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AimTo assess the feasibility and acceptability of massive hepatitis C virus (HCV) testing in point of care on the street using quick tests, determine the characteristics of the population included, and the prevalence of HCV infection in this population.MethodsCross-sectional community-based study including adult men who have sex with men (MSM) who attended the three most important LGTB+ events in Sitges (Catalonia, Spain) in 2022. Points of care were set up on tents on the street and attendees were offered voluntary anti-HCV antibody self-testing. Participants were informed of the study, provided consent, completed the test for identification of risk practices (TIRP), and took the test with the OraQuick® HCV test on a saliva sample (sensitivity: 97.8% [95% confidence interval (CI), 93.2–99.4%] and specificity: 100% [95% CI, 98.4–100%]; gold standard: IgG antibody test for HCV by immunoassay [serum]); participants with positive results were offered HCV virus testing with the Xpert HCV Fingerstick® on a blood drop.ResultsA total of 1249 adults participated in the large-scale screening, of which 1197 (95.8%) were identified as MSM. The screening time was 39 participants/h. Four (0.32%) participants had positive anti-HCV results, all with undetectable HCV RNA levels. Participants’ median (IQR) age was 44 (35, 54) years; most were Europeans, and 13% reported being unaware of their serological HCV status. The mean (SD) TIRP score was 1.40 (1.44) (n = 1062), with 67.41% reporting some risk, and the self-perceived sexually transmitted disease score was 3.0 (2.82) (n = 969).ConclusionThe point-of-care strategy on the street using a quick oral self-test at massive MSM events is feasible, well-accepted, and quick, and may be a useful strategy to reach other populations at risk of HCV infection.

Abstract Introduction Drinking during pregnancy is the leading cause of birth defects and child developmental disorders in Europe. The adverse effects of drinking during pregnancy may include physical, behavioural and cognitive problems, known collectively as fetal alcohol spectrum disorders (FASD). Evidence-based comprehensive recommendations at the European level on how to implement preventive and treatment policies to reduce alcohol-exposed pregnancies are needed. FAR SEAS, a tendered service contract (number 20,187,106) awarded by the European Commission, aimed at developing guidelines to respond to this knowledge gap. Methods FAR SEAS recommendations were built on (1) a two-phase review of interventions, (2) an international expert consultation, and (3) a pilot study on prevention of FASD conducted in the Mazovia region of Poland. The review of interventions included nineteen electronic open access databases, several repositories of grey literature and a key informant consultation covering most European Union (EU) countries and an additional guidelines search. After triangulating sources, 94 records were collected. Experts contributed in the design of the research questions, addressing the gaps in the literature and reviewing the recommendations formulated. The Polish pilot added nuances from real world practice to the formulated recommendations, resulting in the final set of guidelines for dissemination. Results The FAR SEAS Guidelines comprise 23 recommendations grouped into different topics areas of policies, communication strategies, screening, brief intervention and referral to treatment, treatment and social services. The recommendations highlight the need to respect women’s autonomy and avoid discrimination and stigmatization; using universal screening for women of childbearing age, including detection of other psychosocial risks (such as domestic violence); and individualized, comprehensive and multidisciplinary supportive interventions for those who require it, such as those with alcohol use disorders, including women’s partners. Policies to prevent FASD should be multicomponent, and public health communication should combine information about the risks together with self-efficacy messages to promote changes. Conclusions The FAR SEAS guidelines are a tool to support policy-makers and service managers in implementing effective programmes to reduce prenatal alcohol exposure among general and at-risk population groups. FASD prevention has to involve comprehensive and multi-level evidence-based policies and practice, with services and activities tailored to the needs of women at differing levels of risk, and with due attention to reducing stigma.

BackgroundApproximately 1 in 6 cannabis users develop a cannabis use disorder (CUD) and the odds increase to 1 in 2 for daily users. ObjectiveThe Dual use of Cannabis and Tobacco Monitoreing through a Gamified Web app (DuCATA_GAM-CaT) project aims to identify cannabis-tobacco patterns of use and withdrawal symptoms among individuals with CUD who are attending substance abuse programs. MethodsThe project uses a mixed methods approach consisting of 3 studies. First, a participatory qualitative study involves focus groups comprising individuals with CUD, clinicians, project researchers, and an expert gamification company to co-design a gamified web app. Second, a longitudinal prospective study to follow up individuals over 6 weeks with CUD attending substance abuse programs . Participants report their cannabis-tobacco usage patterns, type and frequency of tobacco use, nicotine dependence, withdrawal symptoms, psychoemotional factors, and motivation to quit both substances. Predictive analysis techniques are used to analyze clinical, demographic, psychological, and environmental data to predict the probability of achieving abstinence. Third, homogeneous focus groups to explore participants’ experiences during their CUD treatment. ResultsBy June 2024, the project had completed the first study, defining eligible cannabis user profiles, developed the initial web app prototype, and initiated recruitment across 10 centers, with 74 participants enrolled, aiming to reach 150 participants in total. ConclusionsAll participants are required to provide informed consent, and their information is kept confidential and anonymized following confidentiality rules. The research team is committed to disseminating the results obtained to professional and patient groups, as well as informing public health agents, to positively influence political and social decision makers and design programmers. Additionally, we aim to prioritize the publication of the results in high-impact journals specialized in drug abuse, public health, and health care services research. Trial RegistrationClinicalTrials.gov NCT05512091; https://clinicaltrials.gov/study/NCT05512091 International Registered Report Identifier (IRRID)DERR1-10.2196/58335

Digestive enzymes can selectively degrade proteins, carbohydrates and lipids; and their supplementation alongside food may accelerate the breakdown of complex food matrices, facilitate greater nutrient absorption, decrease food sensitivities and aid in the management of certain disease states. Several intrinsic and extrinsic factors govern food digestion and for every individual this phenomenon is unique. This study was conducted as a randomized, crossover, placebo-controlled design where each participant served as their own control. This post-hoc analysis investigated the impact of a dietary enzyme supplementation blend known as Elevase® on dietary macromolecule digestion in samples from otherwise healthy participants that had previously undergone a small bowel resection, resulting in an ileostomy (NCT04489810). This is the first time this study-paradigm has been used for the assessment of in vivo dietary breakdown following enzyme supplementation. Arguably, this technique offers superior data when compared to that generated in artificial gut digestion models, preclinical animal models, or indeed conventional clinical studies using stool analyses, as it allows real-time access to samples in situ in the small intestine where the majority of nutritional absorption takes place. It was demonstrated that after 4 h, Elevase® significantly increased monosaccharide levels (predominantly glucose and fructose) in the ileostomy samples taken from the same individuals on the same diet on a different day. In addition, the bile salt taurohyodeoxycholic acid was also increased, suggesting a physiological host response to the macromolecule digestion induced by the enzymatic blend. Overall, these findings suggest Elevase® could accelerate food digestion and potentially increase nutrient availability from the diet.

