Using primary care data for research: What are the issues and potential solutions?

BACKGROUND: Interest in using primary care data for research is growing with increasing recognition of its potential for improving healthcare. Many issues exist, some inherent in the data and others external. OBJECTIVE: This paper explores the main issues associated with the use of primary care data for research and proposed solutions to address them. DISCUSSION: Issues related to the use of primary care data for research are complex. Government reimbursement system administrative data have limitations as they lack clinical detail. General practice electronic medical record data are more suitable; however, challenges include variable data quality and interoperability. There are concerns from general practices and the public about data access and use. Strategies to address these issues include incorporating best-practice principles, implementing standards and data quality frameworks, creating partnerships between data custodians and ensuring robust governance systems exist. Leadership and the will of key stakeholders to reform, with governmental support in implementing required actions, must be prioritised.

Evidence for the druggability of aldosterone targets in heart failure: A bioinformatics and data science-driven decision-making approach.

BACKGROUND: Aldosterone plays a key role in the neurohormonal drive of heart failure. Systematic prioritization of drug targets using bioinformatics and database-driven decision-making can provide a competitive advantage in therapeutic R&D. This study investigated the evidence on the druggability of these aldosterone targets in heart failure. METHODS: The target disease predictability of mineralocorticoid receptors (MR) and aldosterone synthase (AS) in cardiac failure was evaluated using Open Targets target-disease association scores. The Open Targets database collections were downloaded to MongoDB and queried according to the desired aggregation level, and the results were retrieved from the Europe PMC (data type: text mining), ChEMBL (data type: drugs), Open Targets Genetics Portal (data type: genetic associations), and IMPC (data type: genetic associations) databases. The target tractability of MR and AS in the cardiovascular system was investigated by computing activity scores in a curated ChEMBL database using supervised machine learning. RESULTS: The medians of the association scores of the MR and AS groups were similar, indicating a comparable predictability of the target disease. The median of the MR activity scores group was significantly lower than that of AS, indicating that AS has higher target tractability than MR [Hodges-Lehmann difference 0.62 (95%CI 0.53-0.70, p < 0.0001]. The cumulative distributions of the overall multiplatform association scores of cardiac diseases with MR were considerably higher than with AS, indicating more advanced investigations on a wider range of disorders evaluated for MR (Kolmogorov-Smirnov D = 0.36, p = 0.0009). In curated ChEMBL, MR had a higher cumulative distribution of activity scores in experimental cardiovascular assays than AS (Kolmogorov-Smirnov D = 0.23, p < 0.0001). Documented clinical trials for MR in heart failures surfaced in database searches, none for AS. CONCLUSIONS: Although its clinical development has lagged behind that of MR, our findings indicate that AS is a promising therapeutic target for the treatment of cardiac failure. The multiplatform-integrated identification used in this study allowed us to comprehensively explore the available scientific evidence on MR and AS for heart failure therapy.

Is the digital workflow more efficient for manufacturing partial-coverage restorations? A systematic review.

STATEMENT OF PROBLEM: A consensus on whether a fully digital workflow can replace conventional methods of manufacturing partial-coverage restorations is lacking. PURPOSE: The purpose of this systematic review was to evaluate the accuracy, fit, and clinical outcomes of inlay, onlay, overlay, and endocrown restorations obtained with both digital and conventional workflows. MATERIAL AND METHODS: This study complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered in the International Prospective Register of Systematic Reviews database (CRD42021258696). Studies evaluating the accuracy, fit, and clinical outcomes of inlay, onlay, overlay, and endocrown restorations obtained with digital and conventional workflows were included from 5 databases searched in November 2022. The Checklist for Reporting Randomized Clinical Studies (ROB 2) and the Checklist for Reporting In vitro Studies (CRIS guidelines) were used to assess the risk of bias. RESULTS: Twenty-three studies were included in this review. Sixteen studies evaluated marginal and internal fit, 5 evaluated accuracy, 3 evaluated fracture resistance, and 1 evaluated long-term clinical performance. Although most studies reported acceptable clinical outcomes for both workflows, 11 studies showed better results with the conventional workflow, 10 with the digital workflow, and 2 reported that the outcomes of the workflows were similar. CONCLUSIONS: Clinically acceptable values have been reported for the parameters evaluated in both digital and conventional workflows, and no consensus has been reached regarding the more efficient method.

