Postmortem imaging reveals patterns of medial temporal lobe vulnerability to tau pathology in Alzheimer's disease.

Our current understanding of the spread and neurodegenerative effects of tau neurofibrillary tangles (NFTs) within the medial temporal lobe (MTL) during the early stages of Alzheimer's Disease (AD) is limited by the presence of confounding non-AD pathologies and the two-dimensional (2-D) nature of conventional histology studies. Here, we combine ex vivo MRI and serial histological imaging from 25 human MTL specimens to present a detailed, 3-D characterization of quantitative NFT burden measures in the space of a high-resolution, ex vivo atlas with cytoarchitecturally-defined subregion labels, that can be used to inform future in vivo neuroimaging studies. Average maps show a clear anterior to poster gradient in NFT distribution and a precise, spatial pattern with highest levels of NFTs found not just within the transentorhinal region but also the cornu ammonis (CA1) subfield. Additionally, we identify granular MTL regions where measures of neurodegeneration are likely to be linked to NFTs specifically, and thus potentially more sensitive as early AD biomarkers.

Trust but Verify: Lessons Learned for the Application of AI to Case-Based Clinical Decision-Making From Postmarketing Drug Safety Assessment at the US Food and Drug Administration.

Adverse drug reactions are a common cause of morbidity in health care. The US Food and Drug Administration (FDA) evaluates individual case safety reports of adverse events (AEs) after submission to the FDA Adverse Event Reporting System as part of its surveillance activities. Over the past decade, the FDA has explored the application of artificial intelligence (AI) to evaluate these reports to improve the efficiency and scientific rigor of the process. However, a gap remains between AI algorithm development and deployment. This viewpoint aims to describe the lessons learned from our experience and research needed to address both general issues in case-based reasoning using AI and specific needs for individual case safety report assessment. Beginning with the recognition that the trustworthiness of the AI algorithm is the main determinant of its acceptance by human experts, we apply the Diffusion of Innovations theory to help explain why certain algorithms for evaluating AEs at the FDA were accepted by safety reviewers and others were not. This analysis reveals that the process by which clinicians decide from case reports whether a drug is likely to cause an AE is not well defined beyond general principles. This makes the development of high performing, transparent, and explainable AI algorithms challenging, leading to a lack of trust by the safety reviewers. Even accounting for the introduction of large language models, the pharmacovigilance community needs an improved understanding of causal inference and of the cognitive framework for determining the causal relationship between a drug and an AE. We describe specific future research directions that underpin facilitating implementation and trust in AI for drug safety applications, including improved methods for measuring and controlling of algorithmic uncertainty, computational reproducibility, and clear articulation of a cognitive framework for causal inference in case-based reasoning.

Prolonged Diabetic Ketoacidosis Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Review of Postmarketing Cases.

OBJECTIVE: To describe reported cases of prolonged or relapsed ketoacidosis (KA) in adults with type 2 diabetes receiving treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors. METHODS: We performed a search of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System and medical literature, to identify our case series and to characterize cases of prolonged KA, relapsed KA, or persistent ketonemia, persistent ketonuria and/or persistent glucosuria in adults receiving SGLT2 inhibitors. RESULTS: The FDA identified 29 unique cases of prolonged or relapsed KA, as well as related terms persistent ketonemia, persistent ketonuria, and persistent glucosuria, in patients receiving SGLT2 inhibitors through July 26, 2022. The patients ranged in age from 26 to 85 years. Treatment duration of KA ranged from 3 to 20 days. There were 7 cases of relapsed KA when insulin was reduced or transitioned to subcutaneous route. Arterial pH value was 7.0 or below in 4 patients, and the median pH was 7.1. Associated factors for prolonged or relapsed KA included surgery, decreased caloric intake, and ketogenic/carbohydrate restricted diet. A total of 62% of the patients were taking 3 or more glycemic control medications including the SGLT2 inhibitor. All patients with sufficient follow-up information recovered. CONCLUSION: Although KA is a well-known risk associated with SGLT2 inhibitors, this case series demonstrated the potential for prolonged or recurrent KA events with serious outcomes. These cases informed updates to FDA's prescribing information to inform prescribers of this risk.

