Subversion of a family of antimicrobial proteins by Salmonella enterica.

Salmonella enterica is a food-borne pathogen able to cause a wide spectrum of diseases ranging from mild gastroenteritis to systemic infections. During almost all stages of the infection process Salmonella is likely to be exposed to a wide variety of host-derived antimicrobial peptides (AMPs). AMPs are important components of the innate immune response which integrate within the bacterial membrane, thus forming pores which lead ultimately to bacterial killing. In contrast to other AMPs Bactericidal/Permeability-increasing Protein (BPI) displayed only weak bacteriostatic or bactericidal effects towards Salmonella enterica sv. Typhimurium (STM) cultures. Surprisingly, we found that sub-antimicrobial concentrations of BPI fold-containing (BPIF) superfamily members mediated adhesion of STM depending on pre-formed type 1 fimbriae. BPIF proteins directly bind to type 1 fimbriae through mannose-containing oligosaccharide modifications. Fimbriae decorated with BPIF proteins exhibit extended binding specificity, allowing for bacterial adhesion on a greater variety of abiotic and biotic surfaces likely promoting host colonization. Further, fimbriae significantly contributed to the resistance against BPI, probably through sequestration of the AMP before membrane interaction. In conclusion, functional subversion of innate immune proteins of the BPIF family through binding to fimbriae promotes Salmonella virulence by survival of host defense and promotion of host colonization.

Desenvolvimento de um Protocolo sobre Processamento de Produtos para Saúde em um Hospital Universitário / Elaboración de un Protocolo de Procesamiento de Productos Sanitarios en un Hospital Universitario / Development of a Protocol on the Processing of Health Products in a University Hospital

Objetivo:Desenvolver e validar um Protocolo sobre Processamento de Produtos para Saúde na Central de Material e Esterilização de um Hospital Universitário de São Paulo. Método: Trata-se de um estudo descritivo metodológico de desenvolvimento de um protocolo sobre processamento de produtos para a saúde.Realizada a revisão da literatura, elaboração do conteúdo escrito e de imagens. A validação foi feita por meio da Técnica Delphi com a participação de juízes. Para medir a concordância das respostas obtidas, foi utilizado o Índice de Validade de Conteúdo (IVC). Resultados: Após a segunda rodada do processo de validação pela Técnica Delphi, o IVC global do protocolo foi de 1.0, alcançando o nível de maior concordância. A versão final do protocolo possui 45 páginas, 8 itens abordados, 32 subitens e 20 ilustrações. Conclusão:O protocolo possibilitou reorganizar processos, estabelecer fluxos e padronizar condutas com embasamento científico para os profissionais de saúde.(AU)

Objective: To develop and validate a Protocol on the Processing of Health Products at the Material and Sterilization Center of a University Hospital in São Paulo. Method: This is a descriptive methodological study of the development of a protocol on the processing of health products. A literature review, written content and images were developed. Validation was performed using the Delphi Technique with the participation of judges. To measure the agreement of the answers obtained, the Content Validity Index (CVI) was used. Results: After the second round of the validation process using the Delphi Technique, the global CVI of the protocol was 1.0, reaching the highest level of agreement. The final version of the protocol has 45 pages, 8 items covered, 32 sub-items and 20 illustrations. Conclusion: The protocol made it possible to reorganize processes, establish flows and standardize scientifically based conducts for health professionals.(AU)

Objetivo: Desarrollar y validar un Protocolo de Procesamiento de Productos de Salud en el Centro de Material y Esterilización de un Hospital Universitario de São Paulo. Método: Se trata de un estudio metodológico descriptivo de la elaboración de un protocolo sobre el procesamiento de productos sanitarios. Se elaboró una revisión de literatura, contenido escrito e imágenes. La validación se realizó mediante la Técnica Delphi con la participación de jueces. Para medir la concordancia de las respuestas obtenidas se utilizó el Índice de Validez de Contenido (IVC). Resultados: Tras la segunda ronda del proceso de validación mediante la Técnica Delphi, el CVI global del protocolo fue de 1,0, alcanzando el mayor nivel de acuerdo. La versión final del protocolo tiene 45 páginas, 8 ítems cubiertos, 32 sub ítems y 20 ilustraciones. Conclusión: El protocolo permitió reorganizar procesos, establecer flujos y estandarizar conductas con base científica para los profesionales de la salud.(AU)

Tailoring an evidence-based clinical intervention and training package for the treatment and prevention of comorbid heavy drinking and depression in middle-income country settings: the development of the SCALA toolkit in Latin America.

