Systematic analysis and network mapping of disease associations in autoimmune polyglandular syndrome.

BACKGROUND: The purpose of our work was to provide a data-driven perspective to APS, a complex autoimmune disorder, supplementing traditional clinical observations. METHODS: Medical records of 7559 patients were analyzed, autoimmune origin was proved in 3180 cases of which 380 (12%) had APS. Associations of component disorders were investigated by computational methods to reveal typical patterns of disease development. RESULTS: Twenty-eight distinct autoimmune disorders were diagnosed forming 113 combinations. The 10 most frequent combinations were responsible for 51,3% of cases. HT and GD were differentiated as main cornerstones of APS, sharing several comorbidities. HT was the most common manifestation (67.4%), followed by GD (26.8%) and T1D (20.8%). APS started significantly earlier in men than in women. Thyroid autoimmunity was frequently linked to gastrointestinal and systemic manifestations and these patterns of associations substantially differed from that of T1D, AD or CeD when present as first manifestations, suggesting the possibility of a common biological cause. CONCLUSION: APS is more frequent than reported. Classifying APS requires a shift of perspective towards disease associations rather than disorder prevalence.

Systemic relations among the variables involved in occupational accidents of the nursing team in a psychiatric hospital.

BACKGROUND: The occupational activities carried out in hospital environments pose occupational risks to professionals. In psychiatric hospitals, due to the characteristics of the patients treated, professionals are also subjected to other risks, such as physical aggression. OBJECTIVE: This research aimed to identify the systemic context, highlighting the cause-and-effect relationships that culminate in occupational accidents that occurred with the nursing staff in a psychiatric hospital in Brazil. METHODS: The current study is an applied research and was divided into three stages. First, the collection of data related to the case study was made and accidents were analyzed and occupational hazards were identified. In the second stage, from the collected information, occupational safety indicators were defined. Lastly, in the third stage, the qualitative aspect of System Dynamics was applied to perform the systemic analysis and to identify how the different variables were related. RESULTS: The results showed that physical aggression was the main cause of accidents. Regarding safety indicators, while both the level of use of Personal Protective Equipment (PPE) by professionals and the high level of PPE protection were positive aspects, the level of training of professionals to use PPE was a negative aspect. The Causal Link Diagram (CLD) showed that the perception of risk influenced the level of use of PPE and those organizational measures influenced the accident rate. CONCLUSION: In conclusion, the systemic analysis of the system dynamics can optimize the diagnostic process of occupational accidents in psychiatric hospitals, and especially help to identify the cause and effect among the variables involved.

Corrigendum: Toxicity profile of combined immune checkpoint inhibitors and thoracic radiotherapy in esophageal cancer: A meta-analysis and systematic review.

[This corrects the article DOI: 10.3389/fimmu.2022.1039020.].

Toxicity profile of combined immune checkpoint inhibitors and thoracic radiotherapy in esophageal cancer: A meta-analysis and systematic review.

Background: Therapies based on the combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) are transforming the treatment landscape of esophageal cancer. Nevertheless, the available data on adverse events (AEs) mainly stemmed from several prospective clinical trials and retrospective studies, in which, AE data are often handled and reported with less rigor than the primary beneficial outcomes of the study. Thus, we conducted a systematic review to investigate the toxicity spectrum of these novel regimens. Method: We searched for all prospective clinical trials investigating the role of ICIs combined with TRT published between January 2010 and August 2022. Study articles and conference proceedings involving esophageal cancers and reporting the overall incidence or details of treatment-related AEs (trAEs) were synthesized to determine the toxicity profile of combination treatment. We compared trAEs between cancer type, programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, and between sequential and concurrent administration of ICIs and TRT to identify potentially high-risk patients. Results: We obtained toxicity data from 14 clinical trials involving 863 patients. The pooled overall incidence was 88.97% for any-grade trAEs and 18.48% for high-grade trAEs. The three most frequent non-hematologic any-grade trAEs were reactive cutaneous capillary endothelial proliferation (RCCEP, 63.80%), esophagitis (51.54%), and fatigue (33.63%). Meanwhile, RCCEP (15.69%) was the most common non-hematologic high-grade trAE, followed by nausea (4.91%) and anorexia (3.81%). The occurrence rates of any-grade and high-grade pneumonitis were 10.82% and 0.66%, respectively. In subgroup analysis, the toxicity profiles of PD-1 and PD-L1 inhibitors were mostly similar, except for any-grade pneumonitis (15.20% vs 4.88%, p=0.03) and high-grade leukopenia (6.25% vs 59.09%, p=0.00). In addition, concurrent treatment seemed to have a higher incidence of any-grade trAEs (95.20% vs 70.85%, p=0.03) compared with sequential treatment. ESCC seems to have higher incidence of any-grade hypothyroidism (22.55% vs 8.96%, p=0.049) compared to EAC. Conclusion: Our study is the first systematic review to provide a toxicity profile of trAEs in esophageal cancer patients who received ICIs combined with TRT. Most AEs of this combination treatment are tolerable, although the incidence of any-grade trAEs was higher in the concurrent group. The difference in any-grade pneumonitis between PD-1 and PD-L1 inhibitor groups needs further validation in a large clinical trial.

