The value of mathematical modelling approaches in epidemiology for public health decisión making

It is discussed the relevance of quantitative approaches, specifically mathematical modelling in epidemiology, in the public health decision-making process. This topic is discussed here based on the experience of various experts in mathematical epidemiology and public health. First, the definition of mathematical modelling is presented, especially in the context of epidemiology. Second, the different uses and socio-political implications, including empirical examples of recent experiences that have taken place at the international level are addressed. Finally, some general considerations regarding the challenges encountered in the use and application of mathematical modelling in epidemiology in the decision-making process at the local and national levels.

Se trata sobre la importancia de los abordajes cuantitativos, específicamente la formulación de modelos matemáticos en epidemiología, dentro del proceso de toma de decisiones en salud pública. Esta importante temática se analiza basándose en la experiencia de algunos expertos en epidemiología matemática y salud pública. En primer lugar, se presenta la definición de modelación matemática, particularmente dentro del contexto de la epidemiología. En segundo lugar, se abordan los diferentes usos y las implicaciones socio-políticas, incluyendo ejemplos de experiencias recientes que han ocurrido a nivel internacional. Finalmente, se hace referencia a ciertas consideraciones generales respecto a los retos que representa el uso y la aplicación de modelos matemáticos en epidemiología para el proceso de toma de decisiones a nivel local y nacional.

Adaptive state restricted barrier Lyapunov-based control of a Stewart platform used as ankle-controlled mobilizer.

In this research project, a closed-chain robotic active ankle orthosis with six degrees of freedom is designed, constructed, numerically valued, instrumented, and experimentally validated. The mechanical arrangement to implement the orthosis corresponds to a six-legged Stewart platform. An adaptive gain control strategy with state constraints based on a state-dependent gains control (that behaves as a diverging function as the states approach the state restrictions) operates the device's motion. The convergence to an invariant positive set centered at the origin of the tracking error space is validated using the stability analysis based on the second method of Lyapunov, with the implementation of a state barrier Lyapunov-like function. The ultimate boundedness of the tracking error is proven with an endorsed gains adjustment method leading to a reachable minimum size of the ultimate bound. Hence, the impact of the state constraints and the formal reason for applying the controller on the suggested orthosis are all established. The orthosis is also controlled using a conventional state feedback strategy to assess the tracking error for an external disturbance and contrast its performance with the proposed control approach. The technology is tested on a few carefully chosen volunteers, successfully limiting the range of motion within a pre-defined region based on the scope of movement reported by patients with ankle illnesses discovered in the literature. Based on a unique mechatronic device, the created system offers a fresh approach to treating this class of impairments.

Increasing support for the prevention of adverse childhood experiences and substance use: Implementation of narrative change strategies in local health departments.

Adverse childhood experiences (ACEs) are potentially traumatic but preventable experiences that occur before the ages of 18, including child abuse, witnessing violence, and parental substance use. ACEs have been linked with increased risk for substance use, along with a variety of other negative health outcomes. However, there is limited evidence of community-level strategies that link ACEs and substance to increase awareness of prevention efforts. This article reports on a $2.9 million program to promote health equity and inform narratives for the prevention of ACEs and substance use within three Midwestern communities. Program partners sought to create new transformational narratives that linked ACEs and substance use, while underscoring the importance of addressing social determinants of health (SDOH) that lead to disparities in ACEs and substance use. A mixed-methods evaluation design included document review, in-depth interviews with program staff (N = 8) and community liaisons (N = 2), and site reports from program staff (N = 8) and their community partners (N = 17). Analyses showed that successful implementation efforts had early leadership buy-in and support, set clear and manageable expectations at the outset of implementation, and developed strong relationships with organizations that engage in health equity work. Training and technical assistance were critical to helping community partners build trust, recognize each other's perspectives, broaden and reframe their world view, and better understand narrative efforts for the primary prevention of ACEs and substance use.

Tumor-specific T cells in head and neck cancer have rescuable functionality and can be identified through single-cell co-culture.

