Neuroinflammation alters GABAergic neurotransmission in hyperammonemia and hepatic encephalopathy, leading to motor incoordination. Mechanisms and therapeutic implications.

Enhanced GABAergic neurotransmission contributes to impairment of motor coordination and gait and of cognitive function in different pathologies, including hyperammonemia and hepatic encephalopathy. Neuroinflammation is a main contributor to enhancement of GABAergic neurotransmission through increased activation of different pathways. For example, enhanced activation of the TNFα-TNFR1-NF-κB-glutaminase-GAT3 pathway and the TNFα-TNFR1-S1PR2-CCL2-BDNF-TrkB pathway in cerebellum of hyperammonemic rats enhances GABAergic neurotransmission. This is mediated by mechanisms affecting GABA synthesizing enzymes GAD67 and GAD65, total and extracellular GABA levels, membrane expression of GABAA receptor subunits, of GABA transporters GAT1 and GAT three and of chloride co-transporters. Reducing neuroinflammation reverses these changes, normalizes GABAergic neurotransmission and restores motor coordination. There is an interplay between GABAergic neurotransmission and neuroinflammation, which modulate each other and altogether modulate motor coordination and cognitive function. In this way, neuroinflammation may be also reduced by reducing GABAergic neurotransmission, which may also improve cognitive and motor function in pathologies associated to neuroinflammation and enhanced GABAergic neurotransmission such as hyperammonemia, hepatic encephalopathy or Parkinson's disease. This provides therapeutic targets that may be modulated to improve cognitive and motor function and other alterations such as fatigue in a wide range of pathologies. As a proof of concept it has been shown that antagonists of GABAA receptors such as bicuculline reduces neuroinflammation and improves cognitive and motor function impairment in rat models of hyperammonemia and hepatic encephalopathy. Antagonists of GABAA receptors are not ideal therapeutic tools because they can induce secondary effects. As a more effective treatment to reduce GABAergic neurotransmission new compounds modulating it by other mechanisms are being developed. Golexanolone reduces GABAergic neurotransmission by reducing the potentiation of GABAA receptor activation by neurosteroids such as allopregnanolone. Golexanolone reduces neuroinflammation and GABAergic neurotransmission in animal models of hyperammonemia, hepatic encephalopathy and cholestasis and this is associated with improvement of fatigue, cognitive impairment and motor incoordination. This type of compounds may be useful therapeutic tools to improve cognitive and motor function in different pathologies associated with neuroinflammation and increased GABAergic neurotransmission.

Biomaterial engineering strategies for modeling the Bruch's membrane in age-related macular degeneration.

Age-related macular degeneration, a multifactorial inflammatory degenerative retinal disease, ranks as the leading cause of blindness in the elderly. Strikingly, there is a scarcity of curative therapies, especially for the atrophic advanced form of age-related macular degeneration, likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier, the prime target tissue of age-related macular degeneration. Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier, integrated by the dynamic interaction of the retinal pigment epithelium, the Bruch's membrane, and the underlying choriocapillaris. The Bruch's membrane provides structural and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier, and therefore adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrier. In the last years, advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials. This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healthy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems. Then, we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling, discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.

Exploring refugees' experience of accessing dental health services in host countries: a scoping review.

Introduction: Refugees often face worse oral health outcomes, such as periodontal diseases and dental caries in host countries due to barriers including language and cultural differences, institutional discrimination, and restricted use of dental health services. This scoping review aims to map and summarise the available studies on refugees' experience of accessing dental health services in the host countries, to identify the main characteristics of the dental health services that refugees access and to explore the barriers and enablers to navigate the dental health service system in their host countries. Methods: The Joanna Briggs Institute (JBI) framework was adopted. PubMed, Scopus, Assia, CINAHL and Social Services Abstract were searched. A search strategy was developed using Medical Subject Headings (MeSH) terms and a combination of search operators and syntax used in MEDLINE were adopted for the remaining databases. Data were synthesised using thematic analysis. Results: Fourteen articles were included. Most studies used qualitative methods and Australia seemed to be the country with the highest number of publications surrounding this topic. The included studies showed that refugees frequently encountered substantial obstacles when attempting to access dental services in host countries. Numerous barriers such as language barriers, cultural differences, and lack of health insurance or financial support hindered refugees' ability to access these services. Additionally, many refugees possessed limited knowledge of the dental care system in their new country. As a result of untreated dental problems, refugees suffered from pain and other health complications. Discussion: This scoping review explored the challenges refugees have experienced in accessing dental health services in host countries, which included the key barriers such as affordability, accessibility, accommodation, availability, awareness, and acceptability. The scarcity of relevant research highlighted the need for a more comprehensive understanding of refugees' experiences accessing dental health services in host countries. Limited data were identified regarding evidence focusing on the characteristics of dental services accessed by refugees in host countries.