Aspects Regarding the Innovative Conceptual Design for Children's Recreational Areas.

Conceptual design approaches the definition of an innovative concept design applied to a product intended for children'-=s recreational area, corresponding to a personal profile located around the age of childhood, namely aged 2 to 5. The case study presented highlights the development of an innovative concept for children's recreational areas, to be precise the design, and the conceptual design applied to a roto-pendular carousel for children's recreational areas. The working method aims at identifying the chronological stages of development and the conceptual design, starting from the idea, prospectographic research, analysis of constructive solutions, and finally the materialization of the assisted design in detail, applied to the new concept. Based on the prospectographic study, several constructive variants are highlighted, at the draft level, and after the analysis, the optimized variant of the carousel concept is established that should match the functions and characteristics pursued and imposed on the new concept. Following the justification of the choice of the optimal variant of the concept, the model is designed in an assisted environment in order to follow aspects related to technology associated with each component of the whole assembly, as well as aspects related to ergonomics, safety in exploration and proportion associated to the typology and to the age criteria of children.

Visioning a food system for equitable transition towards sustainable diets.

The Global Goals to end hunger requires interpretation of problems, and change across multiple domains. We facilitated a workshop aimed at understanding how stakeholders problematise sustainable diet transition (SDT) among a previously-marginalised social group. Using the systems thinking approach, three sub-systems, access to dietary diversity, sustainable beneficiation of natural capital, and 'food choice for well-being', highlighted the main forces governing the current context, and future interventions. Moreover, when viewed as co-evolving processes within the multi-level perspective, our identified microlevel leverage points - multi-faceted literacy, youth empowerment, deliberative policy-making, promotion of sustainable diet aspirations - can be linked and developed through existing national macrolevel strategies. Thus, by reconsidering knowledge use in the pursuit sustainability, transformational SDT can streamline multiple outcomes to restructure socio-technical sectors, reconnect people to nature-based solutions and, support legitimate aspirations. The approach could be applied in countries having complex socio-political legacy and to bridge the local-global goals coherently.

Cardiac Computed Tomography Versus Transesophageal Echocardiography for the Detection of Left Atrial Appendage Thrombus: A Systemic Review and Meta-Analysis.

Background Transesophageal echocardiography (TEE) has been considered the gold standard for left atrial appendage (LAA) thrombus detection. Nevertheless, TEE may sometimes induce discomfort and cause complications. Cardiac computed tomography has been studied extensively for LAA thrombus detection. We performed this systemic review and meta-analysis to assess the diagnostic accuracy of cardiac computed tomography for LAA thrombus detection compared with TEE. Methods and Results A systemic search was conducted in the PubMed, Embase, and Cochrane Library databases from January 1977 to February 2021. Studies performed for assessment diagnostic accuracy of cardiac computed tomography on LAA thrombus compared with TEE were included. Summary sensitivity, specificity, and posterior probability of LAA thrombus was calculated by using bivariate random-effects model. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used for the quality assessment. A total of 27 studies involving 6960 patients were included in our study. The summary sensitivity of early imaging studies was 0.95 (95% CI, 0.79-0.99), and the specificity was 0.89 (95% CI, 0.85-0.92). The positive posterior probability was 19.11%, and the negative posterior probability was 0.16%. The summary sensitivity of delayed imaging studies was 0.98 (95% CI, 0.92-1.00), and the specificity was 1.00 (95% CI, 0.98-1.00). The positive posterior probability was 95.76%, and the negative posterior probability was 0.12%. The delayed imaging method significantly improved the specificity (1.00 versus 0.89; P<0.05) and positive posterior probability (95.76% versus 19.11%; P<0.05). Conclusions Cardiac computed tomography with a delayed imaging is a reliable alternative to TEE. It may save the patient and health care from an excess TEE. Registration URL: https://www.crd.york.ac.uk/PROSPERO; Unique identifier: CRD42021236352.

Toxicity Profile of Combining PD-1/PD-L1 Inhibitors and Thoracic Radiotherapy in Non-Small Cell Lung Cancer: A Systematic Review.

