Economic Impact of Lean Healthcare Implementation on the Surgical Process.

OBJECTIVES: The objective of this study was to analyse and detail surgical process improvement activities that achieve the highest economic impact. METHODS: Over 4 years, a team of technicians and healthcare professionals implemented a set of Lean surgical process improvement projects at Vall d'Hebron University Hospital (VHUH), Barcelona, Spain. Methods employed in the study are common in manufacturing environments and include reducing waiting and changeover time (SMED), reducing first time through, pull, and continuous flow. Projects based on these methods now form part of the daily routine in the surgical process. The economic impact on the hospital's surgical activity budget was analysed. RESULTS: Process improvements have led to annual operational savings of over EUR 8.5 million. These improvements include better patient flow, better management of information between healthcare professionals, and improved logistic circuits. CONCLUSIONS: The current cultural shift towards process management in large hospitals implies shifting towards results-based healthcare, patient-perceived value (VBHC), and value-added payment. A Lean project implementation process requires long-term stability. The reason a considerable number of projects fail to complete process improvement projects is the difficulty involved in establishing the project and improving management routines. Few studies in the literature have investigated the economic impact of implementing Lean management a posteriori, and even fewer have examined actual cases. In this real case study, changes to surgical block management were initiated from stage zero. After being carefully thought through and designed, changes were carried out and subsequently analysed.

The Green Surgical Block 4.0: Automation of the operating theatre's climate conditions through a real-time patient-flow solution.

The energy consumed by surgery units constitutes a staggering part of the overall healthcare carbon footprint. Partly due to the demanding climate conditions necessitated by operating theatres (OTs), energy is also wasted because of poorly managed heating, ventilation and air-conditioning systems (HVACs) that consume up to 57% of the total energy used in a hospital. With their goal of optimising OTs' performance and reducing patient waiting lists, heads of surgery units worldwide do not dare to risk cancelling scheduled surgery because of problems with the OT environment conditions (ie temperature, humidity, pressure). Current solutions are monolithic, complex and completely disconnected from healthcare logic, failing to take into account the idiosyncrasy of hospitals. This article presents an innovation that uses real-time patient flow data to automate and optimise the OT's climate conditions.

Acceptability and usability of oral fluid HCV self-testing for hepatitis C diagnosis: A systematic review and meta-analysis.

Data on the acceptability and usability of hepatitis C virus self-testing (HCVST) remain scarce. We estimated the pooled rates of acceptability/feasibility and re-reading/re-testing agreement of HCVST using oral fluid tests (PROSPERO-CRD42022349874). We searched online databases for studies that evaluated acceptability, usability and inter-reader/operator variability for HCVST using oral fluid tests. Pooled estimates of feasibility, agreement and post-testing perspectives were analysed. Sensitivity analyses were performed in men who have sex with men (MSM) and people who inject drugs (PWID). Heterogeneity was assessed using the I2 statistics. A total of six studies comprising 870 participants were identified: USA (n = 95 with liver disease), Kenya (n = 150 PWID), Egypt (n = 116 from the general population), Vietnam (n = 104 MSM and n = 105 PWID), China (n = 100 MSM) and Georgia (n = 100 MSM and n = 100 PWID)]. All studies used OraQuick® HCV Rapid Antibody Test. The pooled overall estimates for correct sample collection and for people who performed HCVST without needing assistance in any step (95% confidence interval [CI]) were 87.2% [76.0-95.3] (n = 755; I2 = 93.7%) and 62.6% [37.2-84.8] (n = 755; I2 = 98.0%), respectively. The pooled estimate of agreement for re-reading was 95.0% [95% CI 91.5-97.6] (n = 831; I2 = 74.0%) and for re-testing was 94.4% [90.3-97.5] (n = 726; I2 = 77.1%). The pooled estimate of those who would recommend HCVST was 94.4% [84.7-99.6] (n = 625; I2 = 93.7%). Pooled estimates (95% CI) of correct sample collection (72.8% [63.3-81.5] vs. 90.8% [85.9-94.8]) and performance of HCVST without needing assistance (44.1% [14.1-76.7] vs. 78.1% [53.4-95.3]) was lower in PWID compared to MSM. In summary, HCV testing with oral fluid HCVST was feasible and well-accepted. Oral fluid HCVST should be considered in key populations for uptake HCV testing.

Cerebrospinal fluid: a target of some fungi and an overview.