BACKGROUND: Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) remains a treatment-resistance disease with limited response to immunotherapy. While T cells in HNSCC are known to display phenotypic dysfunction, whether they retain rescuable functional capacity and tumor-killing capability remains unclear. METHODS: To investigate the functionality and tumor-specificity of tumor-infiltrating lymphocytes (TILs) across HNSCCs, malignant cell lines and TILs were derived from 31 HPV-negative HNSCCs at the time of standard surgical resection. T cell functional capacity was evaluated through ex vivo expansion, immunophenotyping, and IsoLight single-cell proteomics. Tumor-specificity was investigated through both bulk and single-cell tumor-TIL co-culture. RESULTS: TILs could be successfully generated from 24 patients (77%), including both previously untreated and radiation recurrent HNSCCs. We demonstrate that across HNSCCs, TILs express multiple exhaustion markers but maintain a predominantly effector memory phenotype. After ex vivo expansion, TILs retain immunogenic functionality even from radiation-resistant, exhausted, and T cell-depleted disease. We further demonstrate tumor-specificity of T cells across HNSCC patients through patient-matched malignant cell-T cell co-culture. Finally, we use optofluidic technology to establish an autologous single tumor cell-single T cell co-culture platform for HNSCC. Cells derived from three HNSCC patients underwent single-cell co-culture which enabled identification and visualization of individual tumor-killing TILs in real-time in all patients. CONCLUSIONS: These studies show that cancer-specific T cells exist across HNSCC patients with rescuable immunogenicity and can be identified on a single-cell level. These data lay the foundation for development of patient-specific T cell immunotherapies in HNSCC.

Longitudinal Analysis of Mpox Virus DNA Detectability From Multiple Specimen Types During Acute Illness: A Cohort Study.

Background: Longitudinal data on the detectability of monkeypox virus (MPXV) genetic material in different specimen types are scarce. Methods: We describe MPXV-specific polymerase chain reaction (PCR) results from adults with confirmed mpox infection from Toronto, Canada, including a cohort undergoing weekly collection of specimens from multiple anatomic sites until 1 week after skin lesions had fully healed. We quantified the time from symptom onset to resolution of detectable viral DNA (computed tomography [Ct] ≥ 35) by modeling exponential decay in Ct value as a function of illness day for each site, censoring at the time of tecovirimat initiation. Results: Among 64 men who have sex with men, the median (interquartile range [IQR]) age was 39 (32.75-45.25) years, and 49% had HIV. Twenty received tecovirimat. Viral DNA was detectable (Ct < 35) at baseline in 74% of genital/buttock/perianal skin swabs, 56% of other skin swabs, 44% of rectal swabs, 37% of throat swabs, 27% of urine, 26% of nasopharyngeal swabs, and 8% of semen samples. The median time to resolution of detectable DNA (IQR) was longest for genital/buttock/perianal skin and other skin swabs at 30.0 (23.0-47.9) and 22.4 (16.6-29.4) days, respectively, and shortest for nasopharyngeal swabs and semen at 0 (0-12.1) and 0 (0-0) days, respectively. We did not observe an effect of tecovirimat on the rate of decay in viral DNA detectability in any specimen type (all P > .05). Conclusions: MPXV DNA detectability varies by specimen type and persists for over 3-4 weeks in skin specimens. The rate of decay did not differ by tecovirimat use in this nonrandomized study.

Internet of Things and citizen science as alternative water quality monitoring approaches and the importance of effective water quality communication.

The increasing demand for water and worsening climate change place significant pressure on this vital resource, making its preservation a global priority. Water quality monitoring programs are essential for effectively managing this resource. Current programs rely on traditional monitoring approaches, leading to limitations such as low spatiotemporal resolution and high operational costs. Despite the adoption of novel monitoring approaches that enable better data resolution, the public's comprehension of water quality matters remains low, primarily due to communication process deficiencies. This study explores the advantages and challenges of using Internet of Things (IoT) and citizen science as alternative monitoring approaches, emphasizing the need for enhancing public communication of water quality data. Through a systematic review of studies implemented on-field, we identify and propose strategies to address five key challenges that IoT and citizen science monitoring approaches must overcome to mature into robust sources of water quality information. Additionally, we highlight three fundamental problems affecting the water quality communication process and outline strategies to convey this topic effectively to the public.

