A 2-pyridone amide inhibitor of transcriptional activity in Chlamydia trachomatis.

Chlamydia trachomatis is a strict intracellular bacterium that causes sexually transmitted infections and eye infections that can lead to life-long sequelae. Treatment options are limited to broad-spectrum antibiotics that disturb the commensal flora and contribute to selection of antibiotic-resistant bacteria. Hence, development of novel drugs that specifically target C. trachomatis would be beneficial. 2-pyridone amides are potent and specific inhibitors of Chlamydia infectivity. The first generation compound KSK120, inhibits the developmental cycle of Chlamydia resulting in reduced infectivity of progeny bacteria. Here, we show that the improved, highly potent second-generation 2-pyridone amide KSK213 allowed normal growth and development of C. trachomatis and the effect was only observable upon re-infection of new cells. Progeny elementary bodies (EBs) produced in the presence of KSK213 were unable to activate transcription of essential genes in early development and did not differentiate into the replicative form, the reticulate body (RB). The effect was specific to C. trachomatis since KSK213 was inactive in the closely related animal pathogen C. muridarum and in C. caviae The molecular target of KSK213 may thus be different in C. trachomatis or non-essential in C. muridarum and C. caviae Resistance to KSK213 was mediated by a combination of amino acid substitutions in both DEAD/DEAH RNA helicase and RNAse III, which may indicate inhibition of the transcriptional machinery as the mode of action. 2-pyridone amides provide a novel antibacterial strategy and starting points for development of highly specific drugs for C. trachomatis infections.

Influence of antrum size on gastric emptying and weight-loss outcomes after laparoscopic sleeve gastrectomy (preliminary analysis of a randomized trial).

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has increased in popularity in recent years as a definitive bariatric procedure. Despite its growing popularity worldwide, the surgical technique is not well standardized. There is a lack of evidence on the matter of the antrum size and its relation to gastric emptying and weight-loss outcomes. The aim of the study is to evaluate the influence of antrum size over gastric emptying and weight-loss outcomes. METHODS: Twenty-five patients were prospectively randomized according to the distance between the first firing and the pylorus: AR group (antrum resection-2 cm from the pylorus) and AP group (antrum preservation-5 cm from the pylorus). Gastric emptying (%GE) was evaluated by a gastric emptying scintigraphy before surgery, 2 months and 1 year after LSG. Antrum volume was measured using a MultiSlice CT Scan performed 2 months and 1 year after surgery. The percent of excess weight loss (%EWL) was calculated after 1 year follow-up. RESULTS: At 2 months after LSG the mean %GE was 69.7 ± 18 in the AR group and 72.8 ± 20 in the AP group (p = 0.69). At 1 year it was 66.5 ± 21 and 74.2 ± 16 in the AR and AP groups, respectively (p = 0.30). A significant accelerated gastric emptying was observed at 2 months (p = 0.025) and at 1 year (p = 0.013) in the AP group. Meanwhile in the AR group this increase was not significant (p = 0.12 at 2 months and p = 0.21 at 1 year). Differences regarding the %EWL between groups were no statistically significant (p = 0.74). CONCLUSIONS: After LSG there is a global tendency to an accelerated gastric emptying, although only significant in the antrum preservation group; however, no differences were observed regarding the %EWL between groups after 1 year follow-up.

Rationale, design and preliminary results of the GALIPEMIAS study (prevalence and lipid control of familial dyslipidemia in Galicia, northwest Spain).

AIMS: There is little information on the familial nature of dyslipidemias in the Spanish population. This knowledge could have potential diagnostic and treatment implications. The objective of the GALIPEMIAS study was to determine the prevalence of familial dyslipidemia in Galicia, as well as determine the degree of lipid control in the participants. Prevalence of atherosclerotic cardiovascular disease (ASCVD) was also estimated. This paper presents the design, methodology and selected preliminary results. METHODOLOGY: A cross-sectional study was performed in the population aged ≥18 years using cluster sampling and then random sampling. A sample of 1000 subjects was calculated and divided into three sequential phases with a specific methodology for each one. Phase I: selection of subjects from the general population and collection of informed consent documents; Phase II: collection of data from the digital clinical history to select subjects with dyslipidemia according to study criteria; Phase III: personal interview, blood analysis, family tree, and definitive diagnosis of dyslipidemia. Prevalence of different diseases and active medication was analysed. Corrected prevalence (to the reference population) of different risk factors and ASCVD was estimated. RESULTS: Phase I participation was 89.5%. We extracted complete information from 93% of the participants (Phase II). According to the study's own criteria, 56.5% (n = 527) of the participants had some form of dyslipidemia and almost 33.7% of them had familial dyslipidemia with autosomal dominant inherit pattern. The corrected prevalence of ASCVD was 5.1% (95% CI 3.1-7.2). CONCLUSIONS: Dyslipidemia was the most prevalent cardiovascular risk factor in our population with an autosomal dominant inheritance pattern in one out of every three dyslipidemia cases. Approximately, 5.1% of the sample population aged ≥18 has suffered an episode of ACVD.

