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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people worldwide. While most infected individuals who survive do so with no long-term consequences, approximately 10 to 70% develop long-term sequelae. Of particular concern has been the development of autoimmune diseases. Viral triggers for autoimmune disease have been thoroughly studied for previous viral infections and several recent studies have sought to investigate the link between SARS-CoV-2 and new onset autoimmune disease. Several reviews have also been conducted on the topic, however, many of these reviews are limited in focus, emphasizing biological mechanisms and case reports, as opposed to estimates of risk. Further, these reviews do not capture more recent cohort studies that have been published investigating the association between SARS-CoV-2 and new onset autoimmune disease. Therefore, there is a need for a more comprehensive and temporally updated systematically conducted review of the literature to address the question What is the risk of incident (i.e., new onset) autoimmune disease following a SARS-CoV-2 infection among adults (≥18 years)?. A systematic search of MEDLINE, EMBASE, CINAHL, and grey literature will be conducted, with results screened in duplicate in two stages: 1) Title and abstract screening and 2) Full text screening. A standardized data extraction sheet will be used on any studies passing through both stages of screening to extract details on publication, study population, exposure, and outcomes. Narrative and tabular synthesis of overall findings will be conducted, with diversity and heterogeneity of included studies discussed. If possible, a meta-analysis will also be conducted to combine findings of risk across the included studies. This protocol has been registered to PROSPERO (registration number: CRD42024594446).

Vaccines against SARS-CoV-2 have been shown to reduce risk of infection as well as severe disease among those with breakthrough infection in adults. The latter effect is particularly important as immune evasion by Omicron variants appears to have made vaccines less effective at preventing infection. Therefore, we aimed to quantify the protection conferred by mRNA vaccination against hospitalization due to SARS-CoV-2 in adolescent and pediatric populations. We retrospectively created a cohort of reported SARS-CoV-2 case records from Ontario's Public Health Case and Contact Management Solution among those aged 4 to 17 linked to vaccination records from the COVaxON database on January 19, 2022. We used multivariable logistic regression to estimate the association between vaccination and hospitalization among SARS-CoV-2 cases prior to and during the emergence of Omicron. We included 62 hospitalized and 27,674 non-hospitalized SARS-CoV-2 cases, with disease onset from May 28, 2021 to December 4, 2021 (Pre-Omicron) and from December 23, 2021 to January 9, 2022 (Omicron). Among adolescents, two mRNA vaccine doses were associated with an 85% (aOR = 0.15; 95% CI: [0.04, 0.53]; p<0.01) lower likelihood of hospitalization among SARS-CoV-2 cases caused by Omicron. Among children, one mRNA vaccine dose was associated with a 79% (aOR = 0.21; 95% CI: [0.03, 0.77]; p<0.05) lower likelihood of hospitalization among SARS-CoV-2 cases caused by Omicron. The calculation of E-values, which quantifies how strong an unmeasured confounder would need to be to nullify our findings, suggest that these effects are unlikely to be explained by unmeasured confounding. Despite immune evasion by SARS-CoV-2 variants, vaccination continues to be associated with a lower likelihood of hospitalization among adolescent and pediatric Omicron (B.1.1.529) SARS-CoV-2 cases, even when the vaccines do not prevent infection. Continued efforts are needed to increase vaccine uptake among adolescent and pediatric populations.

