Clinical features and outcomes of mpox in people with and without HIV: a national comparative study.

BACKGROUND: People who live with HIV (PWLH) have been one of the most affected groups during the current mpox outbreak. They are hypothesized to have a more severe clinical course than people without HIV but comparative data is scarce. We aimed to compare clinical features and outcomes of mpox in people with and without HIV in Mexico. SETTING: Country-wide study in Mexico. METHODS: We performed an observational study using nation-wide epidemiological data. We included all people with confirmed mpox diagnosed between May and November 2022 in Mexico. Clinical and sociodemographic characteristics were compared between people with and without HIV. Multivariable logistic regression models were preformed to determine the association between HIV, clinical features, and outcomes and reported with odds ratios (ORs) and 95% confidence intervals (95% CI). ORs for rare outcomes were interpreted as risk ratios. RESULTS: Among 3291 people with mpox, 59% were PWLH. PWLH had an increased risk of severe mpox (OR 2.6, 2.4-2.9) and death (OR 10.8, 9.7-11.9). They also had a higher risk of otalgia, proctitis, and urethritis. Eleven individuals died, of whom ten were PWLH. All deaths were directly attributed to mpox. CONCLUSION: People with HIV have a higher risk of severe mpox and death due to mpox.

Genetic Network Design Automation with LOICA.

Genetic design automation (GDA) is the use of computer-aided design (CAD) in designing genetic networks. GDA tools are necessary to create more complex synthetic genetic networks in a high-throughput fashion. At the core of these tools is the abstraction of a hierarchy of standardized components. The components' input, output, and interactions must be captured and parametrized from relevant experimental data. Simulations of genetic networks should use those parameters and include the experimental context to be compared with the experimental results.This chapter introduces Logical Operators for Integrated Cell Algorithms (LOICA), a Python package used for designing, modeling, and characterizing genetic networks using a simple object-oriented design abstraction. LOICA represents different biological and experimental components as classes that interact to generate models. These models can be parametrized by direct connection to the Flapjack experimental data management platform to characterize abstracted components with experimental data. The models can be simulated using stochastic simulation algorithms or ordinary differential equations with varying noise levels. The simulated data can be managed and published using Flapjack alongside experimental data for comparison. LOICA genetic network designs can be represented as graphs and plotted as networks for visual inspection and serialized as Python objects or in the Synthetic Biology Open Language (SBOL) format for sharing and use in other designs.

Flapjack: Data Management and Analysis for Genetic Circuit Characterization.

Flapjack presents a valuable solution for addressing challenges in the Design, Build, Test, Learn (DBTL) cycle of engineering synthetic genetic circuits. This platform provides a comprehensive suite of features for managing, analyzing, and visualizing kinetic gene expression data and associated metadata. By utilizing the Flapjack platform, researchers can effectively integrate the test phase with the build and learn phases, facilitating the characterization and optimization of genetic circuits. With its user-friendly interface and compatibility with external software, the Flapjack platform offers a practical tool for advancing synthetic biology research.This chapter provides an overview of the data model employed in Flapjack and its hierarchical structure, which aligns with the typical steps involved in conducting experiments and facilitating intuitive data management for users. Additionally, this chapter offers a detailed description of the user interface, guiding readers through accessing Flapjack, navigating its sections, performing essential tasks such as uploading data and creating plots, and accessing the platform through the pyFlapjack Python package.

Retiring the term AIDS for more descriptive language.

The term acquired immunodeficiency syndrome (AIDS) was coined to describe a condition marked by weakened cell-mediated immunity in the absence of a clear cause. Due to unfortunate messaging during the early days of the HIV epidemic, this term became loaded with stigma. After the discovery of HIV, the term AIDS became redundant, but its use has persisted and has come to embody negative connotations in the current landscape of the HIV epidemic. People commonly associate AIDS with a terminal illness. This misconception promotes stigma by others, including health-care workers, but also self-stigma, which can prevent individuals from accessing health care. Also, the link between AIDS and gay men generated during the early epidemic with use of the term gay-related immune disorder is misleading regarding which populations are at risk, which can delay diagnosis. The use of the term AIDS is now discouraged by several professional associations, some of which ironically have the word as part of their name. Ending use of the term AIDS would not eradicate stigma. However, this term has outlasted its usefulness, and we should transition towards more descriptive language that aligns with contemporary challenges in HIV.