Meningitis is a potentially life-threatening infection characterised by the inflammation of the leptomeningeal membranes. The estimated annual prevalence of 8.7 million cases globally and the disease is caused by many different viral, bacterial, and fungal pathogens. Although several genera of fungi are capable of causing infections in the central nervous system (CNS), the most significant number of registered cases have, as causal agents, yeasts of the genus Cryptococcus. The relevance of cryptococcal meningitis has changed in the last decades, mainly due to the increase in the number of people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and medications that impair the immune responses. In this context, coronavirus disease 19 (COVID-19) has also emerged as a risk factor for invasive fungal infections (IFI), including fungal meningitis (FM), due to severe COVID-19 disease is associated with increased pro-inflammatory cytokines, interleukin (IL)-1, IL-6, and tumour necrosis factor-alpha, reduced CD4-interferon-gamma expression, CD4 and CD8 T cells. The gold standard technique for fungal identification is isolating fungi in the culture of the biological material, including cerebrospinal fluid (CSF). However, this methodology has as its main disadvantage the slow or null growth of some fungal species in culture, which makes it difficult to finalise the diagnosis. In conclusions, this article, in the first place, point that it is necessary to accurately identify the etiological agent in order to assist in the choice of the therapeutic regimen for the patients, including the implementation of actions that promote the reduction of the incidence, lethality, and fungal morbidity, which includes what is healthy in the CNS.

Brucella abortus induces mast cell activation through TLR-2 and TLR-4.

The Gram-negative bacteria Brucella abortus is a major cause of brucellosis in animals and humans. The host innate immune response to B. abortus is mainly associated with phagocytic cells such as dendritic cells, neutrophils, and macrophages. However, as mast cells naturally reside in the main bacterial entry sites they may be involved in bacterial recognition. At present, little is known about the role of mast cells during B. abortus infection. The role of the innate immune receptors TLR2 and TLR4 in activation of mast cells by B. abortus (strain RB51) infection was analyzed in this study. The results showed that B. abortus did not induce mast cell degranulation, but did induce the synthesis of the cytokines IL-1ß, IL-6, TNF-α, CCL3, CCL4, and CCL5. Furthermore, B. abortus stimulated key cell signaling molecules involved in mast cell activation such as p38 and NF-κB. Blockade of the receptors TLR2 and TLR4 decreased TNF-α and IL-6 release by mast cells in response to B. abortus. Taken together, our results demonstrate that mast cells are activated by B. abortus and may play a role in inducing an inflammatory response during the initial phase of the infection.

Association of syndemic conditions and quality of life among people living with HIV/AIDS.

The syndemics theory seeks to understand the effect of multiple synergic problems in promoting poor health outcomes. To disentangle which and how syndemic conditions affect the quality of life (QoL) may be important to improve well-being of people living with HIV/AIDS (PLWHA). This study evaluates the association between syndemic conditions and QoL among PLWHA. We performed a secondary analysis using data obtained between 2014 and 2017 among PLWHA under care in Rio de Janeiro, Brazil. The outcomes were the six QoL domains (physical, psychological, level of independence, social relationships, environmental, and spirituality) measured through the World Health Organization Quality of Life in HIV infection scale, abbreviated version (WHOQOL-HIV-BREF). The independent variables were demographic and clinical characteristics, syndemic conditions (binge drinking, compulsive sexual behavior, polysubstance use, intimate partner violence, and depression), and syndemics (two or more syndemic conditions simultaneously). Bivariate analysis (t-test and ANOVA) and linear regressions were performed for each quality-of-life domain. The analytical sample comprised 1530 participants, mostly male at birth (64%) and with median age of 43 years. The syndemic conditions most frequently observed were binge drinking (56%), IPV (13%), and depression (9%). Both individual syndemic conditions and syndemics were associated with worse QoL. In the multivariate analysis, positive screening for depression was associated with worse QoL in all domains. Polysubstance users presented worse QoL at social and environmental domains. Intimate partner violence was associated with worse QoL at environment domain while binge drinking was associated with worse scores in the physical domain. The presence of syndemics increased the likelihood of worse scores in the psychological, social, and environment domains. Our study expands the understanding of QoL in PLWHA, as it considers a holistic/integral, multifactorial, and synergistic approach to the determinants of QoL. Seeking strategies that target syndemics may be important to improve patient-centered outcomes in health.Abbreviations: HIV/AIDS: human immunodeficiency virus/acquired immunodeficiency syndromeWHO: World Health OrganizationQoL: quality of lifeHRQoL: health-related quality of lifePLWHA: people living with HIV/AIDScART: combined antiretroviral therapyIPV: intimate partner violenceINI/FIOCRUZ: Evandro Chagas National Institute of Infectious DiseasesOswaldo Cruz FoundationSRH: self-rated healthVL: viral loadCD4: CD4 cell countNIAAA: National Institute on Alcohol Abuse and AlcoholismCSBcompulsive sexual behaviorWHO-ASSIST: alcoholsmoking and substance involvement screening test developed by the World Health OrganizationPHQ-2: Patient Health Questionnaire-2.