Retromolar canal diagnosed by cone-beam computed tomography and its influence in inferior alveolar nerve block / Canal retromolar diagnosticado por tomografía computarizada de haz cónico y su influencia en el bloqueo del nervio alveolar inferior

The aim of this study was to observed the anesthetic efficacy of the alveolar nerve block on nine patients that CBCT diagnosed unilateral retromolar canal on a double-blind, split-mouth approach. The assessments of patient response to thermal (pulp vitality test) and pressure (compression of soft tissue) stimuli were carried out before and 5 minutes after the inferior alveolar nerve block procedure, using both visual analog scale (VAS) and Mc Gill pain questionnaires (McG). The mean percentage of patient response decreased after alveolar nerve block, according to both VAS and McG, and was statistically similar among hemi mandibles with and without retromolar canal (Wilcoxon>0.05); however, those without retromolar canal presented greater reduction in patient response in 6 out of 9 cases. Therefore, the retromolar canal is not a determinant factor of inferior alveolar nerve block failure.

El objetivo de este estudio fue observar la eficacia anestésica del bloqueo del nervio alveolar en nueve pacientes que CBCT diagnosticó canal retromolar unilateral en un abordaje de boca dividida doble ciego. Las evaluaciones de la respuesta del paciente a los estímulos térmicos (prueba de vitalidad pulpar) y de presión (compresión de los tejidos blandos) se realizaron antes y 5 minutos después del procedimiento de bloqueo del nervio alveolar inferior, utilizando tanto la escala analógica visual (VAS) como los cuestionarios de dolor de Mc Gill ( McG). El porcentaje medio de respuesta de los pacientes disminuyó tras el bloqueo del nervio alveolar, según EVA y McG, y fue estadísticamente similar entre hemimandíbulas con y sin canal retromolar (Wilcoxon>0,05); sin embargo, aquellos sin canal retromolar presentaron mayor reducción en la respuesta del paciente en 6 de 9 casos. Por lo tanto, el canal retromolar no es un factor determinante del fracaso del bloqueo del nervio alveolar inferior.

Comparison of intraoral scanning and CBCT to generate digital and 3D-printed casts by fused deposition modeling and digital light processing.

OBJECTIVES: to evaluate trueness and precision of digital casts from intraoral scanning (IOS) and cone beam computed tomography (CBCT); trueness and precision of 3D-printed casts using digital light processing (DLP) and fused deposition modeling (FDM); the influence of digitizing method in the 3D-printed casts and, to compare STL data after DICOM segmentation and conversion. METHODS: a reference cast was digitized with IOS and CBCT, and 3D-printed using FDM and DLP. Linear measurements of occlusocervical (OC), interarch (IEA), and mesiodistal (MD) dimensions were taken on reference, digital and 3D-printed casts. Trueness was observed as the distortion, and precision was observed as the variation of measurements. One and Two-way ANOVA, Student t-test, and Chi-Square were applied to analyze data. RESULTS: distortion varied between digital casts for all dimensions; at OC, both showed expanded dimensions with IOS being significantly greater; in turn, CBCT digital casts showed higher distortion at IEA and MD. Dimensions of 3D-printed casts showed a predominance of shrinkage, DLP presented higher distortion compared to FDM for both digitizing methods. Digitizing methods influenced the 3D-printing of casts, especially for DLP. Regarding precision, no statistical difference was found. STL converted from DICOM showed statistical difference in IEA (p < 0.001). CONCLUSIONS: digital casts showed distortion depending on the digitizing method. IOS was better in IEA and MD, and CBCT in OC dimensions. Overall, DLP casts presented higher distortion compared to FDM. The digitizing method influences trueness on 3D-printed casts. File conversion from DICOM to STL per se could change the dimension. CLINICAL SIGNIFICANCE: This investigation showed that digital casts from IOS and CBCT as well 3D-printed casts from FDM and DLP can show different trueness. It is clinically relevant as clinicians have various workflows available in Digital Dentistry which involve these digitizing and manufacturing methods.