BackgroundThe COVID-19 pandemic has impacted the mental health of patients with substance use disorder (SUD). However, few longitudinal studies have been done which examine associations between the pandemic, SUD patients’ mental health and their drug use.ObjectivesThis study aimed to examine duration of abstinence according to psychiatric status among SUD outpatients followed-up for 18 months from the pandemic related lockdown.MethodsA follow-up study of 316 SUD outpatients was undertaken. Sociodemographic features, and clinical and consumption related variables were recorded. Pre, during and post lockdown information was evaluated. Abstinence/substance use was monitored at the patient’s scheduled follow-up appointments, and psychiatric disorders and psychological variables were revaluated at 18 months.ResultsSurvival analyses were used to compare the duration of abstinence (in months) from the beginning of the lockdown. It was observed that 70% of patients consumed the main substance for which they were being treated at some point during the follow-up. Men, younger patients, those with more symptoms of anxiety and personality disorders, and patients who experienced increased craving during follow-up, showed shorter duration of abstinence. While patients who had previously maintained at least one year of abstinence, achieved better results.ConclusionsDuring the first year and a half of the pandemic, SUD outpatients presented alterations in mental health, such us anxiety, depression and maladaptive personality traits and a high rate of relapse. For this reason, despite the health and social crisis and their restrictive measures, a comprehensive treatment should be ensured.

IntroductionBacillus coagulans species have garnered much interest in health-related functional food research owing to their desirable probiotic properties, including pathogen exclusion, antioxidant, antimicrobial, immunomodulatory and food fermentation capabilities coupled with their tolerance of extreme environments (pH, temperature, gastric and bile acid resistance) and stability due to their endosporulation ability.MethodsIn this study, the novel strain Bacillus coagulans CGI314 was assessed for safety, and functional probiotic attributes including resistance to heat, gastric acid and bile salts, the ability to adhere to intestinal cells, aggregation properties, the ability to suppress the growth of human pathogens, enzymatic profile, antioxidant capacity using biochemical and cell-based methods, cholesterol assimilation, anti-inflammatory activity, and attenuation of hydrogen peroxide (H2O2)-induced disruption of the intestinal-epithelial barrier.ResultsB. coagulans CGI314 spores display resistance to high temperatures (40°C, 70°C, and 90°C), and gastric and bile acids [pH 3.0 and bile salt (0.3%)], demonstrating its ability to survive and remain viable under gastrointestinal conditions. Spores and the vegetative form of this strain were able to adhere to a mucous-producing intestinal cell line, demonstrated moderate auto-aggregation properties, and could co-aggregate with potentially pathogenic bacteria. Vegetative cells attenuated LPS-induced pro-inflammatory cytokine gene expression in HT-29 intestinal cell lines and demonstrated broad antagonistic activity toward numerous urinary tract, intestinal, oral, and skin pathogens. Metabolomic profiling demonstrated its ability to synthesize several amino acids, vitamins and short-chain fatty acids from the breakdown of complex molecules or by de novo synthesis. Additionally, B. coagulans CGI314’s strong antioxidant capacity was demonstrated using enzyme-based methods and was further supported by its cytoprotective and antioxidant effects in HepG2 and HT-29 cell lines. Furthermore, B. coagulans CGI314 significantly increased the expression of tight junction proteins and partially ameliorated the detrimental effects of H2O2 induced intestinal-epithelial barrier integrity.DiscussionTaken together these beneficial functional properties provide strong evidence for B. coagulans CGI314 as a promising potential probiotic candidate in food products.

Background & Aims: Many people with HCV and HBV infection are unaware of their condition, particularly at-risk and vulnerable populations who face barriers for screening and linkage to care. Emergency departments are often their only point of contact with the health system. Methods: This is a prospective study investigating HBsAg and HCV antibody testing, with reflex testing for HDV antibodies and HCV RNA, in adults attending an emergency department and requiring a blood test. Positive cases were linked to care. A cost-effectiveness analysis was performed. Results: From February 2020 to February 2022, a total of 17,560 individuals were screened. HBsAg was detected in 91 (0.5%), HCV RNA in 128 (0.7%), and HDV antibodies in two (0.01%) individuals. Nearly 40% of positive cases were unaware of their condition. Linkage to care was achieved in 42 of 56 HBsAg-positive and 45 of 69 HCV RNA-positive participants who were candidates for referral. HCV and HBV screening vs. no screening yielded 1.06 and 0.42 additional quality-adjusted life-years, respectively, with incremental cost–utility ratios of €7,629 and -€147 per quality-adjusted life-year gained, respectively, and proved even more cost-effective in patients with hepatitis C aged 40–70 years. Conclusions: On emergency department screening for hepatitis B, C, and D in Barcelona, the prevalence of HBsAg was 0.5% and HCV RNA 0.7%, approximately threefold higher than that observed in the general population. This strategy diagnosed patients with active HCV infection and no risk factors, who would not have been screened according to the current recommendations. Screening and linkage to care of viral hepatitis is cost-effective in this setting. Impact and implications: We evaluated the performance and cost-effectiveness of a viral hepatitis screening programme implemented in an emergency department, which aimed to identify and link to care people living with hepatitis B and C. Our findings reveal a threefold higher prevalence of hepatitis B and C than in the general Spanish population, possibly attributable to the role of the emergency department as the main healthcare gateway for vulnerable populations, who have a higher prevalence of viral hepatitis. Risk factors for viral hepatitis could not be identified in most people living with hepatitis B and C attending the emergency department; hence, screening beyond risk factors should be considered in hepatitis detection strategies. Emergency department screening is cost-effective for hepatitis C and is a cost-saving strategy for hepatitis B in our setting. These data should inform future updates to clinical guidelines.