Challenges to the HIV Care Continuum During the COVID-19 Pandemic in Mexico: A Mixed Methods Study.

The COVID-19 pandemic has been reported to disrupt the access to care of people who live with HIV (PWH). The impact of the pandemic on the longitudinal HIV care continuum, however, has not been properly evaluated. We performed a mixed-methods study using data from the Mexican System of Distribution, Logistics, and ART Surveillance on PWH that are cared for in the state of Oaxaca. We evaluated the number of HIV diagnoses performed in the state before and during the pandemic with an interrupted time series. We used the longitudinal HIV care continuum framework to describe the stages of HIV care before and during the pandemic. Finally, we performed a qualitative analysis to determine which were the challenges faced by staff and users regarding HIV care during the pandemic. New HIV diagnoses were lower during the first year of the pandemic compared with the year immediately before. Among 2682 PWH with enough information to determine their status of care, 728 started receiving care during the COVID-19 pandemic and 1954 before the pandemic. PWH engaged before the pandemic spent 42825 months (58.2% of follow-up) in optimal HIV control compared with 3061 months (56.1% of follow-up) for those engaged in care during the pandemic. Staff and users reported decreases in the frequency of appointments, prioritisation of unhealthy users, larger disbursements of ART medication, and novel communication strategies with PWH. Despite challenges due to government cutbacks, changes implemented by staff helped maintain HIV care due to higher flexibility in ART delivery and individualised attention.

The importance of using disease causal models in studies of preventive interventions: Learning from preeclampsia research.

OBJECTIVE: Interventions aimed at preventing disease are commonly studied as strategies of primary or secondary prevention. Unfortunately, this dichotomy can be misleading, and studies might unknowingly exclude people at high risk of the disease that could benefit from the intervention. Here I use the example of aspirin for prevention of preeclampsia to illustrate this problem. METHODS: I use directed acyclic graphs to represent several causal models of aspirin and preeclampsia, each making different assumptions regarding the causal relation between previous preeclampsia, aspirin, and subsequent preeclampsia. Afterwards, I discuss the implications of each model. RESULTS: Aspirin started being recommended to pregnant women that had presented preeclampsia in previous pregnancies, but not to women at high risk due to other factors. Studies started evaluating aspirin in women at high risk due to these other causes and found it also reduced the risk of preeclampsia in them. Thanks to a shift towards risk-based interventions, guidelines started recommending aspirin to all women considered at high risk of preeclampsia. Furthermore, recent studies have begun using blood markers in women without classic risk factors to identify additional women that might benefit from aspirin. With such advances, performing "secondary prevention" once the first event occurred will increasingly represent a failure to intervene on time. CONCLUSIONS: Explicitly illustrating disease causal models helps to identify those individuals that are most likely to benefit from risk reduction, regardless of whether they were previously afflicted by the disease. This is beneficial when designing studies and when implementing preventive interventions.

Longitudinal clinical phenotyping of post COVID condition in Mexican adults recovering from severe COVID-19: a prospective cohort study.