Premotor, nonmotor and motor symptoms of Parkinson's Disease: A new clinical state of the art.

Parkinson's Disease (PD) is a neurodegenerative disorder that affects dopaminergic neurons in the mesencephalic substantia nigra, causing a progressive clinical course characterized by pre-motor, non-motor and motor symptoms, which negatively impact the quality of life of patients and cause high health care costs. Therefore, the present study aims to discuss the clinical manifestations of PD and to make a correlation with the gut-brain (GB) axis, approaching epidemiology and therapeutic perspectives, to better understand its clinical progression and identify symptoms early. A literature review was performed regarding the association between clinical progression, the gut-brain axis, epidemiology, and therapeutic perspectives, in addition to detailing pre-motor, non-motor symptoms (neuropsychiatric, cognitive, autonomic, sleep disorders, sensory abnormalities) and cardinal motor symptoms. Therefore, this article addresses a topic of extreme relevance, since the previously mentioned clinical manifestations (pre-motor and non-motor) can often act as prodromal markers for the early diagnosis of PD and may precede it by up to 20 years.

State-Space Model of an Electro-Mechanical-Acoustic Contactless Energy Transfer System Based on Multiphysics Networks.

Contactless energy transfer systems are mainly divided into acoustic, inductive, capacitive, and optical, in which main applications are related to biomedical, wireless chargers, and sensors in metal enclosures. When solids are used as transfer media, ultrasound transducers based on piezoelectricity can be used for through-wall power transfer, which can be named as an electro-mechanical-acoustic contactless energy transfer system. This work presents a state-space model derived from a multiphysics network that includes all the multiphysical power conversion without separating the stages and including the real physical elements, like as the piezoelectric parameters and the geometry of the transfer media. The model is compared to the experimental response of the system and evaluated for different scenarios regarding transducers types and solid transfer media. An error analysis has shown that the maximum quadratic error between theoretical and experimental responses is 3.7%.

An IoT-Based System for Monitoring the Health of Guyed Towers in Overhead Power Lines.

The collapse of overhead power line guyed towers is one of the leading causes of power grid failures, subjecting electricity companies to pay considerable, high-value fines. In this way, the current work proposes a novel and complete framework for the remote monitoring of mechanical stresses in guyed towers. The framework method comprises a mesh network for data forwarding and neural networks to improve the performance of Low-Power and Lossy Networks. The method also considers the use of multiple sensors in the sensor fusion technique. As a result, the risk of collapse of guyed cable towers reduces, due to the remote monitoring and preventive actions promoted by the framework. Furthermore, the proposed method uses multiple input variable fusions, such as accelerometers and tension sensors, to estimate the tower's displacement. These estimations help address the structural health of the tower against failures (i.e., loosening of the stay cables, displacement, and vibrations) that can cause catastrophic events, such as tower collapse or even cable rupture.

Comparative Study of Evoked Otoacoustic Emissions in Offshore and Onshore Seafaring Workers. / Estudo comparativo das emissões otoacústicas evocadas em trabalhadores marítimos Offshore e Onshore.

PURPOSE: To evaluate the cochlear function of offshore and onshore seafaring workers of a naval company in the city of Rio de Janeiro and to estimate the degree of association between occupational exposure to noise and/or chemical substances and alteration in cochlear function. METHODS: This study evaluated seafaring workers aged 20 to 49, of both genders, without auditory symptoms, divided into two groups: the Offshore Group, operating in the high seas with occupational exposure; and the Onshore Group, operating in offices without occupational exposure. Exams were performed to evaluate cochlear function, including transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE). RESULTS: The TEOAE and DPOAE responses were on average lower in the Offshore Group, for all frequencies analyzed. The proportion of failures observed was also higher in the exposure group (Offshore), for general response and specific frequency, mainly for the frequencies of 4 kHz for TEOAE and 6 kHz for DPOAE. CONCLUSION: The results suggest that exposure to noise and/or chemical substances can contribute to alterations in cochlear function in seafarers even without manifesting auditory symptoms.