Abstract Background Approximately 80% of people with a substance use disorder (SUD) are smokers. Starting SUD treatment offers the opportunity to also quit smoking. The ACT-ATAC project aims to identify the predictors associated with smoking cessation among persons treated for alcohol and/or cannabis use disorder in Barcelona. This manuscript reports its methodology and the experience of carrying it out during the COVID-19 pandemic. Methods Mixed methods project with three substudies. Substudy 1 (S1) comprises heterogeneous discussion groups among clinicians. S2 has two prospective cohorts composed of smokers under treatment for alcohol and/or cannabis use disorder and the clinicians in charge of these patients. Participating smokers will be followed for 12 months and interviewed about their substance use and the tobacco cessation services received using the Spanish version of the users’ Knowledge, Attitudes, and Services (S-KAS) scale. The clinicians will be asked about their self-reported practices in smoking cessation using the Knowledge, Attitudes, and Practices (S-KAP) scale. S3 comprises heterogeneous discussion groups with smokers. Data will be triangulated using qualitative and quantitative analyses. To facilitate the recruitment process, the researchers have introduced several strategies (design clear protocols, set monthly online meetings, extend the project, provide gift cards, etc.). Discussion The results of S1 were used to develop the questionnaires. S2 required some adjustments due to the COVID-19 pandemic, particularly the follow-up interviews being conducted by phone instead of face-to-face, and the recruitment rhythm was lower than expected. Recruitment will last until reaching at least 200–250 users. The fieldwork could not have been possible without the collaboration of the ACT-ATAC team and the introduction of several strategies. Trial registration The ACT-ATAC project has been successfully registered at Clinicaltrials.gov [NCT04841655].

Abstract Background Harm reduction services and professionals have had to reorganise and adapt to COVID-19 prevention measures while still ensuring health and social services for people who use drugs (PUD). Objective To assess the impact of the COVID-19 pandemic on PUD and on the professionals who provide harm reduction services. Methods A qualitative, exploratory, multicentre design was used. Two focus groups were held with harm reduction professionals, and 40 individual semi-structured interviews were undertaken with PUD in various harm reduction services in Catalonia. Interviews and focus group discussions were transcribed and analysed using thematic content analysis. Results Harm reduction services adapted to the pandemic situation by employing methods such as reducing opening hours and closing drop in areas, along with health protection measures such as access control, which in turn led to stress among both professionals and service users. Despite the changes implemented, PUD continued to have access to sterile drug use equipment and methadone treatment. In addition, those who were not in treatment were able to access it rapidly. Regarding their emotional state, the PUD reported that it was worse during the pandemic than before the lockdown, with women affected to a greater extent than men. The harm reduction professionals reported difficulties in managing service users’ compliance with the security measures at the beginning of the lockdown and having had to focus primarily on providing food and shelter for the PUD. Conclusions It is important to keep PUD in mind and maintain a harm reduction perspective when implementing confinement measures in situations such as those experienced during the COVID pandemic. Guaranteeing that PUD have their basic needs such as food, hygiene and shelter covered is key.

IntroductionWithin FAR SEAS, a multi-component evidence-based community intervention was implemented and evaluated in Mazovia (Poland), with the aim of preventing alcohol-exposed pregnancies, and therefore preventing FASD.MethodsMulti-disciplinary professionals from different services (social, addiction, and psychology), recruited women of child-bearing age (pregnant and not pregnant) in local communities, screened them for alcohol risk, and allocated participants (n = 441) to groups for low- (70%), moderate- (23%), or high-risk (7%) of alcohol exposed pregnancy, to provide interventions tailored to their needs. The non-parametric sign test, testing differences between pairs of observations before and after intervention was used to evaluate the outcomes.ResultsFollow-up data (collected from 93% of participants) indicated positive changes in the key outcome variables: risky alcohol consumption dropped by 81%, contraception use increased by 15% and visiting a gynecologist increased by 39%; as well as in associated psychosocial risk factors (decrease in cigarette and drug use, domestic violence and depressive symptoms). No changes were noted in frequency of other service use (medical, psychological, or social). The most prominent changes were observed in the moderate-risk group.DiscussionChanging risky behaviors (alcohol consumption and sex without contraception) to prevent alcohol exposed pregnancies is feasible at the local level, even without engagement of medical professionals. Key challenges, related to engaging professionals and local authorities, must be addressed; and procedures should be adapted to local contexts and needs.

Objectives To perform a budget impact analysis of the HepClink test-and-treat strategy in which community health agents offer hepatitis C virus (HCV) testing, diagnosis and treatment to the Pakistani population living in Catalonia compared with the current practice of the Catalan health system (without targeted screening programmes).Methods We estimated the population of adult Pakistani migrants registered at the primary care centres in Catalonia by means of the Information System for the Development of Research in Primary Care (n=37 972 in 2019, Barcelona health area). This cohort was followed for a time period of 10 years after HCV diagnosis (2019–2028). The statistical significance of the differences observed in the anti-HCV positivity rate between screened and non-screened was confirmed (α=0.05). The budget impact was calculated from the perspective of the Catalan Department of Health. Sensitivity analyses included different levels of participation in HepClink: pessimistic, optimistic and maximum.Results The HepClink scenario screened a higher percentage of individuals (69.8%) compared with the current scenario of HCV care (39.7%). Viraemia was lower in the HepClink scenario compared with the current scenario (1.7% vs 2.5%, respectively). The budget impact of the HepClink scenario was €884 244.42 in 10 years.Conclusions Scaling up the HepClink strategy to the whole Catalan territory infers a high budget impact for the Department of Health and allows increasing the detection of viraemia (+17.8%) among Pakistani migrants ≥18 years. To achieve a sustainable elimination of HCV by improving screening and treatment rates, there is room for improvement at two levels. First, taking advantage of the fact that 68.08% of the Pakistani population had visited their primary care physicians to reinforce targeted screening in primary care. Second, to use HepClink at the community level to reach individuals with reluctance to use healthcare services.

