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.

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.

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.

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.

Hepatitis C Virus Prevalence and Incidence in a Large Nationwide Sample of Patients in Opioid Substitution Treatment in Germany: A Prospective Cohort Study.

BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent among people who inject drugs (PWID). Accurate data on HCV prevalence and incidence rates among patients receiving opioid substitution treatment (OST) are needed to estimate the current and future burden of HCV infections in this high-risk population. METHODS: Baseline data from routine care were collected between October 2014 and June 2016 from randomly selected OST facilities in Germany. The primary outcome measure was the HCV status (antibody and RNA prevalence). Patients who were HCV antibody-negative at baseline were followed up after 12 months to calculate the HCV incidence rate. RESULTS: Sixty-three facilities from 14 German Federal States provided clinical data for a total of 2466 OST patients. HCV antibody and HCV RNA prevalence were 58.8% (95% confidence interval [CI], 56.8%-60.8%) and 27.3% (95% CI, 25.5%-29.2%), respectively. At baseline, a total of 528 patients (21.4%) had previously undergone antiviral treatment. Moreover, lower HCV RNA prevalence was associated with female gender, employment, younger age, and shorter duration of OST and opioid dependence. The HCV incidence rate was 2.5 cases per 100 person-years. CONCLUSIONS: The low HCV RNA prevalence and HCV incidence rates confirm that OST in Germany is an effective setting both for treating chronic HCV infections and for preventing new infections among PWID. Scaling up the provision of OST, HCV testing, and HCV treatment among OST patients are important public health strategies for reducing HCV infections in this high-risk population.

Structural and functional characterization of SiiA, an auxiliary protein from the SPI4-encoded type 1 secretion system from Salmonella enterica.

Salmonella invasion is mediated by a concerted action of the Salmonella pathogenicity island 4 (SPI4)-encoded type one secretion system (T1SS) and the SPI1-encoded type three secretion system (T3SS-1). The SPI4-encoded T1SS consists of five proteins (SiiABCDF) and secretes the giant adhesin SiiE. Here, we investigated structure-function relationships in SiiA, a non-canonical T1SS subunit. We show that SiiA consists of a membrane domain, an intrinsically disordered periplasmic linker region and a folded globular periplasmic domain (SiiA-PD). The crystal structure of SiiA-PD displays homology to that of MotB and other peptidoglycan (PG)-binding domains. SiiA-PD binds PG in vitro, albeit at an acidic pH, only. Mutation of Arg162 impedes PG binding of SiiA and reduces Salmonella invasion efficacy. SiiA forms a complex with SiiB at the inner membrane (IM), and the observed SiiA-MotB homology is paralleled by a predicted SiiB-MotA homology. We show that, similar to MotAB, SiiAB translocates protons across the IM. Mutating Asp13 in SiiA impairs proton translocation. Overall, SiiA shares numerous properties with MotB. However, MotAB uses the proton motif force (PMF) to energize the bacterial flagellum, it remains to be shown how usage of the PMF by SiiAB assists T1SS function and Salmonella invasion.

Comparative whole genome analysis of three consecutive Salmonella diarizonae isolates.

Infections of very young children or immunocompromised people with Salmonella of higher subspecies are a well-known phenomenon often associated with contact to cold-blooded animals. We describe the molecular characterization of three S. enterica subsp. diarizonae strains, isolated consecutively over a period of several months from a hospital patient suffering from diarrhea and sepsis with fatal outcome. With the initial isolate the first complete genome sequence of a member of subsp. diarizonae is provided and based on this reference we revealed the genomic differences between the three isolates by use of next-generation sequencing and confirmed by phenotypical tests. Genome comparisons revealed mutations within gpt, hfq and purK in the first isolate as a sign of clonal variation rather than host-directed evolution. Furthermore, our work demonstrates that S. enterica subsp. diarizonae possess, besides a conserved set of known Salmonella Pathogenicity Islands, a variable portfolio of additional genomic islands of unknown function.

Geochemical signatures of benthic foraminiferal shells from a heat-polluted shallow marine environment provide field evidence for growth and calcification under extreme warmth.

Shallow marine calcifiers play an important role as marine ecosystem engineers and in the global carbon cycle. Understanding their response to warming is essential to evaluate the fate of marine ecosystems under global change scenarios. A rare opportunity to test the effect of warming acting on natural ecosystems is by investigation of heat-polluted areas. Here, we study growth and calcification in benthic foraminifera that inhabit a thermally polluted coastal area in Israel, where they are exposed to elevated temperatures reaching up to ~42°C in summer. Live specimens of two known heat-tolerant species Lachlanella sp. 1 and Pararotalia calcariformata were collected over a period of 1 year from two stations, representing thermally polluted and undisturbed (control) shallow hard bottom habitats. Single-chamber element ratios of these specimens were obtained using laser ablation, and the Mg/Ca of the most recently grown final chambers were used to calculate their calcification temperatures. Our results provide the first direct field evidence that these foraminifera species not only persist at extreme warm temperatures but continue to calcify and grow. Species-specific Mg/Ca thermometry indicates that P. calcariformata precipitate their shells at temperatures as high as 40°C and Lachlanella sp. 1 at least up to 36°C, but both species show a threshold for calcification at cold temperatures: calcification in P. calcariformata only occurred above 22°C and in Lachlanella sp. 1 above 15°C. Our observations from the heat-polluted area indicate that under future warming scenarios, calcification in heat-tolerant foraminifera species will not be inhibited during summer, but instead the temperature window for their calcification will be expanded throughout much of the year. The observed inhibition of calcification at low temperatures indicates that the role of heat-tolerant foraminifera in carbonate production will most likely increase in future decades.

Epidemiology of hepatitis C virus infection among people receiving opioid substitution therapy (ECHO): study protocol.