Predictive models for health outcomes due to SARS-CoV-2, including the effect of vaccination: a systematic review.

BACKGROUND: The interaction between modelers and policymakers is becoming more common due to the increase in computing speed seen in recent decades. The recent pandemic caused by the SARS-CoV-2 virus was no exception. Thus, this study aims to identify and assess epidemiological mathematical models of SARS-CoV-2 applied to real-world data, including immunization for coronavirus 2019 (COVID-19). METHODOLOGY: PubMed, JSTOR, medRxiv, LILACS, EconLit, and other databases were searched for studies employing epidemiological mathematical models of SARS-CoV-2 applied to real-world data. We summarized the information qualitatively, and each article included was assessed for bias risk using the Joanna Briggs Institute (JBI) and PROBAST checklist tool. The PROSPERO registration number is CRD42022344542. FINDINGS: In total, 5646 articles were retrieved, of which 411 were included. Most of the information was published in 2021. The countries with the highest number of studies were the United States, Canada, China, and the United Kingdom; no studies were found in low-income countries. The SEIR model (susceptible, exposed, infectious, and recovered) was the most frequently used approach, followed by agent-based modeling. Moreover, the most commonly used software were R, Matlab, and Python, with the most recurring health outcomes being death and recovery. According to the JBI assessment, 61.4% of articles were considered to have a low risk of bias. INTERPRETATION: The utilization of mathematical models increased following the onset of the SARS-CoV-2 pandemic. Stakeholders have begun to incorporate these analytical tools more extensively into public policy, enabling the construction of various scenarios for public health. This contribution adds value to informed decision-making. Therefore, understanding their advancements, strengths, and limitations is essential.

Estimation of Societal Values of Health States Preferences at the National Level for Low- and Middle-Income Countries.

OBJECTIVES: Social preference values of health states are a fundamental input for the preparation of studies in health economics. Several countries have undertaken studies to obtain these values. Our objective was to conduct a structured and systematic literature review of articles that calculates this set of representative values at the national level in low- and middle-income countries (LMICs). METHODS: In this systematic review, we searched the Embase, MEDLINE, Ovid, SciELO, and LILACS databases, among others, for studies published up to June 2022 that estimated nationally representative health states preferences values for LMICs. We summarized the information qualitatively and assessed the risk of bias in each article using the consensus-based standards for selecting health measurement instruments checklist tool. RESULTS: Of the 23 663 articles identified, 35 studies were eligible for inclusion. The studies were from 19 countries in Latin-American, Europe, Africa, and Asia. No studies were found for low-income countries. The most commonly applied generic instrument for measuring health-related quality of life was the 5-level version of EQ-5D and 3-level version of EQ-5D. Preference was given to face-to-face administration of these instruments. The sociodemographic variables with the most significant negative correlation versus utility were older adults, marital status (widowed or divorced), and low educational level and income. CONCLUSIONS: Worldwide, there have been few studies that have estimated, in a nationally representative manner, the social values of health states preferences in LMICs. We consider the local estimate of this set of societal values relevant for any society to improve decision making in allocating resources in health budgets.

Appropriate usage of post-exposure prophylaxis-in-pocket for HIV prevention by individuals with low-frequency exposures.