Cerebrospinal fluid: a target of some fungi and an overview

Meningitis is a potentially life-threatening infection characterised by the inflammation of the leptomeningeal membranes. The estimated annual prevalence of 8.7 million cases globally and the disease is caused by many different viral, bacterial, and fungal pathogens. Although several genera of fungi are capable of causing infections in the central nervous system (CNS), the most significant number of registered cases have, as causal agents, yeasts of the genus Cryptococcus. The relevance of cryptococcal meningitis has changed in the last decades, mainly due to the increase in the number of people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and medications that impair the immune responses. In this context, coronavirus disease 19 (COVID-19) has also emerged as a risk factor for invasive fungal infections (IFI), including fungal meningitis (FM), due to severe COVID-19 disease is associated with increased pro-inflammatory cytokines, interleukin (IL)-1, IL-6, and tumour necrosis factor-alpha, reduced CD4-interferon-gamma expression, CD4 and CD8 T cells. The gold standard technique for fungal identification is isolating fungi in the culture of the biological material, including cerebrospinal fluid (CSF). However, this methodology has as its main disadvantage the slow or null growth of some fungal species in culture, which makes it difficult to finalise the diagnosis. In conclusions, this article, in the first place, point that it is necessary to accurately identify the etiological agent in order to assist in the choice of the therapeutic regimen for the patients, including the implementation of actions that promote the reduction of the incidence, lethality, and fungal morbidity, which includes what is healthy in the CNS.

Avaliação da qualidade de vida relacionada à saúde em um programa de reabilitação para pessoas com deficiência visual / Health-related quality of life assessment in a rehabilitation program for people with visual impairment

RESUMO Objetivo: Aplicar um protocolo para avaliar a qualidade de vida relacionada à saúde de participantes de um programa de reabilitação para pessoas com deficiência visual de um instituto de referência. Métodos: Foi realizado um estudo transversal com 60 adultos com deficiência visual participantes de um programa de reabilitação para pessoas com deficiência visual de um instituto de referência no Rio de Janeiro. O protocolo de pesquisa consistiu em um questionário com dados pessoais, sociais, demográficos e informações clínicas; no European Quality of Life 5 Dimensions 3 Level Version para medição genérica de qualidade de vida relacionada à saúde; no Patient Health Questionnaire-2 para rastrear a depressão e no Visual Function Questionnaire 25 para avaliar a qualidade de vida relacionada à saúde específica da função visual. A principal variável independente analisada foi o tempo de exposição ao programa. Modelos de regressão linear foram utilizados para investigar a relação entre o tempo no programa e a qualidade de vida relacionada à saúde do Visual Function Questionnaire 25 e do European Quality of Life 5 Dimensions 3 Level Version. Resultados: A maioria dos participantes (73%) possuía deficiência visual adquirida; 68% tinham menos de 60 anos e 53% perderam a visão há mais de 10 anos. A condição visual autorreferida mais comum foi cegueira em ambos os olhos (48%) e 42% frequentavam o programa há mais de 3 anos. A mediana do índice de utilidade do European Quality of Life 5 Dimensions 3 Level Version foi de 0,75. O instrumento específico para rastreamento de depressão, o Patient Health Questionnaire, identificou proporção de 27% de participantes positivos. O Visual Function Questionnaire 25 apresentou escores abaixo de 50 (escala de zero a cem) nos subdomínios visão geral, atividades de perto e atividades à distância. As medianas de dor ocular e aspectos sociais do Visual Function Questionnaire 25 foram significativamente menores entre aqueles que realizavam tratamento psiquiátrico. O tempo de reabilitação foi independentemente associado a melhores escores dos subdomínios saúde mental e atividades da vida diária. Conclusão: O protocolo demonstrou aplicabilidade para a avaliação de qualidade de vida relacionada à saúde em pessoas com deficiência visual, permitindo concluir que o maior tempo no programa de reabilitação foi associado a maiores escores de qualidade de vida.