Exposure to diverse environmental pollutants and food contaminants is ever-increasing. The risks related to the bioaccumulation of such xenobiotics in the air and food chain have exerted negative effects on human health, such as inflammation, oxidative stress, DNA damage, gastrointestinal disorders, and chronic diseases. The use of probiotics is considered an economical and versatile tool for the detoxification of hazardous chemicals that are persistent in the environment and food chain, potentially for scavenging unwanted xenobiotics in the gut. In this study, Bacillus megaterium MIT411 (Renuspore®) was characterized for general probiotic properties including antimicrobial activity, dietary metabolism, and antioxidant activity, and for the capacity to detoxify several environmental contaminants that can be found in the food chain. In silico studies revealed genes associated with carbohydrate, protein and lipid metabolism, xenobiotic chelation or degradation, and antioxidant properties. Bacillus megaterium MIT411 (Renuspore®) demonstrated high levels of total antioxidant activities, in addition to antimicrobial activity against Escherichia coli, Salmonella enterica, Staphylococcus aureus, and Campylobacter jejuni in vitro. The metabolic analysis demonstrated strong enzymatic activity with a high release of amino acids and beneficial short-chain fatty acids (SCFAs). Moreover, Renuspore® effectively chelated the heavy metals, mercury and lead, without negatively impacting the beneficial minerals, iron, magnesium, or calcium, and degraded the environmental contaminants, nitrite, ammonia, and 4-Chloro-2-nitrophenol. These findings suggest that Renuspore® may play a beneficial role in supporting gut health metabolism and eliminating unwanted dietary contaminants.

The objective of the prospective cohort study (the DESKcohort project) is to describe and monitor health, health behaviors, and their related factors among 12 and 19-year-old adolescents schooled at centers of Compulsory Secondary Education or post-compulsory secondary education in Central Catalonia, considering social determinants of health. The DESKcohort survey is administered biannually between the months of October and June, and the project has been running for three years. We have interviewed 7319 and 9265 adolescents in the academic years 2019/20 and 2021/22, respectively. They responded a questionnaire created by a committee of experts, that included the following variables: sociodemographic factors, physical and mental health, food, physical activity, leisure and mobility, substance use, interpersonal relationships, sexuality, screen use and digital entertainment, and gambling. The results are presented to educational centers, county councils, municipalities, and health and third sector entities to plan, implement, and evaluate prevention and health promotion actions that address the identified needs. Resumen: El objetivo de este estudio prospectivo de cohortes (proyecto DESKcohort) es describir y monitorizar la salud, los comportamientos de salud y sus factores asociados en los adolescentes de entre 12 y 19 años escolarizados en centros de Educación Secundaria Obligatoria o secundaria posobligatoria de la Cataluña Central, considerando los determinantes sociales de la salud. La encuesta DESKcohort se realiza bianualmente, entre los meses de octubre y junio, y el proyecto lleva 3 años en marcha. Se ha entrevistado a 7319 y 9265 adolescentes en los cursos 2019/20 y 2021/22, respectivamente. Respondieron un cuestionario creado por un comité de expertos, que incluía las siguientes variables: sociodemográficas, salud física y mental, alimentación, actividad física, ocio y movilidad, consumo de sustancias, relaciones interpersonales, sexualidad, uso de pantallas y entretenimiento digital, y juegos de azar. Los resultados son presentados a los centros educativos, las diputaciones, los municipios y las entidades sanitarias y del tercer sector para planificar, implementar y evaluar acciones de prevención y promoción de la salud que aborden las necesidades identificadas.

Bacillus subtilis DE111® is a safe, well-tolerated commercially available spore-forming probiotic that has been clinically shown to support a healthy gut microbiome, and to promote digestive and immune health in both adults and children. Recently it was shown that this spore-forming probiotic was capable of germinating in the gastrointestinal tract as early as 3 h after ingestion. However, a better understanding of the mechanisms involved in the efficacy of DE111® is required. Therefore, the present investigation was undertaken to elucidate the functional properties of DE111® through employing a combination of in vitro functional assays and genome analysis. DE111® genome mining revealed the presence of several genes encoding acid and stress tolerance mechanisms in addition to adhesion proteins required to survive and colonize harsh gastrointestinal environment including multi subunit ATPases, arginine deiminase (ADI) pathway genes (argBDR), stress (GroES/GroEL and DnaK/DnaJ) and extracellular polymeric substances (EPS) biosynthesis genes (pgsBCA). DE111® harbors several genes encoding enzymes involved in the metabolism of dietary molecules (protease, lipases, and carbohyrolases), antioxidant activity and genes associated with the synthesis of several B-vitamins (thiamine, riboflavin, pyridoxin, biotin, and folate), vitamin K2 (menaquinone) and seven amino acids including five essential amino acids (threonine, tryptophan, methionine, leucine, and lysine). Furthermore, a combined in silico analysis of bacteriocin producing genes with in vitro analysis highlighted a broad antagonistic activity of DE111® toward numerous urinary tract, intestinal, and skin pathogens. Enzymatic activities included proteases, peptidases, esterase’s, and carbohydrate metabolism coupled with metabolomic analysis of DE111® fermented ultra-high temperature milk, revealed a high release of amino acids and beneficial short chain fatty acids (SCFAs). Together, this study demonstrates the genetic and phenotypic ability of DE111® for surviving harsh gastric transit and conferring health benefits to the host, in particular its efficacy in the metabolism of dietary molecules, and its potential to generate beneficial SCFAs, casein-derived bioactive peptides, as well as its high antioxidant and antimicrobial potential. Thus, supporting the use of DE111® as a nutrient supplement and its pottential use in the preparation of functional foods.

Background & Aims: Significant scale-up of treatment among people who inject drugs (PWID) is crucial to achieve WHO HCV elimination targets. We explored the impact of on-site HCV diagnosis and treatment on PWID in an externalised hepatology clinic at the biggest harm reduction centre (HRC) in Barcelona attending to a marginalised PWID population with ongoing high-risk practices. Methods: On-site HCV point-of-care testing was performed for diagnosis and treatment delivery. HCV-RNA was assessed at SVR12 (sustained virologic response at 12 weeks) and every 6 months. The programme included behavioural questionnaires at baseline and after treatment. Results: Between 2018 and 2020, 919 individuals were prospectively enrolled. Of these, only 46% accepted HCV screening. HCV-RNA+ prevalence was 55.7% (n = 234). Of the 168 (72%) individuals starting treatment, 48% were foreigners, 32% homeless, 73% unemployed, and 62% had a history of incarceration. At enrolment, 70% injected drugs daily and 30% reported sharing needles or paraphernalia. Intention-to-treat SVR12 was 60%; only 4% were virological failures, the remaining were either early reinfections (20%) or losses to follow-up (16%). The overall reinfection rate during follow-up was 31/100 persons/year. HIV coinfection and daily injection were associated with a higher risk of reinfection. Nonetheless, beyond viral clearance, antiviral therapy was associated with a significant reduction in injection frequency, risk practices, and homelessness. Conclusions: HCV treatment can be successfully delivered to active PWID with high-risk practices and has a significant benefit beyond HCV elimination. However, approaching this difficult spectrum of the PWID population implies significant barriers such as low rate of screening acceptance and high dropout and reinfection rates. Lay summary: People who inject drugs attending harm reduction centres represent the most difficult population to treat for hepatitis C. We show that hepatitis C treatment has a significant benefit beyond viral cure, including improving quality of life, and decreasing injection frequency and risk practices. However, intrinsic barriers and the high reinfection rates hamper the achievement of viral microelimination in this setting.

