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1.
Cureus ; 16(7): e63842, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39099993

RESUMEN

OBJECTIVE: The goal of this study is to evaluate the complications and mortality associated with vagus nerve stimulation (VNS). METHODS: We retrospectively reviewed medical records of patients who underwent VNS implantation for the treatment of drug-resistant epilepsy (DRE) between 2000 and 2023. The mean follow-up time was 10.6 years, ranging from three months to 22 years. RESULTS: In total, 55 adult and pediatric patients received VNS therapy with 117 procedures performed over 23 years. The most common early complications were hoarseness and cough which were reported in eight adult patients (6.8%). Four children with intellectual disability (ID) had infection (3.4%), eight patients had lead breakage (6.8%), and two had device migration (1.7%). Four of all patients (7.3%) demonstrated late complications due to chronic nerve stimulation including vocal cord dysfunction, late-onset severe AV block, and obstructive sleep apnea (OSA). Three patients (5.5%) had VNS deactivated permanently due to complications and/or lack of efficacy. Two patients died from probable sudden unexpected death in epilepsy (SUDEP) with an incidence of 3.4/1000 person-years. CONCLUSIONS: VNS therapy is safe over long-term follow-up but not without risks. Most post-operative complications are minor and transient for adults. Children with ID tend to have infection and device migration. Late-onset cardiac complications and OSA can develop in some patients during VNS therapy and should not be overlooked. The SUDEP rate may decrease with VNS therapy over time.

2.
Prev Med Rep ; 45: 102834, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39156724

RESUMEN

Introduction: Accelerating smoking cessation, particularly among young adults, is a national priority for decreasing tobacco-related disease. Healthcare providers play a critical role in delivering tobacco treatment interventions to this population. This study examined associations of demographic and tobacco use characteristics with young adults' self-reported past-year clinical encounters to identify opportunities to facilitate cessation. Methods: We conducted cross-sectional, secondary analyses on a sample of 831 young adults aged 18-34 participating in the first wave of the National Young Adult Health Survey (NYAHS 2018-2019). Demographic and tobacco use characteristics were participants' sex, age, race, current cigarette use, and current other tobacco use. Clinical encounter outcomes were past-year self-report of (1) seeing a clinician, (2) being asked about tobacco use, and among those currently smoking, (3) being advised to quit smoking. Results: After adjustment for covariates, women (vs. men) had 2.16 times greater odds of reporting seeing a clinician, while Non-White (vs. White) young adults and those currently (vs. never) smoking had 69% and 47% lower odds. Women and those currently smoking had 2.98 and 2.66 times greater odds, respectively, of being asked about tobacco use. Among those who currently smoked, being not confident (vs. confident) about quitting smoking was associated with 69% lower odds of being advised to quit; those who reported moderate (vs. low) nicotine dependence had 3.11 times higher odds of being advised to quit. Conclusions: Sex, racial, and smoking status differences in young adults' clinical encounter outcomes suggest multiple opportunities for future smoking prevention and cessation intervention efforts.

3.
JCEM Case Rep ; 2(9): luae155, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39185010
4.
Cureus ; 16(7): e65061, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39171016

RESUMEN

Vagus nerve stimulation (VNS) has been used as an adjunctive therapeutic option for drug-resistant epilepsy for decades. Traditionally, the left vagus nerve is used for stimulation, while the right vagus nerve is rarely used. The long-term efficacy and safety of the right VNS (R-VNS) in humans are unknown. We presented three patients who were treated with R-VNS over a follow-up period of up to eight years. All three patients tolerated R-VNS well with minimal complications. R-VNS displayed reasonable effectiveness in all three patients. One patient had an excellent response and became seizure-free. The other two patients demonstrated a less favorable response to R-VNS compared to their previous left VNS therapy.