Improved likelihood ratios for face recognition in surveillance video by multimodal feature pairing.

In forensic and security scenarios, accurate facial recognition in surveillance videos, often challenged by variations in pose, illumination, and expression, is essential. Traditional manual comparison methods lack standardization, revealing a critical gap in evidence reliability. We propose an enhanced images-to-video recognition approach, pairing facial images with attributes like pose and quality. Utilizing datasets such as ENFSI 2015, SCFace, XQLFW, ChokePoint, and ForenFace, we assess evidence strength using calibration methods for likelihood ratio estimation. Three models-ArcFace, FaceNet, and QMagFace-undergo validation, with the log-likelihood ratio cost (Cllr) as a key metric. Results indicate that prioritizing high-quality frames and aligning attributes with reference images optimizes recognition, yielding similar Cllr values to the top 25% best frames approach. A combined embedding weighted by frame quality emerges as the second-best method. Upon preprocessing facial images with the super resolution CodeFormer, it unexpectedly increased Cllr, undermining evidence reliability, advising against its use in such forensic applications.

Comparative evaluation of lateral flow assays to diagnose chronic Trypanosoma cruzi infection in Bolivia.

Bolivia has the highest incidence of Chagas disease (CD) worldwide. Caused by the parasite Trypanasoma cruzi, CD is generally a chronic condition. Diagnosis is logistically and financially challenging, requiring at least two different laboratory-based serological tests. Many CD cases are missed; in Bolivia it is estimated just 6% of individuals chronically infected with T. cruzi get diagnosed. Achieving control on the way to elimination of CD requires a radical simplification of the current CD testing pathways, to overcome the barriers to accessing CD treatment. We aimed to generate unbiased performance data of lateral flow assays (LFAs) for T. cruzi infection in Bolivia, to evaluate their usefulness for improving T. cruzi diagnosis rates in a precise and efficient manner. This retrospective, laboratory-based, diagnostic evaluation study sought to estimate the sensitivity/specificity of 10 commercially available LFAs for T. cruzi, using the current CD diagnostic algorithm employed in Bolivia as the reference test method. All tests were blinded at the study site and performed by three operators. In total, 470 serum samples were tested, including 221 and 249 characterized as CD-positive/-negative, respectively. The LFAs were scored according to their relative importance using a decision-tree-based algorithm, with the mean decrease in Gini index as the scoring metric. The estimates of sensitivities ranged from 62.2-97.7% (95% confidence interval (CI) lower bound 55.0-94.7%); for specificities the range was 78.6-100% (95% CI lower bound 72.0-97.5%); 5/10 and 6/10 tests had sensitivity >90% and specificity >95%, respectively. Four LFAs showed high values of both sensitivity (93-95%) and specificity (97-99%). The agreement between 6 LFAs and the reference tests was almost perfect (Kappa 0.83-0.94). Most LFAs evaluated thus showed performances comparable with current laboratory-based diagnostic methods.

Cost of illness due to respiratory syncytial virus acute lower respiratory tract infection among infants hospitalized in Argentina.