Background: There is increasing interest in the use of Bacillus species as probiotics since their spore-forming ability favors their survival in the acidic gastric environment over other probiotic species. The subsequent germination of B. subtilis to their vegetative form allows for their growth in the small intestine and may increase their beneficial effect on the host. B. subtilis strains have also previously been shown to have beneficial effects in humans and production animals, however, no reports are available so far on their use in companion animals. Study design: The goal of this study was therefore to investigate the daily administration of 1 × 109 cfu DE-CA9TM orally per day versus placebo on health parameters, fecal scores, fecal microbiome, fecal metabolomics, as well as serum metabolomics and oxidative stress markers in ten healthy Beagle dogs in a parallel, randomized, prospective, placebo-controlled design over a period of 45 days. Results: DE-CA9TM decreased the oxidative status compared to controls for advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances (TBARS) and reactive oxygen metabolites (d-ROMS), suggesting an antioxidant effect of the treatment. Fecal metabolomics revealed a significant reduction in metabolites associated with tryptophan metabolism in the DE-CA9TM-treated group. DE-CA9TM also significantly decreased phenylalanine and homocysteine and increased homoserine and threonine levels. Amino acid metabolism was also affected in the serum metabolome, with increased levels of urea and cadaverine, and reductions in N-acetylornithine in DE-CA9TM compared to controls. Similarly, changes in essential amino acids were observed, with a significant increase in tryptophan and lysine levels and a decrease in homocysteine. An increase in serum guanine and deoxyuridine was also detected, with a decrease in beta-alanine in the animals that ingested DE-CA9TM. Conclusions: Data generated throughout this study suggest that the daily administration of 1 × 109 cfu of DE-CA9TM in healthy Beagle dogs is safe and does not affect markers of general health and fecal scores. Furthermore, DE-CA9TM administration had a potential positive effect on some serum markers of oxidative stress, and protein and lipid metabolism in serum and feces.

In the modern world we are constantly bombarded by environmental and natural stimuli that can result in oxidative stress. Antioxidant molecules and enzymes help the human body scavenge reactive oxygen species and prevent oxidative damage. Most organisms possess intrinsic antioxidant activity, but also benefit from the consumption of antioxidants from their diet. Leafy green vegetables such as spinach are a well-researched rich source of dietary antioxidant molecules. However, plant cell walls are difficult to digest for many individuals and the bio-accessibility of nutrients and antioxidants from these sources can be limited by the degree of digestion and assimilation. Through a specific enzymatic process, Solarplast® contains organic spinach protoplasts without the cell wall, which may facilitate higher yield and efficacy of beneficial antioxidant molecules. In this study, analytical techniques coupled to in vitro bioassays were used to determine the potential antioxidant activity of Solarplast® and determine its antioxidant enzymatic capabilities. Solarplast® demonstrated superior antioxidant activity when compared to frozen spinach leaves in TOC, FRAP and TEAC antioxidant assays. Several antioxidant enzymes were also increased in Solarplast®, when compared to frozen spinach. As a functional readout, Solarplast® attenuated hydrogen peroxide-, ethanol- and acetaminophen-induced increases in oxidative stress and cytotoxicity in both intestinal (HT-29) and liver (HepG2) cell lines. These findings suggest that Solarplast® may represent a non-GMO, plant-based food supplement to help reduce oxidative stress in the human body.

Escherichia coli and Enterococcus faecalis have been implicated as important players in human gut health that have been associated with the onset of inflammatory bowel disease (IBD). Bacteriophage (phage) therapy has been used for decades to target pathogens as an alternative to antibiotics, but the ability of phage to shape complex bacterial consortia in the lower gastrointestinal tract is not clearly understood. We administered a cocktail of six phages (either viable or heat-inactivated) targeting pro-inflammatory Escherichia coli LF82 and Enterococcus faecalis OG1RF as members of a defined community in both a continuous fermenter and a murine colitis model. The two target strains were members of a six species simplified human microbiome consortium (SIHUMI-6). In a 72-h continuous fermentation, the phage cocktail caused a 1.1 and 1.5 log (log10 genome copies/mL) reduction in E. faecalis and E. coli numbers, respectively. This interaction was accompanied by changes in the numbers of other SIHUMI-6 members, with an increase of Lactiplantibacillus plantarum (1.7 log) and Faecalibacterium prausnitzii (1.8 log). However, in germ-free mice colonized by the same bacterial consortium, the same phage cocktail administered twice a week over nine weeks did not cause a significant reduction of the target strains. Mice treated with active or inactive phage had similar levels of pro-inflammatory cytokines (IFN-y/IL12p40) in unstimulated colorectal colonic strip cultures. However, histology scores of the murine lower GIT (cecum and distal colon) were lower in the viable phage-treated mice, suggesting that the phage cocktail did influence the functionality of the SIHUMI-6 consortium. For this study, we conclude that the observed potential of phages to reduce host populations in in vitro models did not translate to a similar outcome in an in vivo setting, with this effect likely brought about by the reduction of phage numbers during transit of the mouse GIT.