Immune checkpoint inhibitor (ICI) therapy for patients undergoing cancer treatment carries a risk of severe immune-related adverse events (IRAEs). Questions remain about whether seasonal influenza vaccination might increase the risk of developing IRAEs among these patients given that vaccines are immunomodulatory. Previous vaccine safety studies on patients with cancer prescribed ICI therapy have demonstrated conflicting results. Using health administrative data from Ontario, Canada among adults diagnosed with cancer who had been prescribed ICI therapy and who had received an influenza vaccine from 2012 to 2019, we conducted a self-controlled case series study. The pre-vaccination control period started 42-days post-ICI initiation until 14-days prior to vaccination, the risk period was 1–42 days post-vaccination, and the post-vaccination control period was after the risk period until ICI discontinuation or a maximum period of two years. Emergency department (ED) visit(s) and/or hospitalization for any cause after ICI initiation was used to identify severe IRAEs. We fitted a fixed-effects Poisson regression model accounting for seasonality and calendar time to estimate relative incidence of IRAEs between risk and control periods. We identified 1133 records of cancer patients who received influenza vaccination while prescribed ICI therapy. Most were aged ≥ 66 years (73 %), were male (63 %), had lung cancer (54 %), and had received ICI therapy with a programmed cell death protein 1(PD-1) inhibitor (91 %). A quarter (26 %) experienced an ED visit and/or hospitalization during the observation period. Rates of ED visits and/or hospitalizations in the risk vs. control periods were similar, with an incidence rate ratio of 1.04 (95 % CI: 0.75–1.45). Subgroup and sensitivity analyses yielded similar results. Seasonal influenza vaccination was not associated with an increased incidence of ED visit or hospitalization among adults with cancer treated with ICI therapy and our results support further evidence of vaccine safety.

Pertussis remains a major public health concern, particularly affecting young children. While most identified cases occur in this group, the burden among older children and adults who undergo less frequent testing is not well characterized. We analyzed pertussis testing and case data in the Greater Toronto Area from 1993 to 2006. We applied a meta-regression-based method for test adjustment by age and sex, estimating case counts in each demographic group as if they were tested at the same rate as the most tested group (< 1-year males). Before adjustment, incidence was highest in the < 1-year group and declined with age, with the ≥ 80-year group having an incidence rate ratio (IRR) of 0.011 (95% CI: 0.006-0.020) relative to male children aged < 1 year. After adjustment, the 2-4-year group showed the highest relative incidence (IRR: 5.503, 95% CI: 2.121-14.281). The highest estimated underdiagnosed case rates were in the 2-4-year group at 13.69 per diagnosed case in males (95% CI: 5.913-21.467) and the 10-19-age group in females at 6.80 per diagnosed case (95% CI: 4.684-8.917). Our use of a novel test-adjustment method for estimating incidence suggests that while pertussis is most diagnosed in infants, it is substantially underdiagnosed in older age groups generally, but particularly so in preschool-aged children and the elderly. As undiagnosed infection in these populations may play a key role in sustaining transmission, this finding has implications for vaccine booster policy. Not applicable (not a clinical trial).

Guidelines recommend that individuals with opioid use disorder (OUD) receive pharmacological and psychosocial interventions; however, the most appropriate psychosocial intervention is not known. In collaboration with people with lived experience, clinicians, and policy makers, we sought to assess the relative benefits of psychosocial interventions as an adjunct to opioid agonist therapy (OAT) among persons with OUD. A review protocol was registered a priori (CRD42018090761), and a comprehensive search for randomized controlled trials (RCT) was conducted from database inception to June 2020 in MEDLINE, Embase, PsycINFO and the Cochrane Central Register of Controlled Trials. Established methods for study selection and data extraction were used. Primary outcomes were treatment retention and opioid use (measured by urinalysis for opioid use and opioid abstinence outcomes). Odds ratios were estimated using network meta-analyses (NMA) as appropriate based on available evidence, and in remaining cases alternative approaches to synthesis were used. Seventy-two RCTs met the inclusion criteria. Risk of bias evaluations commonly identified study limitations and poor reporting with regard to methods used for allocation concealment and selective outcome reporting. Due to inconsistency in reporting of outcome measures, only 48 RCTs (20 unique interventions, 5,404 participants) were included for NMA of treatment retention, where statistically significant differences were found when psychosocial interventions were used as an adjunct to OAT as compared to OAT-only. The addition of rewards-based interventions such as contingency management (alone or with community reinforcement approach) to OAT was superior to OAT-only. Few statistically significant differences between psychosocial interventions were identified among any other pairwise comparisons. Heterogeneity in reporting formats precluded an NMA for opioid use. A structured synthesis was undertaken for the remaining outcomes which included opioid use (n = 18 studies) and opioid abstinence (n = 35 studies), where the majority of studies found no significant difference between OAT plus psychosocial interventions as compared to OAT-only. This systematic review offers a comprehensive synthesis of the available evidence and the limitations of current trials of psychosocial interventions applied as an adjunct to OAT for OUD. Clinicians and health services may wish to consider integrating contingency management in addition to OAT for OUD in their settings to improve treatment retention. Aside from treatment retention, few differences were consistently found between psychosocial interventions adjunctive to OAT and OAT-only. There is a need for high-quality RCTs to establish more definitive conclusions. PROSPERO registration CRD42018090761.