BACKGROUND: Effective interventions exist for heavy drinking and depression but to date there has been limited translation into routine practice in global health systems. This evidence-to-practice gap is particularly evident in low- and middle-income countries. The international SCALA project (Scale-up of Prevention and Management of Alcohol Use Disorders and Comorbid Depression in Latin America) sought to test the impact of multilevel implementation strategies on rates of primary health care-based measurement of alcohol consumption and identification of depression in Colombia, Mexico, and Peru. OBJECTIVE: To describe the process of development and cultural adaptation of the clinical intervention and training package. METHODS: We drew on Barrero and Castro's four-stage cultural adaption model: 1) information gathering, 2) preliminary adaption, 3) preliminary adaption tests, and 4) adaption refinement. The Tailored Implementation in Chronic Diseases checklist helped us identify potential factors that could affect implementation, with local stakeholder groups established to support the tailoring process, as per the Institute for Healthcare Improvement's Going to Scale Framework. RESULTS: In Stage 1, international best practice guidelines for preventing heavy drinking and depression, and intelligence on the local implementation context, were synthesised to provide an outline clinical intervention and training package. In Stage 2, feedback was gathered from local stakeholders and materials refined accordingly. These materials were piloted with local trainers in Stage 3, leading to further refinements including developing additional tools to support delivery in busy primary care settings. Stage 4 comprised further adaptions in response to real-world implementation, a period that coincided with the onset of the COVID-19 pandemic, including translating the intervention and training package for online delivery, and higher priority for depression screening in the clinical pathway. CONCLUSION: Our experience highlights the importance of meaningful engagement with local communities, alongside the need for continuous tailoring and adaptation, and collaborative decision-making.

Vascular endothelial growth factor (VEGF) and interleukin-1 receptor antagonist (IL-1Ra) as promising biomarkers for distinguishing active from latent tuberculosis in children and adolescents.

Since distinguishing pulmonary (PTB) from latent tuberculosis (LTBI) in pediatric patients remains a challenge, we aimed to investigate the efficacy of immune mediators in diagnosing PTB and LTBI in this population. In this cross-sectional study performed with children and adolescents, serum levels of 20 biomarkers were assessed and data were analyzed according to age groups. We included 65 participants (PTB, n = 28 and LTBI, n = 37). Overall, levels of TNF-α, IL-1Ra, IL-6, IL-17A, VEGF, MMP-1, and procalcitonin were significantly higher (P < 0.05) in adolescents and children <10 years-old with PTB. Also, principal component analysis (PCA) showed that immune mediators were able to distinguish PTB from LTBI. VEGF and IL-1Ra presented the highest area under the curve (AUC) values, both separately (AUC 0.890 and 0.785) and combined (AUC 0.99). Taken together, we showed that VEGF and IL-1Ra are promising biomarkers to distinguish PTB from LTBI in pediatric patients, especially in children <5 years-old.

Changes in alcohol use during the COVID-19 pandemic in Europe: A meta-analysis of observational studies.