Counter-regulatory RAS peptides: new therapy targets for inflammation and fibrotic diseases?

The renin-angiotensin system (RAS) is an important cascade of enzymes and peptides that regulates blood pressure, volume, and electrolytes. Within this complex system of reactions, its counter-regulatory axis has attracted attention, which has been associated with the pathophysiology of inflammatory and fibrotic diseases. This review article analyzes the impact of different components of the counter-regulatory axis of the RAS on different pathologies. Of these peptides, Angiotensin-(1-7), angiotensin-(1-9) and alamandine have been evaluated in a wide variety of in vitro and in vivo studies, where not only they counteract the actions of the classical axis, but also exhibit independent anti-inflammatory and fibrotic actions when binding to specific receptors, mainly in heart, kidney, and lung. Other functional peptides are also addressed, which despite no reports associated with inflammation and fibrosis to date were found, they could represent a potential target of study. Furthermore, the association of agonists of the counter-regulatory axis is analyzed, highlighting their contribution to the modulation of the inflammatory response counteracting the development of fibrotic events. This article shows an overview of the importance of the RAS in the resolution of inflammatory and fibrotic diseases, offering an understanding of the individual components as potential treatments.

Fibrosing colonopathy associated with cysteamine bitartrate delayed-release capsules in cystinosis patients.

BACKGROUND: The objective of this report is to identify and characterize cases of fibrosing colonopathy, a rare and underrecognized adverse event, associated with cysteamine delayed-release (DR) in patients with nephropathic cystinosis. METHODS: We searched the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the medical literature for postmarketing reports of fibrosing colonopathy associated with cysteamine through August 2, 2023. RESULTS: We identified four cases of fibrosing colonopathy reported with the use of cysteamine DR. The time to onset ranged from 12 to 31 months. In one case, the patient required surgery to have a resection of a section of the strictured colon and a diverting ileostomy. Fibrosing colonopathy was diagnosed by histopathology in two of the cases. CONCLUSIONS: Our case series identified the risk of fibrosing colonopathy in patients taking cysteamine DR and prompted regulatory action by the FDA. As outlined in changes to the U.S. prescribing information for cysteamine DR, healthcare professionals should be aware of the potential risk of fibrosing colonopathy with cysteamine DR, especially as symptoms can be non-specific leading to misdiagnosis or delayed diagnosis. If the diagnosis of fibrosing colonopathy is confirmed, consideration should be given to permanently discontinuing cysteamine DR and switching to cysteamine immediate-release treatment.

Sociodemographic Characteristics of Adverse Event Reporting in the USA: An Ecologic Study.

INTRODUCTION: The Food and Drug Administration Adverse Event Reporting System (FAERS) is a vital source of new drug safety information, but whether adverse event (AE) information collected from these systems adequately captures experiences of the overall United States (US) population is unknown. OBJECTIVE: To examine determinants of consumer AE reporting in the USA. METHODS: Five-year AE reporting rate per 100,000 residents per US county were calculated, mapped, and quartiled for AE reports received directly from consumers between 2011 and 2015. Associations between county-level sociodemographic factors obtained from County Health Rankings and AE reporting rates were evaluated using negative binomial regression. RESULTS: Reporting rates were variable across US counties with > 17.6 reports versus ≤ 5.5 reports/100,000 residents in the highest and lowest reporting quartile, respectively. Controlling for drug utilization, counties with higher reporting rates had higher proportions of individuals age ≥ 65 years (e.g., 2.4% reporting increase per 1% increase in individuals age > 65, incidence rate ratio (IRR): 1.024, 95% confidence interval (CI): 1.017-1.030), higher proportions of females (IRR: 1.027, 95% CI 1.012-1.043), uninsured (IRR: 1.009, 95% CI 1.005-1.013), higher median log household incomes (IRR: 1.897, 95% CI 1.644-2.189) and more mental health providers per 100,000 residents (IRR: 1.003, 95% CI 1.001-1.004). Lower reporting was observed in counties with higher proportions of individuals age ≤ 18 years (IRR: 0.966, 95% CI 0.959-0.974), American Indian or Alaska Native individuals (IRR: 0.991, 95% CI 0.986-0.996), individuals not proficient in English (IRR: 0.978, 95% CI 0.965-0.991), and individuals residing in rural areas within a county (IRR: 0.998, 95% CI 0.997-0.998). CONCLUSIONS: Observed variations in consumer AE reporting may be related to sociodemographic factors and healthcare access. Because these factors may also correspond to AE susceptibility, voluntary AE reporting systems may be suboptimal for capturing emerging drug safety concerns among more vulnerable populations.

