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Measuring the contact angle at the solid/liquid/vapor triple point in sessile drop experiments is one of the most popular and simple ways to quantify the wettability of surfaces and determine the surface free energy. Despite decades of technical advancements in contact angle measurements, which allowed for improving the precision of sessile drop measurements below ±1°, an often overlooked source of experimental error in these measurements originates from the camera's parallax angle (PA) - the angle between the camera optical axis and the sample stage surface. Here, we quantified the systematic errors in the measurement of contact angles due to the acquisition of drop images at finite PA values by simulating sessile drop experiments in which synthetic drops were created using the Young-Laplace equation. The absolute contact angle error induced by imaging drops at nonzero PAs was found to increase as the true contact angle (TCA) deviates from 90° and resulted in an overestimation (underestimation) of the contact angle for drops having TCAs lower (higher) than 90°. The computed absolute contact angle error reaches values as high as -20° (+12.2°) for drops having a TCA of 175° (5°) when imaged with a PA of 10°, thus indicating the importance of considering the PA when accurately quantifying contact angles in sessile drop experiments. The shape and, by extension, volume of the sessile drop was also found to affect the magnitude of the absolute contact angle error as sessile drops with higher apex curvatures exhibited lower absolute error than those with lower curvatures at any given PA. The outcomes of this work provide guidelines for minimizing systematic errors in sessile drop measurements due to the collection of drop images at nonzero PAs.
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BACKGROUND: Low- and lower-middle-income countries account for a higher percentage of global epidemics and chronic diseases. In most low- and lower-middle-income countries, there is limited access to health care. The implementation of open-source electronic health records (EHRs) can be understood as a powerful enabler for low- and lower-middle-income countries because it can transform the way health care technology is delivered. Open-source EHRs can enhance health care delivery in low- and lower-middle-income countries by improving the collection, management, and analysis of health data needed to inform health care delivery, policy, and planning. While open-source EHR systems are cost-effective and adaptable, they have not proliferated rapidly in low- and lower-middle-income countries. Implementation barriers slow adoption, with existing research focusing predominantly on technical issues preventing successful implementation. OBJECTIVE: This interdisciplinary scoping review aims to provide an overview of contextual barriers affecting the adaptation and implementation of open-source EHR systems in low- and lower-middle-income countries and to identify areas for future research. METHODS: We conducted a scoping literature review following a systematic methodological framework. A total of 7 databases were selected from 3 disciplines: medicine and health sciences, computing, and social sciences. The findings were reported in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist. The Mixed Methods Appraisal Tool and the Critical Appraisal Skills Programme checklists were used to assess the quality of relevant studies. Data were collated and summarized, and results were reported qualitatively, adopting a narrative synthesis approach. RESULTS: This review included 13 studies that examined open-source EHRs' adaptation and implementation in low- and lower-middle-income countries from 3 interrelated perspectives: socioenvironmental, technological, and organizational barriers. The studies identified key issues such as limited funding, sustainability, organizational and management challenges, infrastructure, data privacy and protection, and ownership. Data protection, confidentiality, ownership, and ethics emerged as important issues, often overshadowed by technical processes. CONCLUSIONS: While open-source EHRs have the potential to enhance health care delivery in low- and lower-middle-income-country settings, implementation is fraught with difficulty. This scoping review shows that depending on the adopted perspective to implementation, different implementation barriers come into view. A dominant focus on technology distracts from socioenvironmental and organizational barriers impacting the proliferation of open-source EHRs. The role of local implementing organizations in addressing implementation barriers in low- and lower-middle-income countries remains unclear. A holistic understanding of implementers' experiences of implementation processes is needed. This could help characterize and solve implementation problems, including those related to ethics and the management of data protection. Nevertheless, this scoping review provides a meaningful contribution to the global health informatics discipline.
