Applying two approaches to detect unmeasured confounding due to time-varying variables in a self-controlled risk interval design evaluating COVID-19 vaccine safety signals, using myocarditis as a case example.

We test the robustness of the self-controlled risk interval (SCRI) design in a setting where time between doses may introduce time-varying confounding, using both negative control outcomes (NCOs) and quantitative bias analysis (QBA). All vaccinated cases identified from 5 European databases between 1 September 2020 and end of data availability were included. Exposures were doses 1-3 of the Pfizer, Moderna, AstraZeneca, and Janssen COVID-19 vaccines; outcomes were myocarditis and otitis externa (NCO). The SCRI used a 60-day control window and dose-specific 28-day risk windows, stratified by vaccine brand and adjusted for calendar time. The QBA included two scenarios: (i) baseline probability of the confounder was higher in the control window and (ii) vice versa. The NCO was not associated with any of the COVID-19 vaccine types or doses except Moderna dose 1 (IRR = 1.09, 95%CI 1.01-1.09). The QBA suggested even the strongest literature-reported confounder (COVID-19; RRmyocarditis = 18.3) could only explain away part of the observed effect from IRR = 3 to IRR = 1.40. The SCRI seems robust to unmeasured confounding in the COVID-19 setting, although a strong unmeasured confounder could bias the observed effect upward. Replication of our findings for other safety signals would strengthen this conclusion.

Characterisation of Pasteurella multocida Strains from Different Lesions in Rabbits.

Pasteurellosis, a disease caused by Pasteurella multocida, is responsible for economic losses in rabbit industrial farms due to rhinitis, conjunctivitis, pneumonia, metritis, mastitis, orchitis, subcutaneous abscesses, otitis, encephalitis, and septicaemic forms. Although the occurrence of the disease is conditioned by predisposing factors that affect the rabbit immune response, the strains of P. multocida involved in the infection may have a different pathogenic ability. Therefore, typing of strains spread among the rabbits is important to assess their pathogenic potential. The aim of this study is to investigate the P. multocida strains responsible for disease in rabbit industrial farms. A total of 114 strains identified from different lesions were serotyped. Additionally, the presence of virulence-associated genes was investigated using three PCR (polymerase chain reaction) protocols. Capsular type A was prevalently found in strains from respiratory lesions while types D and F in those from metritis, mastitis, and other lesions. Different associations between some virulence-associated genes and both capsular type and lesions found in rabbits were detected. The presence of 8 virulence-associated genes seems to increase the occurrence of metritis. In addition, strains belonging to capsular type A and responsible for respiratory disorders especially, were found equipped with 10 and 11 virulence-associated genes. Nevertheless, the presence of strains responsible only for rhinitis was also detected among the latter, suggesting that the pathogenic ability of the bacteria depends on the expression rather than the presence of a gene.

A comparison of four self-controlled study designs in an analysis of COVID-19 vaccines and myocarditis using five European databases.

INTRODUCTION: The aim of this study was to assess the possible extent of bias due to violation of a core assumption (event-dependent exposures) when using self-controlled designs to analyse the association between COVID-19 vaccines and myocarditis. METHODS: We used data from five European databases (Spain: BIFAP, FISABIO VID, and SIDIAP; Italy: ARS-Tuscany; England: CPRD Aurum) converted to the ConcePTION Common Data Model. Individuals who experienced both myocarditis and were vaccinated against COVID-19 between 1 September 2020 and the end of data availability in each country were included. We compared a self-controlled risk interval study (SCRI) using a pre-vaccination control window, an SCRI using a post-vaccination control window, a standard SCCS and an extension of the SCCS designed to handle violations of the assumption of event-dependent exposures. RESULTS: We included 1,757 cases of myocarditis. For analyses of the first dose of the Pfizer vaccine, to which all databases contributed information, we found results consistent with a null effect in both of the SCRI and extended SCCS, but some indication of a harmful effect in a standard SCCS. For the second dose, we found evidence of a harmful association for all study designs, with relatively similar effect sizes (SCRI pre = 1.99, 1.40 - 2.82; SCRI post 2.13, 95 %CI - 1.43, 3.18; standard SCCS 1.79, 95 %CI 1.31 - 2.44, extended SCCS 1.52, 95 %CI = 1.08 - 2.15). Adjustment for calendar time did not change these conclusions. Findings using all designs were also consistent with a harmful effect following a second dose of the Moderna vaccine. CONCLUSIONS: In the context of the known association between COVID-19 vaccines and myocarditis, we have demonstrated that two forms of SCRI and two forms of SCCS led to largely comparable results, possibly because of limited violation of the assumption of event-dependent exposures.