ABSTRACT Purpose: This study aimed to implement a health-related quality of life (HRQoL) assessment protocol to measure the consequences of a rehabilitation program for visual impaired people at a leading reference institute in Brazil. Methods: A cross-sectional study was conducted with 60 visual impaired adults enrolled in a Rehabilitation Program of the Instituto Benjamin Constant. The research protocol consisted of a questionnaire with personal data, social, demographic, and clinical information; the EQ-5D-3L instrument for generic HRQoL measurement; the Patient Health Questionnaire-2 (PHQ- 2) to screen for depression, and the 25-Item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) to assess specific HRQoL of visual function. The main independent variable analyzed was the exposure time to the rehabilitation. Linear regression models were used to investigate the relationship between rehabilitation time and HRQoL of the NEI VFQ-25 and EQ 5D-3L instruments. Results: Most participants (73%) have acquired visual impairment, 68% are under 60 years old, 53% lost their vision more than 10 years ago, the most common self-reported visual condition (48%) was blindness in both eyes and 42% are in the Rehabilitation Program for more than 3 years. The median HRQoL utility index for EQ 5D-3L was 0.75. The specific instrument for screening for depression, PHQ-2, identified 27% of participants above the cut-off point. The NEI VFQ-25 instrument showed scores below 50 (scale from 0 to 100) in subdomains: "general vision", "near activities" and "distance activities". The medians of "ocular pain" and "social aspects" of the VFQ-25 were significantly lower among those who have undergone psychiatric treatment. "Rehabilitation time" was independently associated with better scores of "mental health" and "role difficulties" subdomains. Conclusion: The protocol showed applicability for the assessment of HRQoL, allowing the conclusion that longer time in the rehabilitation program was associated with higher quality of life scores.

Hepatitis of unknown etiology in children in Brazil: A new challenge or the usual scenario ?

BACKGROUND: An outbreak of acute hepatitis of unknown etiology in children was recently reported worldwide. We aimed to describe the burden of hospitalizations due to hepatitis of unknown etiology in children/adolescents in Brazilian public hospitals. METHODS: We retrieved a database of all hospitalizations in the Brazilian Unified Health System (SUS) from January/2019 to February/2022 using the "microdatasus" R package. Hepatitis of unknown etiology was defined by the following International Classification of Diseases [ICD-10] codes: B19, B19.0, B19.9, K72.0, K72.9, K75, K75.9, R94.5, or R93.2. The incidence rates (95% confidence interval, IC) per 1,000 all-cause hospitalizations in different age strata [< 6 years; 6-11 years and 12-17 years] were estimated. RESULTS: A total of 94,198 hospitalizations due to hepatic or infectious diseases with potential liver injury were analyzed. Of them, 1,535 children/adolescents [48.2% male sex, 41.6% aged < 6 years] were hospitalized with hepatitis with unknown etiology. The top ICD-10 codes were B19.9 [unspecified viral hepatitis without hepatic coma; 39.9% (n = 612)], K72.9 [hepatic failure, unspecified; 29.8% (n = 457)], and K72.0 [hepatic failure, not elsewhere classified; 14.5% (n = 223)]. A total of 8.5% (n = 131) of individuals required liver transplantation and 7.0% (n = 107) died during the hospital-stay. In 2021, the incidence rates (95% CI) of hospitalizations for hepatitis with unknown etiology were 7.80 (7.63-7.98), 17.96 (17.46-18.48) and 13.28 (12.95-13.62) per 1,000 all-cause hospitalizations in subjects aged < 6 years, 6-11 years and 12-17 years-old, respectively. Similarly, the incidence rates of hospitalization due to hepatitis with unknown etiology per 1,000 all-cause hospitalizations (CI95%) in January-February/2022 were 7.52 (7.11-7.94), 16.82 (15.68-18.03), and 13.96 (13.10-14.85) for children/adolescents with age < 6 years, 6-11 years, and 12-17 years, respectively. CONCLUSIONS: A non-negligible number of hospitalizations due to hepatitis with unknown etiology in children/adolescents was observed in the last years in Brazil. Up to 15% of those cases needed liver transplantation or died.

IL-6, IL-10, sFas, granulysin and indicators of intestinal permeability as early biomarkers for a fatal outcome in COVID-19.