El análisis situacional de la teoría fundamentada en salud: una revisión integrativa de la variante postmoderna de la teoría fundamentada

Introducción: La complejidad de la época actual exige tener en cuenta enfoques cuantitativos y cualitativos, datos de diferentes fuentes, métodos múltiples y un crisol de enfoques. Para dar respuesta a esta complejidad se presenta el análisis situacional como método posible. Metodología: Se presenta una revisión integrativa en relación con la variante de análisis situacional, que sigue los siguientes pasos: 1) identificación del problema (pregunta y objetivo de la investigación claramente definidos); 2) búsqueda bibliográfica (estrategia de búsqueda exhaustiva); 3) evaluación de datos; 4) análisis de datos (reducción de datos, visualización, comparación y conclusiones); y 5) presentación de los resultados así como las implicaciones para la práctica, la política públicas y las futuras investigaciones. Resultados: Emerge literatura que da cuenta del análisis situacional como una metodología utilizada en educación en salud, gestión en salud, políticas públicas y atención en salud, que incorpora elementos del análisis de discurso y teorías poshumanistas. Conclusiones: El análisis situacional es una metodología de comprensión de los fenómenos sociales, culturales, sanitarios y de educación, que está disponible y es acorde con la mirada multidimensional requerida para comprender la complejidad del entorno y fluidez de la era que estamos viviendo.

Introdução: A complexidade da realidade atual exige que se levem em conta enfoques quantitativos e qualitativos, dados de diferentes fontes, múltiplos métodos e uma porção de abordagens. Para responder a essa complexidade, a análise situacional é apresentada como um método possível. Metodologia: É apresentada uma revisão integrativa em relação à variante da análise situacional, que segue as seguintes etapas: 1) identificação do problema (questão e objetivo de pesquisa claramente definidos); 2) pesquisa bibliográfica (estratégia de pesquisa abrangente); 3) avaliação dos dados; 4) análise dos dados (redução, visualização, comparação e conclusões dos dados); e 5) apresentação dos resultados, bem como implicações para a prática, políticas públicas e pesquisas futuras. Resultados: Surge uma literatura que ampara a análise situacional como uma metodologia usada na educação em saúde, na gestão da saúde, nas políticas públicas e na assistência à saúde, incorporando elementos da análise do discurso e das teorias pós-humanistas. Conclusões: A análise situacional é uma metodologia de compreensão de fenômenos sociais, culturais, de saúde e de educação, que está disponível e alinhada com a visão multidimensional necessária para entender a complexidade do ambiente e a fluidez da era em que vivemos.

Introduction: The complexity of the current era requires considering quantitative and qualitative perspectives, data from different sources, multiple methods, and a melting pot of approaches. To respond to this complexity, situational analysis is presented as a possible method. Methodology: An integrative review is presented in relation to the variant of situational analysis, which follows the following steps: 1) problem identification (clearly defined research question and objective); 2) literature search (comprehensive search strategy); 3) data assessment; 4) data analysis (data reduction, visualization, comparison, and conclusions); and 5) presentation of results as well as implications for practice, public policy, and future research. Results: Literature emerges that accounts for situational analysis as a methodology used in health education, health management, public policy, and health care, which incorporates elements of discourse analysis and posthumanist theories. Conclusions: Situational analysis is a methodology for understanding social, cultural, health and educational phenomena, which is available and in accordance with the multidimensional view required to understand the complexity of the environment and fluidity of the era we are living in.

