Importance: Atrial fibrillation and obesity are common, and both are increasing in prevalence. Obesity is associated with failure of cardioversion of atrial fibrillation using a standard single set of defibrillator pads, even at high output. Objective: To compare the efficacy and safety of dual direct-current cardioversion (DCCV) using 2 sets of pads, with each pair simultaneously delivering 200 J, with traditional single 200-J DCCV using 1 set of pads in patients with obesity and atrial fibrillation. Design, Setting, and Participants: This was a prospective, investigator-initiated, patient-blinded, randomized clinical trial spanning 3 years from August 2020 to 2023. As a multicenter trial, the setting included 3 sites in Louisiana. Eligibility criteria included body mass index (BMI) of 35 or higher (calculated as weight in kilograms divided by height in meters squared), age 18 years or older, and planned nonemergent electrical cardioversion for atrial fibrillation. Patients who met inclusion criteria were randomized 1:1. Exclusions occurred due to spontaneous cardioversion, instability, thrombus, or BMI below threshold. Interventions: Dual DCCV vs single DCCV. Main Outcomes and Measures: Return to sinus rhythm, regardless of duration, immediately after the first cardioversion attempt of atrial fibrillation, adverse cardiovascular events, and chest discomfort after the procedure. Results: Of 2079 sequential patients undergoing cardioversion, 276 met inclusion criteria and were approached for participation. Of these, 210 participants were randomized 1:1. After exclusions, 200 patients (median [IQR] age, 67.6 [60.1-72.4] years; 127 male [63.5%]) completed the study. The mean (SD) BMI was 41.2 (6.5). Cardioversion was successful more often with dual DCCV compared with single DCCV (97 of 99 patients [98%] vs 87 of 101 patients [86%]; P = .002). Dual cardioversion predicted success (odds ratio, 6.7; 95% CI, 3.3-13.6; P = .01). Patients in the single cardioversion cohort whose first attempt failed underwent dual cardioversion with all subsequent attempts (up to 3 total), all of which were successful: 12 of 14 after second cardioversion and 2 of 14 after third cardioversion. There was no difference in the rating of postprocedure chest discomfort (median in both groups = 0 of 10; P = .40). There were no cardiovascular complications. Conclusions and Relevance: In patients with obesity (BMI ≥35) undergoing electrical cardioversion for atrial fibrillation, dual DCCV results in greater cardioversion success compared with single DCCV, without any increase in complications or patient discomfort. Trial Registration: ClinicalTrials.gov Identifier: NCT04539158.
The role for routine whole genome and transcriptome analysis (WGTA) for poor prognosis pediatric cancers remains undetermined. Here, we characterize somatic mutations, structural rearrangements, copy number variants, gene expression, immuno-profiles and germline cancer predisposition variants in children and adolescents with relapsed, refractory or poor prognosis malignancies who underwent somatic WGTA and matched germline sequencing. Seventy-nine participants with a median age at enrollment of 8.8 y (range 6 months to 21.2 y) are included. Germline pathogenic/likely pathogenic variants are identified in 12% of participants, of which 60% were not known prior. Therapeutically actionable variants are identified by targeted gene report and whole genome in 32% and 62% of participants, respectively, and increase to 96% after integrating transcriptome analyses. Thirty-two molecularly informed therapies are pursued in 28 participants with 54% achieving a clinical benefit rate; objective response or stable disease ≥6 months. Integrated WGTA identifies therapeutically actionable variants in almost all tumors and are directly translatable to clinical care of children with poor prognosis cancers.