Background: The addition of dendritic cell vaccines (DCV) to NAC could induce immune responses in those patients with residual disease (RD) by transforming the tumor microenvironment. Methods: Core diagnostic biopsies and surgical specimens from 80 patients (38 in the vaccinated group plus NAC (VG) and 42 in the control group (CG, treated only with NAC) were selected. We quantify TILs (CD8, CD4 and CD45RO) using immunohistochemistry and the automated cellular imaging system (ACIS III) in paired samples. Results: A CD8 rise in TNBC samples was observed after NAC plus DCV, changing from 4.48% in the biopsy to 6.70% in the surgical specimen, not reaching statistically significant differences (p = 0.11). This enrichment was seen in up to 67% of TNBC patients in the experimental arm as compared with the CG (20%). An association between CD8 TILs before NAC (4% cut-off point) and pathological complete response in the VG was found in the univariate and multivariate analysis (OR = 1.41, IC95% 1.05–1.90; p = 0.02, and OR = 2.0, IC95% 1.05–3.9; p = 0.03, respectively). Conclusion: Our findings suggest that patients with TNBC could benefit from the stimulation of the antitumor immune system by using DCV together with NAC.

Significant threats to the long-term persistence of coral reefs have accelerated the adoption of coral propagation and out-planting approaches. However, how materials commonly used for propagation structures could potentially affect coral-associated bacterial communities remains untested. Here, we examined the impact of metal propagation structures on coral-associated bacterial communities. Fragments of the coral species Acropora millepora were grown on aluminium, sand/epoxy-coated steel (Reef Stars), and uncoated steel (rebar) structures. After 6 months, the functional and taxonomic profiles of coral-associated bacterial communities of propagated corals and reef colonies were characterised using amplicon (16S rRNA gene) and shotgun metagenomic sequencing. No differences in the phylogenetic structure or functional profile of coral-associated bacterial communities were observed between propagated corals and reef colonies. However, specific genes and pathways (e.g., lipid, nucleotide, and carbohydrate metabolism) were overrepresented in corals grown on different materials, and different taxa were indicative of the materials. These findings indicate that coral propagation on different materials may lead to differences in the individual bacterial taxa and functional potential of coral-associated bacterial communities, but how these contribute to changed holobiont fitness presents a key question to be addressed.

Background/Objectives: Radiculopathy leads to pain, consequently reducing patient’s quality of life (QoL). Research indicates that certain nucleotides, such as cytidine and uridine, along with vitamins B1 and B12, may help alleviate pain and enhance QoL. This study assessed the impact of adding a supplement containing cytidine and uridine nucleotides and vitamins B1 and B12, alongside standard treatment, on radiculopathy-associated pain. Methods: A multicenter, prospective, two-cohort, randomized, open-label study was conducted. The control group received standard treatment, while the experimental group received standard treatment plus the supplement. The primary endpoint was pain reduction measured by a Visual Analog Scale (VAS). Secondary endpoints included functional improvement (Roland Morris questionnaire), clinical improvement (Clinical Global Impression [CGI] scale), and QoL improvement (EQ-5D-5L questionnaire). Results: A total of 122 patients were included from 17 centers across Spain. Both groups showed pain improvement, but the VAS reduction (control: 24.58 vs. experimental: 31.35) was not statistically significant. The Roland Morris score decreased significantly in the experimental group (estimate: −1.70, 95% CI −3.29 to −0.10; p = 0.038), and these patients were 5 times more likely to progress to a better CGI category (OR = 0.20, 95% CI 0.07 to 0.57; p = 0.003). No significant differences were observed in EQ-5D-5L scores or analgesic consumption. Conclusions: The addition of supplemental pyrimidine nucleotides and vitamins B1 and B12 to standard of care treatment improved radiculopathy functional and clinical outcomes. Regarding pain, however, although there was a numerical improvement, it did not reach statistical significance.