PEP-In-Pocket (Post-Exposure Prophylaxis-In-Pocket, or "PIP") is a biobehavioural HIV prevention strategy wherein patients are proactively identified and given a prescription for HIV post-exposure prophylaxis (PEP) medications to self-initiate in case of high-risk exposures. We evaluated this strategy in a prospective observational study at two hospital-based clinics in Toronto, Canada. HIV-negative adults using PIP underwent chart review and completed quarterly electronic questionnaires over 12 months. The primary objective was to quantify appropriate PIP initiation, defined as starting PIP within 72 h of a high-risk exposure. Secondary objectives were to quantify HIV seroconversions, changes in sexual risk behaviour, sexual satisfaction, and satisfaction with the PIP strategy. From 11/2017 to 02/2020, 43 participants enrolled and completed ≥1 questionnaire. PIP was self-initiated on 27 occasions by 15 participants, of which 24 uses (89%) were appropriate, 2 were unnecessary, and 1 was for an unknown exposure. Chart review identified no inappropriate non-use. Over 32 person-years of testing follow-up, we observed zero HIV seroconversions. Sexual risk declined modestly over follow-up, with a HIRI-MSM (HIV Incidence Risk Index for MSM) change of -0.39 (95% CI = -0.58, -0.21 per 3 months, p < .001). Sexual satisfaction was stable over time. At 12 months, 31 (72%) remained on PIP, 8 (19%) had transitioned to pre-exposure prophylaxis and 4 (9%) were lost-to-follow-up. Among participants who remained on PIP and completed questionnaires at 12 months, 24/25 (96%) strongly/somewhat agreed that PIP decreased their anxiety about contracting HIV and 25/25 (100%) strongly/somewhat agreed that they would recommend PIP to a friend. PIP is a feasible HIV prevention strategy in carefully selected individuals at modest HIV risk.

Loss ratio of the capitation payment unit of the health-promoting entities in Colombia between 2017 and 2021: a financial-actuarial approach.

BACKGROUND: Because of a change of government, the Colombian Ministry of Health and Social Protection is in the process of presenting a structural reform for the General System of Social Security in Health (GSSSH), in order to implement a 'preventive and predictive health model'. However, it will always be relevant to review and analyze the fiscal implications of any proposed public policy program, to protect financial sustainability and to promote the better functioning of the system in question. METHODS: To contribute to this topic, we have calculated, using a financial-actuarial approach, the loss ratio for the years 2017 to 2021 for the Capitation Payment Unit (CPU) for all the Health-Promoting Entities (HPE) for both contributory and subsidized schemes. This information, derived from public reports available on the official website of the National Health Superintendency, allows us to estimate the financial burden of the institutions that guarantee access to and provision of health services and technologies in Colombia. RESULTS: The study shows that close to half of the HPEs in Colombia (which represent 11.6 million affiliates) have CPU loss ratios of more than 100% for the year 2021, evidencing insufficient resources for the operation of health insurance. CONCLUSIONS: Finally, we propose some policy recommendations regarding the strengthening of informed decision-making to allow the healthy financial sustainability of the Colombian GSSSH.

Detecting unexpected growths in health technologies expenditures: the case of MIPRES in Colombia.

We developed an algorithm to explore unexpected growth in the usage and costs of health technologies. We exploit data from the expenditures on technologies funded by the Colombian government under the compulsory insurance system, where all prescriptions for technologies not included in an explicit list must be registered in a centralized information system, covering the period from 2017 to 2022. The algorithm consists of two steps: an outlier detection method based on the density of the expenditures for selecting a first set of technologies to consider (39 technologies out of 106,957), and two anomaly detection models for time series to determine which insurance companies, health providers, and regions have the most notorious increases. We have found that most medicines associated with atypical behavior and significant monetary growth could be linked to the use of recently introduced drugs in the market. These drugs have valid patents and very specific clinical indications, often involving high-cost pharmacological treatments. The most relevant case is the Burosumab, approved in 2018 to treat a rare genetic disorder affecting skeletal growth. Secondly, there is clear evidence of anomalous increasing trend evolutions in the identified enteral nutritional support supplements or Food for Special Medical Purposes. The health system did not purchase these products before July 2021, but in 2022 they represented more than 500,000 USD per month.