BACKGROUND: Information is scarce regarding the economic burden of respiratory syncytial virus (RSV) disease in low-resource settings. This study aimed to estimate the cost per episode of hospital admissions due to RSV severe disease in Argentina. METHODS: This is a prospective cohort study that collected information regarding 256 infants under 12 months of age with acute lower respiratory tract infection (ALRTI) due to RSV in two public hospitals of Buenos Aires between 2014 and 2016. Information on healthcare resource use was collected from the patient's report and its associated costs were estimated based on the financial database and account records of the hospitals. We estimated the total cost per hospitalization due to RSV using the health system perspective. The costs were estimated in US dollars as of December 2022 (1 US dollar = 170 Argentine pesos). RESULTS: The mean costs per RSV hospitalization in infants was US$587.79 (95% confidence interval [CI] $535.24 - $640.33). The mean costs associated with pediatric intensive care unit (PICU) admission more than doubled from those at regular pediatric wards ($1,556.81 [95% CI $512.21 - $2,601.40] versus $556.53 [95% CI $514.59 - $598.48]). CONCLUSIONS: This study shows the direct economic impact of acute severe RSV infection on the public health system in Argentina. The estimates obtained from this study could be used to inform cost-effectiveness analyses of new preventive RSV interventions being developed.

Performance of graphene oxide as a water-repellent coating nanomaterial to extend the service life of concrete structures.

Surface treatments help to protect the built heritage against damage (environmental, accidental, etc.), reducing repair and restitution costs and increasing the useful life of building materials. The use of nanomaterials is currently the most important field of research in surface treatment technology for the preservation of building materials and, more specifically, to improve their durability and prevent their deterioration, extending their useful life. This paper studies the influence of a graphene oxide (GO) suspension as a surface treatment on the properties of concrete. The results indicate that, at best, surface treatment with GO can decrease both the water absorption and capillary absorption of concrete by about 15 %. The increase in the amount of GO deposited as a surface treatment leads to a further reduction in concrete water absorption. It is shown that, at best, GO coating also reduces water penetration at low and high pressures by approximately 20 % and 60 %, respectively. In addition, scanning electron microscopy analysis shows that GO surface treatment facilitates the hydration process and densifies the concrete microstructure. A simple aqueous suspension of GO is revealed as a tool with a high potential to protect concrete surfaces in a fast and cost-effective way, thanks to the easy application by spraying and the small amount of material needed to obtain great results.

Autophagy Modulation and Its Implications on Glioblastoma Treatment.

Autophagy is a vital cellular process that functions to degrade and recycle damaged organelles into basic metabolites. This allows a cell to adapt to a diverse range of challenging conditions. Autophagy assists in maintaining homeostasis, and it is tightly regulated by the cell. The disruption of autophagy has been associated with many diseases, such as neurodegenerative disorders and cancer. This review will center its discussion on providing an in-depth analysis of the current molecular understanding of autophagy and its relevance to brain tumors. We will delve into the current literature regarding the role of autophagy in glioma pathogenesis by exploring the major pathways of JAK2/STAT3 and PI3K/AKT/mTOR and summarizing the current therapeutic interventions and strategies for glioma treatment. These treatments will be evaluated on their potential for autophagy induction and the challenges associated with their utilization. By understanding the mechanism of autophagy, clinical applications for future therapeutics in treating gliomas can be better targeted.

Depression and Suicide Risk Among Nursing Staff at a Honduran National Hospital.

BACKGROUND: Depression and suicide risk among nursing staff have become increasingly concerning, especially given the demanding nature of their profession. The World Health Organization identifies depression as a primary factor contributing to global disability and suicide deaths. METHODS: A descriptive, non-experimental, cross-sectional cohort study was conducted, encompassing the eligible personnel (n=82) out of a total of 102 nurses at the Mario Catarino Rivas Hospital in San Pedro Sula, Honduras, from October to November 2022. The study utilized the Okasha assessment tool to gauge the prevalence of suicidal risk and the Beck Depression Inventory-II (BDI-II) instrument to analyze the extent and severity of depression. In addition, the participants completed a demographic survey.  Results: The average age of participants was 34.91 years, with a majority (86.6%) being female. In terms of work assignments, 54.9% were employed in the inpatient area. Regarding the mental health of the nursing staff, 78% displayed no or minimal depression, 9.7% presented mild depression, 7.3% showed moderate depression, 4.8% displayed severe depression, and 14.6% exhibited a suicide risk. Young adults had the highest prevalence of all three levels of depression, and the emergency department and inpatient area had the most at-risk individuals for suicidal tendencies. CONCLUSION: The study offers a comprehensive insight into the demographics, work environment, and mental health of the nursing staff at the Honduran National Hospital. The results highlight the importance of specialized measures and strong support systems to safeguard the mental health of nursing staff.