The Incidence of Screw Failure in Fenestrated Polyaxial Pedicle Screws vs. Conventional Pedicle Screws in the Treatment of Adolescent Idiopathic Scoliosis (AIS).

Background: Adolescent idiopathic scoliosis (AIS) is a spinal pathology affecting 0.47-5.2% of the population, often requiring surgical intervention to control deformity progression. Posterior spinal instrumentation and fusion with pedicle screw fixation are standard procedures for AIS curve correction; however, implant failure remains a significant complication, especially in multi-level fusions. This retrospective cohort study aims to compare the failure rates between conventional pedicle screws (CPSs) and fenestrated pedicle screws (FPSs) in AIS treatment, with a focus on investigating potential causes of these failures. Methods: This study, conducted from January 2016 to December 2020, involves a two-center retrospective analysis of AIS patients undergoing posterior instrumented fusion. Results: Data from a total of 162 patients (122 females and 40 males) revealed a mean age of 14.95 years (range: 11-18). The CPS group consisted of 80 patients (56 females and 24 males), whereas the FPS group consisted of 82 patients (66 females and 16 males) stratified by Risser grade and Lenke Classification. Radiological assessments, clinical outcomes, and SRS-22 scores were evaluated pre-operatively, at 6 months, and post-operatively (minimum follow-up of 2 years). Conclusions: Fenestrated pedicle screws (FPSs) pose concerns due to their lower mechanical strength compared to solid screws. Understanding their limitations and optimizing their application in AIS treatment is essential.

Effectiveness of homologous/heterologous booster COVID-19 vaccination schedules against severe illness in general population and clinical subgroups in three European countries.

Using 4 data-sources (Spain, Italy, United Kingdom) data and a 1:1 matched cohort study, we aimed to estimate vaccine effectiveness (VE) in preventing SARS-CoV-2 infections with hospitalisations (±30 days) and death (±56 days) in general population and clinical subgroups with homologous/heterologous booster schedules (Comirnaty-BNT and Spikevax-MOD original COVID-19 vaccines) by comparison with unboosted individuals, during Delta and beginning of Omicron variants. Hazard Ratio (HR, by Cox models) and VE ([1-HR]*100) were calculated by inverse probability weights. Between December 2020-February 2022, in adults without prior SARS-CoV-2 infection, we matched 5.5 million people (>1 million with immunodeficiency, 343,727 with cancer) with a booster (3rd) dose by considering doses 1 and 2 vaccine brands and calendar time, age, sex, region, and comorbidities (immunodeficiency, cancer, severe renal disease, transplant recipient, Down Syndrome). We studied booster doses of BNT and MOD administered after doses 1 and 2 with BNT, MOD, or Oxford-AstraZeneca during a median follow-up between 9 and 16 weeks. BNT or MOD showed VE ranging from 70 to 86% across data sources as heterologous 3rd doses, whereas it was 42-88% as homologous 3rd doses. Depending on the severity and available follow-up, 3rd-dose effectiveness lasted between 1 and 5 months. In people with immunodeficiency and cancer, protection across data sources was detected with both heterologous (VE = 54-83%) and homologous (VE = 49-80%) 3rd doses. Overall, both heterologous and homologous 3rd doses with BTN or MOD showed additional protection against the severe effects of SARS-CoV-2 infections for the general population and for patients at potentially high risk of severe COVID-19 (elderly, people with immunodeficiency and cancer) in comparison with two doses schemes during Delta or early Omicron periods. The early VE after vaccination may be due to less testing among vaccinated pairs and unknown confounders, deserving cautious interpretation. The VE wane over time needs further in-depth research to properly envisage when or whether a booster of those vaccines should be administered.

Mapping the evidence of the effects of environmental factors on the prevalence of antibiotic resistance in the non-built environment: Protocol for a systematic evidence map.