OBJETIVO: Avaliar a função coclear de trabalhadores marítimos Offshore e Onshore de uma empresa naval da cidade do Rio de Janeiro e estimar a magnitude de associação entre a exposição ocupacional ao ruído e/ou substâncias químicas e alterações na função coclear. MÉTODO: Neste estudo, foram avaliados trabalhadores marítimos entre 20-49 anos, de ambos os gêneros, sem queixas auditivas, distribuídos em dois grupos: o Grupo Offshore, que operam em alto mar com exposição ocupacional; e o Grupo Onshore, que operam em escritórios sem exposição ocupacional. Para avaliação da função coclear, foram realizados os exames de emissões otoacústicas evocadas por estímulo transiente (EOAT) e por produto de distorção (EOAPD). RESULTADOS: As respostas das EOAT e EOAPD foram, em média, menores no Grupo Offshore, para todas as frequências analisadas. A proporção de falhas observadas também foi maior no grupo de exposição (Offshore), tanto no critério geral quanto por frequência específica, principalmente para as frequências mais agudas de cada teste, 4 kHz para EOAT e 6 kHz para EOAPD. CONCLUSÃO: Os resultados sugerem que a exposição a ruído e/ou a substâncias químicas pode contribuir significativamente para alterações da função coclear de trabalhadores marítimos, mesmo antes de manifestarem queixas auditivas.

Can diagnostic changes caused by cone beam computed tomography alter the clinical decision in impacted lower third molar treatment plan?

OBJECTIVES: This study observed whether changes in diagnosis caused by analysis of three-dimensional images can lead to alterations in the treatment plans of impacted lower third molars (ILTMs). METHODS: Sets of panoramic (PAN) - cone beam computed tomography (CBCT) of 218 patients were assessed for ILTM classification, contact with mandibular canal, contact and resorption of the lower second molar (LSM), intraoperative planning and post-operative expectations. RESULTS: Percentage agreement and McNemar test compared PAN vs CBCT assessments. Logistic regression analyzed the dependency of change in surgical planning considering the changes in diagnostic features; descriptive statistics was used to observe the expectation of post-operative complications and paresthesia. Differences were found between PAN vs CBCT for classification of impaction and positioning, LSM relationship, choice for crown and root sectioning and expectation of post-operative complications (all with p < 0.001). Logistic regression indicated that the change in diagnosis caused by CBCT examination did not change the clinical decision to extract ILTM but altered the planning of intraoperative steps such as osteotomy, crown sectioning and relaxing incision. The expectation of post-operative complications decreased when professionals planned the ILTM removal using tri-dimensional images. CONCLUSIONS: We concluded that changes in the diagnosis after CBCT examination can lead to alterations in the treatment plan of impacted lower third molar.

Estudo comparativo das emissões otoacústicas evocadas em trabalhadores marítimos Offshore e Onshore / Comparative Study of Evoked Otoacoustic Emissions in Offshore and Onshore Seafaring Workers