Postcardiotomy Shock Syndrome: A Narrative Review of Perioperative Diagnosis and Management.

Postcardiotomy shock (PCS) is generally described as the inability to separate from cardiopulmonary bypass due to ineffective cardiac output after cardiotomy, which is caused by a primary cardiac disorder, resulting in inadequate tissue perfusion. Postcardiotomy shock occurs in 0.5% to 1.5% of contemporary cardiac surgery cases, and is accompanied by an in-hospital mortality of approximately 67%. In the last 2 decades, the incidence of PCS has increased, likely due to the increased age and baseline morbidity of patients requiring cardiac surgery. In this narrative review, the authors discuss the epidemiology and pathophysiology of PCS, the rationale and evidence behind the initiation, continuation, escalation, and discontinuation of mechanical support devices in PCS, and the anesthetic implications.

Zinc-Doped Iron Oxide Nanoparticles as a Proton-Activatable Agent for Dose Range Verification in Proton Therapy.

Proton therapy allows the treatment of specific areas and avoids the surrounding tissues. However, this technique has uncertainties in terms of the distal dose fall-off. A promising approach to studying the proton range is the use of nanoparticles as proton-activatable agents that produce detectable signals. For this, we developed an iron oxide nanoparticle doped with Zn (IONP@Zn-cit) with a hydrodynamic size of 10 nm and stability in serum. Cytotoxicity, defined as half of the surveillance, was 100 µg Zn/mL in the U251 cell line. The effect on clonogenic cell death was tested after X-ray irradiation, which suggested a radioprotective effect of these nanoparticles at low concentrations (1-10 µg Zn/mL). To evaluate the production of positron emitters and prompt-gamma signals, IONP@Zn-cit was irradiated with protons, obtaining prompt-gamma signals at the lowest measured concentration (10 mg Zn/mL). Finally, 67Ga-IONP@Zn-cit showed accumulation in the liver and spleen and an accumulation in the tumor tissue of 0.95% ID/g in a mouse model of U251 cells. These results suggest the possibility of using Zn nanoparticles as proton-activatable agents to verify the range by prompt gamma detection and face the challenges of prompt gamma detection in a specific biological situation, opening different avenues to go forward in this field.

Efficacy of invasive and non-invasive methods for the treatment of Parkinson's disease: Nanodelivery and enriched environment.

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterised by the loss of dopaminergic neurons in the substantia nigra pars compacta and the subsequent motor disability. The most frequently used treatments in clinics, such as L-DOPA, restore dopaminergic neurotransmission in the brain. However, these treatments are only symptomatic, have temporary efficacy, and produce side effects. Part of the side effects are related to the route of administration as the consumption of oral tablets leads to unspecific pulsatile activation of dopaminergic receptors. For this reason, it is necessary to not only find alternative treatments, but also to develop new administration systems with better security profiles. Nanoparticle delivery systems are new administration forms designed to reach the pharmacological target in a highly specific way, leading to better drug bioavailability, efficacy and safety. Some of these delivery systems have shown promising results in animal models of PD not only when dopaminergic drugs are administered, but even more when neurotrophic factors are released. These latter compounds promote maturation and survival of dopaminergic neurons and can be exogenously administered in the form of pharmacological therapy or endogenously generated by non-pharmacological methods. In this sense, experimental exposure to enriched environments, a non-invasive strategy based on the combination of social and inanimate stimuli, enhances the production of neurotrophic factors and produces a neuroprotective effect in parkinsonian animals. In this review, we will discuss new nanodelivery systems in PD with a special focus on therapies that increase the release of neurotrophic factors.