BACKGROUND: Human, animal, and environmental health are increasingly threatened by the emergence and spread of antibiotic resistance. Inappropriate use of antibiotic treatments commonly contributes to this threat, but it is also becoming apparent that multiple, interconnected environmental factors can play a significant role. Thus, a One Health approach is required for a comprehensive understanding of the environmental dimensions of antibiotic resistance and inform science-based decisions and actions. The broad and multidisciplinary nature of the problem poses several open questions drawing upon a wide heterogeneous range of studies. OBJECTIVE: This study seeks to collect and catalogue the evidence of the potential effects of environmental factors on the abundance or detection of antibiotic resistance determinants in the outdoor environment, i.e., antibiotic resistant bacteria and mobile genetic elements carrying antibiotic resistance genes, and the effect on those caused by local environmental conditions of either natural or anthropogenic origin. METHODS: Here, we describe the protocol for a systematic evidence map to address this, which will be performed in adherence to best practice guidelines. We will search the literature from 1990 to present, using the following electronic databases: MEDLINE, Embase, and the Web of Science Core Collection as well as the grey literature. We shall include full-text, scientific articles published in English. Reviewers will work in pairs to screen title, abstract and keywords first and then full-text documents. Data extraction will adhere to a code book purposely designed. Risk of bias assessment will not be conducted as part of this SEM. We will combine tables, graphs, and other suitable visualisation techniques to compile a database i) of studies investigating the factors associated with the prevalence of antibiotic resistance in the environment and ii) map the distribution, network, cross-disciplinarity, impact and trends in the literature.

Myocarditis and pericarditis associated with SARS-CoV-2 vaccines: A population-based descriptive cohort and a nested self-controlled risk interval study using electronic health care data from four European countries.

Background: Estimates of the association between COVID-19 vaccines and myo-/pericarditis risk vary widely across studies due to scarcity of events, especially in age- and sex-stratified analyses. Methods: Population-based cohort study with nested self-controlled risk interval (SCRI) using healthcare data from five European databases. Individuals were followed from 01/01/2020 until end of data availability (31/12/2021 latest). Outcome was first myo-/pericarditis diagnosis. Exposures were first and second dose of Pfizer, AstraZeneca, Moderna, and Janssen COVID-19 vaccines. Baseline incidence rates (IRs), and vaccine- and dose-specific IRs and rate differences were calculated from the cohort The SCRI calculated calendar time-adjusted IR ratios (IRR), using a 60-day pre-vaccination control period and dose-specific 28-day risk windows. IRRs were pooled using random effects meta-analysis. Findings: Over 35 million individuals (49·2% women, median age 39-49 years) were included, of which 57·4% received at least one COVID-19 vaccine dose. Baseline incidence of myocarditis was low. Myocarditis IRRs were elevated after vaccination in those aged < 30 years, after both Pfizer vaccine doses (IRR = 3·3, 95%CI 1·2-9.4; 7·8, 95%CI 2·6-23·5, respectively) and Moderna vaccine dose 2 (IRR = 6·1, 95%CI 1·1-33·5). An effect of AstraZeneca vaccine dose 2 could not be excluded (IRR = 2·42, 95%CI 0·96-6·07). Pericarditis was not associated with vaccination. Interpretation: mRNA-based COVID-19 vaccines and potentially AstraZeneca are associated with increased myocarditis risk in younger individuals, although absolute incidence remains low. More data on children (≤ 11 years) are needed.

Contamination of Soil, Water, Fresh Produce, and Bivalve Mollusks with Toxoplasma gondii Oocysts: A Systematic Review.

Toxoplasma gondii is a major foodborne pathogen capable of infecting all warm-blooded animals, including humans. Although oocyst-associated toxoplasmosis outbreaks have been documented, the relevance of the environmental transmission route remains poorly investigated. Thus, we carried out an extensive systematic review on T. gondii oocyst contamination of soil, water, fresh produce, and mollusk bivalves, following the PRISMA guidelines. Studies published up to the end of 2020 were searched for in public databases and screened. The reference sections of the selected articles were examined to identify additional studies. A total of 102 out of 3201 articles were selected: 34 articles focused on soil, 40 focused on water, 23 focused on fresh produce (vegetables/fruits), and 21 focused on bivalve mollusks. Toxoplasma gondii oocysts were found in all matrices worldwide, with detection rates ranging from 0.09% (1/1109) to 100% (8/8) using bioassay or PCR-based detection methods. There was a high heterogeneity (I2 = 98.9%), which was influenced by both the sampling strategy (e.g., sampling site and sample type, sample composition, sample origin, season, number of samples, cat presence) and methodology (recovery and detection methods). Harmonized approaches are needed for the detection of T. gondii in different environmental matrices in order to obtain robust and comparable results.

A Combined Experimental-Numerical Framework for Assessing the Load-Bearing Capacity of Existing PC Bridge Decks Accounting for Corrosion of Prestressing Strands.