The clinical presentation of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranges between mild respiratory symptoms and a severe disease that shares many of the features of sepsis. Sepsis is a deregulated response to infection that causes life-threatening organ failure. During sepsis, the intestinal epithelial cells are affected, causing an increase in intestinal permeability and allowing microbial translocation from the intestine to the circulation, which exacerbates the inflammatory response. Here we studied patients with moderate, severe and critical COVID-19 by measuring a panel of molecules representative of the innate and adaptive immune responses to SARS-CoV-2, which also reflect the presence of systemic inflammation and the state of the intestinal barrier. We found that non-surviving COVID-19 patients had higher levels of low-affinity anti-RBD IgA antibodies than surviving patients, which may be a response to increased microbial translocation. We identified sFas and granulysin, in addition to IL-6 and IL-10, as possible early biomarkers with high sensitivity (>73 %) and specificity (>51 %) to discriminate between surviving and non-surviving COVID-19 patients. Finally, we found that the microbial metabolite d-lactate and the tight junction regulator zonulin were increased in the serum of patients with severe COVID-19 and in COVID-19 patients with secondary infections, suggesting that increased intestinal permeability may be a source of secondary infections in these patients. COVID-19 patients with secondary infections had higher disease severity and mortality than patients without these infections, indicating that intestinal permeability markers could provide complementary information to the serum cytokines for the early identification of COVID-19 patients with a high risk of a fatal outcome.

Valproic acid restricts mast cell activation by Listeria monocytogenes.

Mast cells (MC) play a central role in the early containment of bacterial infections, such as that caused by Listeria monocytogenes (L.m). The mechanisms of MC activation induced by L.m infection are well known, so it is possible to evaluate whether they are susceptible to targeting and modulation by different drugs. Recent evidence indicates that valproic acid (VPA) inhibits the immune response which favors L.m pathogenesis in vivo. Herein, we examined the immunomodulatory effect of VPA on L.m-mediated MC activation. To this end, bone marrow-derived mast cells (BMMC) were pre-incubated with VPA and then stimulated with L.m. We found that VPA reduced MC degranulation and cytokine release induced by L.m. MC activation during L.m infection relies on Toll-Like Receptor 2 (TLR2) engagement, however VPA treatment did not affect MC TLR2 cell surface expression. Moreover, VPA was able to decrease MC activation by the classic TLR2 ligands, peptidoglycan and lipopeptide Pam3CSK4. VPA also reduced cytokine production in response to Listeriolysin O (LLO), which activates MC by a TLR2-independent mechanism. In addition, VPA decreased the activation of critical events on MC signaling cascades, such as the increase on intracellular Ca2+ and phosphorylation of p38, ERK1/2 and -p65 subunit of NF-κB. Altogether, our data demonstrate that VPA affects key cell signaling events that regulate MC activation following L.m infection. These results indicate that VPA can modulate the functional activity of different immune cells that participate in the control of L.m infection.

Global distribution of animal sporotrichosis: A systematic review of Sporothrix sp. identified using molecular tools.

Sporotrichosis is a subcutaneous mycosis caused by thermodimorphic fungi of the genus Sporothrix. The phenotypic and genotypic differences of the isolates within the genus Sporothrix have been associated with their geographic distribution, virulence capacity, or clinical manifestation of sporotrichosis. Therefore, it is crucial to identify the causative agent of sporotrichosis. However, there are few case reports and studies in animals compared to those in humans, despite the substantial increase in the number of cases of sporotrichosis by zoonotic transmission, especially in endemic areas. Considering the epidemiological importance, taxonomic evolution and worldwide distribution of these fungi in the last decade, there is interest in identifying the species of the genus Sporothrix in different regions of the world. This study aimed to analyze the geographic distribution of animal sporotrichosis in the world, caused by pathogenic species identified by use of molecular tools. This systematic review of articles from 2007 to 2021 analyzed the geographic distribution of species that cause sporotrichosis in cats, dogs and other animals. It demonstrated that the most identified species were S. brasiliensis, isolated from cats in Brazil and S. schenckii isolated from cats in Malaysia. We show the lack of studies in global areas and reinforce the need to use molecular tools to identify and monitor potential pathogens.

Surgical block 4.0: a digital intervention based on a real-time location patient-flow solution to support the automation of surgical pathways.

