the search terms, 507 publications were found. Of these, 491 were excluded from the screening by title and abstract. Of the full reading of the remaining articles, 6 were selected for qualitative analysis. The kappa values ranged from slight agreement, kappa = 0.17, to substantial agreement, 0.69 obtained from pathologists dedicated or experienced in breast pathology and who received a prior tutorial session to review the general criteria for atypia. CONCLUSIONS: This study reviews the reproducibility in the diagnosis of atypical ductal hyperplasia. A better concordance was obtained with a previous teaching process offered to pathologists dedicated or experienced in breast pathology.

Analysis of the Effects of Lockdown on Staff and Students at Universities in Spain and Colombia Using Natural Language Processing Techniques.

The aim of this study is to analyze the effects of lockdown using natural language processing techniques, particularly sentiment analysis methods applied at large scale. Further, our work searches to analyze the impact of COVID-19 on the university community, jointly on staff and students, and with a multi-country perspective. The main findings of this work show that the most often related words were "family", "anxiety", "house", and "life". Besides this finding, we also have shown that staff have a slightly less negative perception of the consequences of COVID-19 in their daily life. We have used artificial intelligence models such as swivel embedding and a multilayer perceptron as classification algorithms. The performance that was reached in terms of accuracy metrics was 88.8% and 88.5% for students and staff, respectively. The main conclusion of our study is that higher education institutions and policymakers around the world may benefit from these findings while formulating policy recommendations and strategies to support students during this and any future pandemics.

The Impact of COVID 19 on University Staff and Students from Iberoamerica: Online Learning and Teaching Experience.

(1) Background: The COVID-19 pandemic has created a great impact on mental health in society. Considering the little attention paid by scientific studies to either students or university staff during lockdown, the current study has two aims: (a) to analyze the evolution of mental health and (b) to identify predictors of educational/professional experience and online learning/teaching experience. (2) Methods: 1084 university students and 554 staff in total from four different countries (Spain, Colombia, Chile and Nicaragua) participated in the study, affiliated with nine different universities, four of them Spanish and one of which was online. We used an online survey known as LockedDown, which consists of 82 items, analyzed with classical multiple regression analyses and machine learning techniques. (3) Results: Stress level and feelings of anxiety and depression of students and staff either increased or remained over the weeks. A better online learning experience for university students was associated with the age, perception of the experience as beneficial and support of the university. (4) Conclusions: The study has shown evidence of the emotional impact and quality of life for both students and staff. For students, the evolution of feelings of anxiety and depression, as well as the support offered by the university affected the educational experience and online learning. For staff who experienced a positive professional experience, with access to services and products, the quality-of-life levels were maintained.

Efficiency of Diagnostic Testing for Helicobacter pylori Infections-A Systematic Review.

BACKGROUND: The most recommended treatment for a Helicobacter pylori infection is high doses of combined antibiotics. The objective of this article is to perform a systematic review of the economic evaluation studies applied to assess the efficiency of diagnostic testing for H. pylori infections, so that their main characteristics can be identified and to learn from the literature how the antimicrobial resistance (AMR) issue is incorporated into these economic evaluations. METHODS: We conducted a systematic review to compare the costs and clinical effectiveness of diagnostic strategies for H. pylori infections. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and extracted the items from the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: We found thirteen articles that were of good quality according to CHEERS: six studies focused on diagnostics of Helicobacter pylori infections associated with dyspepsia and four on duodenal ulcers. Testing was found to be the most cost-effective strategy in eight articles. Four studies considered AMR. CONCLUSIONS: Testing was more cost-effective than empirical treatment, except in cases of high prevalence (as with developing countries) or when patients could be stratified according to their comorbidities. The introduction of AMR into the model may change the efficiency of the testing strategy.

Diagnostic Testing for Sepsis: A Systematic Review of Economic Evaluations.

INTRODUCTION: Sepsis is a serious and expensive healthcare problem, when caused by a multidrug-resistant (MDR) bacteria mortality and costs increase. A reduction in the time until the start of treatment improves clinical results. The objective is to perform a systematic review of economic evaluations to analyze the cost-effectiveness of diagnostic methods in sepsis and to draw lessons on the methods used to incorporate antimicrobial resistance (AMR) in these studies. MATERIAL AND METHODS: the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the Consolidated Health Economic Evaluation Reporting standards (CHEERS) checklist was used to extract the information from the texts. RESULTS: A total of 16 articles were found. A decision model was performed in 14. We found two ways to handle resistance while modelling: the test could identify infections caused by a resistant pathogen or resistance-related inputs, or outcomes were included (the incidence of AMR in sepsis patients, antibiotic use, and infection caused by resistant bacterial pathogens). CONCLUSION: Using a diagnostic technique to detect sepsis early on is more cost-effective than standard care. Setting a direct relationship between the implementation of a testing strategy and the reduction of AMR cases, we made several assumptions about the efficacy of antibiotics and the length-of-stay of patients.