Burden and Management of Multi-Drug Resistant Organism Infections in Solid Organ Transplant Recipients Across the World: A Narrative Review.

Solid organ transplant (SOT) recipients are particularly susceptible to infections caused by multidrug-resistant organisms (MDRO) and are often the first to be affected by an emerging resistant pathogen. Unfortunately, their prevalence and impact on morbidity and mortality according to the type of graft is not systematically reported from high-as well as from low and middle-income countries (HIC and LMIC). Thus, epidemiology on MDRO in SOT recipients could be subjected to reporting bias. In addition, screening practices and diagnostic resources may vary between countries, as well as the availability of new drugs. In this review, we aimed to depict the burden of main Gram-negative MDRO in SOT patients across HIC and LMIC and to provide an overview of current diagnostic and therapeutic resources.

Beyond SARS-CoV-2: epidemiological surveillance of respiratory viruses in Jalisco, Mexico.

Introduction: Respiratory viral infections represent a significant global health burden. Historically, influenza, rhinovirus, respiratory syncytial virus, and adenovirus have been the prevalent viruses; however, the landscape shifted with the widespread emergence of SARS-CoV-2. The aim of this study is to present a comprehensive epidemiological analysis of viral respiratory infections in Jalisco, Mexico. Methods: Data encompassing individuals with flu-like symptoms from July 2021 to February 2023 was scrutinized for viral diagnosis through PCR multiplex. The effect of social mobility on the increase in respiratory viral diagnosis infection was considered to estimate its impact. Additionally, sequences of respiratory viruses stored in public databases were retrieved to ascertain the phylogenetic classification of previously reported viruses in Mexico. Results: SARS-CoV-2 was the most detected virus (n = 5,703; 92.2%), followed by influenza (n = 479; 7.78%). These viruses were also found as the most common co-infection (n = 11; 50%), and for those with influenza, a higher incidence of severe disease was reported (n = 122; 90.4%; p < 0.001). Regarding comorbidities and unhealthy habits, smoking was found to be a risk factor for influenza infection but a protective factor for SARS-CoV-2 (OR = 2.62; IC 95%: 1.66-4.13; OR = 0.65; IC 95%: 0.45-0.94), respectively. Furthermore, our findings revealed a direct correlation between mobility and the prevalence of influenza infection (0.214; p < 0.001). Discussion: The study presents evidence of respiratory virus reemergence and prevalence during the social reactivation, facilitating future preventive measures.

Clinical and Economic Impact of COVID-19 on Agricultural Workers, Guatemala1.

We evaluated clinical and socioeconomic burdens of respiratory disease in banana farm workers in Guatemala. We offered all eligible workers enrollment during June 15-December 30, 2020, and annually, then tracked them for influenza-like illnesses (ILI) through self-reporting to study nurses, sentinel surveillance at health posts, and absenteeism. Workers who had ILI submitted nasopharyngeal swab specimens for testing for influenza virus, respiratory syncytial virus, and SARS-CoV-2, then completed surveys at days 0, 7, and 28. Through October 10, 2021, a total of 1,833 workers reported 169 ILIs (12.0 cases/100 person-years), and 43 (25.4%) were laboratory-confirmed infections with SARS-CoV-2 (3.1 cases/100 person-years). Workers who had SARS-CoV-2‒positive ILIs reported more frequent anosmia, dysgeusia, difficulty concentrating, and irritability and worse clinical and well-being severity scores than workers who had test result‒negative ILIs. Workers who had positive results also had greater absenteeism and lost income. These results support prioritization of farm workers in Guatemala for COVID-19 vaccination.

AmazonForest: In Silico Metaprediction of Pathogenic Variants.

ClinVar is a web platform that stores ∼789,000 genetic associations with complex diseases. A partial set of these cataloged genetic associations has challenged clinicians and geneticists, often leading to conflicting interpretations or uncertain clinical impact significance. In this study, we addressed the (re)classification of genetic variants by AmazonForest, which is a random-forest-based pathogenicity metaprediction model that works by combining functional impact data from eight prediction tools. We evaluated the performance of representation learning algorithms such as autoencoders to propose a better strategy. All metaprediction models were trained with ClinVar data, and genetic variants were annotated with eight functional impact predictors cataloged with SnpEff/SnpSift. AmazonForest implements the best random forest model with a one hot data-encoding strategy, which shows an Area Under ROC Curve of ≥0.93. AmazonForest was employed for pathogenicity prediction of a set of ∼101,000 genetic variants of uncertain significance or conflict of interpretation. Our findings revealed ∼24,000 variants with high pathogenic probability (RFprob≥0.9). In addition, we show results for Alzheimer's Disease as a demonstration of its application in clinical interpretation of genetic variants in complex diseases. Lastly, AmazonForest is available as a web tool and R object that can be loaded to perform pathogenicity predictions.