Years of life lost to COVID-19 in 49 countries: A gender- and life cycle-based analysis of the first two years of the pandemic.

Specific mortality rates have been widely used to monitor the main impacts of the COVID-19 pandemic; however, a more meaningful measure is the Years of Life Lost (YLL) due to the disease, considering it takes into account the premature nature of each death. We estimated the YLL due to COVID-19 between January 2020 and December 2021 in 49 countries for which information was available, developing an analytical method that mathematically refines that proposed by the World Health Organization. We then calculated YLL rates overall, as well as by sex and life cycle. Additionally, we estimated the national cost-effective budgets required to manage COVID-19 from a health system perspective. During the two years of analysis, we estimated that 85.6 million years of life were lost due to COVID-19 in the 49 countries studied. However, due to a lack of data, we were unable to analyze the burden of COVID-19 in about 75% of the countries in the world. We found no difference in the magnitude of YLL rates by gender but did find differences according to life cycle, with older adults contributing the greatest burden of YLL. The COVID-19 pandemic has posed a significant burden of disease, which has varied between countries. However, due to the lack of quality and disaggregated data, it has been difficult to monitor and compare the pandemic internationally. Therefore, it is imperative to strengthen health information systems in order to prepare for future pandemics as well as to evaluate their impacts.

Disjuncture between self-perceived and clinically assessed risk of HIV among gay, bisexual, and other men who have sex with men in Ontario and British Columbia, Canada.

BACKGROUND: Self-perceived and clinically assessed HIV risk do not always align. We compared self-perceived and clinically assessed risk of HIV and the reasons for self-perceived low risk of HIV among gay, bisexual, and other men who have sex with men (GBM) from large urban centers in Ontario and British Columbia, Canada. METHODS: Never PrEP users recruited from sexual health clinics or online, completed a cross-sectional survey between July/2019 and August/2020. We contrasted self-perceived HIV risk against criteria from the Canadian PrEP guidelines and participants were categorized as concordant or discordant. We used content analysis to categorize participants' free-text explanations for perceived low HIV risk. These were compared with answers to quantitative responses about condomless sex acts and number of partners. RESULTS: Of 315 GBM who self-perceived low risk of HIV, 146 (46%) were considered at high risk according to the guidelines. Participants with discordant assessment were younger, had less years of formal education, were more often in an open relationship and were more likely to self-identify as gay. Reasons for self-perceived low HIV risk in the discordant group were condom use (27%), being in a committed relationship/having one main partner (15%), having no or infrequent anal sex (12%) and having few partners (10%). CONCLUSIONS: There is a disjuncture between self-perceived and clinically assessed risk of HIV. Some GBM may underestimate their HIV risk and clinical criteria may overestimate risk. Bridging these gaps requires efforts to increase HIV risk awareness in the community, and refinement of clinical assessments based on individualized discussions between the provider and the user.

Reasons for not using pre-exposure prophylaxis for HIV and strategies that may facilitate uptake in Ontario and British Columbia among gay, bisexual and other men who have sex with men: a cross-sectional survey.

BACKGROUND: Pre-exposure prophylaxis (PrEP) for HIV is underutilized. We aimed to identify barriers to use of PrEP and strategies that may facilitate its uptake. METHODS: Gay, bisexual and other men who have sex with men, aged 19 years or older and living in Ontario and British Columbia, Canada, completed a cross-sectional survey in 2019-2020. Participants who met Canadian PrEP guideline criteria and were not already using PrEP identified relevant barriers and which strategies would make them more likely to start PrEP. We described the barriers and strategies separately for Ontario and BC. RESULTS: Of 1527 survey responses, 260 respondents who never used PrEP and met criteria for PrEP were included. In Ontario, the most common barriers were affordability (43%) and concern about adverse effects (42%). In BC, the most common reasons were concern about adverse effects (41%) and not feeling at high enough risk (36%). In Ontario, preferred strategies were short waiting time (63%), the health care provider informing about their HIV risk being higher than perceived (62%), and a written step-by-step guide (60%). In BC, strategies were short waiting time (68%), people speaking publicly about PrEP (68%), and the health care provider counselling about their HIV risk being higher than perceived (64%), adverse effects of PrEP (65%) and how well PrEP works (62%). INTERPRETATION: Concern about adverse effects and not self-identifying as having high risk for HIV were common barriers, and shorter waiting times may increase PrEP uptake. In Ontario, the findings suggested lack of affordability, whereas in BC, strategies involving health care providers were valued.