N-Acylated Derivatives of Sulfamethoxazole Block Chlamydia Fatty Acid Synthesis and Interact with FabF.

The type II fatty acid synthesis (FASII) pathway is essential for bacterial lipid biosynthesis and continues to be a promising target for novel antibacterial compounds. Recently, it has been demonstrated that Chlamydia is capable of FASII and this pathway is indispensable for Chlamydia growth. Previously, a high-content screen with Chlamydia trachomatis-infected cells was performed, and acylated sulfonamides were identified to be potent growth inhibitors of the bacteria. C. trachomatis strains resistant to acylated sulfonamides were isolated by serial passage of a wild-type strain in the presence of low compound concentrations. Results from whole-genome sequencing of 10 isolates from two independent drug-resistant populations revealed that mutations that accumulated in fabF were predominant. Studies of the interaction between the FabF protein and small molecules showed that acylated sulfonamides directly bind to recombinant FabF in vitro and treatment of C. trachomatis-infected HeLa cells with the compounds leads to a decrease in the synthesis of Chlamydia fatty acids. This work demonstrates the importance of FASII for Chlamydia development and may lead to the development of new antimicrobials.

User-centered design improves the usability of drug-drug interaction alerts: Experimental comparison of interfaces.

Clinical Decision Support Systems can alert health professionals about drug interactions when they prescribe medications. The Hospital Italiano de Buenos Aires in Argentina developed an electronic health record with drug-drug interaction alerts, using traditional software engineering techniques and requirements. Despite enhancing the drug-drug interaction knowledge database, the alert override rate of this system was very high. We redesigned the alert system using user-centered design (UCD) and participatory design techniques to enhance the drug-drug interaction alert interface. This paper describes the methodology of our UCD. We used crossover method with realistic, clinical vignettes to compare usability of the standard and new software versions in terms of efficiency, effectiveness, and user satisfaction. Our study showed that, compared to the traditional alert system, the UCD alert system was more efficient (alerts faster resolution), more effective (tasks completed with fewer errors), and more satisfying. These results indicate that UCD techniques that follow ISO 9241-210 can generate more usable alerts than traditional design.

Characterising endourologist learning curve during percutaneous nephrolithotomy: implications on occupational dose and patients.

In this study we have characterised the learning curve for percutaneous nephrolithotomy procedures over 301 cases for six years. Different surrogate parameters of clinical expertise have been used, such as dose area product, total procedure time, fluoroscopy time and personal equivalent doses. In addition, two different endourologists have been monitored; one of whom had specific Radiation Protection training (ICRP 85). Eye lens dose was estimated from thermoluminescent dosimeters. Significant differences were observed between both endourologists, especially in the fluoroscopy time. Finally, both entrance skin dose and effective doses of patients have been determined.

Evaluation and optimization of occupational eye lens dosimetry during positron emission tomography (PET) procedures.

The last recommendations of the International Commission on Radiological Protection for eye lens dose suggest an important reduction on the radiation limits associated with early and late tissue reactions. The aim of this work is to quantify and optimize the eye lens dose associated to nurse staff during positron emission tomography (PET) procedures. PET is one of the most important diagnostic methods of oncological and neurological cancer disease involving an important number of workers exposed to the high energy isotope F-18. We characterize the relevant stages as preparation and administration of monodose syringes in terms of occupational dose. A direct reading silicon dosimeter was used to measure the lens dose to staff. The highest dose of radiation was observed during preparation of the fluorodesoxyglucose (FDG) syringes. By optimizing a suitable vials' distribution of FDG we find an important reduction in occupational doses. Extrapolation of our data to other clinical scenarios indicates that, depending on the work load and/or syringes activity, safety limits of the dose might be exceeded.