DNA Copy Number Variations , Gene Expression Profiling , Neoplasms , Humans , Child , Neoplasms/genetics , Neoplasms/therapy , Female , Adolescent , Male , Child, Preschool , Prognosis , Gene Expression Profiling/methods , Infant , Transcriptome , Young Adult , Whole Genome Sequencing , Germ-Line Mutation , Mutation , Genome, Human/genetics , Genetic Predisposition to Disease
Purpose: We investigated the health-related quality of life (HRQoL) of an adolescent and young adult (AYA)-aged South African childhood cancer survivor (CCS) cohort. Methods: Participants completed the Minneapolis-Manchester Quality of Life adolescent and adult forms. The overall Cronbach's alpha coefficients were 0.81 (adolescent form) and 0.92 (adult form). The scale-level content validity indexes were acceptable (0.88 and 0.89 for the adolescent and adult forms, respectively). The total domain and overall HRQoL scores were calculated. Results: Sixty-two survivors completed the adolescent form and 30 completed the adult form. The median age was 17.5 years (range 13-34 years), and the median time from diagnosis was 12 years (male:female ratio 1:1.2). Risk factors for poor physical functioning included age at study visit (p = 0.015), solid tumor diagnosis (p = 0.012), radiotherapy (p = 0.021), and surgery (p = 0.006). Six or more late effects impacted most domains negatively; severe late effects (p = 0.020) decreased physical functioning. Lower socioeconomic status was associated with poorer physical (p = 0.006) and cognitive (p = 0.047) functioning. The adult form cohort had poorer psychological (p = 0.014) and social functioning (p = 0.005) and body image (p = 0.016) than the adolescent form cohort. Conclusion: Older age, radiotherapy, surgery, solid tumor diagnosis, and the number and severity of late effects negatively influenced HRQoL in AYA-aged CCSs. A long-term follow-up (LTFU) risk stratification system should include HRQoL status to assist with holistic LTFU care.
Purpose: In 2005, the Food and Drug Administration (FDA) issued a decision memorandum regarding nonsteroidal anti-inflammatory drugs (NSAIDs). The memorandum recommended the withdrawal of certain NSAIDs due to potential cardiovascular adverse effects. It highlighted the issue of cardiovascular risk associated with NSAIDs as a class. The NSAID medication guide includes a wide range of adverse drug reactions (ADRs), such as increased blood pressure, liver failure, allergic reactions, heart attack, and intestinal bleeding. Although both sexes have an increased risk of ADRs with NSAID use, females have a greater risk than males due to differences in pharmacodynamics and higher medication concentrations (mg/kg). In particular, females with high blood pressure, coronary heart, kidney, and liver disease are at an additional risk of harm from NSAID ADRs. This study quantifies sex-specific differences and other factors associated with prescription NSAID use. Method: The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES), a complex survey conducted by the Centers for Disease Control and Prevention (CDC) in two-year cycles. A survey-weighted logistic regression model was utilized to investigate potential sex differences with prescription NSAIDs in the context of other factors, including kidney disease, hypertension, liver disease, insurance status, coronary heart disease, and age, within the 2011-2018 NHANES survey data. Results: Females reported a slightly higher percentage of high blood pressure and kidney disease than males, while males reported a slightly higher percentage of coronary heart and liver disease than females. Last, the model indicated that females were 58% more likely to have used a prescription NSAID than males. Conclusion: The results confirm that women and people with medical conditions, who would potentially suffer greater harm from NSAID ADRs, are more likely to use a prescription NSAID than individuals without these conditions.
Knowledge of Eurasian aspen's (Populus tremula L.) ecological and growth characteristics is of high importance to plant and wildlife community ecology, and noncommercial forest ecosystem services. This research assessed these characteristics, identified aspen's habitat optimum, and examined causality of its current scarce distribution in central Europe. We analyzed a robust database of field measurements (4,656,130 stands) for forest management planning over 78,000 km2 of the Czech territory. Our analysis we used GIS techniques, with basic and multivariate statistics such as general linear models, ordination, and classification. Results describe a species of broad ecological amplitude that has heretofore attracted little research attention. Spatial analysis showed significant differences between aspen and other forest non-forest cover types. Additionally, we found significant association between the proportion of aspen in a stand, the size of forest property, and the forest category. The results demonstrate historic reasons for aspen's widespread presence, though contemporary occurrence is limited. This study advances the concept of a quantitatively based aspen ecological optimum (niche), which we believe may be beneficial for numerous aspen associates in the context of anticipated warming. Irrespective of local ecology (i.e., the realized aspen niche), the study confirms that profit-driven policy in forestry is chiefly responsible for historic aspen denudation in central Europe. Even so, we demonstrate that ample habitat is present. Further solutions for improving aspen resilience are provided to support these keystone systems so vital to myriad dependent flora and fauna.