Statistical actuarial estimation of the Capitation Payment Unit from copula functions and deep learning: historical comparability analysis for the Colombian health system, 2015-2021.

The Capitation Payment Unit (CPU) financing mechanism constitutes more than 70% of health spending in Colombia, with a budget allocation of close to 60 trillion Colombian pesos for the year 2022 (approximately 15.7 billion US dollars). This article estimates actuarially, using modern techniques, the CPU for the contributory regime of the General System of Social Security in Health in Colombia, and compares it with what is estimated by the Ministry of Health and Social Protection. Using freely available information systems, by means of statistical copulas functions and artificial neural networks, pure risk premiums are calculated between 2015 and 2021. The study concludes that the weights by risk category are systematically different, showing historical pure premiums surpluses in the group of 0-1 years and deficits (for the regions normal and cities) in the groups over 54 years of age.

Characterization of the population affiliated to the subsidized health insurance scheme in Colombia: a systematic review and meta-analysis.

BACKGROUND: Some reports suggest there are differences in health needs between the population affiliated to the subsidized health insurance scheme (SS) and those affiliated to the contributory health insurance scheme (CS) in Colombia. The objective of this study was to identify the epidemiological profile of the population affiliated to the SS in Colombia and to compare the main epidemiological features of the SS to the CS. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) methodology, the search was carried out from 1993, with no other restriction. The information was synthesized into five categories according to the most important risk populations. We estimated combined incidences from epidemiological surveillance data, prevalence ratio, and other measures to estimate the difference between the studied groups. A 95% confidence interval was considered. A random effects model was used weighted by the inverse of the variance of the cumulative incidence calculated for each disease. The risk of bias was assessed using the Joanna Briggs Institute's critical appraisal tools. RESULTS: A total of 16,236 articles were identified; 14,972 were excluded after title and abstract screening, 725 articles were verified as full text, and finally 268 articles were included. The relative risk of non-communicable and communicable diseases was lower in the SS than in the CS (RR: 0.37 and 0.72, respectively, p-value < 0.05). However, the risk of presenting obstetric and maternal conditions in the SS versus the CS was RR 1.55 for frequent conditions during early childhood, and for other diseases it was RR 1.28 with a p-value of < 0.05. The use of health services was different by scheme, with less demand, access, and provision being found in health services in the SS. CONCLUSIONS: This study allowed us to conclude that there are differences in the incidence, prevalence, and use of health services between health affiliation schemes (SS and CS) in Colombia, thereby assisting in decision-making for stakeholders. TRIAL REGISTRATION: PROSPERO Registration number CRD42021279234.

Dietary choline intake is necessary to prevent systems-wide organ pathology and reduce Alzheimer's disease hallmarks.