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Países em Desenvolvimento , Registros Eletrônicos de Saúde , HumanosRESUMO
In the last 6 years, hospitals in developed countries have been trialling the use of command centres for improving organizational efficiency and patient care. However, the impact of these command centres has not been systematically studied in the past. It is a retrospective population-based study. Participants were patients who visited the Bradford Royal Infirmary hospital, Accident and Emergency (A&E) Department, between 1 January 2018 and 31 August 2021. Outcomes were patient flow (measured as A&E waiting time, length of stay, and clinician seen time) and data quality (measured by the proportion of missing treatment and assessment dates and valid transition between A&E care stages). Interrupted time-series segmented regression and process mining were used for analysis. A&E transition time from patient arrival to assessment by a clinician marginally improved during the intervention period; there was a decrease of 0.9 min [95% confidence interval (CI): 0.35-1.4], 3 min (95% CI: 2.4-3.5), 9.7 min (95% CI: 8.4-11.0), and 3.1 min (95% CI: 2.7-3.5) during 'patient flow program', 'command centre display roll-in', 'command centre activation', and 'hospital wide training program', respectively. However, the transition time from patient treatment until the conclusion of consultation showed an increase of 11.5 min (95% CI: 9.2-13.9), 12.3 min (95% CI: 8.7-15.9), 53.4 min (95% CI: 48.1-58.7), and 50.2 min (95% CI: 47.5-52.9) for the respective four post-intervention periods. Furthermore, the length of stay was not significantly impacted; the change was -8.8 h (95% CI: -17.6 to 0.08), -8.9 h (95% CI: -18.6 to 0.65), -1.67 h (95% CI: -10.3 to 6.9), and -0.54 h (95% CI: -13.9 to 12.8) during the four respective post-intervention periods. It was a similar pattern for the waiting and clinician seen times. Data quality as measured by the proportion of missing dates of records was generally poor (treatment date = 42.7% and clinician seen date = 23.4%) and did not significantly improve during the intervention periods. The findings of the study suggest that a command centre package that includes process change and software technology does not appear to have a consistent positive impact on patient safety and data quality based on the indicators and data we used. Therefore, hospitals considering introducing a command centre should not assume there will be benefits in patient flow and data quality.
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Hospitais , Medicina Estatal , Humanos , Estudos Retrospectivos , Encaminhamento e Consulta , Reino Unido , Serviço Hospitalar de Emergência , Tempo de InternaçãoRESUMO
Process mining techniques can be used to analyse business processes using the data logged during their execution. These techniques are leveraged in a wide range of domains, including healthcare, where it focuses mainly on the analysis of diagnostic, treatment, and organisational processes. Despite the huge amount of data generated in hospitals by staff and machinery involved in healthcare processes, there is no evidence of a systematic uptake of process mining beyond targeted case studies in a research context. When developing and using process mining in healthcare, distinguishing characteristics of healthcare processes such as their variability and patient-centred focus require targeted attention. Against this background, the Process-Oriented Data Science in Healthcare Alliance has been established to propagate the research and application of techniques targeting the data-driven improvement of healthcare processes. This paper, an initiative of the alliance, presents the distinguishing characteristics of the healthcare domain that need to be considered to successfully use process mining, as well as open challenges that need to be addressed by the community in the future.
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Atenção à Saúde , Hospitais , HumanosRESUMO
As the use of closed incision negative pressure therapy (ciNPT) becomes more widespread, dressing designs have evolved to address implementation challenges and meet surgeon demand. While traditional application of ciNPT was limited to the immediate suture line, a novel dressing that covers the incision and additional surrounding tissues has become available. To expand upon previous ciNPT recommendations and provide guidance on this new dressing, an expert panel of plastic surgeons convened to review the current literature, identify challenges to the implementation and sustainability of ciNPT, and use a modified Delphi technique to form a consensus on the appropriate use of ciNPT with full-coverage dressings. After three rounds of collecting expert opinion via the Delphi method, consensus was reached if 80% of the panel agreed upon a statement. This manuscript establishes 10 consensus statements regarding when ciNPT with full-coverage foam dressings should be considered or recommended in the presence of patient or incision risk factors, effective therapeutic settings and duration, precautions for use, and tools and techniques to support application. The panel also discussed areas of interest for future study of ciNPT with full-coverage dressings. High-quality, controlled studies are needed to expand the understanding of the benefits of ciNPT over the incision and surrounding tissues.