Introduction: Few studies have evaluated the presence of Post COVID-19 conditions (PCC) in people from Latin America, a region that has been heavily afflicted by the COVID-19 pandemic. In this study, we describe the frequency, co-occurrence, predictors, and duration of 23 symptoms in a cohort of Mexican patients with PCC. Methods: We prospectively enrolled and followed adult patients hospitalized for severe COVID-19 at a tertiary care centre in Mexico City. The incidence of PCC symptoms was determined using questionnaires. Unsupervised clustering of PCC symptom co-occurrence and Kaplan-Meier analyses of symptom persistence were performed. The effect of baseline clinical characteristics was evaluated using Cox regression models and reported with hazard ratios (HR). Results: We found that amongst 192 patients with PCC, respiratory problems were the most prevalent and commonly co-occurred with functional activity impairment. 56% had ≥5 persistent symptoms. Symptom persistence probability at 360 days 0.78. Prior SARS-CoV-2 vaccination and infection during the Delta variant wave were associated with a shorter duration of PCC. Male sex was associated with a shorter duration of functional activity impairment and respiratory symptoms. Hypertension and diabetes were associated with a longer duration of functional impairment. Previous vaccination accelerated PCC recovery. Discussion: In our cohort, PCC symptoms were frequent (particularly respiratory and neurocognitive ones) and persistent. Importantly, prior SARS-CoV-2 vaccination resulted in a shorter duration of PCC.

Predictors of laboratory-confirmed mpox in people with mpox-like illness.

OBJECTIVES: We aimed to identify predictors of confirmed monkeypox (mpox) among people with mpox-like illness and to develop a multivariable model for confirmed mpox. METHODS: We performed an observational study using national epidemiologic surveillance data in Mexico from May to November 2022. People with mpox-like illness were reported to the Mexican Ministry of Health and real-time polymerase chain reaction was performed in clinical samples to confirm mpox. Sociodemographic and clinical data were collected with a case report form. We performed univariable logistic regressions to estimate the predictive capability of individual characteristics, reported with ORs and 95% CIs. Variables of interest were included in multivariable logistic regression models and Akaike information criterion was used to retain variables for the final model. Discrimination and calibration of the model were estimated in bootstrap resamples. RESULTS: A total of 5078 people were reported with mpox-like illness. Of 5078 people, 3291 (64.8%) had confirmed mpox. The strongest clinical predictors of confirmed mpox in univariable models were proctitis (OR 6.54, 5.93-7.21), inguinal adenopathy (OR 5.91, 5.36-6.52), and anogenital lesions (OR 5.45, 4.94-6.02). The final model included being a man who has sex with men (8.75, 7.37-10.38), HIV diagnosis (3.04, 2.51-3.69), inguinal adenopathy (2.24, 1.81-2.77), anogenital lesions (2.32, 1.97-2.74), and pustules (1.55, 1.32-1.81). Discrimination capability was excellent (c-statistic 0.88, 95% CI 0.87-0.89) and it was well calibrated (calibration slope 1, 95% CI 0.95-1.05). DISCUSSION: A third of people with mpox-like illness do not have mpox. Factors such as being a man who has sex with men, HIV diagnosis, inguinal adenopathy, pustules, and anogenital lesions are associated with confirmed mpox.

Home or hospital? An observational study of what affects the place of death of people with COVID-19 in Mexico.

BACKGROUND: Out-of-hospital deaths increased during peak coronavirus disease 2019 (COVID-19) pandemic periods. However, aside from COVID-19 severity, which variables are related to being hospitalized have not been properly studied. We examine the association of several variables with dying at home from COVID-19 as opposed to in a hospital. METHODS: We used COVID-19 open data from Mexico City from March 2020 until February 2021. A causal model was prespecified to identify variables of interest. Adjusted logistic regressions were performed to calculate ORs for associations between variables of interest and dying out of hospital due to COVID-19. RESULTS: Among 61 112 people who died due to COVID-19, 8080 died out of hospital. Older age (OR 3.49, age 90 vs 60 y), male sex (OR 1.18) and higher bed occupancy (OR 2.68, 90% vs 50% occupancy) were positively associated with dying outside of hospital. CONCLUSION: Older age could confer different patient wishes or less ability to look for healthcare. Higher bed occupancy may have prevented hospital admission from people who required in-hospital care.

Epidemiological and clinical characteristics of patients with human monkeypox infection in Mexico: a nationwide observational study.