Ecosystem , Populus , Forests , Trees , Europe
We conducted a feasibility study to evaluate micronutrients and body mass index (BMI). Fat soluble vitamins A, D, E and trace elements copper (Cu), selenium (Se), and zinc (Zn) levels were evaluated. Weight, height, BMI, and Z-scores were recorded. Side effects or specific adverse events were documented. No patient had a Z-score for height, weight, or BMI of less than 2 SD or greater than 2 SD. Ninety percent of patients had one or more micronutrient levels below normal. These results suggest that micronutrient abnormalities are common despite no obvious evidence of malnutrition. Side effects of chemotherapy may be exacerbated by micronutrient depletion.
The growing application of silver nanoparticles (AgNPs) in consumer, healthcare, and industrial products has raised concern over potential health implications due to increasing exposure. The evaluation of the immune response to nanomaterials is one of the key criteria to assess their biocompatibility. There are well-recognized sex-based differences in innate and adaptive immune responses. However, there is limited information available using human models. The aim was to investigate the potential sex-based differences in immune functions after exposure to AgNPs using human peripheral blood mononuclear cells (PBMCs) and plasma from healthy donors. These functions include inflammasome activation, cytokine expression, leukocyte proliferation, chemotaxis, plasma coagulation, and complement activation. AgNPs were characterized by dynamic light scattering and transmission electron microscopy. Inflammasome activation by AgNPs was measured after 6- and 24-hours incubations. AgNPs-induced inflammasome activation was significantly higher in the females, especially for the 6-hour exposure. No sex-based differences were observed for Ag ions controls. Younger donors exhibited significantly more inflammasome activation than older donors after 24-hours exposure. IL-10 was significantly suppressed in males and females after exposure. AgNPs suppressed leukocyte proliferation similarly in males and females. No chemoattractant effects, no alterations in plasma coagulation, or activation of the complement were observed after AgNPs exposure. In conclusion, the results highlight that there are distinct sex-based differences in inflammasome activation after exposure to AgNPs in human PBMCs. The results highlight the importance of considering sex-based differences in inflammasome activation induced by exposure to AgNPs in any future biocompatibility assessment for products containing AgNPs.
Leukocytes, Mononuclear , Metal Nanoparticles , Silver , Humans , Silver/toxicity , Silver/chemistry , Metal Nanoparticles/toxicity , Metal Nanoparticles/chemistry , Female , Male , Leukocytes, Mononuclear/drug effects , Adult , Inflammasomes/drug effects , Inflammasomes/immunology , Middle Aged , Cell Proliferation/drug effects , Cytokines/metabolism , Sex Factors , Young Adult
The opioid epidemic has become a serious national crisis in the United States. An indepth systematic analysis of opioid-related adverse events (AEs) can clarify the risks presented by opioid exposure, as well as the individual risk profiles of specific opioid drugs and the potential relationships among the opioids. In this study, 92 opioids were identified from the list of all Food and Drug Administration (FDA)-approved drugs, annotated by RxNorm and were classified into 13 opioid groups: buprenorphine, codeine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, tapentadol, and tramadol. A total of 14,970,399 AE reports were retrieved and downloaded from the FDA Adverse Events Reporting System (FAERS) from 2004, Quarter 1 to 2020, Quarter 3. After data processing, Empirical Bayes Geometric Mean (EBGM) was then applied which identified 3317 pairs of potential risk signals within the 13 opioid groups. Based on these potential safety signals, a comparative analysis was pursued to provide a global overview of opioid-related AEs for all 13 groups of FDA-approved prescription opioids. The top 10 most reported AEs for each opioid class were then presented. Both network analysis and hierarchical clustering analysis were conducted to further explore the relationship between opioids. Results from the network analysis revealed a close association among fentanyl, oxycodone, hydrocodone, and hydromorphone, which shared more than 22 AEs. In addition, much less commonly reported AEs were shared among dihydrocodeine, meperidine, oxymorphone, and tapentadol. On the contrary, the hierarchical clustering analysis further categorized the 13 opioid classes into two groups by comparing the full profiles of presence/absence of AEs. The results of network analysis and hierarchical clustering analysis were not only consistent and cross-validated each other but also provided a better and deeper understanding of the associations and relationships between the 13 opioid groups with respect to their adverse effect profiles.