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Tratamento de Ferimentos com Pressão Negativa , Ferida Cirúrgica , Bandagens , Humanos , Tratamento de Ferimentos com Pressão Negativa/métodos , Fatores de Risco , Ferida Cirúrgica/terapia , Infecção da Ferida Cirúrgica/etiologiaRESUMO
BACKGROUND: Global evidence suggests a range of benefits for introducing electronic health record (EHR) systems to improve patient care. However, implementing EHR within healthcare organisations is complex and, in the United Kingdom (UK), uptake has been slow. More research is needed to explore factors influencing successful implementation. This study explored staff expectations for change and outcome following procurement of a commercial EHR system by a large academic acute NHS hospital in the UK. METHODS: Qualitative interviews were conducted with 14 members of hospital staff who represented a variety of user groups across different specialities within the hospital. The four components of Normalisation Process Theory (Coherence, Cognitive participation, Collective action and Reflexive monitoring) provided a theoretical framework to interpret and report study findings. RESULTS: Health professionals had a common understanding for the rationale for EHR implementation (Coherence). There was variation in willingness to engage with and invest time into EHR (Cognitive participation) at an individual, professional and organisational level. Collective action (whether staff feel able to use the EHR) was influenced by context and perceived user-involvement in EHR design and planning of the implementation strategy. When appraising EHR (Reflexive monitoring), staff anticipated short and long-term benefits. Staff perceived that quality and safety of patient care would be improved with EHR implementation, but that these benefits may not be immediate. Some staff perceived that use of the system may negatively impact patient care. The findings indicate that preparedness for EHR use could mitigate perceived threats to the quality and safety of care. CONCLUSIONS: Health professionals looked forward to reaping the benefits from EHR use. Variations in level of engagement suggest early components of the implementation strategy were effective, and that more work was needed to involve users in preparing them for use. A clearer understanding as to how staff groups and services differentially interact with the EHR as they go about their daily work was required. The findings may inform other hospitals and healthcare systems on actions that can be taken prior to EHR implementation to reduce concerns for quality and safety of patient care and improve the chance of successful implementation.
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Atitude do Pessoal de Saúde , Registros Eletrônicos de Saúde , Recursos Humanos em Hospital/psicologia , Humanos , Motivação , Pesquisa Qualitativa , Reino UnidoRESUMO
"Nonsurgical rhinoplasty" refers to the use of injectable temporary fillers used to augment select areas of the nose to achieve improved appearance or function in select patients. Nonpermanent fillers can be used safely and must be properly chosen based on their properties and the desired effect. In addition to proper patient and product selection, a thorough understanding of nasal anatomy, analysis of the deformity, and recommended injection techniques are absolutely necessary to obtain good outcomes and avoid complications. The proper plane for injection is the deep fatty layer, just superficial to the perichondrium and periosteum. Erring on the side of undercorrection, small incremental boluses, and constant reassessment are the best way to avoid overfilling or producing irregularities and asymmetries. The most devastating and feared complications are vascular compromise, tissue necrosis, and even blindness, making the nose a challenging area to treat with fillers. The surgeon wishing to use fillers in the nose should be familiar with proper technique, recognition of developing problems, and have a practical plan in place for immediate reversal and treatment.