ISSUES: Numerous studies have examined the impact of the COVID-19 pandemic on alcohol use changes in Europe, with concerns raised regarding increased use and related harms. APPROACH: We synthesised observational studies published between 1 January 2020 and 31 September 2021 on self-reported changes in alcohol use associated with COVID-19. Electronic databases were searched for studies evaluating individual data from European general and clinical populations. We identified 646 reports, of which 56 general population studies were suitable for random-effects meta-analyses of proportional differences in alcohol use changes. Variations by time, sub-region and study quality were assessed in subsequent meta-regressions. Additional 16 reports identified were summarised narratively. KEY FINDINGS: Compiling reports measuring changes in overall alcohol use, slightly more individuals indicated a decrease than an increase in their alcohol use during the pandemic [3.8%, 95% confidence interval (CI) 0.00-7.6%]. Decreases were also reported more often than increases in drinking frequency (8.0%, 95% CI 2.7-13.2%), quantity consumed (12.2%, 95% CI 8.3-16.2%) and heavy episodic drinking (17.7%, 95% CI 13.6-21.8%). Among people with pre-existing high drinking levels/alcohol use disorder, high-level drinking patterns appear to have solidified or intensified. IMPLICATIONS: Pandemic-related changes in alcohol use may be associated with pre-pandemic drinking levels. Increases among high-risk alcohol users are concerning, suggesting a need for ongoing monitoring and support from relevant health-care services. CONCLUSION: Our findings suggest that more people reduced their alcohol use in Europe than increased it since the onset of the pandemic. However high-quality studies examining specific change mechanisms at the population level are lacking.

Ecosystem design as an avenue for improving services provided by carbonate producing marine ecosystems.

Ecosystem Design (ED) is an approach for constructing habitats that places human needs for ecosystem services at the center of intervention, with the overarching goal of establishing self-sustaining habitats which require limited management. This concept was originally developed for use in mangrove ecosystems, and is understandably controversial, as it markedly diverges from other protection approaches that assign human use a minor priority or exclude it. However, the advantage of ED lies within the considered implementation of these designed ecosystems, thus preserving human benefits from potential later disturbances. Here, we outline the concept of ED in tropical carbonate depositional systems and discuss potential applications to aid ecosystem services such as beach nourishment and protection of coastlines and reef islands at risk from environmental and climate change, CO2 sequestration, food production, and tourism. Biological carbonate sediment production is a crucial source of stability of reef islands and reef-rimmed coastlines. Careful implementation of designed carbonate depositional ecosystems could help counterbalance sea-level rise and manage documented erosion effects of coastal constructions. Importantly, adhering to the core ethos of ED, careful dynamic assessments which provide a balanced approach to maximizing ecosystem services (e.g., carbonate production), should identify and avoid any potential damages to existing functioning ecosystems.

Effect of Community Support on the Implementation of Primary Health Care-Based Measurement of Alcohol Consumption.

Alcohol measurement delivered by health care providers in primary health care settings is an efficacious and cost-effective intervention to reduce alcohol consumption among patients. However, this intervention is not yet routinely implemented in practice. Community support has been recommended as a strategy to stimulate the delivery of alcohol measurement by health care providers, yet evidence on the effectiveness of community support in this regard is scarce. The current study used a pre-post quasi-experimental design in order to investigate the effect of community support in three Latin American municipalities in Colombia, Mexico, and Peru on health care providers' rates of measuring alcohol consumption in their patients. The analysis is based on the first 5 months of implementation. Moreover, the study explored possible mechanisms underlying the effects of community support, through health care providers' awareness of support, as well as their attitudes, subjective norms, self-efficacy, and subsequent intention toward delivering the intervention. An ANOVA test indicated that community support had a significant effect on health care providers' rates of measuring alcohol consumption in their patients (F (1, 259) = 4.56, p = 0.034, ηp2 = 0.018). Moreover, a path analysis showed that community support had a significant indirect positive effect on providers' self-efficacy to deliver the intervention (b = 0.07, p = 0.008), which was mediated through awareness of support. Specifically, provision of community support resulted in a higher awareness of support among health care providers (b = 0.31, p < 0.001), which then led to higher self-efficacy to deliver brief alcohol advice (b = 0.23, p = 0.010). Results indicate that adoption of an alcohol measurement intervention by health care providers may be aided by community support, by directly impacting the rates of alcohol measurement sessions, and by increasing providers' self-efficacy to deliver this intervention, through increased awareness of support. Trial Registration ID: NCT03524599; Registered 15 May 2018; https://clinicaltrials.gov/ct2/show/NCT03524599.

Training primary health care providers in Colombia, Mexico and Peru to increase alcohol screening: Mixed-methods process evaluation of implementation strategy.