Analgesics, Opioid , Oxycodone , Analgesics, Opioid/adverse effects , Bayes Theorem , Data Mining , Fentanyl , Hydrocodone , Hydromorphone , Meperidine , Oxymorphone , Tapentadol , United States/epidemiology
Mice were immunized with a combination of self-amplifying (sa) RNA constructs for the F1 and V antigens of Yersinia pestis at a dose level of 1 µg or 5 µg or with the respective protein sub-units as a reference vaccine. The immunization of outbred OF1 mice on day 0 and day 28 with the lowest dose used (1 µg) of each of the saRNA constructs in lipid nanoparticles protected 5/7 mice against subsequent sub-cutaneous challenge on day 56 with 180 cfu (2.8 MLD) of a 2021 clinical isolate of Y. pestis termed 10-21/S whilst 5/7 mice were protected against 1800cfu (28MLD) of the same bacteria on day 56. By comparison, only 1/8 or 1/7 negative control mice immunized with 10 µg of irrelevant haemagglutin RNA in lipid nanoparticles (LNP) survived the challenge with 2.8 MLD or 28 MLD Y. pestis 10-21/S, respectively. BALB/c mice were also immunized with the same saRNA constructs and responded with the secretion of specific IgG to F1 and V, neutralizing antibodies for the V antigen and developed a recall response to both F1 and V. These data represent the first report of an RNA vaccine approach using self-amplifying technology and encoding both of the essential virulence antigens, providing efficacy against Y. pestis. This saRNA vaccine for plague has the potential for further development, particularly since its amplifying nature can induce immunity with less boosting. It is also amenable to rapid manufacture with simpler downstream processing than protein sub-units, enabling rapid deployment and surge manufacture during disease outbreaks.
Background: The Charlson Comorbidity Index (CCI) is a frequently used mortality predictor based on a scoring system for the number and type of patient comorbidities health researchers have used since the late 1980s. The initial purpose of the CCI was to classify comorbid conditions, which could alter the risk of patient mortality within a one-year time frame. However, the CCI may not accurately reflect risk among American Indians because they are a small proportion of the U.S. population and possibly lack representation in the original patient cohort. A motivating factor in calibrating a CCI for American Indians is that this population, as a whole, experiences a greater burden of comorbidities, including diabetes mellitus, obesity, cancer, cardiovascular disease, and other chronic health conditions, than the rest of the U.S. population. Methods: This study attempted to modify the CCI to be specific to the American Indian population utilizing the data from the still ongoing The Strong Heart Study (SHS) - a multi-center population-based longitudinal study of cardiovascular disease among American Indians.A one-year survival analysis with mortality as the outcome was performed using the SHS morbidity and mortality surveillance data and assessing the impact of comorbidities in terms of hazard ratios with the training cohort. A Kaplan-Meier plot for a subset of the testing cohort was used to compare groups with selected mCCI-AI scores. Results: A total of 3,038 Phase VI participants from the SHS comprised the study population for whom mortality and morbidity surveillance data were available through December 2019. The weights generated by the SHS participants for myocardial infarction, congestive heart failure, and high blood pressure were greater than Charlson's original weights. In addition, the weights for liver illness were equivalent to Charlson's severe form of the disease. Lung cancer had the greatest overall weight derived from a hazard ratio of 8.308. Conclusions: The mCCI-AI was a statistically significant predictor of one-year mortality, classifying patients into different risk strata X2 (8, N = 1,245) = 30.56 (p = .0002). The mCCI-AI exhibited superior performance over the CCI, able to discriminate between participants who died and those who survived 73% of the time.
Many South African children live in poverty and food insecurity; therefore, malnutrition within the context of childhood cancer should be examined. Parents/caregivers completed the Poverty-Assessment Tool (divided into poverty risk groups) and the Household Hunger Scale questionnaire in five pediatric oncology units. Height, weight, and mid-upper arm circumference assessments classified malnutrition. Regression analysis evaluated the association of poverty and food insecurity with nutritional status, abandonment of treatment, and one-year overall survival (OS). Nearly a third (27.8%) of 320 patients had a high poverty risk, associated significantly with stunting (p = 0.009), food insecurity (p < 0.001) and residential province (p < 0.001) (multinomial regression). Stunting was independently and significantly associated with one-year OS on univariate analysis. The hunger scale was significant predictor of OS, as patients living with hunger at home had an increased odds ratio for treatment abandonment (OR 4.5; 95% CI 1.0; 19.4; p = 0.045) and hazard for death (HR 3.2; 95% CI 1.02, 9.9; p = 0.046) compared to those with food security. Evaluating sociodemographic factors such as poverty and food insecurity at diagnosis is essential among South African children to identify at-risk children and implement adequate nutritional support during cancer treatment.