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Preenchedores Dérmicos/administração & dosagem , Rinoplastia/efeitos adversos , Rinoplastia/métodos , Preenchedores Dérmicos/efeitos adversos , Durapatita/administração & dosagem , Humanos , Ácido Hialurônico/administração & dosagem , Injeções/efeitos adversos , Nariz/anatomia & histologiaRESUMO
BACKGROUND: The purpose of this study is to identify whether intraoperative use of vasoactive medications increases the risk of free flap failure or complications through a systematic review and meta-analysis. MATERIALS AND METHODS: PubMed/MEDLINE, EMBASE, and Scopus databases were searched for studies published through January 2015. English publications that met the following criteria were included: (1) adult patients undergoing head and neck free flap reconstruction; (2) comparison of patients with and without intraoperative vasopressor administration; and (3) documentation of flap failure rate and/or flap complications. The primary outcome was the incidence of flap failure. The secondary outcome was the incidence of overall flap complications. Meta-analysis was performed to obtain pooled odds ratios (ORs) of the effect of intraoperative use of vasopressors on flap failure and complication rates. RESULTS: Four cohort studies met inclusion criteria. All studies were of high methodological quality with an average Methodological Index for Non-Randomized Studies score of 18.75 (range 16-23). A total of 933 patients undergoing head and neck free flap reconstruction were included. Meta-analysis demonstrated no statistically significant difference in the incidence of flap failure (2.9 vs. 3.6%; OR, 0.68; 95% confidence interval [CI], 0.23-1.99; p = 0.48) or incidence of flap complications (16.8 vs. 18.6%; OR, 0.92; 95% CI, 0.60-1.42; p = 0.71). CONCLUSION: Based on the current evidence, intraoperative use of vasopressors has no impact on the incidence of flap failure or flap complications.
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Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos de Cirurgia Plástica , Complicações Pós-Operatórias/prevenção & controle , Vasoconstritores/uso terapêutico , Sobrevivência de Enxerto , Humanos , Período Intraoperatório , Razão de Chances , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A 19-year-old woman who underwent conjunctivodacryocystorhinostomy with Medpor-Coated Tear Drain 2 years ago presented with diplopia on left gaze for 4 months. Limitation of extraocular movement of OS on left gaze was observed on duction test. The forced duction test revealed restriction of the left medial rectus muscle. Orbital MRI demonstrated an enhancing soft tissue lesion surrounding the tube in inferomedial aspect of left orbit. Removal of the tube and adhesiolysis were performed. Histologic findings were consistent with a chronic inflammation with fibrosis. After surgery, limitation of extraocular movement and diplopia were completely resolved. Jones tube coated with a thin layer of porous polyethylene allows the ingrowth of fibrovascular tissue into the coating, decreasing the probability of tube extrusion, but can also accelerate fibrotic changes around the tube causing restrictive strabismus.
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Materiais Revestidos Biocompatíveis , Túnica Conjuntiva/cirurgia , Dacriocistorinostomia/instrumentação , Diplopia/etiologia , Polietilenos , Próteses e Implantes/efeitos adversos , Estrabismo/etiologia , Diplopia/diagnóstico , Feminino , Humanos , Intubação , Imageamento por Ressonância Magnética , Procedimentos Cirúrgicos Oftalmológicos , Complicações Pós-Operatórias , Estrabismo/diagnóstico , Adulto JovemRESUMO
Hospitals improve safety and workflow efficiency by implementing systems for identification of items and patients. Little is known about the implementation of these systems across entire hospitals. The aim of this study is to identify challenges and enablers of adoption of such systems at scale, within a hospital organisation and across the English NHS. The focus is on the experience of the Scan4Safety project at Leeds Teaching Hospital NHS Trust (UK). Study methods are qualitative and include interviews with staff and review of documents. This poster paper presents preliminary findings of research in progress.
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Segurança do Paciente , Medicina Estatal , Humanos , Inglaterra , Sistemas de Informação Hospitalar , Gestão da SegurançaRESUMO
An overview of autoindexing diffraction images based on one-dimensional fast Fourier transforms is presented. The implementation of the algorithm in the Mosflm/iMosflm program suite is described with a discussion of practical issues that may arise and ways of assessing the success or failure of the procedure. Recent developments allow indexing of images that show multiple lattices, and several examples demonstrate the success of this approach in real cases.