The Evolutionary Landscape of SARS-CoV-2 Variant B.1.1.519 and Its Clinical Impact in Mexico City.

The SARS-CoV-2 pandemic is one of the most concerning health problems around the globe. We reported the emergence of SARS-CoV-2 variant B.1.1.519 in Mexico City. We reported the effective reproduction number (Rt) of B.1.1.519 and presented evidence of its geographical origin based on phylogenetic analysis. We also studied its evolution via haplotype analysis and identified the most recurrent haplotypes. Finally, we studied the clinical impact of B.1.1.519. The B.1.1.519 variant was predominant between November 2020 and May 2021, reaching 90% of all cases sequenced in February 2021. It is characterized by three amino acid changes in the spike protein: T478K, P681H, and T732A. Its Rt varies between 0.5 and 2.9. Its geographical origin remain to be investigated. Patients infected with variant B.1.1.519 showed a highly significant adjusted odds ratio (aOR) increase of 1.85 over non-B.1.1.519 patients for developing a severe/critical outcome (p = 0.000296, 1.33-2.6 95% CI) and a 2.35-fold increase for hospitalization (p = 0.005, 1.32-4.34 95% CI). The continuous monitoring of this and other variants will be required to control the ongoing pandemic as it evolves.

[Analysis of the diversity of Actinomyces/Actinotignum clinical isolates in a university hospital]. / Análisis de la diversidad de aislados clínicos de Actinomyces/Actinotignum en un hospital universitario.

Actinomyces and related genera are grampositive bacilli, opportunistic pathogens, which have been mainly involved in endogenous infections. However, due to the complexity in identifying them for most clinical laboratories, there is scant knowledge about their real clinical significance. In this work, 166 isolates of 13 different species of Actinomyces/Actinotignum species recovered from clinical samples of patients treated in a university hospital were studied. The identification was performed by MALDI-TOF MS and molecular identification. MALDI-TOF MS identified 91.57% of the isolates (152/166) at the species level using a score ≥ 1.7 and 3.61% (6/166) of the isolates were identified only at the gender level with a score ≥ 1.5. MALDI-TOF MS did not yield reliable identification results for 4.82% (8/166) of the isolates. Actinomyces/Actinotignum species were isolated from: soft tissue (n: 47), urine samples (n: 35), head / neck abscesses (n: 19), genital abscesses (n: 11), blood samples (n: 10), breast abscesses (n: 8), osteoarticular samples (n: 6), abdominal/ascitic fluids (n: 3), abdominal abscesses (n: 5), sputum/BAL (n: 4), brain abscesses (n: 3), and others (n: 15). The results obtained from the statistical analysis showed a high differential frequency (> 2) for the location/species association: urine/A. schaalii/sanguinis; brain abscesses/A. europaeus; osteoarticular samples/A. urogenitalis; abdominal abscesses/ A. turicensis; respiratory samples/A. naeslundii/viscosus. This information provides a greater understanding of the clinical and epidemiological relevance of these species. The pathogenic role of Actinomyces spp. will be increasingly revealed as these microorganisms could be recognized thanks to prolonged culture and the advances in identification technology facilitated by MALDI-TOF MS.

Impact of an ultrasound-driven diagnostic protocol at early intensive-care stay: a randomized-controlled trial.

BACKGROUND: Point-of-care ultrasound (POCUS) is a tool in increasing use, but there is still a lack of basics for its routine use and evidence of its impact in intensive care. OBJECTIVE: To measure the impact of POCUS on resource utilization, diagnostic accuracy, and clinical management in medical-surgical intensive care units (ICUs). METHODS: Prospective, controlled study, in two polyvalent ICUs. The patients were randomly assigned to POCUS or control group. INTERVENTIONS: POCUS patients received systematic ultrasound examination of optic nerve, lung/pleura, heart, abdomen, and venous system, performed at the bedside by trained intensivists. Control patients were treated by critical care specialists who do not perform ultrasound in their clinical practice. RESULTS: We included 80 patients, 40 per group. There were no significant differences in age, sex, APACHE II score, or admission diagnosis. POCUS group used fewer resources per patient in the first 5 days of hospitalization: chest radiography (2.6 ± 2.0 vs 4.1 ± 3.5, P = 0.01), additional ultrasound evaluations performed by a radiology specialist (0.6 ± 0.7 vs 1.1 ± 0.7, P = 0.002), and computed tomography studies (0.5 ± 0.6 vs 0.9 ± 0.7, P = 0.007). Time to perform any requested ultrasound evaluation after ICU admission was 2.1 ± 1.6 h versus 7.7 ± 6.7 h (P = 0.001). Systematic ultrasound evaluation led to better characterization of ICU admission diagnosis in 14 (35%) patients and change in clinical management in 24 (60%). POCUS group had lower fluid balance at 48 and 96 h after admission (P = 0.01) and spent less time mechanically ventilated (5.1 ± 5.7 days vs 8.8 ± 9.4, P = 0.03). CONCLUSIONS: Systematic application of POCUS may decrease utilization of conventional diagnostic imaging resources and time of mechanical ventilation, and facilitate meticulous intravenous fluid administration in critically ill patients during the first week of stay in the ICU. Trial registration ClinicalTrials.gov Identifier: NCT03608202.