Malnutrition , Neoplasms , Child , Humans , South Africa/epidemiology , Hunger , Prevalence , Food Supply , Malnutrition/complications , Malnutrition/diagnosis , Malnutrition/epidemiology , Poverty , Growth Disorders/epidemiology , Neoplasms/diagnosis , Neoplasms/epidemiology
INTRODUCTION: Guidelines indicate primary-prevention implantable cardioverter-defibrillators (ICDs) for most patients with left ventricular ejection fraction (LVEF) ≤ 35%. Some patients' LVEFs improve during the life of their first ICD. In patients with recovered LVEF who never received appropriate ICD therapy, the utility of generator replacement upon battery depletion remains unclear. Here, we evaluate ICD therapy based on LVEF at the time of generator change, to educate shared decision-making regarding whether to replace the depleted ICD. METHODS: We followed patients with a primary-prevention ICD who underwent generator change. Patients who received appropriate ICD therapy for ventricular tachycardia or ventricular fibrillation (VT/VF) before generator change were excluded. The primary endpoint was appropriate ICD therapy, adjusted for the competing risk of death. RESULTS: Among 951 generator changes, 423 met inclusion criteria. During 3.4 ± 2.2 years follow-up, 78 (18%) received appropriate therapy for VT/VF. Compared to patients with recovered LVEF > 35% (n = 161 [38%]), those with LVEF ≤ 35% (n = 262 [62%]) were more likely to require ICD therapy (p = .002; Fine-Gray adjusted 5-year event rates: 12.7% vs. 25.0%). Receiver operating characteristic analysis revealed the optimal LVEF cutoff for VT/VF prediction to be 45%, the use of which further improved risk stratification (p < .001), with Fine-Gray adjusted 5-year rates 6.2% versus 25.1%. CONCLUSION: Following ICD generator change, patients with primary-prevention ICDs and recovered LVEF have significantly lower risk of subsequent ventricular arrhythmias compared to those with persistent LVEF depression. Risk stratification at LVEF 45% offers significant additional negative predictive value over a 35% cutoff, without a significant loss in sensitivity. These data may be useful during shared decision-making at the time of ICD generator battery depletion.
Defibrillators, Implantable , Tachycardia, Ventricular , Humans , Ventricular Function, Left , Stroke Volume , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/therapy , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/therapy , Ventricular Fibrillation/diagnosis , Ventricular Fibrillation/therapy , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Risk Factors
AbstractUnifying models have shown that the amount of space used by animals (e.g., activity space, home range) scales allometrically with body mass for terrestrial taxa; however, such relationships are far less clear for marine species. We compiled movement data from 1,596 individuals across 79 taxa collected using a continental passive acoustic telemetry network of acoustic receivers to assess allometric scaling of activity space. We found that ectothermic marine taxa do exhibit allometric scaling for activity space, with an overall scaling exponent of 0.64. However, body mass alone explained only 35% of the variation, with the remaining variation best explained by trophic position for teleosts and latitude for sharks, rays, and marine reptiles. Taxon-specific allometric relationships highlighted weaker scaling exponents among teleost fish species (0.07) than sharks (0.96), rays (0.55), and marine reptiles (0.57). The allometric scaling relationship and scaling exponents for the marine taxonomic groups examined were lower than those reported from studies that had collated both marine and terrestrial species data derived using various tracking methods. We propose that these disparities arise because previous work integrated summarized data across many studies that used differing methods for collecting and quantifying activity space, introducing considerable uncertainty into slope estimates. Our findings highlight the benefit of using large-scale, coordinated animal biotelemetry networks to address cross-taxa evolutionary and ecological questions.
