Glocal Clinical Registries: Pacemaker Registry Design and Implementation for Global and Local Integration – Methodology and Case Study

Background

The ability to apply standard and interoperable solutions for implementing and managing medical registries as well as aggregate, reproduce, and access data sets from legacy formats and platforms to advanced standard formats and operating systems are crucial for both clinical healthcare and biomedical research settings.

Purpose

Our study describes a reproducible, highly scalable, standard framework for a device registry implementation addressing both local data quality components and global linking problems.

Methods and Results

We developed a device registry framework involving the following steps: (1) Data standards definition and representation of the research workflow, (2) Development of electronic case report forms using REDCap (Research Electronic Data Capture), (3) Data collection according to the clinical research workflow and, (4) Data augmentation by enriching the registry database with local electronic health records, governmental database and linked open data collections, (5) Data quality control and (6) Data dissemination through the registry Web site. Our registry adopted all applicable standardized data elements proposed by American College Cardiology / American Heart Association Clinical Data Standards, as well as variables derived from cardiac devices randomized trials and Clinical Data Interchange Standards Consortium. Local interoperability was performed between REDCap and data derived from Electronic Health Record system. The original data set was also augmented by incorporating the reimbursed values paid by the Brazilian government during a hospitalization for pacemaker implantation. By linking our registry to the open data collection repository Linked Clinical Trials (LinkedCT) we found 130 clinical trials which are potentially correlated with our pacemaker registry.

Conclusion

This study demonstrates how standard and reproducible solutions can be applied in the implementation of medical registries to constitute a re-usable framework. Such approach has the potential to facilitate data integration between healthcare and research settings, also being a useful framework to be used in other biomedical registries.     

Length-weight relationships of seven fish species from the laguna del cisne basin (Canelones,Uruguay)

This work provides new length-weight information for seven species of freshwater fishes. The analyzed specimens were collected monthly during a year (April 2018–March 2019) in a coastal lagoon system and its associated streams in southern Uruguay. During each sampling campaign, fishes were captured using gillnets in the lagoon and electrofishing in the streams. This study reports a new maximum size for four species and the first length-weight relationship report for Gymnogeophagus terrapurpura. Length-weight estimates and their confidence intervals are provided for all species.     

Length-weight relationship of twelve mesopelagic fishes from the western Tropical Atlantic

Length-weight relationship parameters were calculated for twelve mesopelagic fish species from the western Tropical Atlantic: Diretmus argenteus, Melamphaes polylepis, Bolinichthys distofax, Diaphus lucidus, Diaphus splendidus, Electrona risso, Hygophum taaningi, Taaningichthys bathyphilus, Melanolagus bericoides, Winteria telescopa, Diplophos taenia, Astronesthes similus. Data was collected off northeastern Brazil from April 9th to May 6th, 2017. Hauls were conducted during day and night at 47 stations by using a micronekton trawl (body mesh: 40 mm, cod-end mesh: 10 mm) from 10 to 1,113 m depth. The material was fixed in a 4% formalin solution for 1 month and then preserved in a 70% alcohol solution for proximally 6 months before processing for length (nearest 0.1 cm of standard length) and weight (nearest 0.01 g of total weight). A new maximum standard length for Winteria telescopa is also provided.     

Molecular Identification of Candida Species in the Oral Microbiota of Individuals with Down Syndrome: A Case–Control Study

Mycopathologia - Candida species are common in the human oral microbiota and may cause oral candidiasis (OC) when the microbiota equilibrium is disturbed. Immunosuppressed individuals are...     

A new species of Hyphessobrycon Durbin (Characiformes: Characidae) from the western Amazon basin in Colombia and Peru

Hyphessobrycon chiribiquete n. sp. is described from the Río Caquetá drainage in Colombia and the Río Ucayali drainage in Peru, western Amazon. The new species is diagnosed from its congeners by having the following combination of characters: a conspicuous narrow midlateral stripe, starting on the sides of the body behind the opercle near the lateral line; lateral stripe overlapped anteriorly with a vertically elongated humeral blotch; inner premaxillary teeth pentacuspid; margin of anal fin falcate in mature males.     

Traffic of Leukocytes and Cytokine Up-regulation in the Central Nervous System in a Murine Model of Neuroparacoccidioidomycosis

Background

Paracoccidioidomycosis is the most important systemic mycosis in South America. In the last decades, it was observed that central nervous system involvement is frequent, occurring in 12.5 % of the cases. The aim of this study was to report the early inflammatory changes associated with an experimental model of neuroparacoccidioidomycosis (NPCM).

Methods

C57BL/6 mice were infected by intracranial route with 10⁶ yeast cells of PB18 strain of Paracoccidioides brasiliensis. Leukocyte–endothelium interactions were assessed by intravital microscopy 1, 2, 4, and 8 weeks post-infection (p.i.). Chemokine/cytokine levels in the brain and histopathological changes were assessed 4 and 8 weeks p.i..

Results

Intravital microscopy analysis revealed a progressive increase in leukocyte recruitment in the vessels of pia mater with a peak 4 weeks p.i. The chemokine CXCL9 was increased at 4 and 8 weeks p.i., while CCL2, CCL3, and CCL5 were increased at 8 weeks p.i. Histopathological analysis revealed the infiltration of inflammatory cells and the development of progressive granulomatous meningoencephalitis. CCL3 levels correlated with clinical manifestations of disease, as measured by the SHIRPA battery.