Abstract Background Confinement due to COVID-19 has increased mental ill-health. Few studies unpack the risk and protective factors associated with mental ill-health and addictions that might inform future preparedness. Methods Cross-sectional on-line survey with 37,810 Catalan residents aged 16+ years from 21 April to 20 May 2020 reporting prevalence of mental ill-health and substance use and associated coping strategies and behaviours. Results Weighted prevalence of reported depression, anxiety and lack of mental well-being was, respectively, 23, 26, and 75%, each three-fold higher than before confinement. The use of prescribed hypnosedatives was two-fold and of non-prescribed hypnosedatives ten-fold higher than in 2018. Women, younger adults and students were considerably more likely, and older and retired people considerably less likely to report mental ill-health. High levels of social support, dedicating time to oneself, following a routine, and undertaking relaxing activities were associated with half the likelihood of reported mental ill-health. Worrying about problems living at home, the uncertainty of when normality would return, and job loss were associated with more than one and a half times the likelihood of mental ill-health. With the possible exception of moderately severe and severe depression, length of confinement had no association with reported mental ill-health. Conclusions The trebling of psychiatric symptomatology might lead to either to under-identification of cases and treatment gap, or a saturation of mental health services if these are not matched with prevalence increases. Special attention is needed for the younger adult population. In the presence of potential new confinement, improved mental health literacy of evidence-based coping strategies and resilience building are urgently needed to mitigate mental ill-health.

Abstract Background The gut phageome comprises a complex phage community of thousands of individual strains, with a few highly abundant bacteriophages. CrAss-like phages, which infect bacteria of the order Bacteroidales, are the most abundant bacteriophage family in the human gut and make an important contribution to an individual’s core virome. Based on metagenomic data, crAss-like phages form a family, with four sub-families and ten candidate genera. To date, only three representatives isolated in pure culture have been reported: ΦcrAss001 and two closely related phages DAC15 and DAC17; all are members of the less abundant candidate genus VI. The persistence at high levels of both crAss-like phage and their Bacteroidales hosts in the human gut has not been explained mechanistically, and this phage-host relationship can only be properly studied with isolated phage-host pairs from as many genera as possible. Results Faeces from a healthy donor with high levels of crAss-like phage was used to initiate a faecal fermentation in a chemostat, with selected antibiotics chosen to inhibit rapidly growing bacteria and selectively enrich for Gram-negative Bacteroidales. This had the objective of promoting the simultaneous expansion of crAss-like phages on their native hosts. The levels of seven different crAss-like phages expanded during the fermentation, indicating that their hosts were also present in the fermenter. The enriched supernatant was then tested against individual Bacteroidales strains isolated from the same faecal sample. This resulted in the isolation of a previously uncharacterised crAss-like phage of candidate genus IV of the proposed Alphacrassvirinae sub-family, ΦcrAss002, that infects the gut commensal Bacteroides xylanisolvens. ΦcrAss002 does not form plaques or spots on lawns of sensitive cells, nor does it lyse liquid cultures, even at high titres. In keeping with the co-abundance of phage and host in the human gut, ΦcrAss002 and Bacteroides xylanisolvens can also co-exist at high levels when co-cultured in laboratory media. Conclusions We report the isolation and characterisation of ΦcrAss002, the first representative of the proposed Alphacrassvirinae sub-family of crAss-like phages. ΦcrAss002 cannot form plaques or spots on bacterial lawns but can co-exist with its host, Bacteroides xylanisolvens, at very high levels in liquid culture without impacting on bacterial numbers. Video abstract

We have previously isolated and characterized food-dwelling strains of Lactiplantibacillus (Lpb.) plantarum that are consumed naturally as part of the microbiota of table olives and raw milk cheeses. Despite being consumed at relatively high levels, the impact of such strains on the human gut microbiota is currently unclear. In the current study we evaluated the potential impact of food-dominant Lpb. plantarum strains on the human gut microbiota using a continuous fecal fermentation system. Daily inoculation of Lpb. plantarum strains led to significant, detectable levels in the fecal fermentation system. We examined the impact of the presence of Lpb. plantarum on the microbiota derived from two separate donors. For one donor, Lpb. plantarum increased alpha diversity and beta diversity. This was reflected in significant alterations in abundance of the unclassified genera, dominated by Enterobacteriaceae_unclass and Ruminococcaceae_unclass. The microbiota of the other donor was relatively unaffected following introduction of the Lpb. plantarum strains. Overall, the work describes the response of the human microbiota to the introduction of high levels of food-dominant Lpb. plantarum strains and indicates that the response may reflect interindividual differences between donor samples.

Abstract Background Containment policies and other restrictions introduced by the Spanish government in response to the COVID-19 pandemic present challenges for marginalised populations, such as people who use drugs. Harm reduction centres are often linked to social services, mental health services, and infectious disease testing, in addition to tools and services that help to reduce the harms associated with injecting drugs. This study aimed to explore the impact of the pandemic on these services in four autonomous communities in Spain. Methods This is a cross-sectional study that employed a seven-section structured survey administered electronically to 20 centres in July 2020. Data from the most heavily affected months (March–June) in 2020 were compared to data from the same period in 2019. Averages were calculated with their ranges, rates, and absolute numbers. Results All 11 responding centres reported having had to adapt or modify their services during the Spanish state of alarm (14 March–21 June 2020). One centre reported complete closure for 2 months and four reported increases in their operating hours. The average number of service users across all centres decreased by 22% in comparison to the same period in the previous year and the average needle distribution decreased by 40% in comparison to 2019. Most centres reported a decrease in infectious disease testing rates (hepatitis B and C viruses, human immunodeficiency virus, and tuberculosis) for March, April, and May in 2020 compared to the previous year. Reported deaths as a result of overdose did not increase during the state of alarm, but 2/11 (18%) centres reported an increase in overdose deaths immediately after finalisation of the state of alarm. Conclusion Overall, Spanish harm reduction centres were able to continue operating and offering services by adjusting operating hours. The number of overall service users and needles distributed fell during the Spanish state of alarm lockdown period, suggesting that fewer clients accessed harm reduction services during this time, putting them at greater risk of reusing or sharing injecting equipment, overdosing, acquiring infectious diseases with decreased access to testing or discontinuing ongoing treatment such as methadone maintenance therapy, hepatitis C treatment, or antiretroviral therapy.