Bridges constitute important elements of the transportation network. A vast part of the Italian existing infrastructural system dates to around 60 years ago, which implies that the related bridge structures were constructed according to past design guidelines and underwent a probable state of material deterioration (e.g., steel corrosion, concrete degradation), especially in those cases in which proper maintenance plans have not been periodically performed over the structural lifetime. Consequently, elaborating rapid yet effective safety assessment strategies for existing bridge structures represents a topical research line. This contribution presents a systematic experimental-numerical approach for assessing the load-bearing capacity of existing prestressed concrete (PC) bridge decks. This methodology is applied to the Longano PC viaduct (southern Italy) as a case study. Initially, natural frequencies and mode shapes of the bridge deck are experimentally identified from vibration data collected in situ through Operational Modal Analysis (OMA), based on which a numerical finite element (FE) model is developed and calibrated. In situ static load tests are then carried out to investigate the static deflections under maximum allowed serviceability loads, which are compared to values provided by the FE model for further validation. Since prestressing strands appear corroded in some portions of the main girders, numerical static nonlinear analysis with a concentrated plasticity approach is finally conducted to quantify the effects of various corrosion scenarios on the resulting load-bearing capacity of the bridge at ultimate limit states. The proposed methodology, encompassing both serviceability and ultimate conditions, can be used to identify critical parts of a large infrastructure network prior to performing widespread and expensive material test campaigns, to gain preliminary insight on the structural health of existing bridges and to plan a priority list of possible repairing actions in a reasonable, safe, and costly effective manner.

[Thyroid microcarcinoma in benign thyroid diseases]. / Il microcarcinoma tiroideo nelle tireopatie benigne.

INTRODUCTION: Thyroid microcarcinoma is a malignant thyroid tumor with potential multifocality and a maximum of 1 cm of diameter. This carcinoma has been discovered more frequently like incidentaloma. AIM OF THE STUDY: To appraise the incidence of MCT in the benign thyroid diseases and the advantages offered from the total thyroidectomy, performed for benign diffused thyroid diseases, which surgical treatment "therapeutic" performed for these malignant tumors. MATERIALS AND METHODS: The study was conducted on 600 patients operated with total thyroidectomy for benign thyroid disease, admitted from 1999 to 2003. RESULTS: All patients were alive and free of disease at last control. DISCUSSION: The MCT is a carcinoma that presents frequently a behavior little malignant and a good prognosis. His principal characteristic is the absence of clinical demonstrations. Therefore his discovery, almost always accidental on a thyroid removed for other pathology, it has signaled by histologic study CONCLUSIONS: Thyroid microcarcinoma is a slow growing tumor, with a good prognosis and with a good disease-free survival. It can present a better aggressiveness for his multifocal localization and invasion. Therefore total thyroidectomy can be considered best treatment and also be surgical treatment oncologically correct for this tumor.

[The lobe of Zuckerkandl: an important sign of recurrent laryngeal nerve]. / Il lobo di Zuckerkandl: faro del nervo laringeo ricorrente.

INTRODUCTION: The accurate acquaintance of the anatomy of the thyroid gland allows reduction of complications to interventions of thyroidectomy, where for the existing topography, the nervous and vascular structures could result vulnerable. The identification of Zuckerkandl's tuberculum could reduce the lesions to the recurrent laryngeal nerve, for constant relationship between the recurrent laryngeal nerve and tuberculum. MATERIALS AND METHODS: The Authors have studied 605 patients underwent to thyroid surgery for benign or malignant thyroid diseases. The aim was to verify if the incidence of recurrent nerve lesions can be reduced with the identification of the Zuckerkandl's tuberculum and with a knowledge of its anatomical relationships with vascular, nervous and glandular structures near the thyroid. RESULTS: The Zuckerkandls tuberculum was found in the majority of the cases, with prevalence to the right. Its identification has allowed an immediate and safe identification of recurrent laryngeal nerve, with setting of time of the operation and especially with setting of possible injury to the recurrent nerves. DISCUSSION: The lobe of Zuckerkandl is the extension of the lateral lobes of the thyroid, composed of thyroid tissue only and so it can be interested in thyroid lesions. This tubercle is considered a constant anatomical landmark for the recurrent laryngeal nerve and the superior parathyroid glands. The knowledge of the lobe of Zuckerkandl is essential to perform "safety thyroidectomy", without injury for the vascular and nervous structures. CONCLUSIONS: TZ identification is not always easy and/or possible but, when that happens become aware of possible, systematically, the isolation of the recurrent nerve and of the superior parathyroid gland, preserve such structures from possible lesions in surgery of the thyroid gland.