As internet of things (IoT) technologies are increasingly adopted by healthcare and hospitals, new opportunities are emerging to transform patient pathways and achieve efficient delivery of care. This implemented project follows the drivers and requirements of industry 4.0, based on surgical process analysis and optimisation using IoT technology, with the goal of creating '4.0 hospitals'. Our study presents the implementation of a novel IoT application, aiming to give support to multidisciplinary surgical teams through the optimisation of patient pathways to facilitate the surgical process. The implemented solution is based on real-time location systems (RTLS) technology, a subgroup within IoT, and it originated through the hospital needing to address the sudden surge of surgical elective care demand. The solution also enhances patient safety, facilitates quality of care by increasing communication and reduces costs. This IoT tool has facilitated the increase of theatre utilisation from 70.02% to 82.5% in 2 years, which has translated into an increase of surgical activity capacity, with an impact on reducing the waiting list.

Cost-effectiveness of an exercise-based cardiovascular rehabilitation program in patients with chronic Chagas cardiomyopathy in Brazil: An analysis from the PEACH study.

OBJECTIVES: The present study aimed to perform a cost-effectiveness analysis of an exercise-based cardiovascular rehabilitation (CR) program in patients with chronic Chagas cardiomyopathy (CCC). METHODS: Cost-effectiveness analysis alongside a randomised clinical trial evaluating the effects of a 6-month exercise-based CR program. The intervention group underwent 3 weekly exercise sessions. The variation of peak oxygen consumption (VO2peak ) was used as a measurement of clinical outcome. Cost information from all healthcare expenses (examinations, healthcare visits, medication and hospitalisation) were obtained from the medical records in Brazilian reais (R$) and transformed into dollars using the purchasing power parity ($PPP). The longitudinal costs variation was evaluated through linear mixed models, represented by ß coefficient, adjusted for the baseline values of the dependent variable. The cost-effectiveness evaluation was determined through an incremental cost-effectiveness ratio using the HEABS package (Stata 15.0). RESULTS: The intervention group presented higher costs with healthcare visits (ß = +3317.3; p < 0.001), hospitalisation (ß = +2810.4; p = 0.02) and total cost (ß = +6407.9; p < 0.001) after 3 months of follow-up. Costs related to healthcare visits (ß = +2455.8; p < 0.001) and total cost (ß = +4711.4; p < 0.001) remained higher in the intervention group after 6 months. The CR program showed an incremental cost-effectiveness ratio (ICER) of $PPP 1874.3 for each increase of 1.0 ml kg-1  min-1 of VO2peak . CONCLUSIONS: The CR program can be considered a cost-effective alternative and should be included as an intervention strategy in the care of patients with CCC.

Accuracy of rapid point-of-care serological tests for leprosy diagnosis: a systematic review and meta-analysis.

BACKGROUND: Leprosy is a chronic infectious disease, still endemic in many countries that may lead to neurological, ophthalmic, and motor sequelae if not treated early. Access to timely diagnosis and multidrug therapy (MDT) remains a crucial element in the World Health Organization's strategy to eliminate the disease as a public health problem. OBJECTIVES: This systematic review aims to evaluate the accuracy of rapid point-of-care (POC) tests for diagnosis of leprosy. METHODS: Searches were carried out in electronic databases (PubMed, EMBASE, CRD, Cochrane Library and LILACS) in April 2021 for patients with suspicion or confirmatory diagnostic of leprosy, classified in multibacillary (MB) or paucibacillary (PB) cases, performing rapid POC serological tests compared to clinical evaluation, smear microscopy and immunohistochemistry analysis. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). A meta-analysis was undertaken to generate pooled estimates of diagnostic parameters, presenting sensitivity, specificity and diagnostic odds ratio (DOR) values. The review protocol was registered at PROSPERO, CRD # 42014009658. FINDINGS: From 893 potentially relevant references, 12 articles were included reporting 16 diagnostic tests accuracy studies with 5395 individuals enrolled. Meta-analysis of NDO-LID and PGL-I tests data in MB patients showed sensitivity and specificity [95% confidence interval (CI)] of 0.83 (0.71-0.91), 0.91 (0.72-0.97); and 0.92 (0.86-0.96), 0.93 (0.78-0.98); respectively, with high heterogeneity among the studies. MAIN CONCLUSIONS: Our results can inform policymakers regarding the possibility of implementing accurate, rapid POC tests for leprosy in public health services, especially within primary health care.