Improving Waiting Time for Chemotherapy with Ahead-of-Time Drug Preparation.

Waiting time for chemotherapy infusion is a fundamental factor to measure quality of care. It has been shown that a prolonged waiting time is related to a higher incidence of anticipatory nausea and poor patient adherence to scheduled appointments and recommended oncology treatment programs. Some chemotherapy regimens can be prepared hours ahead-of-time, due to long stability. We aimed to study the effect of an informatic-led workflow redesign intervention, facilitating workflow changes in the Oncology Pharmacy, on patient waiting time. This intervention included changes on EHR processes and the chemotherapy CPOE. Their main effect was allowing ahead-of-time preparation of selected chemotherapy regimes. We conducted a cross sectional study, comparing waiting times pre and post intervention periods. A total of 4600 programmed chemotherapy episodes were included. We found a 26.5 % decrease in the mean wait time in the post intervention period (p > 0.02). We were able to show a decrease in waiting time and a measurable impact of the intervention. This evaluation produced valuable and actionable data for Oncology units and adds a valuable, Latin American experience to the literature.

Integrating Dermoscopic Images into PACS Using DICOM and Modality Worklist.

Dermatology is one of the medical fields outside the radiology service that uses image acquisition and analysis in its daily medical practice, mostly through digital dermoscopy imaging modality. The acquisition, transfer, and storage of dermatology images has become an important issue to resolve. We aimed to describe our experience in integrating dermoscopic images into PACS using DICOM as a guide for the health informatics and dermatology community. During 2022 we integrated the video dermoscopy equipment through a strategic plan with an 8-step procedure. We used the DICOM standard with Modality Worklist and Storage commitment. Three systems were involved (video dermoscopy software, the EHR, and PACS). We identified critical steps and faced many challenges, such as the lack of a final model of DICOM standard for dermatology images.

Unscheduled Emergency Department Revisits Within 48 Hours of Discharge.

This study aimed to analyze early revisits (within 48 hours of discharge) in an Emergency Department. Among the 178,295 visits, 11,686 were revisits, resulting in a rate of 6.55% (95%CI 6.43-6.67). A total of 1,410 revisits required hospitalization, and 252 were due to preventable errors (17.87%). These errors were mainly related to an inadequate therapeutic plan at discharge (47.22%), an incomplete diagnostic process (29.37%), and misdiagnoses (13.10%). These findings represent a technology-enabled clinical audit tool. Electronic Healthcare Records have the potential to: provide quality metrics of hospital performance, help to keep revisit rates updated (assessment through a real-time dashboard), and improve clinical management (by transparency initiatives about errors, and a supportive learning environment regarding lessons learned).

Single incision versus reduced port splenectomy--searching for the best alternative to conventional laparoscopic splenectomy.

BACKGROUND: Laparoscopic splenectomy (LS) is a well accepted approach for the treatment of multiple hematologic diseases. Single port access splenectomy (SPAS) emphasizes the concept of surgery through one small incision. The reduced port access splenectomy (RPAS) entails the use of fewer trocars of smaller sizes. The aim of this study was to compare the clinical outcomes after LS, SPAS, and RPAS, and to analyze the aesthetic result and patient satisfaction. METHODS: We included patients who underwent LS (group 1, n = 15), SPAS (group 2, n = 8), and RPAS (group 3, n = 10) between June 2008 and February 2012, whose final spleen weight was less of 500 g. The outcome parameters analyzed were operative time, need of additional trocars, blood loss, blood transfusion, weight of the spleen, postoperative complications, and duration of hospital stay. To evaluate the cosmetic result, patients were asked to take the Body Image Questionnaire. RESULTS: Patients in group 3 were younger than group 1. Operative time was significantly longer in group 2 compared to groups 1 and 3 (83 ± 19 vs. 131 ± 43 vs. 81 ± 22 min, p = 0.01). There was no need to convert to open surgery in any group, nor were there differences in intra- or postoperative outcome. There were no differences between the groups in relation to the analgesic requirements. Twenty-two out of the 33 patients answered the questionnaire. There was a significant advantage in group 2 and 3 in the body image index with respect to group 1. There were no differences between groups 2 and 3 (7.3 ± 2.8 vs. 5.8 ± 1.3 vs. 5.1 ± 0.4, p < 0.02). CONCLUSIONS: RPAS is a good alternative to LS and SPAS. It improves the aesthetic results as compared to LS, whereas minimizes the technical challenges faced with SPAS.