BACKGROUND: Hepatitis C virus infection is highly prevalent among people who inject drugs. Opioid substitution therapy, the standard treatment for opioid dependence, provides an excellent opportunity for the treatment of hepatitis C virus infection due to the close and regular contact between patients and clinicians. However, there is little research on the impact of opioid substitution therapy on the prevalence of the hepatitis C virus at a national level. This paper describes the protocol for the Epidemiology of Hepatitis C Virus Infection among People Receiving Opioid Substitution Therapy (ECHO) study. The aim of this study is to estimate the national prevalence and incidence of hepatitis C virus infection among people receiving opioid substitution therapy in Germany and to describe factors associated with hepatitis C treatment uptake and seroconversion. METHODS/DESIGN: An observational, longitudinal, multicentre study is being conducted between 2014 and 2016 in a representative sample of approximately 2500 people receiving opioid substitution therapy from about 100 clinicians providing opioid substitution therapy in Germany. Data will be collected during routine patient care and by means of patient and clinician questionnaires at baseline and 12-month follow-up. Stratified sampling will be performed to obtain a representative sample of clinicians providing opioid substitution therapy. The strata will be constructed based on the distribution of the total sample of clinicians providing opioid substitution therapy in Germany according to German Federal State and the number of patients per clinician. DISCUSSION: Opioid substitution therapy may be an important strategy to prevent the spread of hepatitis C virus in opioid dependent populations, but its effectiveness may be diminished by our limited understanding of factors associated with treatment uptake and seroconversion. The present study will provide important information for developing strategies to address hepatitis C virus-related disease burden in people receiving opioid substitution therapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02395198.

The impact of brief alcohol interventions in primary healthcare: a systematic review of reviews.

AIMS: The aim of the study was to assess the cumulative evidence on the effectiveness of brief alcohol interventions in primary healthcare in order to highlight key knowledge gaps for further research. METHODS: An overview of systematic reviews and meta-analyses of the effectiveness of brief alcohol intervention in primary healthcare published between 2002 and 2012. FINDINGS: Twenty-four systematic reviews met the eligibility criteria (covering a total of 56 randomized controlled trials reported across 80 papers). Across the included studies, it was consistently reported that brief intervention was effective for addressing hazardous and harmful drinking in primary healthcare, particularly in middle-aged, male drinkers. Evidence gaps included: brief intervention effectiveness in key groups (women, older and younger drinkers, minority ethnic groups, dependent/co-morbid drinkers and those living in transitional and developing countries); and the optimum brief intervention length and frequency to maintain longer-term effectiveness. CONCLUSION: This overview highlights the large volume of primarily positive evidence supporting brief alcohol intervention effects as well as some unanswered questions with regards to the effectiveness of brief alcohol intervention across different cultural settings and in specific population groups, and in respect of the optimum content of brief interventions that might benefit from further research.

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.

Psychoeducation improves hepatitis C virus treatment during opioid substitution therapy: a controlled, prospective multicenter trial.

BACKGROUND: People who inject drugs (PWID) have a high prevalence of hepatitis C virus (HCV) infection. However, PWID are considered "difficult to treat," requiring a specifically adapted treatment setting, including psychosocial support. METHODS: In this prospective, German trial, the impact of psychoeducation (PE) on retention and sustained virologic response (SVR) during HCV therapy among PWID was evaluated. We included 198 patients in opiate substitution therapy, who fulfilled indications for antiviral treatment. All patients received pegylated interferon alfa-2a and ribavirin therapy. Patients in the intervention group (n = 82) received manualized PE sessions. RESULTS: In patients with HCV genotype 1 or 4 (GT 1/4), PE was associated with increased treatment completion (76% vs 55%, P = .038), whereas PE had no such effect among GT 2/3 patients, who showed fewer dropouts and higher SVR rates. Among GT 1/4 patients, a minimum of 5 PE sessions was associated with increased SVR (71% vs 48%, P = .037). Multivariate regression analyses confirmed the impact of PE in GT 1/4 and revealed further predictors for retention and SVR, such as preexisting mental distress and adverse events. CONCLUSIONS: In patients with a higher risk of dropout due to GT 1/4 or mental distress, PE was shown to improve retention and SVR. PE is an effective supportive intervention for HCV therapy among PWID.

Gaussia princeps luciferase as a reporter for transcriptional activity, protein secretion, and protein-protein interactions in Salmonella enterica serovar typhimurium.

Gaussia princeps luciferase (Gluc) is widely used as a reporter in eukaryotes, but data about its applicability in bacteria are very limited. Here we show that a codon-optimized Gluc gene can be efficiently expressed in Salmonella enterica serovar Typhimurium. To test different Gluc variants as transcriptional reporters, we used the siiA promoter of Salmonella pathogenicity island 4 (SPI-4) driving expression of either an episomal or a chromosomally integrated Gluc gene. Most reliable results were obtained from lysates of single-copy Gluc reporter strains. Given the small size, high activity, and cofactor independence of Gluc, it might be especially suited to monitor secretion of bacterial proteins. We demonstrate its usefulness by luminescence detection of fusion proteins of Gluc and C-terminal portions of the SPI-4-encoded, type I-secreted adhesin SiiE in supernatants. The SiiE C-terminal moiety including immunoglobulin (Ig) domain 53 is essential and sufficient for mediating type I-dependent secretion of Gluc. In eukaryotes, protein-protein interaction studies based on split-Gluc protein complementation assays (PCA) could be established. We adapted these methods for use in Salmonella, demonstrating the interaction between the SPI-1-encoded effector SipA and its cognate secretion chaperone InvB. In conclusion, the versatile Gluc can be used to address a variety of biological questions, thus representing a valuable addition to the toolbox of modern molecular biology and microbiology.

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.

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.

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.

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.