Background: Initial results from the SCALA study demonstrated that training primary health care providers is an effective implementation strategy to increase alcohol screening in Colombia, Mexico and Peru, but did not show evidence of superior performance for the standard compared to the shorter training arm. This paper elaborates on those outcomes by examining the relationship of training-related process evaluation indicators with the alcohol screening practice. Methods: A mix of convergent and exploratory mixed-methods design was employed. Data sources included training documentation, post-training questionnaires, observation forms, self-report forms and interviews. Available quantitative data were compared on outcome measure - providers' alcohol screening. Results: Training reach was high: three hundred fifty-two providers (72.3% of all eligible) participated in one or more training or booster sessions. Country differences in session length reflected adaptation to previous topic knowledge and experience of the providers. Overall, 49% of attendees conducted alcohol screening in practice. A higher dose received was positively associated with screening, but there was no difference between standard and short training arms. Although the training sessions were well received by participants, satisfaction with training and perceived utility for practice were not associated with screening. Profession, but not age or gender, was associated with screening: in Colombia and Mexico, doctors and psychologists were more likely to screen (although the latter represented only a small proportion of the sample) and in Peru, only psychologists. Conclusions: The SCALA training programme was well received by the participants and led to half of the participating providers conducting alcohol screening in their primary health care practice. The dose received and the professional role were the key factors associated with conducting the alcohol screening in practice.Plain Language Summary: Primary health care providers can play an important role in detecting heavy drinkers among their consulting patients, and training can be an effective implementation strategy to increase alcohol screening and detection. Existing training literature predominantly focuses on evaluating trainings in high-income countries, or evaluating their effectiveness rather than implementation. As part of SCALA (Scale-up of Prevention and Management of Alcohol Use Disorders in Latin America) study, we evaluated training as implementation strategy to increase alcohol screening in primary health care in a middle-income context. Overall, 72.3% of eligible providers attended the training and 49% of training attendees conducted alcohol screening in practice after attending the training. Our process evaluation suggests that simple intervention with sufficient time to practice, adapted to limited provider availability, is optimal to balance training feasibility and effectiveness; that booster sessions are especially important in context with lower organizational or structural support; and that ongoing training refinement during the implementation period is necessary.

Effectiveness of digital interventions for people with comorbid heavy drinking and depression: A systematic review and narrative synthesis.

INTRODUCTION: Heavy drinking and depression frequently co-occur and make a substantial contribution to the global non-communicable disease burden. Positive evidence exists for the use of digital interventions with these conditions alone, but there has been limited assessment of combined approaches. OBJECTIVE: A systematic review of the effectiveness of combined digital interventions for comorbid heavy drinking and major depression in community-dwelling populations. METHODS AND ANALYSIS: Electronic databases were searched to October 2021 for randomised controlled trials that evaluated any personalised digital intervention for comorbid heavy drinking and depression. Primary outcomes were changes in quantity of alcohol consumed and depressive symptoms. Two reviewers independently assessed study eligibility, extracted data, and undertook risk of bias assessment. Due to the limited number and heterogeneity of studies identified, meta-analysis was not possible, therefore data were synthesised narratively. RESULTS: Of 898 articles identified, 24 papers were reviewed in full, five of which met the inclusion criteria (N = 1503 participants). Three utilised web-based intervention delivery; two computer programmes delivered in a clinic setting. All involved multi-component interventions; treatment length varied from one to ten sessions. Four studies found no evidence for the superiority of combined digital interventions for comorbid heavy drinking and depression over therapist-delivered approaches, single condition interventions (including online), or assessment-only controls. Positive impacts of integrated online therapy compared to generalist online health advice were reported in a fifth study, but not maintained beyond the 1-month follow-up. LIMITATIONS: Few eligible, heterogeneous studies prevented meta-analysis. CONCLUSION: Limited evidence exists of the effectiveness of combined digital interventions for comorbid heavy drinking and depression in community dwelling populations.

Diversity and flexibility of algal symbiont community in globally distributed larger benthic foraminifera of the genus Amphistegina.