Physicians perceptions of an educational support system integrated into an electronic health record.

The purpose of this study is to determine the perceptions by physicians of an educational system integrated into an electronic health record (EHR). Traditional approaches to continuous medical education (CME) have not shown improvement in patient health care outcomes. Hospital Italiano de Buenos Aires (HIBA) has implemented a system that embeds information pearls into the EHR, providing learning opportunities that are integrated into the patient care process. This study explores the acceptability and general perceptions of the system by physicians when they are in the consulting room. We interviewed 12 physicians after one or two weeks of using this CME system and we performed a thematic analysis of these interviews. The themes that emerged were use and ease of use of the system; value physicians gave to the system; educational impact on physicians; respect for the individual learning styles; content available in the system; and barriers that were present or absent for using the CME system. We found that the integrated CME system developed at HIBA was well accepted and perceived as useful and easy to use. Future work will involve modifications to the system interface, expansion of the content offered and further evaluation.

A multi-firearm, multi-orientation audio dataset of gunshots.

Early detection of firearm discharge has become increasingly critical for situational awareness in both civilian and military domains. The ability to determine the location and model of a discharged firearm is vital, as this can inform effective response plans. To this end, several gunshot audio datasets have been released that aim to facilitate gunshot detection and classification of a discharged firearm based on acoustic signatures. However, these datasets often suffer from a lack of variety in the orientations of recording devices around the source of the gunshot. Additionally, these datasets often suffer from the absence of proper time synchronization, which prevents the usage of these datasets for determining the Direction of Arrival (DoA) of the sound. In this paper, we present a multi-firearm, multi-orientation time-synchronized audio dataset collected in a semi-controlled real-world setting - providing us a degree of supervision - using several edge devices positioned in and around an outdoor firing range.

Neural inference at the frontier of energy, space, and time.

Computing, since its inception, has been processor-centric, with memory separated from compute. Inspired by the organic brain and optimized for inorganic silicon, NorthPole is a neural inference architecture that blurs this boundary by eliminating off-chip memory, intertwining compute with memory on-chip, and appearing externally as an active memory chip. NorthPole is a low-precision, massively parallel, densely interconnected, energy-efficient, and spatial computing architecture with a co-optimized, high-utilization programming model. On the ResNet50 benchmark image classification network, relative to a graphics processing unit (GPU) that uses a comparable 12-nanometer technology process, NorthPole achieves a 25 times higher energy metric of frames per second (FPS) per watt, a 5 times higher space metric of FPS per transistor, and a 22 times lower time metric of latency. Similar results are reported for the Yolo-v4 detection network. NorthPole outperforms all prevalent architectures, even those that use more-advanced technology processes.

Clinical Decision Support System for PIM in Elderly Patients: Implementation and Initial Evaluation in Ambulatory Care.

The high prevalence of PIMs in elderly is a major healthcare concern and indicates the need for medication monitoring systems. Most PIM CDSS have shown positive effects respecting PIM prescription but these results were more consistently in hospital settings compared with ambulatory care. We describe the post-implementation evaluation of a PIM CDSS for general practitioners (GP) in the ambulatory setting and explore GP interactions with the PIM alerts. The CDSS generated 3218 unique alerts and involved 2863 elderly patients. Benzodiazepines was the drug with the most alerts triggered. Only 129 (4 %) were opened by GP during patient appointments. We need to develop an understanding of how alerts should be designed and display information to support the workflow of general practitioners. Pos-implementation evaluations are the key of CDSS improvements.

Recurrence of Hypoglycemia in Hospitalized Adult Patients in Non-Critical Areas: An Opportunity to Improve Patient Care Using Electronic Health Records.

Electronic Health Records offer an opportunity to improve patient care (in terms of quality and/or safety) by making available patient health information stored in a single Clinical Data Repository. We aimed to estimate the frequency of hypoglycemic recurrences in hospitalized adult patients in non-critical areas. We designed a cross sectional study with hospitalizations between 2017 and 2018, which included patients with at least one hypoglycemia health record (defined as a value <70 mg/dL, either by capillary glycemic monitoring or serum measurement). Recurrence was defined as those who presented a second event, with at least 2 hours of difference. We included 1884 patients, and 573 presented recurrences, yielding a global prevalence of 30.41% (95%CI 28.34-32.54). Due to the high frequency, it is important to identify vulnerable populations, to implement preventive measures to assist clinicians for decision-making tasks, as a clinical decision support system.