A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, a global health issue. Hyperglycemia, in concert with cytokines, activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway to induce inflammation and oxidative stress contributing to renal damage. There is evidence of microRNA-155 (miR-155) involvement in diabetes complications, but the underlying mechanisms are unclear. In this study, gain- and loss-of-function experiments were conducted to investigate the interplay between miR-155-5p and suppressor of cytokine signaling 1 (SOCS1) in the regulation of the JAK/STAT pathway during renal inflammation and DKD. In experimental models of mesangial injury and diabetes, miR-155-5p expression correlated inversely with SOCS1 and positively with albuminuria and expression levels of cytokines and prooxidant genes. In renal cells, miR-155-5p mimic downregulated SOCS1 and promoted STAT1/3 activation, cytokine expression, and cell proliferation and migration. Conversely, both miR-155-5p antagonism and SOCS1 overexpression protected cells from inflammation and hyperglycemia damage. In vivo, SOCS1 gene delivery decreased miR-155-5p and kidney injury in diabetic mice. Moreover, therapeutic inhibition of miR-155-5p suppressed STAT1/3 activation and alleviated albuminuria, mesangial damage, and renal expression of inflammatory and fibrotic genes. In conclusion, modulation of the miR-155/SOCS1 axis protects kidneys against diabetic damage, thus highlighting its potential as therapeutic target for DKD.

Relationship between adverse events prevalence, patient safety culture and patient safety perception in a single sample of patients: a cross-sectional and correlational study.

OBJECTIVE: To assess the relationship between adverse events prevalence (AEP), patient safety culture (PSC) and patient safety perception (PSP). DESIGN: Cross-sectional, ex post facto comparative study on a single sample of patients. SETTING: Four medium-high-level hospitals were included in the study-two public and two private from Zulia State in Venezuela. PARTICIPANTS: 556 medical records and patients were studied for the prevalence and PSP study, and 397 of the healthcare providers involved in the care of these patients were surveyed for the PSC study, at two public and two private hospitals. OUTCOME MEASUREMENT: The primary outcome of this study was the association between AEP, PSC and PSP, and according to hospital funding type, private and public. RESULTS: An inverse association was observed between AEP and its severity and Patient Safety Culture Index (rho=-0.8, p=0.5) (95% CI 0.26-0.10) and Patient Safety Perception Index (rho=-0.6, p=0.18) (95% CI 0.10-0.28), which were protective factors for patient safety. No association was identified between PSC and PSP (rho=0.0001). No statistical differences were identified by hospital type (p=0.93) (95% CI 0.70-1.2). CONCLUSIONS: The analysis of the variable correlations studied (AEP, PSC and PSP) within the same sample offers an interesting and useful perspective. In this sample, although no correlation was observed between the three variables as an interacting set, some correlation patterns were observed between pairs of variables that could guide further studies.

Characterization of Pediatric Reports in the US Food and Drug Administration Adverse Event Reporting System from 2010-2020: A Cross-Sectional Study.

INTRODUCTION: The Food and Drug Administration Adverse Event Reporting System (FAERS) is a database of adverse event (AE) and medication error reports for drugs and therapeutic biologics. Examining trends of reported individual case safety reports (ICSRs) provides context for evaluating safety concerns. OBJECTIVE: Characterize pediatric FAERS ICSRs and compare trends (1) to adult reports; (2) within pediatric subgroups. METHODS: This cross-sectional study examined FAERS ICSRs received between January 1, 2010, through December 31, 2020. Stratified age bands were neonates, infants, younger children, older children, adolescents, and adults. We characterized groups by patient demographic information, suspect products, AEs, and reporter type. RESULTS: From 2010 to 2020, there were 11,258,995 FAERS ICSRs; 3.1% described pediatric patients. Compared to adults, pediatric ICSRs had higher proportions of all serious outcomes except death. Within pediatric subgroups, neonates had the highest proportions of serious outcomes (96.2%) compared to infants, younger children, older children, and adolescents (79.8%, 67.9%, 59.5%, and 52.7%, respectively). Younger pediatric age groups were more likely to have weight information than older age groups but were less likely to include gender information. The most frequently reported AE was off label use for pediatrics and drug ineffective for adults. Products and AEs reported also differed among pediatric subgroups. Neonates, infants, and adolescents had entirely distinct sets of top five product-event combinations. CONCLUSION: Pediatric ICSRs represent a minority of FAERS reports but have distinctly different attributes relative to adult ICSRs. Reporting trends also vary within pediatric subgroups, which highlights the need for unique considerations for pediatric safety surveillance.