Aquatic Organisms , Fishes , Animals , Homing Behavior
This study investigates the prevalence of vitamin and iron deficiencies at cancer diagnosis. Newly diagnosed children between October 2018 and December 2020 at two South African pediatric oncology units (POUs) were assessed for nutritional and micronutrient status (Vit A, Vit B12, Vit D, folate, and iron). A structured interview with caregivers provided information regarding hunger and poverty risks. There were 261 patients enrolled with a median age of 5.5 years and a male-to-female ratio of 1:0.8. Nearly half had iron deficiency (47.6%), while a third had either Vit A (30.6%), Vit D (32.6%), or folate (29.7%) deficiencies. Significant associations existed between moderate acute malnutrition (MAM) and low levels of Vit A (48.4%; p = .005), Vit B12 (29.6%; p < .001), and folate (47.3%; p = .003), while Vit D deficiency was associated with wasting (63.6%) (p < .001). Males had significantly lower Vit D levels (respectively, 40.9%; p = .004). Folate deficiency was significantly associated with patients born at full term (33.5%; p = .017), age older than five years (39.8%; p = .002), residing in provinces Mpumalanga (40.9%) and Gauteng (31.5%) (P = .032); as well as having food insecurity (46.3%; p < .001), or hematological malignancies (41.3%; p = .004). This study documents the high prevalence of Vit A, Vit D, Vit B12, folate, and iron deficiency in South African pediatric cancer patients, demonstrating the need to include micronutrient assessment at diagnosis to ensure optimal nutritional support for macro-and micronutrients.
Iron Deficiencies , Neoplasms , Child , Humans , Male , Female , Child, Preschool , Vitamins , South Africa/epidemiology , Prevalence , Folic Acid , Micronutrients , Vitamin D , Nutritional Status , Neoplasms/epidemiology
BACKGROUND: We investigated psychological distress in a South African childhood cancer survivor (CCS) cohort. METHODS: Adult CCSs treated at Tygerberg Hospital, Cape Town, completed the Brief Symptom Inventory-18. Internal consistency was acceptable: Cronbach's alpha values were 0.91 (Global Severity Index (GSI)), 0.85 (depression), 0.83 (somatization), and 0.75 (anxiety). We compared results utilizing different case rules (GSI T scores of ≥50, ≥57, and ≥63) for the identification of psychological distress. RESULTS: Forty CCSs (median age 24 years; median follow-up period 16 years) participated. Most (58%; 23 out of 40) completed school or tertiary education, were unmarried (90%; 36 out of 40), and unemployed (59.5%; 22 out of 37). The diagnoses included hematological malignancies (65%; 26 out of 40) and solid tumors (35%; 14 out of 40). The GSI T scores of ≥63, ≥57, and ≥50 identified 10% (four out of 40), 32.5% (13 out of 40), and 45% (18 out of 40) of survivors with psychological distress, respectively. Radiotherapy (odds ratio (OR) 4.6; p = .035), presence of ≥six late effects (OR 7.5; p = .026), and severe late effects (OR 6.6; p = .024) were significant risk factors (GSI T score ≥57). Follow-up period of 11-20 years (OR 7.3; p = .034) was significant for a GSI T score ≥50. CONCLUSION: This South African CCS cohort had higher levels of psychological distress utilizing the GSI T score ≥50 and ≥57 case rules than reported in the literature. Most were unmarried or unemployed. Significant contributing factors were radiotherapy, number and severity of late effects, and follow-up period. CCSs must be screened for psychological distress.
Cancer Survivors , Neoplasms , Psychological Distress , Humans , Child , Adolescent , Young Adult , Adult , Neoplasms/therapy , Neoplasms/psychology , Cancer Survivors/psychology , South Africa/epidemiology , Stress, Psychological/epidemiology , Stress, Psychological/etiology , Stress, Psychological/psychology
BACKGROUND/AIM: Prostate cancer (PCa) is one of the most common types of cancer in men. Prostate-specific antigen (PSA) is currently the only biomarker used to screen for the risk of developing PCa. Because PSA tests may show false positives, identifying novel PCa-specific biomarkers would improve prediction and diagnosis at an early stage. Previously, we identified a number of genes/microRNAs (miRNAs) in prostate tissue as potential biomarkers of chronic prostatitis in a rat model of chemical-induced prostatitis. The current study aimed to evaluate their potential for use as translational, diagnostic markers in humans. MATERIALS AND METHODS: We performed quantitative polymerase chain reaction analysis using pathologically clear (normal) or confirmed PCa tissue samples from the same patients (N=18 per group). RESULTS: Levels (relative fold changes) of bone morphogenetic protein 7 (BMP7) transcripts were significantly lower in PCa tissues, compared with clear tissues, in a paired t-test (p=0.0075). Although neural cell adhesion molecule 1 (NCAM1) transcripts tended to be altered in PCa tissues, statistically insignificant differences were observed (p=0.0521). No statistically significant differences were observed for the other genes/miRNAs analyzed in PCa tissues due to a high degree of individual variance in expression. CONCLUSION: Similar to the results previously observed in rats, changes in the levels of BMP7 and NCAM1 transcripts were evident in human PCa tissues, suggesting that these genes may serve as potential diagnostic biomarkers during the early stages of PCa. Further studies are needed to determine the potential use of these molecules as biomarkers.