Temporal assessment of disparities in California COVID-19 mortality by industry: a population-based retrospective cohort study.

PURPOSE: To assess changes in the COVID-19 mortality rate and disparities over variants or waves by industry. METHODS: We identified COVID-19 deaths that occurred between January 2020 and May 2022 among California workers aged 18-64 years using death certificates, and estimated Californians at risk using the Current Population Survey. The waves in deaths were wave 1: March-June 2020, wave 2: July-November 2020, wave 3/Epsilon and Alpha variants: December 2020-May 2021, wave 4/Delta variant: June 2021-January 2022, and wave 5/Omicron variant: February-May 2022. We used Poisson regression to generate wave-specific mortality rate ratios (MRR) and included an interaction term between industry and wave in different models to assess significance of the change in MRR. RESULTS: In all waves of the pandemic, healthcare, other services, manufacturing, transportation, and retail trade industries had higher mortality rates than the professional, scientific, and technical industry. The healthcare industry had the highest relative rate earlier in the pandemic, while other services, utilities, and accommodation and food services industries had substantial increases in MRR in later waves. CONCLUSIONS: Industries that consistently had disproportionate COVID-19 mortality may have benefitted from protections that consider workers' increased exposure and vulnerability to severe outcomes.

Estudio longitudinal del efecto del confinamiento por COVID-19 en la aparición de trastornos del sueño en una muestra clínica de niños y adolescentes españoles / Longitudinal study of the impact of confinement in a sample of Spanish children and adolescents

Aunque abundantes estudios aportan evidencia sobre el impacto del confinamiento en el sueño en población adulta, ésta resulta escasa en población infanto-juvenil. Así, el estudio surge de la necesidad de ampliar el conocimiento al respecto para amortiguar la urgencia clínica actual. El presente trabajo se propone estudiar el efecto de las restricciones debidas a la COVID-19 en las alteraciones del sueño de una muestra de niños y adolescentes que fueron atendidos en la consulta de psicología clínica del servicio público de salud. Se contó con una muestra de pacientes de entre 3 y 16 años, (Medad = 10.51, DT = 3.28). Como instrumentos de medida se utilizaron la Escala de Alteraciones del Sueño de Bruni, en tres momentos de medida, y un cuestionario con variables sociodemográficas. Se realiza un análisis descriptivo de evolución de la prevalencia y comparaciones de proporciones. Los resultados muestran que un 82% de la muestra tenía una alteración del sueño, que se mantuvo 6 meses y un descenso significativo al 22% un año después, coincidiendo con la flexibilización de las medidas. También se encuentran diferencias significativas entre la presencia o la ausencia de alteración del sueño y algunas de las variables recogidas: consumo de psicofármacos de los padres y uso de pantallas. Estos datos sugieren que el confinamiento tuvo un impacto emocional en la población infanto-juvenil, en concreto sobre el sueño. (AU)

This study highlights the need to expand the evidence on the impact of lockdown on the sleep of children and adolescents. Although several studies provide evidence in this regard, research on child and adolescent population is still scarce. The paper also aims at exploring whether the possible effects vanish over time. The sample is formed by patients ranging from 3 to 16 years old. The mean age was 10.51 and the SD was 3.28. Two assessment instruments were used: the Sleep Disturbances Scale for Children (SDSC) and a socieconomic questionnaire. The SDSC was measured three times during one year and a descriptive analysis of the sample and the evolution of the prevalence according to the results of the scale was executed. A comparison of proportions was made in those patients who exceeded the cut-off point in the different variables collected. The results indicate that 82% of the sample had a sleep disorder, which remained for 6 months and it experienced a significant decrease to 22% after one year, when COVID-19 restrictions were relaxed. There are also significant differences between sleep disorder and some of the variables collected: parents’ use of psychotropic drugs and use of screens. This data suggests that lockdown had an emotional impact on children and adolescent population, specifically on their sleep. (AU)

End-To-End Procedure For IORT in Brain Metastases and Film Dosimetry.