High seropositivity against NDO-LID in a group of household contacts of leprosy patients. Are we close to leprosy elimination in Colombia?

INTRODUCTION: Leprosy is a chronic infectious disease caused by two mycobacteria (Mycobacterium leprae and Mycobacterium lepromatosis). The household contacts (HHC) of leprosy index cases are at higher risk of being infected with these mycobacteria. Therefore, serological testing in HHC would be an effective strategy to eliminate leprosy in Colombia. OBJECTIVE: To determine the seroprevalence and factors associated with the infection by M. leprae in HHC. METHODS: An observational study was conducted in 428 HHC located in the Colombian Caribbean, Andean, Pacific, and Amazonian regions. We evaluated the seropositivity and titrations of IgM, IgG, and protein A against NDO-LID. RESULTS: The evaluated HHC showed high seropositivity, precisely 36.9% anti-NDO-LID IgM, 28.3% anti-NDO-LID IgG, and 47.7% protein A. Furthermore, Protein A showed a greater capacity to detect infected individuals than other anti-NDO-LID conjugates (p < 0.0001). This study did not show differences in the seropositivity according to sex or age of the HHC (p > 0.05). Higher seropositivity for IgM was evidenced mainly in HHC located in the Colombian Pacific region (p 0.001). This research did not show differences in the seropositivity for these serological tests between HHC of PB or MB leprosy patients (p > 0.05). CONCLUSION: Leprosy transmission is still active between Colombian HHC. Consequently, controlling leprosy transmission in this population is fundamental to eradicating this disease.

The urban structure and pedestrian injuries: A typological analysis of pedestrian crashes in the city of Hermosillo, Mexico.

OBJECTIVE: In this study, we aim to identify social typologies of pedestrian crashes considering demographics, health impacts, involved vehicle, temporality of the collision, and place of impact in Hermosillo, Mexico. METHODS: A socio-spatial analysis was performed by using local urban planning information and vehicles-pedestrian crashes records collected by the police department (N = 950) between 2014 and 2017. Multiple Correspondence Analysis and Hierarchical Cluster Analysis were used to determine typologies. Geographical distribution of typologies was obtained with spatial analysis techniques. RESULTS: The results suggest there are four typologies, which portray the physical vulnerability of pedestrians, which reflect the vulnerability to collisions associated to the variables age, gender, and street speed limits. Findings show that children are more likely to be injured during weekends in residential zones (Typology 1), while older females are more likely to be injured during the first three days of the week (Monday - Wednesday) in the downtown area (Typology 2). Injured males during the afternoon in arterial streets represented the most frequent cluster (Typology 3). Also, males were likely to be severely injured by heavy trucks during nighttime in peri-urban areas (Typology 4). These findings indicate that vulnerability and risk exposure vary according to the type of pedestrian involved in the crash, which are linked to the types of places they visit. CONCLUSIONS: The design of the built environment plays a major role in the number of pedestrian injuries particularly when it favors motor vehicles over pedestrians or non-motorized vehicles. Because traffic crashes are considered preventable events, cities must embrace a diversity of mobility modes and incorporate the appropriate infrastructures that safeguard the lives of all their travelers, especially pedestrians.

Assessment of the Impact of Mandated Postmarketing Pediatric-Focused Safety Reviews on Safety-Related Regulatory Actions 2013-2019.