Cost-Effectiveness and Clinical Impact of Antiviral Strategies of HBeAG-Positive and Negative Chronic Hepatitis B

ABSTRACT Introduction. Chronic hepatitis B (CHB) is associated with high burden and healthcare costs. Virologic response achieved with antivirals is associated with progression avoidance. This study aimed to estimate the efficiency and clinical impact of antiviral strategies in CHB patients. Material and methods. A Markov model estimated lifetime complications and direct costs in both, HBeAg-positive and HBeAg-negative cohorts. Strategy 1 (71% of treated population) and strategy 2 (100%), both based on pegylated interferon (peg-IFN) followed by oral tenofovir or entecavir, were compared to no treatment. Progression was based on HBV-DNA levels. Rescue therapy with oral antivirals was applied for peg-IFN failure. Disease costs (€, 2014) and utilities were obtained from literature. Results. Compared to natural history, strategy 1 increased QALY (3.98 in HBeAg-positive, 2.16 in -negative cohort). With strategy 2, survival was up to 5.60 (HBeAg-positive) and 3.05 QALY (in HBeAg-negative). The model predicted avoidance of 128 and 86 carcinomas in HBeAg-positive and -negative patients with strategy 1, and up to 181 and 121 in HBeAg-positive and -negative for strategy 2. Total cost increased up to €102,841 (strategy 1) and €105,408 (strategy 2) in HBeAg-positive, and €85,858 and €93,754 in HBeAg-negative. A€1,581/QALY gained ratio was estimated versus the natural history for both strategies. In conclusion, increasing antiviral coverage would be efficient, reducing complications.

Impacto clínico y económico de las intervenciones farmacéuticas / Clinical and economic impact of pharmaceutical interventions

Se realizó un estudio retrospectivo durante el periodo comprendido entre noviembre del 2008 y abril del 2009 a partir del sistema de distribución de medicamentos en dosis unitarias, con el objetivo de documentar el valor de la intervención farmacéutica, tanto en datos descriptivos como en datos económicos y de eficiencia, mediante el empleo de un programa de equivalentes terapéuticos. Las intervenciones farmacéuticas se agruparon en dosis/intervalo, sustitución, vía de administración, interacciones, alergias y otros. En cuanto al impacto económico, los valores de precios se obtuvieron a partir de los precios de compra de los medicamentos y del catálogo de especialidades farmacéuticas. Se realizaron un total de 297 intervenciones repartidas en 50 dosis/intervalo, 174 sustituciones, 34 de vía, 25 de interacciones, 3 de alergia y 11 en el apartado de otros. El ahorro real calculado supuso 18 146,39 euros. El registro de las intervenciones se valora como beneficioso para la detección de problemas prioritarios y áreas de actuación, además de constituir una herramienta útil para poder demostrar el coste/efectividad de las acciones.

A retrospective study was conducted from November 2008 to April 2009 in the unit-dose drug distribution system. The objective was to document the value of the pharmaceutical intervention both in descriptive and economic/efficiency data by using a program of therapeutic equivalences. The pharmaceutical interventions were grouped into dose/interval, substitutions, route of administration, interactions, allergies and others. Regarding the economic impact, the values of prices were derived from the drug purchase prices and the catalogue of pharmaceutical specialties. Two hundred ninety seven interventions were performed and distributed as follows: 50 dose / interval, 174 substitutions, 34 routes of administration, 25 interactions, 3 allergies and 11 of other types. Actual estimated savings amounted to 18 146.39 euros. The record of interventions is considered advantageous for the detection of priority problems and areas for action, in addition to being a useful tool to prove the cost-effectiveness of actions. Key words: Pharmaceutical intervention, clinical impact, economic impact.