Spore-forming bacteria of the Bacillus genus have demonstrated potential as probiotics for human use. Bacillus clausii have been recognized as efficacious and safe agents for preventing and treating diarrhea in children and adults, with pronounced immunomodulatory properties during several in vitro and clinical studies. Herein, we characterize the novel strain of B. clausii CSI08 (Munispore®) for probiotic attributes including resistance to gastric acid and bile salts, the ability to suppress the growth of human pathogens, the capacity to assimilate wide range of carbohydrates and to produce potentially beneficial enzymes. Both spores and vegetative cells of this strain were able to adhere to a mucous-producing intestinal cell line and to attenuate the LPS- and Poly I:C-triggered pro-inflammatory cytokine gene expression in HT-29 intestinal cell line. Vegetative cells of B. clausii CSI08 were also able to elicit a robust immune response in U937-derived macrophages. Furthermore, B. clausii CSI08 demonstrated cytoprotective effects in in vitro cell culture and in vivo C. elegans models of oxidative stress. Taken together, these beneficial properties provide strong evidence for B. clausii CSI08 as a promising potential probiotic.

Background: Brief interventions (BI) for risky drinkers in primary healthcare have been demonstrated to be cost-effective but they are still poorly implemented. Digital BI seems to be a complementary strategy to overcome some barriers to implementation but there is a scarcity of studies in clinical environments. We present the results of a randomized controlled non-inferiority trial which tests the non-inferiority of facilitated access to a digital intervention (experimental condition) for risky drinkers against a face-to-face BI (control condition) provided by primary healthcare professionals. Method: In a non-inferiority randomized controlled trial, unselected primary healthcare patients (≥ 18 years old) were given a brief introduction and asked to log on to the study website to fill in the 3-item version of the Alcohol Use Disorders Identification Test. Positively screened patients (4+ for women and 5+ for men) received further online assessment (AUDIT, socio-demographic characteristics and EQ-5D-5L) and were automatically randomized to either face-to-face or digital BI (1:1). The primary outcome was the proportion of patients classified as risky drinkers by the digitally administered AUDIT at month 3. A multiple imputation approach for the missing data was performed. Results: Of the 4499 patients approached by 115 healthcare professionals, 1521 completed the AUDIT-C. Of the 368 positively screened patients, 320 agreed to participate and were randomized to either intervention. At month 3, there were more risky drinkers in the experimental group (59.8%) than in the control group (52%), which was similar to the distribution at baseline and less than the pre-specified margin of 10%. The difference was not significant when accounting for possible confounders. Conclusion: Digital BI was not inferior to face-to-face BI, in line with previous findings and the a priori hypothesis. However, the low power of the final sample, due to the low recruitment and loss to follow-up, limits the interpretation of the findings. New approaches in this field are required to ensure the effective implementation of digital interventions in actual practice.

Spore-based probiotics offer important advantages over other probiotics as they can survive the harsh gastric conditions of the stomach and bile salts in the small intestine, ultimately germinating in the digestive tract. A novel clinical trial in 11 ileostomy participants was conducted to directly investigate the presence and germination of the probiotic strain Bacillus subtilis DE111® in the small intestine. Three hours following ingestion of DE111®, B. subtilis spores (6.4 × 104 ± 1.3 × 105 CFU/g effluent dry weight) and vegetative cells (4.7 × 104 ± 1.1 × 105 CFU/g effluent dry weight) began to appear in the ileum effluent. Six hours after ingestion, spore concentration increased to 9.7 × 107 ± 8.1 × 107 CFU/g and remained constant to the final time point of 8 h. Vegetative cells reached a concentration of 7.3 × 107 ± 1.4 × 108 CFU/g at 7 h following ingestion. These results reveal orally ingested B. subtilis DE111® spores are able to remain viable during transit through the stomach and germinate in the small intestine of humans within 3 h of ingestion.

Background: Hepatitis C virus (HCV) management is a challenge in patients with substance use disorder (SUD). This study aimed to describe an HCV screening and linkage to care program in SUD patients, and analyze the characteristics of this population in relation to HCV infection, particularly the impact of psychiatric comorbidities (dual diagnosis). Methods: This study was a prospective clinical cohort study using a collaborative, multidisciplinary model to offer HCV care (screening, diagnosis, and therapy) to individuals with SUD attending a dedicated hospital clinic. The characteristics of the participants, prevalence of HCV infection, percentage who started therapy, and adherence to treatment were compared according to the patients’ consumption characteristics and presence of dual diagnosis. HCV screening, diagnosis, treatment initiation, and sustained virologic response were analyzed. Results: 528 individuals attended the center (November 2018–June 2019) and 401 (76%) accepted screening. In total, 112 (28%) were anti-HCV-positive and 42 (10%) had detectable HCV RNA, but only 20 of the latter started HCV therapy. Among the 253 (63%) patients with a dual diagnosis, there were no differences in HCV infection prevalence versus patients with SUD alone ( p = 0.28). Dual diagnosis did not lead to a higher risk of HCV infection or interfere with linkage to care or treatment. Conclusion: This study found a high prevalence of dual diagnosis and HCV infection in SUD patients, but dual diagnosis was not associated with an increased risk of acquiring HCV or more complex access to care. Despite use of a multidisciplinary management approach, considerable barriers to HCV care remain in this population that would need more specific focus.

This study aimed to describe the impact of the COVID-19 pandemic on the social situation, self-perceived health status, and mental well-being of adolescents in Catalonia during home confinement, and to evaluate factors that are associated with poor overall mental well-being. An online cross-sectional study among a cohort of students (14–18 years old) of central Catalonia (DESKcohort) was performed during June–July 2020. Poisson regression models with robust variance were used to identify variables associated with “poor overall well-being,” measured by the short version of the Warwick–Edinburgh Mental Wellbeing Scale. Out of 303 participants, 42.1% reported a decrease in family income, and 32.8% a loss of parental employment due to the COVID-19 pandemic, and these percentages were higher among people living in low socioeconomic neighborhoods (53.3% and 43.2%, respectively). Overall, 56.8% presented a poor overall well-being. Participants reporting a decrease in their family’s income (aPR = 1.33) and those knowing a close person or family who died of COVID-19 (aPR = 1.42) were more likely to report a poor overall well-being. This study highlights the patterns of inequality and social vulnerability for COVID-19 pandemic outcomes. Considering social inequalities, interventions are needed to mitigate the impact of COVID-19 pandemic on the physical and the psychological wellbeing of children and their families.