Background: Human monkeypox, a zoonosis historically endemic to West and South Africa, has led to a worldwide outbreak driven by human-to-human transmission resulting in an international public health emergency. Endemic and outbreak monkeypox cases may differ in their affected populations, clinical features, and outcomes. Thus, profiling cases of the current monkeypox outbreak worldwide is crucial. Methods: We performed a nationwide observational surveillance-based study from May 24 to September 5, 2022. Patients that met the operational clinical definition of monkeypox or symptomatic close contacts of confirmed cases were tested by real-time polymerase chain reaction. Clinical data were collected with a standardized case-report form. We report epidemiologic, sociodemographic, and clinical characteristics of confirmed cases. Findings: Five-hundred and sixty-five human monkeypox confirmed cases were analysed; 97.2% were men, of whom 59.5% identified as men who have sex with men, and 54.5% had human immunodeficiency virus infection. The median age was 34 years. All patients but one had rash (99.8%), 78.9% had fever, and 47.8% reported myalgia. The anogenital area was the most commonly affected one by rash (49.6%), and proctitis occurred in 6.2% of patients. Six patients required hospitalization, of which one died due to causes unrelated to monkeypox. Interpretation: The 2022 monkeypox outbreak in Mexico is mainly driven by middle-aged men who have sex with men, of which a large proportion are persons who live with human immunodeficiency virus infection. Clinical features such as the high proportion of anogenital lesions suggest sexual contact is a pivotal transmission mechanism in this outbreak. Funding: This research was supported by grant A1-S-18342 from Consejo Nacional de Ciencia y Tecnología (CONACyT), Mexico (to S.I.V.-F.).

Impact of healthcare strain on access to mechanical ventilation and mortality of hospitalized COVID-19 patients: a retrospective cohort study.

OBJECTIVE: Healthcare saturation has been a prominent worry during the COVID-19 pandemic. Increase of hospital beds with mechanical ventilators has been central in Mexico's approach, but it is not known whether this actually improves access to care and the resulting quality of it. This study aimed to determine the impact of healthcare strain and other pre-specified variables on dying from coronavirus disease 2019 (COVID-19) without receiving invasive mechanical ventilation (IMV). METHODS: A retrospective cohort study was conducted using open data from Mexico City between 8 May 2020 and 5 January 2021. We performed Cox proportional hazards models to identify the strength of the association between proposed variables and the outcomes. RESULTS: Of 33 797 hospitalized patients with suspected or confirmed COVID-19, 19 820 (58.6%) did not require IMV and survived, 5414 (16.1%) required IMV and were intubated and 8563 (25.3%) required IMV but died without receiving it. A greater occupation of IMV-capable beds increased the hazard of death without receiving IMV (hazard ratio [HR] 1.56, comparing 90% with 50% occupation). Private healthcare was the most protective factor for death without IMV (HR 0.14). CONCLUSIONS: Higher hospital bed saturation increased the hazard of dying without being intubated and worsened the outcomes among mechanically ventilated patients. Older age also increased the hazard of the outcomes, while private healthcare dramatically decreased them.

Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial.

BACKGROUND: Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19. METHODS: We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described. RESULTS: We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44-64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24-0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively). CONCLUSION: Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.

Seizures following COVID-19 vaccination in Mexico: A nationwide observational study.

The COVID-19 pandemic led to the development and emergency approval of an array of effective vaccines against SARS-CoV-2. Given the relatively small number of patients included in vaccine trials, postapproval epidemiological surveillance is crucial to detect infrequent vaccine-related adverse events. We conducted a nationwide retrospective descriptive study evaluating the incidence of seizures among recipients of SARS-CoV-2 vaccines in Mexico from December 24, 2020 (date of administration of first doses nationwide) to October 29, 2021. Among 81 916 351 doses of any vaccine that were administered, we documented seizures in 53 patients, of which 31 (60%) were new onset seizures. The incidence rate of seizures per million doses was highest for mRNA-1273 (Moderna) with 2.73 per million, followed by BNT162b2 (Pfizer-BioNTech) with 1.02 per million, and Ad5-nCoV (CanSino) with 1.01 per million. Thus, we found that seizures following SARS-CoV-2 vaccination are exceedingly rare events.