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Cristalografia por Raios X , Processamento Eletrônico de Dados , Processamento de Imagem Assistida por Computador , Software , AlgoritmosRESUMO
BACKGROUND: Command centres have been piloted in some hospitals across the developed world in the last few years. Their impact on patient safety, however, has not been systematically studied. Hence, we aimed to investigate this. METHODS: This is a retrospective population-based cohort study. Participants were patients who visited Bradford Royal Infirmary Hospital and Calderdale & Huddersfield hospitals between 1 January 2018 and 31 August 2021. A five-phase, interrupted time series, linear regression analysis was used. RESULTS: After introduction of a Command Centre, while mortality and readmissions marginally improved, there was no statistically significant impact on postoperative sepsis. In the intervention hospital, when compared with the preintervention period, mortality decreased by 1.4% (95% CI 0.8% to 1.9%), 1.5% (95% CI 0.9% to 2.1%), 1.3% (95% CI 0.7% to 1.8%) and 2.5% (95% CI 1.7% to 3.4%) during successive phases of the command centre programme, including roll-in and activation of the technology and preparatory quality improvement work. However, in the control site, compared with the baseline, the weekly mortality also decreased by 2.0% (95% CI 0.9 to 3.1), 2.3% (95% CI 1.1 to 3.5), 1.3% (95% CI 0.2 to 2.4), 3.1% (95% CI 1.4 to 4.8) for the respective intervention phases. No impact on any of the indicators was observed when only the software technology part of the Command Centre was considered. CONCLUSION: Implementation of a hospital Command Centre may have a marginal positive impact on patient safety when implemented as part of a broader hospital-wide improvement programme including colocation of operations and clinical leads in a central location. However, improvement in patient safety indicators was also observed for a comparable period in the control site. Further evaluative research into the impact of hospital command centres on a broader range of patient safety and other outcomes is warranted.
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Hospitais , Pacientes , Humanos , Análise de Séries Temporais Interrompida , Estudos Retrospectivos , Estudos de CoortesRESUMO
BACKGROUND: Knowledge of post-myocardial infarction (MI) disease risk to date is limited-yet the number of survivors of MI has increased dramatically in recent decades. We investigated temporally ordered sequences of all conditions following MI in nationwide electronic health record data through the application of process mining. METHODS: We conducted a national retrospective cohort study of all hospitalisations (145,670,448 episodes; 34,083,204 individuals) admitted to NHS hospitals in England (1st January 2008-31st January 2017, final follow-up 27th March 2017). Through process mining, we identified trajectories of all major disease diagnoses following MI and compared their relative risk (RR) and all-cause mortality hazard ratios (HR) to a risk-set matched non-MI control cohort using Cox proportional hazards and flexible parametric survival models. FINDINGS: Among a total of 375,669 MI patients (130,758 females; 34.8%) and 1,878,345 matched non-MI patients (653,790 females; 34.8%), we identified 28,799 unique disease trajectories. The accrual of multiple circulatory diagnoses was more common amongst MI patients (RR 4.32, 95% CI 3.96-4.72) and conferred an increased risk of death (HR 1.32, 1.13-1.53) compared with matched controls. Trajectories featuring neuro-psychiatric diagnoses (including anxiety and depression) following circulatory disorders were markedly more common and had increased mortality post MI (HR ranging from 1.11 to 1.73) compared with non-MI individuals. INTERPRETATION: These results provide an opportunity for early intervention targets for survivors of MI-such as increased focus on the psychological and behavioural pathways-to mitigate ongoing adverse disease trajectories, multimorbidity, and premature mortality. FUNDING: British Heart Foundation; Alan Turing Institute.