Accuracy of rapid point-of-care serological tests for leprosy diagnosis: a systematic review and meta-analysis

BACKGROUND Leprosy is a chronic infectious disease, still endemic in many countries that may lead to neurological, ophthalmic, and motor sequelae if not treated early. Access to timely diagnosis and multidrug therapy (MDT) remains a crucial element in the World Health Organization's strategy to eliminate the disease as a public health problem. OBJECTIVES This systematic review aims to evaluate the accuracy of rapid point-of-care (POC) tests for diagnosis of leprosy. METHODS Searches were carried out in electronic databases (PubMed, EMBASE, CRD, Cochrane Library and LILACS) in April 2021 for patients with suspicion or confirmatory diagnostic of leprosy, classified in multibacillary (MB) or paucibacillary (PB) cases, performing rapid POC serological tests compared to clinical evaluation, smear microscopy and immunohistochemistry analysis. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). A meta-analysis was undertaken to generate pooled estimates of diagnostic parameters, presenting sensitivity, specificity and diagnostic odds ratio (DOR) values. The review protocol was registered at PROSPERO, CRD # 42014009658. FINDINGS From 893 potentially relevant references, 12 articles were included reporting 16 diagnostic tests accuracy studies with 5395 individuals enrolled. Meta-analysis of NDO-LID and PGL-I tests data in MB patients showed sensitivity and specificity [95% confidence interval (CI)] of 0.83 (0.71-0.91), 0.91 (0.72-0.97); and 0.92 (0.86-0.96), 0.93 (0.78-0.98); respectively, with high heterogeneity among the studies. MAIN CONCLUSIONS Our results can inform policymakers regarding the possibility of implementing accurate, rapid POC tests for leprosy in public health services, especially within primary health care.

Hepatitis of unknown etiology in children in Brazil: A new challenge or the usual scenario ?

ABSTRACT Background: An outbreak of acute hepatitis of unknown etiology in children was recently reported worldwide. We aimed to describe the burden of hospitalizations due to hepatitis of unknown etiology in children/adolescents in Brazilian public hospitals. Methods: We retrieved a database of all hospitalizations in the Brazilian Unified Health System (SUS) from January/2019 to February/2022 using the "microdatasus" R package. Hepatitis of unknown etiology was defined by the following International Classification of Diseases [ICD-10] codes: B19, B19.0, B19.9, K72.0, K72.9, K75, K75.9, R94.5, or R93.2. The incidence rates (95% confidence interval, IC) per 1,000 all-cause hospitalizations in different age strata [< 6 years; 6-11 years and 12-17 years] were estimated. Results: A total of 94,198 hospitalizations due to hepatic or infectious diseases with potential liver injury were analyzed. Of them, 1,535 children/adolescents [48.2% male sex, 41.6% aged < 6 years] were hospitalized with hepatitis with unknown etiology. The top ICD-10 codes were B19.9 [unspecified viral hepatitis without hepatic coma; 39.9% (n = 612)], K72.9 [hepatic failure, unspecified; 29.8% (n = 457)], and K72.0 [hepatic failure, not elsewhere classified; 14.5% (n = 223)]. A total of 8.5% (n = 131) of individuals required liver transplantation and 7.0% (n = 107) died during the hospital-stay. In 2021, the incidence rates (95% CI) of hospitalizations for hepatitis with unknown etiology were 7.80 (7.63-7.98), 17.96 (17.46-18.48) and 13.28 (12.95-13.62) per 1,000 all-cause hospitalizations in subjects aged < 6 years, 6-11 years and 12-17 years-old, respectively. Similarly, the incidence rates of hospitalization due to hepatitis with unknown etiology per 1,000 all-cause hospitalizations (CI95%) in January-February/2022 were 7.52 (7.11-7.94), 16.82 (15.68-18.03), and 13.96 (13.10-14.85) for children/adolescents with age < 6 years, 6-11 years, and 12-17 years, respectively. Conclusions: A non-negligible number of hospitalizations due to hepatitis with unknown etiology in children/adolescents was observed in the last years in Brazil. Up to 15% of those cases needed liver transplantation or died.

Production and Characterization of Cross-Linked Aggregates of Geobacillus thermoleovorans CCR11 Thermoalkaliphilic Recombinant Lipase.