5.
Hum Genet ; 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38969939

RESUMEN

An elevated resting heart rate (RHR) is associated with increased cardiovascular mortality. Genome-wide association studies (GWAS) have identified > 350 loci. Uniquely, in this study we applied genetic fine-mapping leveraging tissue specific chromatin segmentation and colocalization analyses to identify causal variants and candidate effector genes for RHR. We used RHR GWAS summary statistics from 388,237 individuals of European ancestry from UK Biobank and performed fine mapping using publicly available genomic annotation datasets. High-confidence causal variants (accounting for > 75% posterior probability) were identified, and we collated candidate effector genes using a multi-omics approach that combined evidence from colocalisation with molecular quantitative trait loci (QTLs), and long-range chromatin interaction analyses. Finally, we performed druggability analyses to investigate drug repurposing opportunities. The fine mapping pipeline indicated 442 distinct RHR signals. For 90 signals, a single variant was identified as a high-confidence causal variant, of which 22 were annotated as missense. In trait-relevant tissues, 39 signals colocalised with cis-expression QTLs (eQTLs), 3 with cis-protein QTLs (pQTLs), and 75 had promoter interactions via Hi-C. In total, 262 candidate genes were highlighted (79% had promoter interactions, 15% had a colocalised eQTL, 8% had a missense variant and 1% had a colocalised pQTL), and, for the first time, enrichment in nervous system pathways. Druggability analyses highlighted ACHE, CALCRL, MYT1 and TDP1 as potential targets. Our genetic fine-mapping pipeline prioritised 262 candidate genes for RHR that warrant further investigation in functional studies, and we provide potential therapeutic targets to reduce RHR and cardiovascular mortality.

6.
Eur J Endocrinol ; 191(1): 47-54, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38941271

RESUMEN

OBJECTIVE: The aim of this study is to assess whether clinical and imaging characteristics are associated with the hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACAs). DESIGN: This is a single-center cohort study. METHODS: Consecutive adult patients with incidental ACA were diagnosed between 2000 and 2016. RESULTS: Of the 1516 patients with incidental ACA (median age 59 years, 62% women), 699 (46%) had nonfunctioning adenomas (NFAs), 482 (31%) had mild autonomous cortisol secretion (MACS), 62 (4%) had primary aldosteronism (PA), 39 (3%) had Cushing syndrome, 18 (1%) had PA and MACS, and 226 (15%) had incomplete work-up. Age, sex, tumor size, and tumor laterality, but not unenhanced computed tomography Hounsfield units (HU), were associated with hormonal subtypes. In a multivariable analysis, ≥1 cm growth was associated with younger age (odds ratio [OR] = 0.8 per 5-year increase, P = .0047) and longer imaging follow-up (OR = 1.2 per year, P < .0001). Adrenalectomy was performed in 355 (23%) patients, including 38% of MACS and 15% of NFA. Adrenalectomy for NFA and MACS was more common in younger patients (OR = 0.79 per 5-year increase, P = .002), larger initial tumor size (OR = 2.3 per 1 cm increase, P < .0001), ≥1 cm growth (OR = 15.3, P < .0001), and higher postdexamethasone cortisol (OR = 6.6 for >5 vs <1.8 µg/dL, P = .002). CONCLUSIONS: Age, sex, tumor size, and laterality were associated with ACA hormonal subtype and can guide diagnosis and management. Tumor growth was more common with younger age and longer follow-up. Unenhanced HU did not predict hormonal subtype or growth. Adrenalectomy for MACS and NFA was mainly performed in younger patients with larger tumor size, growth, and elevated postdexamethasone cortisol.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Adrenalectomía , Adenoma Corticosuprarrenal , Hallazgos Incidentales , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adenoma Corticosuprarrenal/cirugía , Adenoma Corticosuprarrenal/diagnóstico por imagen , Adenoma Corticosuprarrenal/patología , Estudios Retrospectivos , Neoplasias de la Corteza Suprarrenal/cirugía , Neoplasias de la Corteza Suprarrenal/diagnóstico por imagen , Neoplasias de la Corteza Suprarrenal/patología , Anciano , Adulto , Estudios de Cohortes , Hidrocortisona/sangre , Síndrome de Cushing/cirugía , Síndrome de Cushing/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Hiperaldosteronismo/cirugía , Hiperaldosteronismo/diagnóstico por imagen
7.
Prev Med ; 185: 108056, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38944058

RESUMEN

INTRODUCTION: Widespread misperceptions about nicotine may have unintended effects on public health. We examined associations between existing messages about nicotine or tobacco and beliefs about nicotine and reduced nicotine cigarettes (RNC). METHODS: 2962 U.S. 18-45-year-olds were randomized in a May 2022 web-based survey to view one of 26 text-based messages about tobacco or nicotine from three sources: ongoing research (n = 8), messages authorized by FDA for VLN cigarettes (n = 6), and FDA's "From Plant to Product to Puff" campaign (n = 12); six messages from FDA's campaign did not reference nicotine and were treated as the reference source. Analyses examined associations between messages, grouped by source and individually, with beliefs about nicotine and RNC addictiveness and harms. RESULTS: Relative to FDA messages that did not reference nicotine, all message sources were associated with greater odds of a correct belief about nicotine (Odds Ratios [ORs] = 1.40-1.87, p's < 0.01); VLN messages were associated with greater correct beliefs about RNC addictiveness (b = 0.23, p < .05). No campaign produced greater correct beliefs about RNC harms. At the individual level, only five messages were associated with a correct belief about nicotine (ORs = 2.12-2.56, p-values < .01), and one with correct beliefs about RNC harms (b = 1.09, p < .05), vs. the reference message. CONCLUSIONS: Few existing messages improved understanding of the risks of nicotine separately from the risks of combustible products. Communication research is needed to promote greater public understanding of nicotine while minimizing unintended effects on nicotine and tobacco use.