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Infarto do Miocárdio , Feminino , Humanos , Estudos Retrospectivos , Fatores de Risco , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Modelos de Riscos Proporcionais , HospitalizaçãoRESUMO
Pneumomediastinum and pneumothorax are recognised complications encountered in COVID-19 before or during invasive mechanical ventilation (IMV). The clinical course of patients developing pneumomediastinum before IMV is yet to be evaluated.Four-thousand, one-hundred and thirty-one patients hospitalised with COVID-19 over a 12-month period were retrospectively reviewed to evaluate for incidence, clinical characteristics and outcomes. A subgroup analysis was done to identify any clinical traits between survivors and non-survivors. The overall incidence of pneumomediastinum prior to IMV was 0.92% (n=38) and was seen at admission or during non-invasive respiratory support. Thirty-seven per cent had associated pneumothorax most commonly unilateral (right side). The median (interquartile range (IQR)) duration from admission to developing pneumomediastinum was 7 days (3-11) and complete resolution was seen in 53% of patients; median (IQR) duration to resolution was 8 days (4-17). The in-hospital mortality associated with pneumomediastinum in patients with SARS-CoV-2 (PneumoCoV) was 55%. Increasing age (68 ± 12 years vs 56 ± 14 years; p=0.01), higher body mass index (31 ± 5 kg/m2 vs 28 ± 5 kg/m2; p=0.04), lack of resolution of pneumomediastinum (67% vs 24%; p=0.01; odds ratio (OR) 6.5; 95% confidence interval (CI) 1.5-27.5), presence of concurrent pneumothorax (65% vs 14%; p=0.002; OR 11; 95% CI 2.2-53.1) and elevated procalcitonin levels (>0.5 ng/mL; 81% vs 41%; p=0.01; OR 6; 95% CI 1.4-26) were significant features in those who did not survive.The incidence of PneumoCoV, despite being low, is associated with increased mortality. It is a hallmark of moderate to severe disease with multifaceted contributory factors. Both demographic and clinical factors predict survival.
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COVID-19 , Enfisema Mediastínico , Pneumotórax , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/terapia , Humanos , Enfisema Mediastínico/epidemiologia , Enfisema Mediastínico/etiologia , Enfisema Mediastínico/terapia , Pessoa de Meia-Idade , Pneumotórax/epidemiologia , Pneumotórax/etiologia , Pneumotórax/terapia , Respiração Artificial/efeitos adversos , Estudos Retrospectivos , SARS-CoV-2RESUMO
Oesophago-gastric cancer is difficult to diagnose in the early stages given its typical non-specific initial manifestation. We hypothesise that machine learning can improve upon the diagnostic performance of current primary care risk-assessment tools by using advanced analytical techniques to exploit the wealth of evidence available in the electronic health record. We used a primary care electronic health record dataset derived from the UK General Practice Research Database (7471 cases; 32,877 controls) and developed five probabilistic machine learning classifiers: Support Vector Machine, Random Forest, Logistic Regression, Naïve Bayes, and Extreme Gradient Boosted Decision Trees. Features included basic demographics, symptoms, and lab test results. The Logistic Regression, Support Vector Machine, and Extreme Gradient Boosted Decision Tree models achieved the highest performance in terms of accuracy and AUROC (0.89 accuracy, 0.87 AUROC), outperforming a current UK oesophago-gastric cancer risk-assessment tool (ogRAT). Machine learning also identified more cancer patients than the ogRAT: 11.0% more with little to no effect on false positives, or up to 25.0% more with a slight increase in false positives (for Logistic Regression, results threshold-dependent). Feature contribution estimates and individual prediction explanations indicated clinical relevance. We conclude that machine learning could improve primary care cancer risk-assessment tools, potentially helping clinicians to identify additional cancer cases earlier. This could, in turn, improve survival outcomes.