Purpose: The study is intended to perform an end-to-end test of the entire intraoperative process using cadaver heads. A simulation of tumor removal was performed, followed by irradiation of the bed and measurement of absorbed doses with radiochromic films. Materials and Methods: Low-energy X-ray intraoperative radiotherapy (IORT) was used for irradiation. A computed tomography study was performed at each site and the absorbed doses calculated by the treatment planning system, as well as absorbed doses with radiochromic films, were studied. Results: The absorbed doses in the organs at risk (OAR) were evaluated in each case, obtaining maximum doses within the tolerance limits. The absorbed doses in the target were verified and the deviations were <1%. Conclusions: These tests demonstrated that this comprehensive procedure is a reproducible quality assurance tool which allows continuous assessment of the dosimetric and geometric accuracy of clinical brain IORT treatments. Furthermore, the absorbed doses measured in both target and OAR are optimal for these treatments.

Exploring the use of digital technology to deliver healthcare services with explicit consideration of health inequalities in UK settings: A scoping review.

Objective: To map and explore existing evidence on the use of digital technology to deliver healthcare services with explicit consideration of health inequalities in UK settings. Methods: We searched six bibliographic databases, and the National Health Service (NHS) websites of each UK nation (England, Scotland, Wales, Northern Ireland). Restrictions were applied on publication date (2013-2021) and publication language (English). Records were independently screened against eligibility criteria by pairs of reviewers from the team. Articles reporting relevant qualitative and/or quantitative research were included. Data were synthesised narratively. Results: Eleven articles, reporting data from nine interventions, were included. Articles reported findings from quantitative (n = 5), qualitative (n = 5), and mixed-methods (n = 1) studies. Study settings were mainly community based, with only one hospital based. Two interventions targeted service users, and seven interventions targeted healthcare providers. Two studies were explicitly and directly aimed at (and designed for) addressing health inequalities, with the remaining studies addressing them indirectly (e.g. study population can be classed as disadvantaged). Seven articles reported data on implementation outcomes (acceptability, appropriateness, and feasibility) and four articles reported data on effectiveness outcomes, with only one intervention demonstrating cost-effectiveness. Conclusions: It is not yet clear if digital health interventions/services in the UK work for those most at risk of health inequalities. The current evidence base is significantly underdeveloped, and research/intervention efforts have been largely driven by healthcare provider/system needs, rather than those of service users. Digital health interventions can help address health inequalities, but a range of barriers persist, alongside a potential for exacerbation of health inequalities.

Response to Vaccine-Derived Polioviruses Detected through Environmental Surveillance, Guatemala, 2019.

Guatemala implemented wastewater-based poliovirus surveillance in 2018, and three genetically unrelated vaccine-derived polioviruses (VDPVs) were detected in 2019. The Ministry of Health (MoH) response included event investigation through institutional and community retrospective case searches for acute flaccid paralysis (AFP) during 2018-2020 and a bivalent oral polio/measles, mumps, and rubella vaccination campaign in September 2019. This response was reviewed by an international expert team in July 2021. During the campaign, 93% of children 6 months <7 years of age received a polio-containing vaccine dose. No AFP cases were detected in the community search; institutional retrospective searches found 37% of unreported AFP cases in 2018‒2020. No additional VDPV was isolated from wastewater. No evidence of circulating VDPV was found; the 3 isolated VDPVs were classified as ambiguous VDPVs by the international team of experts. These detections highlight risk for poliomyelitis reemergence in countries with low polio vaccine coverage.

Occupational COVID-19 Exposures and Illnesses among Workers in California-Analysis of a New Occupational COVID-19 Surveillance System.