RESUMO Objetivo Avaliar a função coclear de trabalhadores marítimos Offshore e Onshore de uma empresa naval da cidade do Rio de Janeiro e estimar a magnitude de associação entre a exposição ocupacional ao ruído e/ou substâncias químicas e alterações na função coclear. Método Neste estudo, foram avaliados trabalhadores marítimos entre 20-49 anos, de ambos os gêneros, sem queixas auditivas, distribuídos em dois grupos: o Grupo Offshore, que operam em alto mar com exposição ocupacional; e o Grupo Onshore, que operam em escritórios sem exposição ocupacional. Para avaliação da função coclear, foram realizados os exames de emissões otoacústicas evocadas por estímulo transiente (EOAT) e por produto de distorção (EOAPD). Resultados As respostas das EOAT e EOAPD foram, em média, menores no Grupo Offshore, para todas as frequências analisadas. A proporção de falhas observadas também foi maior no grupo de exposição (Offshore), tanto no critério geral quanto por frequência específica, principalmente para as frequências mais agudas de cada teste, 4 kHz para EOAT e 6 kHz para EOAPD. Conclusão Os resultados sugerem que a exposição a ruído e/ou a substâncias químicas pode contribuir significativamente para alterações da função coclear de trabalhadores marítimos, mesmo antes de manifestarem queixas auditivas.

ABSTRACT Purpose To evaluate the cochlear function of offshore and onshore seafaring workers of a naval company in the city of Rio de Janeiro and to estimate the degree of association between occupational exposure to noise and/or chemical substances and alteration in cochlear function. Methods This study evaluated seafaring workers aged 20 to 49, of both genders, without auditory symptoms, divided into two groups: the Offshore Group, operating in the high seas with occupational exposure; and the Onshore Group, operating in offices without occupational exposure. Exams were performed to evaluate cochlear function, including transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE). Results The TEOAE and DPOAE responses were on average lower in the Offshore Group, for all frequencies analyzed. The proportion of failures observed was also higher in the exposure group (Offshore), for general response and specific frequency, mainly for the frequencies of 4 kHz for TEOAE and 6 kHz for DPOAE. Conclusion The results suggest that exposure to noise and/or chemical substances can contribute to alterations in cochlear function in seafarers even without manifesting auditory symptoms.

Effects of the FGF receptor-1 inhibitor, infigratinib, with or without sildenafil, in experimental pulmonary arterial hypertension.

BACKGROUND AND PURPOSE: Pulmonary arterial hypertension (PAH) is a progressive disease associated with high morbidity and mortality, despite advances in medical therapy. We compared the effects of infigratinib (NVP-BGJ398), a new FGF receptor-1 inhibitor, with or without the PDE-5 inhibitor sildenafil, on vascular function and remodelling as well as on gene expression of signal transducers for receptors of TGF-ß (Smads-1/2/4) and transcription factor of endothelial-mesenchymal transition (Twist-1) in established experimental PAH. Types I and III pro-collagen and TGF-ß expressions in lung fibroblasts were analysed in vitro after the different treatments. EXPERIMENTAL APPROACH: PAH was induced in male Wistar rats with monocrotaline. 14 days later, treatments [sildenafil (SIL), infigratinib (INF) or their combination (SIL+INF)] were given for another 14 days. On Day 28, echocardiography and haemodynamic assays were performed, and lungs and pulmonary vessels were removed for analysis by histology, immunohistochemistry and RT-PCR. Fibroblasts prepared from PAH lungs were also analysed for TGF-ß and pro-collagen. KEY RESULTS: Only the combination of infigratinib and sildenafil significantly improved right ventricular systolic pressure and vascular remodelling parameters (right ventricular hypertrophy, smooth muscle α-actin, vessel wall thickness, and vascular collagen content). Infigratinib may act by reducing gene expression of Smads-1/4 and Twist-1 in lung tissue, as well as TGF-ß and types I and III pro-collagen in lung fibroblasts. CONCLUSIONS AND IMPLICATIONS: In this model of monocrotaline-induced PAH, the combination of the new inhibitor of FGF receptor-1, infigratinib, and sildenafil effectively improved haemodynamics and decreased vascular remodelling.

Mesenchymal stromal cell therapy reduces lung inflammation and vascular remodeling and improves hemodynamics in experimental pulmonary arterial hypertension.