Background: The combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) has shown significant clinical activity in patients with non-small cell lung cancer (NSCLC). However, the currently available data on adverse events (AEs) were derived from a small subset of patients included in prospective clinical trials or retrospective studies. Thus, we conducted this systematic review to determine the AEs associated with this combination treatment. Methods: An electronic literature search was performed in databases and conference proceedings of prospective clinical trials assessing the combination of ICIs and TRT for patients with NSCLC. The systematic analysis was conducted to determine the profile and incidence of AEs of combination treatment. We further performed the comparison of AEs between programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, and sequential and concurrent administration of ICIs and TRT to help identify high risk patients. The systematic analyses were conducted with the Review Manager (version 5.3; The Cochrane Collaboration, Oxford, United Kingdom) and Stata version 12.0 (StataCorp, College Station, TX, USA) software. Results: Eleven clinical trials involving 1,113 patients with NSCLC were eligible for analysis. The incidence of all-grade AEs was 95.5%; that of high-grade AEs (grade ≥3) was 30.2%. The most frequent all-grade AE was fatigue (49.7%), while pneumonitis was the most common high-grade AE (3.8%) and grade 5 AE (0.6%). Notably, the toxicity profiles of PD-1 and PD-L1 inhibitors were similar. Concurrent treatment was associated with a higher incidence of higher-grade AEs (41.6% vs 24.8%, P=0.17) and pneumonitis (7.1% vs 3.9%, P=0.14) compared to sequential treatment, but no significant difference was observed. Conclusion: Most AEs of this combination treatment are tolerable; as the most common high-grade AE, pneumonitis deserves the utmost attention of physicians. The toxicity profiles of patients receiving PD-1 or PD-L1 were similar, and no significant difference was observed between concurrent and sequential treatment.

Systemic analysis of medication administration omission errors in a tertiary-care hospital in Quebec.

OBJECTIVE: Medication administration omission errors (MAOEs) occur frequently in hospitals and can significantly affect patient health. An interdisciplinary committee was formed in summer 2012 to analyse incident/accident reports (AH-223-1 forms) of MAOEs for the 2011-2012 fiscal year in order to identify contributing factors and to propose preventive solutions. Special attention was paid to events with consequences for patients. METHOD: An aggregate data analysis involving four major steps was conducted: sampling, categorisation, identification of contributing factors, and seeking preventive solutions. One hundred omissions were randomly selected from the 889 reported for this period. All omissions categorised as having had consequences for patients were then added, making a final total of 145 omissions. The omissions were categorised using an Ishikawa diagram developed from an exploratory literature review and process mapping. Subsequent to failure modes, effects and criticality analysis, cause-and-effect diagrams were constructed with the main prioritised categories to differentiate the proximal causes from the root causes. Brainstorming was used to develop solutions, which were then prioritised with an impact/effort matrix. RESULTS: This study identified 27 categories of MAOEs, of which the 7 most frequent and the most critical accounted for 79.3% of the reports. The event categories, in decreasing order of importance, were related to intravenous (IV) therapy (29.0%), failure in using the medication administration record (MAR; 23.4%), failure in creating/updating the MAR (10.3%), medications on the patient's bedside (7.6%), and three types of MAOEs related to transcribing prescriptions (9.0%). CONCLUSION: The interdisciplinary committee formulated 10 main recommendations related to these 7 categories, including 3 for IV therapy and 4 for failure in using or creating/updating the MAR.

[Experience feedback committees (CREX) in French radiotherapy departments in 2019]. / Comités de retour d'expérience (CREX) dans les centres de radiothérapie français en 2019.

Ten years after the beginning of CREX in radiotherapy departments we wanted to know about users' feeling. We sent a survey to 168 centers in the whole country and a hundred of them answer. The time, top management's involvement and professionals' training seem to be the key success factors. Systemic analysis methods and mainly the Orion© one are not identified as an issue. The main challenge for the next years will be the effectiveness check of actions.

The informative value of an overview on antibiotic consumption, treatment efficacy and cost of clinical mastitis at farm level.

This paper addresses whether it is worthwhile investing time in a more comprehensive documentation and analysis of farm specific data for mastitis treatment. Whilst most farmers keep some records, many refrain from investing more effort in making them more detailed. Therefore, information on farm-specific antibiotic consumption, effectiveness of treatments and the costs of mastitis are lacking; as well as the ability to identify and realise possibilities for improvement. An observational study was conducted on 30 dairy farms, to obtain an overview of farming practice, recording detailed data (using herd management software) on: milk records, diagnostics, preventive and therapeutic treatments and cost of mastitis, on an individual cow level. Out of a total of 30,633 cows, 67% received medication for the treatment or prevention of mastitis over a year. Antibiotics were chosen for 96% of udder treatments; including those for dry cows. Over 32% of the antibiotics used during lactation belonged to the 'highest priority critically important antimicrobial' category. Success of therapeutic treatment (assessed by individual somatic cell count (SCC)) ranged from 18% to 59% and total costs of mastitis per cow and year from € 158 to € 483. The high variations in antibiotic consumption, treatment outcomes and cost of mastitis between farms, showed that average or incomplete figures risk giving the wrong impression of a farm. It is thus worthwhile to invest in documentation and analysis of data, so that it is clear where action is required and which investments can be expected to be financially feasible. Benefits emerge from knowledge of antibiotic consumption allowing monitoring and reduction in antibiotic use (as demanded by consumers and legislation), improvements in animal health and welfare thanks to regular checks of how effective a treatment is, and economic benefits due to knowledge of the costs caused by mastitis.