ObjectiveDesign a risk model to predict bacteraemia in patients attended in emergency departments (ED) for an episode of infection.MethodsThis was a national, prospective, multicentre, observational cohort study of blood cultures (BC) collected from adult patients (≥ 18 years) attended in 71 Spanish EDs from October 1 2019 to March 31, 2020. Variables with a p value < 0.05 were introduced in the univariate analysis together with those of clinical significance. The final selection of variables for the scoring scale was made by logistic regression with selection by introduction. The results obtained were internally validated by dividing the sample in a derivation and a validation cohort.ResultsA total of 4,439 infectious episodes were included. Of these, 899 (20.25%) were considered as true bacteraemia. A predictive model for bacteraemia was defined with seven variables according to the Bacteraemia Prediction Model of the INFURG-SEMES group (MPB-INFURG-SEMES). The model achieved an area under the curve-receiver operating curve of 0.924 (CI 95%:0.914–0.934) in the derivation cohort, and 0.926 (CI 95%: 0.910–0.942) in the validation cohort. Patients were then split into ten risk categories, and had the following rates of risk: 0.2%(0 points), 0.4%(1 point), 0.9%(2 points), 1.8%(3 points), 4.7%(4 points), 19.1% (5 points), 39.1% (6 points), 56.8% (7 points), 71.1% (8 points), 82.7% (9 points) and 90.1% (10 points). Findings were similar in the validation cohort. The cut-off point of five points provided the best precision with a sensitivity of 95.94%, specificity of 76.28%, positive predictive value of 53.63% and negative predictive value of 98.50%.ConclusionThe MPB-INFURG-SEMES model may be useful for the stratification of risk of bacteraemia in adult patients with infection in EDs, together with clinical judgement and other variables independent of the process and the patient.

Key message A holistic approach, molecular and eco-physiological, has provided a better understanding of the response of eucalyptus and poplar genotypes to salt stress. Different tolerance mechanisms with varying degrees of effectiveness as well as differences in the response of genes linked to xylem differentiation have been identified. We studied the behavior of four eucalyptus genotypes ( Eucalyptus camaldulensis Dehnh: ‘169’; E. grandis Hill ex Maiden ×  E. urophylla S.T. Blake: ‘5E’; Eucalyptus globulus Labill: ‘Anselmo’ and ‘Odiel’) and four poplar genotypes ( Populus alba L.: ‘PO 10-10-20’ and ‘J 1-3-18’, P. tremula L. ×  P. alba : ‘7171-B4’ and P.  ×  canadensis Moench.: ‘Oudenberg’) in relation to their response to saline conditions and their capacity to grow in short rotation for biomass production. For this purpose, plants were grown under greenhouse conditions and subjected to two different saline concentrations of NaCl, one moderate (50 mM) and one severe (125 mM), as well as a control treatment. Growth, as well as several functional, morphological and biochemical parameters were considered. We also performed an expression analysis of genes that encode enzymes and transcription factors involved in wood formation. The four eucalyptus genotypes showed a very high survival rate under both moderate and severe salt treatments, as did both white poplar genotypes (‘PO 10-10-20’ and ‘J 1-3-18’). All of them displayed a tolerant behavior toward salinity stress. In contrast, the poplar hybrids (‘7171-B4’ and ‘Oudenberg’) exhibited medium-tolerance or sensitive behavior. Possible tolerance mechanisms based on stomatal control, water use efficiency, capacity of dilute toxic ions through decreasing the specific leaf area and higher root/aerial biomass ratios were detected. These mechanisms were deemed to have varying degrees of effectiveness. A molecular approach identified changes in the expression of genes linked to xylem differentiation, the more tolerant genotypes being those with fewer modifications. These findings could contribute towards enabling the cultivation of fast-growing species in short rotation on marginal land affected by salinity for the production of lignocellulosic biomass. The response variability detected could lead to advances in breeding for tolerance to this type of stress.