There is an urgent need to identify modifiable environmental risk factors that reduce the incidence of Alzheimer's disease (AD). The B-like vitamin choline plays key roles in body- and brain-related functions. Choline produced endogenously by the phosphatidylethanolamine N-methyltransferase protein in the liver is not sufficient for adequate physiological functions, necessitating daily dietary intake. ~90% of Americans do not reach the recommended daily intake of dietary choline. Thus, it's imperative to determine whether dietary choline deficiency increases disease outcomes. Here, we placed 3xTg-AD, a model of AD, and non-transgenic (NonTg) control mice on either a standard laboratory diet with sufficient choline (ChN; 2.0 g/kg choline bitartrate) or a choline-deficient diet (Ch-; 0.0 g/kg choline bitartrate) from 3 to 12 (early to late adulthood) months of age. A Ch- diet reduced blood plasma choline levels, increased weight, and impaired both motor function and glucose metabolism in NonTg mice, with 3xTg-AD mice showing greater deficits. Tissue analyses showed cardiac and liver pathology, elevated soluble and insoluble Amyloid-ß and Thioflavin S structures, and tau hyperphosphorylation at various pathological epitopes in the hippocampus and cortex of 3xTg-AD Ch- mice. To gain mechanistic insight, we performed unbiased proteomics of hippocampal and blood plasma samples. Dietary choline deficiency altered hippocampal networks associated with microtubule function and postsynaptic membrane regulation. In plasma, dietary choline deficiency altered protein networks associated with insulin metabolism, mitochondrial function, inflammation, and fructose metabolic processing. Our data highlight that dietary choline intake is necessary to prevent systems-wide organ pathology and reduce hallmark AD pathologies.

Necrosis, netosis, and apoptosis in pulmonary tuberculosis and type-2 diabetes mellitus. Clues from the patient's serum.

Pulmonary tuberculosis (PTB) and type 2 diabetes mellitus (T2DM) are two inflammatory diseases whose pathology involves neutrophils (NEU) as key participants. Countless inflammatory elements produced at the lesion sites leak into the blood and are distributed systemically. The study aimed to investigate the effect of the serum of patients with PTB, T2DM, and PTB + T2DM on the cellular and nuclear morphology of healthy NEU. Monolayers of NEU were prepared and incubated with sera from PTB (n꓿ 10), T2DM (n꓿10), PTB + T2DM (n꓿ 10) patients, or sera from healthy people (n = 10). Monolayers were stained for histones, elastase, and myeloperoxidase for NETosis, annexin V for apoptosis, and Iris fuchsia for necrosis. Hoechst stain (DNA) was used to identify the nuclear alterations. Necrosis was the predominant alteration. Sera from PTB + T2DM were the most potent change inducers. Normal sera did not induce cell alterations. The blood of TBP and T2DM patients carries a myriad of abnormal elements that induce necrosis of NEU in normal people, thus reflecting what might occur in the neutrophils of the patients themselves. These findings reinforce the participation of NEU in the pathology of these diseases. Necrosis is expected to be the most frequent neutrophil-induced alteration in tuberculosis and diabetes mellitus.

PrEP-related stigma and PrEP use among gay, bisexual and other men who have sex with men in Ontario and British Columbia, Canada.

BACKGROUND: We aimed to explore the association between PrEP-related stereotypes and perceived disapproval (hereafter PrEP-related stigma), and PrEP use. METHODS: We used data from a cross-sectional online survey among adult gay, bisexual, other men who have sex with men in Ontario and British Columbia, Canada. Participants were recruited 2019-2020 in-person from sexual health clinics and outreach programs, and online through dating mobile applications and websites. We used logistic regression models to explore the relationship between PrEP-related stigma and: 1-being a 'never' versus 'current' PrEP user, and 2-being a 'former' versus 'current' user. RESULTS: The median age of the sample was 32 (Q1-Q3 = 27-40), most were white born in Canada (48%), 45% had never used PrEP, 16% were former PrEP users and 39% were current PrEP users. Of 1527 individuals who started the survey, 1190 participants answered questions about PrEP-related stigma: 254 (21.3%) were classified as having low level of PrEP-related stigma, 776 (65.2%) intermediate, and 160 (13.5%) high. No significant association was found when never PrEP users and current PrEP users were compared: adjusted OR = 1.44 (95%-CI: 0.8-2.5). High PrEP-related stigma was positively associated with being a former PrEP user compared to being a current PrEP user: adjusted OR = 2.5 (95%-CI: 1.3-4.9). CONCLUSION: PrEP-related stigma is associated with not using PrEP, particularly with PrEP discontinuation. Our findings indicate that stigma persists as a barrier to PrEP use.