BACKGROUND: Understanding the specificity and flexibility of the algal symbiosis-host association is fundamental for predicting how species occupy a diverse range of habitats. Here we assessed the algal symbiosis diversity of three species of larger benthic foraminifera from the genus Amphistegina and investigated the role of habitat and species identity in shaping the associated algal community. RESULTS: We used next-generation sequencing to identify the associated algal community, and DNA barcoding to identify the diatom endosymbionts associated with species of A. lobifera, A. lessonii, and A. radiata, collected from shallow habitats (< 15 m) in 16 sites, ranging from the Mediterranean Sea to French Polynesia. Next-generation sequencing results showed the consistent presence of Ochrophyta as the main algal phylum associated with all species and sites analysed. A significant proportion of phylotypes were classified as Chlorophyta and Myzozoa. We uncovered unprecedented diversity of algal phylotypes found in low abundance, especially of the class Bacillariophyta (i.e., diatoms). We found a significant influence of sites rather than host identity in shaping algal communities in all species. DNA barcoding revealed the consistent presence of phylotypes classified within the order Fragilariales as the diatoms associated with A. lobifera and A. lessonii, while A. radiata specimens host predominately diatoms of the order Triceratiales. CONCLUSIONS: We show that local habitat is the main factor influencing the overall composition of the algal symbiont community. However, host identity and the phylogenetic relationship among hosts is relevant in shaping the specific endosymbiont diatom community, suggesting that the relationship between diatom endosymbiont and hosts plays a crucial role in the evolutionary history of the genus Amphistegina. The capacity of Amphistegina species to associate with a diverse array of diatoms, and possibly other algal groups, likely underpins the ecological success of these crucial calcifying organisms across their extensive geographic range.

Primary care-based screening and management of depression amongst heavy drinking patients: Interim secondary outcomes of a three-country quasi-experimental study in Latin America.

INTRODUCTION: Implementation of evidence-based care for heavy drinking and depression remains low in global health systems. We tested the impact of providing community support, training, and clinical packages of varied intensity on depression screening and management for heavy drinking patients in Latin American primary healthcare. MATERIALS AND METHODS: Quasi-experimental study involving 58 primary healthcare units in Colombia, Mexico and Peru randomized to receive: (1) usual care (control); (2) training using a brief clinical package; (3) community support plus training using a brief clinical package; (4) community support plus training using a standard clinical package. Outcomes were proportion of: (1) heavy drinking patients screened for depression; (2) screen-positive patients receiving appropriate support; (3) all consulting patients screened for depression, irrespective of drinking status. RESULTS: 550/615 identified heavy drinkers were screened for depression (89.4%). 147/230 patients screening positive for depression received appropriate support (64%). Amongst identified heavy drinkers, adjusting for country, sex, age and provider profession, provision of community support and training had no impact on depression activity rates. Intensity of clinical package also did not affect delivery rates, with comparable performance for brief and standard versions. However, amongst all consulting patients, training providers resulted in significantly higher rates of alcohol measurement and in turn higher depression screening rates; 2.7 times higher compared to those not trained. CONCLUSIONS: Training using a brief clinical package increased depression screening rates in Latin American primary healthcare. It is not possible to determine the effectiveness of community support on depression activity rates due to the impact of COVID-19.

Factors associated with primary health care providers' alcohol screening behavior in Colombia, Mexico and Peru.

Background: Screening for unhealthy alcohol use in routine consultations can aid primary health care (PHC) providers in detecting patients with hazardous or harmful consumption and providing them with appropriate care. As part of larger trial testing strategies to improve implementation of alcohol screening in PHC, this study investigated the motivational (role security, therapeutic commitment, self-efficacy) and organizational context (leadership, work culture, resources, monitoring, community engagement) factors that were associated with the proportion of adult patients screened with AUDIT-C by PHC providers in Colombia, Mexico and Peru. Additionally, the study investigated whether the effect of the factors interacted with implementation strategies and the country. Methods: Pen-and-paper questionnaires were completed by 386 providers at the start of their study participation (79% female, Mage = 39.5, 37.6% doctors, 15.0% nurses, 9.6% psychologists, 37.8% other professional roles). They were allocated to one of four intervention arms: control group; short training only; short training in presence of municipal support; and standard (long) training in presence of municipal support. Providers documented their screening practice during the five-month implementation period. Data were collected between April 2019 and March 2020. Results: Negative binomial regression analysis found an inverse relationship of role security with the proportion of screened patients. Self-efficacy was associated with an increase in the proportion of screened patients only amongst Mexican providers. Support from leadership (formal leader in organization) was the only significant organizational context factor, but only in non-control arms. Conclusion: Higher self-efficacy is a relevant factor in settings where screening practice is already ongoing. Leadership support can enhance effects of implementation strategies.