Conclusions

The experimental model of NPCM showed increased leukocyte recruitment associated with increased expression of chemokines and nervous tissue inflammation which correlated with clinical manifestations of disease.     

Onychomycosis Due to Neoscytalidium Treated with Oral Terbinafine, Ciclopirox Nail Lacquer and Nail Abrasion: A Pilot Study of 25 Patients

Background

Onychomycosis by Neoscytalidium constitutes chronic infection of the nails, and its frequency has increased in recent decades. Currently, no effective standard treatment exists and literature data remain scarce. This work aimed to conduct a pilot project of combined treatment for this infection.

Methods

Thirty patients were divided into three treatment groups: oral terbinafine plus ciclopirox nail lacquer twice a week; ciclopirox nail lacquer twice a week; and ciclopirox nail lacquer 5 days a week, all associated with nail abrasion when required, for 12 months, with 6 months posttreatment follow-up. Clinical and mycological criteria were used for evaluation.

Results

Twenty-five patients completed the study. Significant clinical lesion reduction in disease occurred in all three treatment groups: 21 patients (84 %) entered the study with more than 50 % of diseased nail plate, at the end of treatment, and at 6-month follow-up, 84 and 96 %, respectively, presented less than 25 % nail lesion. Negative microscopy was observed in 36 % of the patients at the end of treatment and in 24 % of the patients at 6-month follow-up. At treatment completion (12 months), culture was negative in 21 patients (84 %) and in 18 (72 %) at follow-up. It was not possible to establish any clinical or mycological statistical differences between groups (p > 0.05). Global medical evaluation upon treatment completion revealed that one patient (4 %) presented complete cure, 8 (32 %) presented partial cure, 16 (64 %) presented therapeutic failure. At the end of follow-up period, 6 patients (24 %) were considered to have recurrence/reinfection.

Conclusions

The results obtained at the 6-month period of follow-up showed marked improvement (96 % of clinical improvement and 72 % of negative culture) of the patients treated for onychomycosis caused by Neoscytalidium in the three tested groups with no statistical differences between them. Multicentric studies with greater number of patients enrolled are necessary to confirm these results.     

Computational study of conformational changes in human 3-hydroxy-3-methylglutaryl coenzyme reductase induced by substrate binding

Abstract

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is mainly involved in the regulation of cholesterol biosynthesis. HMGR catalyses the reduction of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonate at the expense of two NADPH molecules in a two-step reversible reaction. In the present study, we constructed a model of human HMGR (hHMGR) to explore the conformational changes of HMGR in complex with HMG-CoA and NADPH. In addition, we analysed the complete sequence of the Flap domain using molecular dynamics (MD) simulations and principal component analysis (PCA). The simulations revealed that the Flap domain plays an important role in catalytic site activation and substrate binding. The apo form of hHMGR remained in an open state, while a substrate-induced closure of the Flap domain was observed for holo hHMGR. Our study also demonstrated that the phosphorylation of Ser872 induces significant conformational changes in the Flap domain that lead to a complete closure of the active site, suggesting three principal conformations for the first stage of hHMGR catalysis. Our results were consistent with previous proposed models for the catalytic mechanism of hHMGR.

Communicated by Ramaswamy H. Sarma     

Short Sleep Is Associated with Obesity among Truck Drivers

Recent studies suggest that short‐sleep duration is independently associated with obesity in the general population. The population of truck drivers is of particular interest, because they frequently work irregular shifts that in turn are associated with short‐sleep duration. In addition, truck drivers have a high prevalence of sedentary habits, poor diet, and obesity. The present study aimed at verifying the association between sleep patterns and factors associated with obesity in this population. The study sample consisted in 4,878 truck drivers who participated in a campaign promoted by a highway company in the State of São Paulo, Brazil. This campaign offered highway truck drivers a medical and laboratorial evaluation. The truck drivers completed a questionnaire concerning demographic data, sleep duration, consumption of medications, and medical problems, such as diabetes, cardiopathy, and hypertension; as well as the Berlin questionnaire, which is able to discriminate low and high risk for obstructive sleep apnea. Blood samples were collected to measure glucose and cholesterol levels. Also, body weight and height were registered to calculate the body mass index (BMI). The mean age (±SD) of the truck drivers studied was 40±10 years. Out of the truck drivers analyzed, 28.3% (n=1,379) had a BMI ≥30.0 Kg/m² (obesity). Among the 4,878 drivers included in the study, 1,199 (24.6%) were on medications and 334 (6.8%) were diabetic. Drivers (26.9%) with the greater BMI had a short sleep length. The independent factors associated with obesity were sleep duration <8 h/day (OR=1.24), age >40 years (OR=1.20), glucose levels >200 (OR=2.02), cholesterol levels >240 (OR=1.57), snoring (OR=1.74), and hypertension (OR=2.14). Smoking was not associated with obesity (OR=0.69), and diabetes was considered a control variable. In conclusion, this study supports the hypothesis that short sleep duration as well as age >40 years are independently associated with obesity. This particular combination (short‐sleep duration and obesity) is independently associated with several healthcare problems, including high levels of cholesterol, glucose, snoring, and hypertension. However, due to the cross‐sectional nature of this study, no cause–effect relationship can be drawn from these results.