Partially digested gluten fragments from grains including wheat, rye, spelt and barley are responsible for triggering an inflammatory response in the intestinal tract of Celiac Disease (CD) and Non-Celiac Gluten Sensitive (NCGS) individuals. Fermentation is an effective method to metabolize gluten, with enzymes from bacterial or fungal species being released to help in this process. However, the levels of gluten in commercially available enzymes, including those involved in gluten fermentation, are unknown. In this study we investigated gluten levels in commercially available dietary enzymes combined with assessing their effect on inflammatory response in human cell culture assays. Using antibodies that recognize different gluten epitopes (G12, R5, 2D4, MloBS and Skerritt), we employed ELISA and immunoblotting methodologies to determine gluten content in crude gluten, crude gliadin, pepsin-trypsin digested gluten and a selection of commercially available enzymes. We further investigated the effect of these compounds on inflammatory response in immortalized immune and intestinal human cell lines, as well as in peripheral blood mononuclear cells (PBMCs) from coeliac individuals. All tested supplemental enzyme products reported a gluten concentration that was equivalent to or below 20 parts per million (ppm) as compared with an intact wheat reference standard and a pepsin-trypsin digested standard. Similarly, the inflammatory response to IL-8 and TNF-α inflammatory cytokines in mammalian cell lines and PBMCs from coeliac individuals to the commercial enzymes was not significantly different to 20 ppm of crude gluten, crude gliadin or pepsin-trypsin digested gluten. This combined approach provides insight into the extent of gluten breakdown in the fermentation process and the safety of these products to gluten-sensitive individuals.

Objective: To systematically review guidance documents for the estimation of the social cost of illegal drugs, and to define standards for this estimation. Method: A systematic literature search was conducted between April and May 2015 and updated in November 2015. Pubmed, Scopus, and Google Scholar were searched. Studies were included only if they provided indications of analytical methods for calculating the social cost of illegal drugs consumption. Results: A total of 21 papers were selected for a final review. Four main areas of discussion were identified: a) alternative theories for the framework design; b) basic concepts definition; c) theoretical issues in the application of the framework and; d) definition of the cost matrix and its elements. The review exercise enabled the definition of two analytical approaches, which are proposed as references for estimation in the field. Conclusions: although social cost is a well-established method in the literature, there is a lack of agreement on the most appropriate approaches in the area of estimation of the social cost of illegal drugs consumption. Moreover, the two analytical approaches proposed are aimed at promoting more research focused at sophisticating the methodology in the field. Resumen: Objetivo: Revisar sistemáticamente las guías para la estimación del coste social del consumo de drogas ilegales y definir estándares para su estimación. Método: La búsqueda sistemática de la literatura se realizó entre abril y mayo de 2015, y se actualizó en noviembre de 2015. Se realizaron búsquedas en Pubmed, Scopus y Google Scholar. Los estudios se incluyeron solo si explicitaban los métodos analíticos para calcular el coste social del consumo de drogas ilegales. Resultados: Se seleccionaron 21 trabajos para su revisión final. Se identificaron cuatro áreas principales de discusión: a) teorías alternativas para el diseño del marco; b) definición de conceptos básicos; c) aspectos teóricos en la aplicación del marco; y d) definición de la matriz de costes y sus elementos. El ejercicio de revisión permitió la definición de dos enfoques analíticos, que se proponen como referencia para estimación en este campo. Conclusiones: Aunque el coste social es un método bien establecido en la literatura, existe falta de acuerdo sobre los enfoques más apropiados en su aplicación al consumo de drogas ilegales. Los dos enfoques analíticos propuestos tienen como objetivo promover una mayor investigación enfocada a mejorar la metodología en este campo. Keywords: Socioeconomic factors, Costs and cost analysis, Cost of illness, Guideline, Substance-related disorders, Palabras clave: Factores socioeconómicos, Costes y análisis de coste, Coste de la enfermedad, Guía, Trastornos relacionados con sustancias

Abstract Background Hazardous and harmful alcohol use and high blood pressure are central risk factors related to premature non-communicable disease (NCD) mortality worldwide. A reduction in the prevalence of both risk factors has been suggested as a route to reach the global NCD targets. This study aims to highlight that screening and interventions for hypertension and hazardous and harmful alcohol use in primary healthcare can contribute substantially to achieving the NCD targets. Methods A consensus conference based on systematic reviews, meta-analyses, clinical guidelines, experimental studies, and statistical modelling which had been presented and discussed in five preparatory meetings, was undertaken. Specifically, we modelled changes in blood pressure distributions and potential lives saved for the five largest European countries if screening and appropriate intervention rates in primary healthcare settings were increased. Recommendations to handle alcohol-induced hypertension in primary healthcare settings were derived at the conference, and their degree of evidence was graded. Results Screening and appropriate interventions for hazardous alcohol use and use disorders could lower blood pressure levels, but there is a lack in implementing these measures in European primary healthcare. Recommendations included (1) an increase in screening for hypertension (evidence grade: high), (2) an increase in screening and brief advice on hazardous and harmful drinking for people with newly detected hypertension by physicians, nurses, and other healthcare professionals (evidence grade: high), (3) the conduct of clinical management of less severe alcohol use disorders for incident people with hypertension in primary healthcare (evidence grade: moderate), and (4) screening for alcohol use in hypertension that is not well controlled (evidence grade: moderate). The first three measures were estimated to result in a decreased hypertension prevalence and hundreds of saved lives annually in the examined countries. Conclusions The implementation of the outlined recommendations could contribute to reducing the burden associated with hypertension and hazardous and harmful alcohol use and thus to achievement of the NCD targets. Implementation should be conducted in controlled settings with evaluation, including, but not limited to, economic evaluation.

An intestinal epithelium model able to produce mucus was developed to provide an environment suitable for testing the therapeutic activity of gut bacteriophages. We show that Enterococcus faecalis adheres more effectively in the presence of mucus, can invade the intestinal epithelia and is able to translocate after damaging tight junctions. Furthermore, Enterococcus phage vB_EfaM_A2 (a member of Herelleviridae that possesses virion associated immunoglobin domains) was found to translocate through the epithelium in the presence and absence of its host bacteria. Phage A2 protected eukaryotic cells by reducing mortality and maintaining the structure of the cell layer structure. We suggest the mammalian cell model utilized within this study as an adaptable in vitro model that can be employed to enable a better understanding of phage–bacteria interactions and the protective impact of phage therapy relating to the intestinal epithelium.