The US Food and Drug Administration's (FDA's) routine postmarketing drug safety monitoring may lead to safety-related labeling changes for identified risks. Additionally, the Best Pharmaceuticals for Children Act (BPCA) and Pediatric Research Equity Act (PREA) require the FDA to conduct postmarket pediatric-focused safety reviews of adverse events. The purpose of these pediatric reviews is to identify risks associated with drug or biological products 18 months after the FDA approves a pediatric labeling change pursuant to studies conducted under the BPCA or PREA. These reviews are presented to the FDA Pediatric Advisory Committee (PAC) or publicly posted on FDA's website. The aim of this study was to evaluate the impact of pediatric reviews prompted by BPCA/PREA from October 1, 2013, to September 30, 2019. The impact was quantified by the number of new safety signals identified and the subsequent safety-related labeling changes resulting from pediatric reviews relative to safety-related labeling changes triggered by other data sources. Among 163 products with at least one pediatric review completed, a new safety signal that resulted in a safety-related labeling change was found for 5 of these products (representing 3 active ingredients); none described risks specific to the pediatric population. Between October 2013 and September 2021, there were 585 safety-related labeling changes implemented for products with at least one completed pediatric review. Less than 1% of 585 safety-related labeling changes were the result of a mandated pediatric review. Our study suggests that mandated pediatric reviews conducted 18 months after a pediatric labeling change provided minimal value over other postmarket safety surveillance activities.

A case of Rothmund-Thomson syndrome originally thought to be a case of Bloom syndrome.

Rothmund-Thomson syndrome, a heterogeneous genodermatosis with autosomal recessive hereditary pattern, is an uncommon cancer susceptibility genetic syndrome. To date, only 400 cases have been reported in the literature, and the severity of the features varies among individuals with the condition. Here, we describe a 55-year-old male who had been diagnosed with Bloom Syndrome during childhood due to the suggestive physical features such as short stature, chronic facial erythema, poikiloderma in face and extremities, microtia and microcephaly. However, the genetic test demonstrated that the patient carried two pathogenic variants resulting in compound heterozygous in the RECQL4 gene (c.2269C>T and c.2547_2548delGT). He subsequently developed a calcaneal osteosarcoma, which was successfully treated, and has currently been oncologic disease-free for 3 years.

Monitoring Drug Safety in Pregnancy with Scan Statistics: A Comparison of Two Study Designs.

BACKGROUND: Traditional surveillance of adverse infant outcomes following maternal medication exposures relies on pregnancy exposure registries, which are often underpowered. We characterize the statistical power of TreeScan, a data mining tool, to identify potential signals in the setting of perinatal medication exposures and infant outcomes. METHODS: We used empirical data to inform background incidence of major congenital malformations and other birth conditions. Statistical power was calculated using two probability models compatible with TreeScan, Bernoulli and Poisson, while varying the sample size, magnitude of the risk increase, and incidence of a specified outcome. We also simulated larger referent to exposure matching ratios when using the Bernoulli model in the setting of fixed N:1 propensity score matching. Finally, we assessed the impact of outcome misclassification on power. RESULTS: The Poisson model demonstrated greater power to detect signals than the Bernoulli model across all scenarios and suggested a sample size of 4,000 exposed pregnancies is needed to detect a twofold increase in risk of a common outcome (approximately 8 per 1,000) with 85% power. Increasing the fixed matching ratio with the Bernoulli model did not reliably increase power. An outcome definition with high sensitivity is expected to have somewhat greater power to detect signals than an outcome definition with high positive predictive value. CONCLUSIONS: Use of the Poisson model with an outcome definition that prioritizes sensitivity may be optimal for signal detection. TreeScan is a viable method for surveillance of adverse infant outcomes following maternal medication use.

Coping Strategies and Social Skills of School-Aged Children: Association with Performance-Based Measures and Behavioral Ratings of Executive Function.

The aim of the present study was to analyze the association of executive function (EF) based on performance-based measures and behavioral ratings (Behavior Rating Inventory of Executive Function-2 [BRIEF-2]) with coping and social skills in children. To this end, we first examined the structure of EF based on performance-based measures in a Chilean sample of 275 girls and boys aged 8-12 years. Confirmatory factor analysis showed the best fit for the three-factor solution, with (1) working memory, (2) cognitive flexibility, and (3) inhibition as separate but related components. Selective associations were found between EF and coping and social skills, with differences according to the assessment method for EF. Specifically, only inhibitory control was related to the constructs when EF was assessed based on the performance-based measures. Meanwhile, EF assessed based on the behavioral ratings, including all dimensions of the BRIEF-2, were selectively associated with coping and social skills, mainly when the evaluation was performed by the teachers. Finally, structural equation models (SEM) showed that inhibitory control had direct effects on coping and social skills. However, when EF was assessed based on ratings, differences were observed between the teachers' and parents' reports. These results reveal the varying effects of EF on coping and social skills depending not only on the modality of assessment but also on the informant, emphasizing the relevance of comprehensive EF evaluation; they also provide relevant information regarding the relationship between EF and coping and social skills in children.