Transgenic rescue of Atg5-null mice from neonatal lethality with neuron-specific expression of ATG5: Systemic analysis of adult Atg5-deficient mice.

Atg5-null mice are neonatal lethal. We have revealed in our recent paper that these mice die due to neuronal dysfunction resulting in suckling failure. Our new mouse model, atg5-/-;Eno2/Nse-Atg5 mice, where Atg5 is deficient in the whole body except for neurons, enables us to analyze the consequences of macroautophagy/autophagy-deficiency in the whole body of adult mice.

[The analysis of the medication error, in practice]. / L'analyse de l'erreur médicamenteuse, en pratique.

By performing a systemic analysis of medication errors which occur in practice, the multidisciplinary teams can avoid a reoccurrence with the aid of an improvement action plan. The methods must take into account all the factors which might have contributed to or favoured the occurrence of a medication incident or accident.

[Learning from errors after a care-related adverse event]. / Apprendre de ses erreurs après un événement indésirable associé aux soins.

The mobilisation of all health professionals with regard to the detection and analysis of care-related adverse events is an essential element in the improvement of the safety of care. This approach is required by the authorities and justifiably expected by users.

[Experience feedback committees (CREX) and beyond ]. / Les Crex et après .

Since the late 2,000 years, under the incentive of the French agencies ANAP (previously MEAH) and HAS and following the decision DC-0103 of the ASN, experience feedback committees (known as 'Comité de retour d'expérience or Crex' in French) have widely been implemented within radiation oncology departments in France. Based on the declaration of error/near misses (precursor events) occurring during medical care to patients, an intuitive method of systematic analysis of these events is basically the aim of such committees (such as the Orion method(©) derived from the air transportation industry). Our article aims at summarizing the paths and pitfalls attached to this methodology, emphasizing what could be the next step, beyond the 'Crex' committees, in the long march to know how to secure care to patients within a radiotherapy medical team.

Abordaje metodológico para emprender acciones interinstitucionales e intersectoriales sobre cambio climático en el departamento de caldas / Methodlogical appproac to undertake inter-institutional and inter-secctorial actions about climate change in the department of caldas

Se presenta un abordaje metodológico para emprender acciones coordinadas incluyentes e interinstitucionales sobre el cambio climático en el departamento de Caldas, estableciendo como eje de acción la gestión integral del riesgo asociado a dicho cambio, direccionando acciones a corto, mediano y largo plazo en torno a cinco alertas develadas mediante una investigación cualitativa sobre los imaginarios sociales que la población caldense tiene sobre el mismo; categorizadas como variables críticas, variables dependientes y variables independientes a través de un análisis perceptual estructural sistémico. Se pretende plasmar la voz de la comunidad y hacer explícita la determinación y el compromiso de distintas instituciones del departamento para establecer sinergias en consonancia con sus potencialidades, de tal forma que se logre avanzar en el conocimiento de los efectos producidos por este fenómeno en nuestra región; así mismo contribuir de manera organizada y efectiva en la gestión integral del riesgo asociado al cambio climático de nuestro departamento, trabajando permanentemente en la prevención, mitigación y adaptación, para la preservación de nuestros ecosistemas y un desarrollo sustentable.

A methodological approach to undertake inclusive coordinated and inter-institutional actions about climate change in the Caldas Department is presented, establishing as the axis of action the comprehensive risk management associated to such change, directing short, medium and long term actions about the five alerts uncovered through the qualitative research about the social imaginary people from Caldas have about it, categorized as critical variables, dependent variables, and independent variables through a perceptual structural systemic analysis This article aims to give expression to the voice of the community and make explicit the determination and compromise of different institutions in the Department of Caldas to establish synergies according to their potentialities so that it can be possible to advance in the knowledge of the effects produced by this phenomenon in our region. Likewise, this text seeks to contribute in an organized and effective manner to comprehensive risk management associated with climate change in our Department, working permanently in prevention, mitigation, and adaptation for the preservation of our ecosystems and for sustainable development.