Impact of Training and Municipal Support on Primary Health Care-Based Measurement of Alcohol Consumption in Three Latin American Countries: 5-Month Outcome Results of the Quasi-experimental Randomized SCALA Trial.

PURPOSE: We aimed to test the effects of providing municipal support and training to primary health care providers compared to both training alone and to care as usual on the proportion of adult patients having their alcohol consumption measured. METHODS: We undertook a quasi-experimental study reporting on a 5-month implementation period in 58 primary health care centres from municipal areas within Bogotá (Colombia), Mexico City (Mexico), and Lima (Peru). Within the municipal areas, units were randomized to four arms: (1) care as usual (control); (2) training alone; (3) training and municipal support, designed specifically for the study, using a less intensive clinical and training package; and (4) training and municipal support, designed specifically for the study, using a more intense clinical and training package. The primary outcome was the cumulative proportion of consulting adult patients out of the population registered within the centre whose alcohol consumption was measured (coverage). RESULTS: The combination of municipal support and training did not result in higher coverage than training alone (incidence rate ratio (IRR) = 1.0, 95% CI = 0.6 to 0.8). Training alone resulted in higher coverage than no training (IRR = 9.8, 95% CI = 4.1 to 24.7). Coverage did not differ by intensity of the clinical and training package (coefficient = 0.8, 95% CI 0.4 to 1.5). CONCLUSIONS: Training of providers is key to increasing coverage of alcohol measurement amongst primary health care patients. Although municipal support provided no added value, it is too early to conclude this finding, since full implementation was shortened due to COVID-19 restrictions. TRIAL REGISTRATION: Clinical Trials.gov ID: NCT03524599; Registered 15 May 2018; https://clinicaltrials.gov/ct2/show/NCT03524599.

Addiction Recovery Among Opioid-Dependent Patients Treated With Injectable Subcutaneous Depot Buprenorphine: Study Protocol of a Non-randomized Prospective Observational Study (ARIDE).

Introduction: Once-weekly or once-monthly injectable depot buprenorphine is a new opioid substitution treatment (OST) medication that provides clinically relevant plasma concentrations without daily peaks. Together with a high tolerability and acceptance reported by patients, the prolonged release of injectable depot buprenorphine might have beneficial implications on the patients' quality of life and social participation. The primary objective of this prospective non-interventional observational study is to evaluate the effects of subcutaneous injectable depot buprenorphine on the quality of life of patients in routine OST care in Germany. Secondary outcomes like illicit substance use, psychological distress, social participation and activity are assessed to provide an overall evaluation toward addiction recovery. Methods and Analysis: The present study is a non-randomized prospective observational study with a control group (treatment-as-usual). To ensure comparability between both patient groups, suitable control patients (n = 213) from the same OST unit will be matched pairwise to each patient treated with injectable depot buprenorphine (n = 213). Matching variables are gender, duration of OST, take-home prescription and psychosocial functioning (according to the Global Assessment of Functioning scale). Primary study endpoint is the difference of change in quality of life, assessed with the recently developed Opioid Substitution Treatment Quality of Life scale (OSTQOL), within the depot buprenorphine group between baseline and month 12. The primary analysis will be carried out according to the intention-to-treat principle (ITT) by comparing OSTQOL mean scores using dependent t-tests. For secondary analyses, group comparisons will be done by mixed model approaches with baseline OSTQOL score and the (pairwise) cluster term as covariates. Discussion: The study combines clinical, routine OST care data with relevant patient reported outcome data. The pairwise matching allows conclusions on effects of different OST medications. The study findings will provide new insights in the addiction recovery processes of OST patients treated with depot buprenorphine. Ethics and Dissemination: The study protocol has been approved by the Ethics Committee of the Hamburg Chamber of Physicians (Ärztekammer Hamburg) (reference number: PV7078). The study results will be disseminated through peer-reviewed publications and presentations on scientific conferences. Clinical Trial Registration: German Clinical Trials Register DRKS-ID: DRKS00020797.