Little is known about occupational SARS-CoV-2 exposures and COVID-19 outcomes. We established a Doctor's First Reports of Occupational Injury or Illness (DFR)-based surveillance system to study cases of work-related COVID-19 exposures and disease. The surveillance data included demographics, occupation, industry, exposure, and illness, details including hospitalization and lost work. We classified workers into 'healthcare', non-healthcare 'public-facing', or 'other' worker groups, and rural-urban commuting areas (RUCAs). We describe worker exposures and outcomes overall by worker group and RUCA. We analyzed 2848 COVID-19 DFRs representing workers in 22 detailed occupation groups and 19 industry groups. Most DFRs were for workers in metropolitan RUCAs (89%) and those in healthcare (42%) and public-facing (24%) worker groups. While DFRs were from 382 unique worksites, 52% were from four hospitals and one prison. Among 1063 DFRs with a suspected exposure, 73% suspected exposure to a patient or client. Few DFRs indicated hospitalization (3.9%); however, the proportion hospitalized was higher among nonmetropolitan (7.4%) and public-facing (6.7%) workers. While 56% of DFRs indicated some lost work time, the proportion was highest among public-facing (80%) workers. Healthcare and prison workers were the majority of reported occupational COVID-19 exposures and illnesses. The risk of COVID-19 hospitalization and lost work may be highest among nonmetropolitan and public-facing workers.

Adherence and Toxicity during the Treatment of Latent Tuberculous Infection in a Referral Center in Spain.

The screening and treatment of latent tuberculosis infection (LTBI) in countries with a low incidence of TB is a key strategy for the elimination of tuberculosis (TB). However, treatment can result in adverse events (AEs) and have poor adherence. This study aimed to describe treatment outcomes and AEs for LTBI patients at two departments in Vall d'Hebron University Hospital in Barcelona, Spain. A retrospective study was conducted on all persons treated for LTBI between January 2018 and December 2020. Variables collected included demographics, the reason for LTBI screening and treatment initiation, AEs related to treatment, and treatment outcome. Out of 261 persons who initiated LTBI treatment, 145 (55.6%) were men, with a median age of 42.1 years. The indications for LTBI screening were household contact of a TB case in 96 (36.8%) persons, immunosuppressive treatment in 84 (32.2%), and recently arrived migrants from a country with high TB incidence in 81 (31.0%). Sixty-three (24.1%) persons presented at least one AE during treatment, and seven (2.7%) required definitive discontinuation of treatment. In the multivariate analysis, AE development was more frequent in those who started LTBI treatment due to immunosuppression. Overall, 226 (86.6%) completed treatment successfully. We concluded that LTBI screening and treatment groups had different risks for adverse events and treatment outcomes. Persons receiving immunosuppressive treatment were at higher risk of developing AEs, and recently arrived immigrants from countries with a high incidence of TB had greater LTFU. A person-centered adherence and AE management plan is recommended.

Harms of third- and fourth-generation combined oral contraceptives in premenopausal women: A systematic review and meta-analysis.

We assessed the available evidence regarding adverse effects on surrogate and patient-important health outcomes of third- and fourth-generation combined oral contraceptives among premenopausal women. We performed a systematic review and meta-analysis including randomized controlled trials and observational studies comparing third- and fourth-generation combined oral contraceptives with other generation contraceptives or placebo. Studies that enrolled women aged 15 to 50 years, with at least three cycles of intervention and 6 months of follow-up were included. A total of 33 studies comprising 629,783 women were included. Low-density lipoprotein cholesterol levels were significantly lower in fourth-generation oral contraceptives (mean differences (MD): -0.24 mmol/L; [95% CI -0.39 to -0.08]), while total cholesterol was significantly increased in levonorgestrel users when compared to third-generation oral contraceptives (MD: 0.27 mmol/L; [95% CI 0.04 to 0.50]). A decreased arterial thrombosis incidence was shown in fourth-generation oral contraceptive users, as compared to levonorgestrel (incidence rate ratio (IRR): 0.41; [95% CI 0.19 to 0.86]). No difference was found in the occurrence of deep venous thrombosis between fourth-generation oral contraceptives and levonorgestrel users (IRR: 0.91; [95% CI 0.66 to 1.27]; p = 0.60; I2 = 0%). Regarding the remaining outcomes, data were heterogeneous and showed no clear difference. In premenopausal women, the use of third- and fourth-generation oral contraceptives is associated with an improved lipid profile and lower risk of arterial thrombosis. Data were inconclusive regarding the rest of outcomes assessed. This review was registered in PROSPERO with CRD42020211133.