Novel methods for pregnancy drug safety surveillance in the FDA Sentinel System.

PURPOSE: It is a priority of the US Food and Drug Administration (FDA) to monitor the safety of medications used during pregnancy. Pregnancy exposure registries and cohort studies utilizing electronic health record data are primary sources of information but are limited by small sample sizes and limited outcome assessment. TreeScan™, a statistical data mining tool, can be applied within the FDA Sentinel System to simultaneously identify multiple potential adverse neonatal and infant outcomes after maternal medication exposure. METHODS: We implemented TreeScan using the Sentinel analytic tools in a cohort of linked live birth deliveries and infants nested in the IBM MarketScan® Research Database. As a case study, we compared first trimester fluoroquinolone use and cephalosporin use. We used the Bernoulli and Poisson TreeScan statistics with compatible propensity score-based study designs for confounding control (matching and stratification) and used multiple propensity score models with various strategies for confounding control to inform best practices. We developed a hierarchical outcome tree including major congenital malformations and outcomes of gestational length and birth weight. RESULTS: A total of 1791 fluoroquinolone-exposed and 8739 cephalosporin-exposed mother-infant pairs were eligible for analysis. Both TreeScan analysis methods resulted in single alerts that were deemed to be due to uncontrolled confounding or otherwise not warranting follow-up. CONCLUSIONS: In this implementation of TreeScan using Sentinel analytic tools, we did not observe any new safety signals for fluoroquinolone use in the first trimester. TreeScan, with tailored or high-dimensional propensity scores for confounding control, is a valuable tool in addition to current safety surveillance methods for medications used during pregnancy.

Guía Técnica: Procedimiento para la determinación de la hemoglobina mediante hemoglobinómetro portátil / Technical Guide: Procedure for determining hemoglobin using a portable hemoglobinometer

Los principales cambios en la presente guía contemplan una mejor distribución en la presentación de los procedimientos priorizando los que involucran a los niños menores de un año, se actualiza los valores de concentración de hemoglobina en cuanto a la severidad. La atención de la salud requiere de una permanente mejora para prestar un servicio de calidad que incluye información confiable a partir de los instrumentos de medición como en este caso la determinación de la hemoglobina, por lo que esperamos esta segunda edición, sea de utilidad

Benzonatate Exposure Trends and Adverse Events.

BACKGROUND AND OBJECTIVES: Adverse events (AE), including death, occur in children with benzonatate use. This study aims to understand recent trends in benzonatate exposure and clinical consequences in pediatric patients. METHODS: This retrospective analysis of data from IQVIA pharmacy drug dispensing, National Poison Data System, National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project, FDA Adverse Event Reporting System, and the medical literature evaluated exposure trends and medication-related AEs with benzonatate. Trends for comparator narcotic and nonnarcotic antitussive medications were analyzed where possible for context. RESULTS: During the study period, pediatric benzonatate prescription utilization increased but remained low compared with pediatric utilization of dextromethorphan-containing prescription antitussive medications. Among the 4689 pediatric benzonatate exposure cases reported to US poison control centers from 2010 to 2018, 3727 cases (80%) were for single-substance exposures. Of these, 3590 cases (77%) were unintentional exposures and most involved children 0 to 5 years old (2718 cases, 83%). Cases involving intentional benzonatate exposure increased among children 10 to 16 years old with a more pronounced increase for multiple-substance exposures. Most benzonatate cases involving misuse or abuse were for children 10 to 16 years old (59 cases, 61%). The proportion of cases with serious adverse effects was low. There were few cases annually of serious AEs with benzonatate in children. CONCLUSIONS: There were rising patterns of unintentional ingestion of benzonatate in children 0 to 5 years old and intentional benzonatate ingestion in children 10 to 16 years old. Rational prescribing and improved provider and caregiver awareness of benzonatate toxic effects may reduce risks associated with benzonatate exposure.