MicroRNAs , Prostatic Neoplasms , Prostatitis , Male , Humans , Animals , Rats , Prostate/metabolism , Prostate-Specific Antigen/analysis , Prostate-Specific Antigen/metabolism , Prostatitis/diagnosis , Prostatitis/metabolism , Translational Research, Biomedical , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism
Numerous studies have been conducted on the US Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database to assess post-marketing reporting rates for drug safety review and risk assessment. However, the drug names in the adverse event (AE) reports from FAERS were heterogeneous due to a lack of uniformity of information submitted mandatorily by pharmaceutical companies and voluntarily by patients, healthcare professionals, and the public. Studies using FAERS and other spontaneous reporting AEs database without drug name normalization may encounter incomplete collection of AE reports from non-standard drug names and the accuracies of the results might be impacted. In this study, we demonstrated applicability of RxNorm, developed by the National Library of Medicine, for drug name normalization in FAERS. Using prescription opioids as a case study, we used RxNorm application program interface (API) to map all FDA-approved prescription opioids described in FAERS AE reports to their equivalent RxNorm Concept Unique Identifiers (RxCUIs) and RxNorm names. The different names of the opioids were then extracted, and their usage frequencies were calculated in collection of more than 14.9 million AE reports for 13 FDA-approved prescription opioid classes, reported over 17 years. The results showed that a significant number of different names were consistently used for opioids in FAERS reports, with 2,086 different names (out of 7,892) used at least three times and 842 different names used at least ten times for each of the 92 RxNorm names of FDA-approved opioids. Our method of using RxNorm API mapping was confirmed to be efficient and accurate and capable of reducing the heterogeneity of prescription opioid names significantly in the AE reports in FAERS; meanwhile, it is expected to have a broad application to different sets of drug names from any database where drug names are diverse and unnormalized. It is expected to be able to automatically standardize and link different representations of the same drugs to build an intact and high-quality database for diverse research, particularly postmarketing data analysis in pharmacovigilance initiatives.
INTRODUCTION: Heart failure (HF) is a major cause of morbidity and mortality, with nearly half of all HF-related deaths resulting from sudden cardiac death (SCD), most often from an arrhythmic event. The pathophysiologic changes that occur in response to the hemodynamic stress of HF may lead to increased arrhythmogenesis. Theoretically, medications that block these arrhythmogenic substrates would decrease the risk of SCD. The combined angiotensin receptor and neprilysin inhibitor (ARNi; tradename Entresto) is the newest commercially available medication for the treatment of heart failure. METHODS AND RESULTS: We reviewed and synthesized the available literature regarding sacubitril/valsartan and its effects on cardiac rhythm. ARNi has been shown to decrease cardiovascular mortality and hospitalization in patients with HF with reduced ejection fraction (HFrEF). Emerging evidence suggests that ARNi also may play a role in reducing arrhythmogenesis and thereby SCD. CONCLUSION: This review summarizes the current data regarding this ARNi and its potential antiarrhythmic effects.
Anti-Arrhythmia Agents , Heart Failure , Humans , Anti-Arrhythmia Agents/adverse effects , Heart Failure/diagnosis , Heart Failure/drug therapy , Neprilysin/pharmacology , Neprilysin/therapeutic use , Tetrazoles/adverse effects , Angiotensin Receptor Antagonists/adverse effects , Stroke Volume , Valsartan/pharmacology , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/drug therapy , Treatment Outcome
Given the need for real time data to aid in decision-making at the community level, contact tracing applications (apps) are explored as a potential method of gauging overall community well-being. The context of contact tracing effectiveness and integration with artificial intelligence is provided, as well as ideas and suggestions for how to expand for use as a community-wide data gathering approach. This commentary seeks to explore dimensions around the use of such apps to help manage in times of crisis given the widespread and destructive impacts the pandemic has on community well-being, including negative economic impacts and social declines. By connecting with community well-being, the idea of a contact tracing framework would enable communities to track data and make decisions to help foster well-being across public health, economic and social domains.