Diagnosis of pulmonary tuberculosis in children and adolescents: comparison of two versions of the Brazilian Ministry of Health scoring system.

The aim of this study was to evaluate the concordance between two versions of the scoring system (2011 and 2019), recommended by the Brazilian Ministry of Health, for the diagnosis of pulmonary tuberculosis (PTB) in children and adolescents. A retrospective descriptive study was performed to assess the medical records of children and adolescents with PTB, in TB units from Brazilian cities located in Rio de Janeiro, Minas Gerais, and Parana States, from January 1 st , 2004, to December 1 st , 2018. Patients aged 0 to 18 years old with a diagnosis of PTB were included. The comparison between the two scoring systems showed a moderate concordance according to the κ coefficient value = 0.625. Fourteen patients showed a reduction in the TB score, going from 30 points in the 2011, to 25 points or less in the 2019 one. Seventy one percent of these 14 patients had radiological changes suggestive of PTB and 86% had tuberculin skin tests greater than 10 mm. The study concluded that a moderate agreement was observed between the 2011 and 2019 scoring systems, with an increase in the number of patients scoring 25 points or less in 2019, which can eventually hinder the diagnosis of PTB.

Clinical and Patient-Reported Outcomes of Direct-Acting Antivirals for the Treatment of Chronic Hepatitis C Among Patients on Opioid Agonist Treatment: A Real-world Prospective Cohort Study.

BACKGROUND: Patient-reported outcomes (PROs) can help to reduce uncertainties about hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) among people who inject drugs and increase treatment uptake in this high-risk group. Besides clinical data, this study analyzed for the first time PROs in a real-world sample of patients on opioid agonist treatment (OAT) and HCV treatment with DAAs. METHODS: HCV treatment data including virological response, adherence, safety, and PROs of 328 German patients on OAT were analyzed in a pragmatic prospective cohort study conducted from 2016 to 2018. Clinical effectiveness was defined as sustained virological response (SVR) at week 12 after end of treatment and calculated in per-protocol (PP) and intention-to-treat (ITT) analyses. Changes over time in PROs on health-related quality of life, physical and mental health, functioning, medication tolerability, fatigue, concentration, and memory were analyzed by repeated-measures analyses of variances (ANOVAs). RESULTS: We found high adherence and treatment completion rates, a low number of mainly mild adverse events, and high SVR rates (PP: 97.5% [n = 285]; ITT: 84.5% [n = 328]). Missing SVR data in the ITT sample were mainly caused by patients lost to follow-up after treatment completion. Most PROs showed statistically significant but modest improvements over time, with more pronounced improvements in highly impaired patients. CONCLUSIONS: This real-world study confirms that DAA treatment among OAT patients is feasible, safe, and effective. PROs show that all patients, but particularly those with higher somatic, mental, and social burden, benefit from DAA treatment.

Serological biomarkers for monitoring response to treatment of pulmonary and extrapulmonary tuberculosis in children and adolescents.

Key measures to halt the spread of tuberculosis (TB) include early diagnosis, effective treatment, and monitoring disease management. We sought to evaluate the use of serum immunoglobulin levels against antigens present in cell envelope of Mycobacterium tuberculosis to monitor TB treatment response in children and adolescents with pulmonary (PTB) or extrapulmonary TB (EPTB). Blood samples were collected prior to and one, two, and six months following treatment initiation. Serum immunoglobulin levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein were measured by ELISA. Serum from 53 TB patients and 12 healthy participants were analyzed. After six months of successful treatment, there was a significant decrease (p < 0.0001) in IgM levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein and IgG levels against Mce1A protein when compared to baseline immunoglobulin levels. There was no significant variation in antibody levels during follow-up between participants with PTB and EPTB, confirmed and unconfirmed TB diagnosis, and HIV infection status. Antibody levels in control participants without TB did not decrease during follow-up. These results suggest that immunoglobulin responses to mycobacterial cell wall products may be a useful tool to monitor treatment response in children and adolescents with PTB or EPTB.