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The COVID-19 pandemic has highlighted some of the opportunities, problems and barriers facing the application of Artificial Intelligence to the medical domain. It is becoming increasingly important to determine how Artificial Intelligence will help healthcare providers understand and improve the daily practice of medicine. As a part of the Artificial Intelligence research field, the Process-Oriented Data Science community has been active in the analysis of this situation and in identifying current challenges and available solutions. We have identified a need to integrate the best efforts made by the community to ensure that promised improvements to care processes can be achieved in real healthcare. In this paper, we argue that it is necessary to provide appropriate tools to support medical experts and that frequent, interactive communication between medical experts and data miners is needed to co-create solutions. Process-Oriented Data Science, and specifically concrete techniques such as Process Mining, can offer an easy to manage set of tools for developing understandable and explainable Artificial Intelligence solutions. Process Mining offers tools, methods and a data driven approach that can involve medical experts in the process of co-discovering real-world evidence in an interactive way. It is time for Process-Oriented Data scientists to collaborate more closely with healthcare professionals to provide and build useful, understandable solutions that answer practical questions in daily practice. With a shared vision, we should be better prepared to meet the complex challenges that will shape the future of healthcare.
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Inteligência Artificial , COVID-19 , COVID-19/epidemiologia , Ciência de Dados , Atenção à Saúde , Humanos , Pandemias/prevenção & controleRESUMO
Overproduction of the exopolysaccharide alginate contributes to the pathogenicity and antibiotic tolerance of Pseudomonas aeruginosa in chronic infections. The second messenger, c-di-GMP, is a positive regulator of the production of various biofilm matrix components and is known to regulate alginate synthesis at the posttranslational level in P. aeruginosa. We provide evidence that c-di-GMP also regulates transcription of the alginate operon in P. aeruginosa. Previous work has shown that transcription of the alginate operon is regulated by nine different proteins, AmrZ, AlgP, IHFα, IHFß, CysB, Vfr, AlgR, AlgB, and AlgQ, and we investigated if some of these proteins function as a c-di-GMP effector. We found that deletion of algP, algQ, IHFα, and IHFß had only a marginal effect on the transcription of the alginate operon. Deletion of vfr and cysB led to decreased transcription of the alginate operon, and the dependence of the c-di-GMP level was less pronounced, indicating that Vfr and CysB could be partially required for c-di-GMP-mediated regulation of alginate operon transcription. Our experiments indicated that the AmrZ, AlgR, and AlgB proteins are absolutely required for transcription of the alginate operon. However, differential radial capillary action of ligand assay (DRaCALA) and site-directed mutagenesis indicated that c-di-GMP does not bind to any of the AmrZ, AlgR, and AlgB proteins. IMPORTANCE The proliferation of alginate-overproducing P. aeruginosa variants in the lungs of cystic fibrosis patients often leads to chronic infection. The alginate functions as a biofilm matrix that protects the bacteria against host immune defenses and antibiotic treatment. Knowledge about the regulation of alginate synthesis is important in order to identify drug targets for the development of medicine against chronic P. aeruginosa infections. We provide evidence that c-di-GMP positively regulates transcription of the alginate operon in P. aeruginosa. Moreover, we revisited the role of the known alginate regulators, AmrZ, AlgP, IHFα, IHFß, CysB, Vfr, AlgR, AlgB, and AlgQ, and found that their effect on transcription of the alginate operon is highly varied. Deletion of algP, algQ, IHFα, or IHFß only had a marginal effect on transcription of the alginate operon, whereas deletion of vfr or cysB led to decreased transcription and deletion of amrZ, algR, or algB abrogated transcription.
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Regulação Bacteriana da Expressão Gênica , Pseudomonas aeruginosa , Alginatos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Humanos , Óperon , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismoRESUMO
The fourth industrial revolution is based on cyber-physical systems and the connectivity of devices. It is currently unclear what the consequences are for patient safety as existing digital health technologies become ubiquitous with increasing pace and interact in unforeseen ways. In this paper, we describe the output from a workshop focused on identifying the patient safety challenges associated with emerging digital health technologies. We discuss six challenges identified in the workshop and present recommendations to address the patient safety concerns posed by them. A key implication of considering the challenges and opportunities for Patient Safety Informatics is the interdisciplinary contribution required to study digital health technologies within their embedded context. The principles underlying our recommendations are those of proactive and systems approaches that relate the social, technical and regulatory facets underpinning patient safety informatics theory and practice.