BACKGROUND: Experimental research has reported beneficial effects of mesenchymal stromal cell (MSC) therapy in pulmonary arterial hypertension (PAH). However, these studies either were based on prophylactic protocols or assessed basic remodeling features without evaluating possible mechanisms. We analyzed the effects of MSC therapy on lung vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH. METHODS: Twenty-eight Wistar rats were randomly divided into two groups. In the PAH group, animals received MCT 60 mg/kg intraperitoneally, while a control group received saline (SAL) instead. On day 14, both groups were further randomized to receive 105 adipose-derived MSCs or SAL intravenously (n = 7/group). On day 28, right ventricular systolic pressure (RVSP) and the gene expression of mediators associated with apoptosis, inflammation, fibrosis, Smad-1 levels, cell proliferation, and endothelial-mesenchymal transition were determined. In addition, lung histology (smooth muscle cell proliferation and plexiform-like injuries), CD68+ and CD163+ macrophages, and plasma levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were evaluated. RESULTS: In the PAH group, adipose-derived MSCs, compared to SAL, reduced mean RVSP (29 ± 1 vs 39 ± 2 mmHg, p < 0.001), lung tissue collagen fiber content, smooth muscle cell proliferation, CD68+ macrophages, interleukin-6 expression, and the antiapoptotic mediators Bcl-2 and survivin. Conversely, expression of the proapoptotic mediator procaspase-3 and plasma VEGF increased, with no changes in PDGF. In the pulmonary artery, MSCs dampened the endothelial-mesenchymal transition. CONCLUSION: In MCT-induced PAH, MSC therapy reduced lung vascular remodeling, thus improving hemodynamics. These beneficial effects were associated with increased levels of proapoptotic markers, mesenchymal-to-endothelial transition, reduced cell proliferation markers, and inflammation due to a shift away from the M1 phenotype.

Effects of bone marrow mononuclear cells from healthy or ovalbumin-induced lung inflammation donors on recipient allergic asthma mice.

INTRODUCTION: Asthma is characterized by a chronic inflammatory process which may lead to several changes in bone marrow cell composition. We hypothesized that bone marrow mononuclear cells (BMMCs) obtained from ovalbumin (OVA)-induced lung inflammation mice may promote different effects compared to BMMCs from healthy donors in a model of allergic asthma. METHODS: C57BL/6 mice were randomly assigned to two groups. In the OVA group, mice were sensitized and challenged with ovalbumin, while healthy animals (control group) received saline using the same protocol. BMMCs were analyzed by flow cytometry 24 hours after the last challenge. After BMMC characterization, another group of OVA mice were further randomized into three subgroups to receive intratracheal saline (BMMC-SAL), BMMCs from control or BMMCs from OVA mice (BMMC-Control and BMMC-OVA, respectively; 2x106 cells/mouse), 24 hours after the last challenge. RESULTS: BMMC-OVA exhibited an increased percentage of eosinophils, monocytes and hematopoietic precursors, while mesenchymal stem cells decreased, as compared with BMMC-Control. BMMCs from both donor groups reduced airway resistance, alveolar collapse, bronchoconstriction index, eosinophil infiltration, collagen fiber content in alveolar septa and levels of interleukin (IL)-4, IL-5, IL-13, interferon-γ, transforming growth factor-ß, and vascular endothelial growth factor in lung homogenates. However, the benefits of BMMCs were significantly more pronounced when cells were obtained from control donors. CONCLUSION: Both BMMC-Control and BMMC-OVA reduced the inflammatory and remodeling processes; nevertheless, BMMC-Control led to a greater improvement in lung morphofunction, which may be due to different BMMC composition and/or properties.

The role of perioperative radiotherapy in gastric cancer.

Gastric cancer is one of the most common neoplasms and a main cause of cancer-related mortality worldwide. Surgery remains the mainstay for cure and is considered for all patients with potentially curable disease. However, despite the fact that surgery alone usually leads to favorable outcomes in early stage disease, late diagnosis usually means a poor prognosis. In these settings, multimodal therapy has become the established treatment for locally advanced tumors, while the high risk of locoregional relapse has favored the inclusion of radiotherapy in the comprehensive therapeutic strategy. We provide a critical, non-systematic review of gastric cancer and discuss the role of perioperative radiation therapy in its treatment.