Adherence to Growth Hormone Treatment Using a Connected Device in Latin America: Real-World Exploratory Descriptive Analysis Study.

BACKGROUND: Recombinant human growth hormone (rhGH) therapy is an effective treatment for children with growth disorders. However, poor outcomes are often associated with suboptimal adherence to treatment. OBJECTIVE: The easypod connected injection device records and transmits injection settings and dose data from patients receiving rhGH. In this study, we evaluated adherence to rhGH treatment, and associated growth outcomes, in Latin American patients. METHODS: Adherence and growth data from patients aged 2-18 years from 12 Latin American countries were analyzed. Adherence data were available for 6207 patients with 2,449,879 injections, and growth data were available for 497 patients with 2232 measurements. Adherence was categorized, based on milligrams of rhGH injected versus milligrams of rhGH prescribed, as high (≥85%), intermediate (>56%-<85%), or low (≤56%). Transmission frequency was categorized as high (≥1 per 3 months) or low (<1 per 3 months). Chi-square tests were applied to study the effect of pubertal status at treatment start and sex on high adherence, and to test differences in frequency transmission between the three adherence levels. Multilevel linear regression techniques were applied to study the effect of adherence on observed change in height standard deviation score (∆HSDS). RESULTS: Overall, 68% (4213/6207), 25% (n=1574), and 7% (n=420) of patients had high, intermediate, and low adherence, respectively. Pubertal status at treatment start and sex did not have a significant effect on high adherence. Significant differences were found in the proportion of patients with high transmission frequency between high (2018/3404, 59%), intermediate (608/1331, 46%), and low (123/351, 35%) adherence groups (P<.001). Adherence level had a significant effect on ∆HSDS (P=.006). Mean catch-up growth between 0-24 months was +0.65 SD overall (+0.52 SD in patients with low/intermediate monthly adherence and +0.69 SD in patients with high monthly adherence). This difference translated into 1.1 cm greater catch-up growth with high adherence. CONCLUSIONS: The data extracted from the easypod Connect ecosystem showed high adherence to rhGH treatment in Latin American patients, with positive growth outcomes, indicating the importance of connected device solutions for rhGH treatment in patients with growth disorders.

Can CPOE Based on Electronic Order Sets Cause Unintended Consequences (Expensive and Unnecessary Tests) at the Emergency Department?

Computerized Provider Order Entry (CPOE) systems may cause unintended consequences. This study aimed to describe the on-going system for CPOE order sets, and to explore an economic evaluation at the Emergency Department. First, we developed a costs dashboard which showed us the significant and excessive use of medical tests per consultation. We identified the top 10 most widely used and most expensive tests. Additionally we noticed that the labs seemed to continually increase. Then, we found that 27% of the consultations have at least one item of laboratory practice between January and February 2020, and this represents more than 80% of the consultation costs. Health care spending has reached epic proportions globally. We think that it is time to rethink effective strategies. Maybe it is time to deactivate/remove electronic order sets (EOSs) and the functionality to develop and create their own "private" order sets, in order to eliminate waste and inefficiencies.

Mobile Application for Home Healthcare: Physician's Expectations and Perceptions.

The aging of the population and the increase in chronic diseases generated the need for care at home for pluripathological patients, who can no longer access outpatient care due to functional and social problems. The use of Electronic Medical Records (EMR) improves continuity of care, simplifies data collection, decreases overhead costs, and reduces mortality in chronically ill patients. The use of an App to check and record data in the EMR during the home visit saves time for professionals and helps to avoid transcription errors. This article shares our experience with the design and implementation of a Mobile Application with EMR functionalities for the Homecare setting of the Hospital Italiano de Buenos Aires network.

An Improved Immunization Record to Support Vaccination During the COVID-19 Pandemic at a University Hospital in Argentina.

WHO and UNICEF highlight vaccination as the most cost-effective method of prevention of infectious diseases. An effective public health strategy requires efficient tracking of vaccination to assess coverage, safety, and efficacy of these vaccines. Paper-based immunization records are still being used in most low and middle-income countries. Adequate Electronic Logistic Management Information Systems, Immunization Registries and Records are crucial for proper data collection and analysis, and for making better decisions at an individual and at a population level. In this paper we share our experience in the redesign of an interoperable immunization record to track vaccination, including the recently developed vaccines for the novel coronavirus SARS-CoV-2 (COVID-19).