Immobilization of enzymes has many advantages for their application in biotechnological processes. In particular, the cross-linked enzyme aggregates (CLEAs) allow the production of solid biocatalysts with a high enzymatic loading and the advantage of obtaining derivatives with high stability at low cost. The purpose of this study was to produce cross-linked enzymatic aggregates (CLEAs) of LipMatCCR11, a 43 kDa recombinant solvent-tolerant thermoalkaliphilic lipase from Geobacillus thermoleovorans CCR11. LipMatCCR11-CLEAs were prepared using (NH4)2SO4 (40% w/v) as precipitant agent and glutaraldehyde (40 mM) as cross-linker, at pH 9, 20 °C. A U10(56) uniform design was used to optimize CLEA production, varying protein concentration, ammonium sulfate %, pH, glutaraldehyde concentration, temperature, and incubation time. The synthesized CLEAs were also analyzed using scanning electron microscopy (SEM) that showed individual particles of <1 µm grouped to form a superstructure. The cross-linked aggregates showed a maximum mass activity of 7750 U/g at 40 °C and pH 8 and retained more than 20% activity at 100 °C. Greater thermostability, resistance to alkaline conditions and the presence of organic solvents, and better durability during storage were observed for LipMatCCR11-CLEAs in comparison with the soluble enzyme. LipMatCCR11-CLEAs presented good reusability by conserving 40% of their initial activity after 9 cycles of reuse.

Effect of Hyperbaric Oxygen Therapy (HBOT) on Insulin Resistance Associated with Abdominal Obesity in Wistar Rats with Dietary Sucrose-Induced Metabolic Syndrome.

Metabolic syndrome (MS) is a combination of risk factors related to the development of mainly type 2 diabetes mellitus, cardiovascular disease (CVD) and nonalcoholic fatty liver disease (NAFLD). Its prevalence has increased worldwide, and healthcare systems will face major challenges in addressing this problem. The aim of this work was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on insulin resistance (IR) and obesity associated with MS in Wistar rats. The experimental design consisted of three groups of sucrose-induced MS rats: the MS group that consumed sucrose (MS-Suc; n=5), the MS group that ingested sucrose and HBOT (MS-Suc-HBOT; n=5), the MS group that did not consume sucrose and that received HBOT (MS-HBOT; n=5) and the control group. The rats received HBOT for 20 d at 2.4 atmospheres absolute (ATA) for 60 min. Subsequently, the rats were euthanized, and body fat weight, serum biochemical parameters and microscopic analysis of adipose tissue were determined. Rats with hyperoxia had decreased body weight, adipose tissue hypertrophy, and abdominal and epididymal fat. Likewise, markers of insulin resistance (glucose, insulin and HOMA-IR), biochemical parameters of dyslipidemia (cholesterol and triglycerides) and nonalcoholic fatty liver (AST and ALT) decreased; in contrast, compared to the control group, HBOT increased the 1/HOMA-IR, HOMA-ßCell and McAuley indexes, which were related to the improvement in insulin sensitivity (p<0.05; p<0.01). HBOT showed beneficial effects in the treatment of IR and obesity associated with sucrose-induced metabolic syndrome in Wistar rats.

Increased survival in puppies affected by Canine Parvovirus type II using an immunomodulator as a therapeutic aid.

Canine parvovirus type II (CPV-2) infection induces canine parvoviral enteritis (CPE), which in turn promotes sepsis and systemic inflammatory response syndrome (SIRS). Mortality in this disease is usually registered within 48-72 h post-hospitalization, the critical period of the illness. It has been recently described that the use of an immunomodulator, whose major component is monomeric ubiquitin (mUb) without the last two glycine residues (Ub∆GG), in pediatric human patients with sepsis augments survival. It is known that CXCR4 is the cell receptor of extracellular ubiquitin in humans. This work aimed to explore the effect of one immunomodulator (human Dialyzable Leukocyte Extract-hDLE) as a therapeutic auxiliary in puppies with sepsis and SIRS induced by CPE. We studied two groups of puppies with CPV-2 infection confirmed by polymerase chain reaction. The first group received conventional treatment (CT) and vehicle (V), while the second group received CT plus the immunomodulator (I). We assessed both groups' survival, clinical condition, number of erythrocytes, neutrophils, and lymphocytes during the hospitalization period. In addition, hematocrit, hemoglobin, plasma proteins and cortisol values, as well as norepinephrine/epinephrine and serotonin concentration were determined. Puppies treated with CT + I showed 81% survival, mild clinical signs, and a significant decrease in circulating neutrophils and lymphocytes in the critical period of the treatment. In contrast, the CT + V group presented a survival of 42%, severe clinical status, and no improvement of the parameters evaluated in the critical period of the disease. We determined in silico that human Ub∆GG can bind to dog CXCR4. In conclusion, the administration of a human immunomodulator (0.5 mg/day × 5 days) to puppies with CPE under six months of age reduces the severity of clinical signs, increases survival, and modulates inflammatory cell parameters. Further studies are necessary to take full advantage of these clinical findings, which might be mediated by the human Ub∆GG to canine CXCR4 interaction.