Asunto(s)
Nicotina , Productos de Tabaco , Humanos , Masculino , Femenino , Adulto , Nicotina/administración & dosificación , Nicotina/efectos adversos , Estados Unidos , Encuestas y Cuestionarios , Mercadotecnía/métodos , Adolescente , Persona de Mediana Edad , Conocimientos, Actitudes y Práctica en Salud , Sistemas Electrónicos de Liberación de Nicotina , Adulto Joven
8.
Drug Alcohol Depend ; 261: 111291, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38851035

RESUMEN

INTRODUCTION: We assessed adults' perceived relative harm and addictiveness of products using FDA-authorized modified risk tobacco products (MRTP) claims and associations with intentions to use MRTPs. METHODS: Data were from the May 2022 Rutgers Omnibus study among US 18-45-year-old adults (n=2964), collected by the Rutgers Institute for Nicotine and Tobacco Studies (INTS). Outcomes were perceived relative harm and addictiveness versus a typical cigarette and intentions to use a product stating a reduced harm claim (General Snus) or a reduced exposure claim (VLN King). We conducted regression analyses of associations between perceived relative harm and addictiveness and intentions to use each product, stratified by smoking status. RESULTS: The minority of participants perceived products with a reduced harm claim as much less harmful vs. cigarettes (21 %, 19 %, 7 %, and 8 % among persons who smoked daily, smoked some days, formerly smoked, and never smoked respectively) and products with a reduced exposure claim as much less addictive vs. cigarettes (24 %, 26 %, 14 %, 20 % respectively). Perceived lower relative harm and addictiveness were significantly associated with higher intentions to use products stating reduced harm or reduced exposure claim across all smoking statuses with one exception (relative addictiveness was not associated with intention to use products stating the reduced harm claim among persons who formerly smoked). CONCLUSIONS: Two current FDA-authorized MRTP claims were not effective in conveying that MRTPs were less harmful or addictive than cigarettes to most participants. Perceiving products as less harmful or addictive were significantly associated with intentions to use MRTPs.


Asunto(s)
Intención , Productos de Tabaco , United States Food and Drug Administration , Humanos , Estados Unidos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Conducta Adictiva/psicología , Mercadotecnía
9.
Nat Genet ; 56(5): 778-791, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38689001

RESUMEN

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.


Asunto(s)
Presión Sanguínea , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Hipertensión , Herencia Multifactorial , Polimorfismo de Nucleótido Simple , Femenino , Humanos , Masculino , Presión Sanguínea/genética , Puntuación de Riesgo Genético , Hipertensión/genética , Factores de Riesgo
10.
J Math Biol ; 88(6): 68, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38661851

RESUMEN

The coexistence of multiple phytoplankton species despite their reliance on similar resources is often explained with mean-field models assuming mixed populations. In reality, observations of phytoplankton indicate spatial aggregation at all scales, including at the scale of a few individuals. Local spatial aggregation can hinder competitive exclusion since individuals then interact mostly with other individuals of their own species, rather than competitors from different species. To evaluate how microscale spatial aggregation might explain phytoplankton diversity maintenance, an individual-based, multispecies representation of cells in a hydrodynamic environment is required. We formulate a three-dimensional and multispecies individual-based model of phytoplankton population dynamics at the Kolmogorov scale. The model is studied through both simulations and the derivation of spatial moment equations, in connection with point process theory. The spatial moment equations show a good match between theory and simulations. We parameterized the model based on phytoplankters' ecological and physical characteristics, for both large and small phytoplankton. Defining a zone of potential interactions as the overlap between nutrient depletion volumes, we show that local species composition-within the range of possible interactions-depends on the size class of phytoplankton. In small phytoplankton, individuals remain in mostly monospecific clusters. Spatial structure therefore favours intra- over inter-specific interactions for small phytoplankton, contributing to coexistence. Large phytoplankton cell neighbourhoods appear more mixed. Although some small-scale self-organizing spatial structure remains and could influence coexistence mechanisms, other factors may need to be explored to explain diversity maintenance in large phytoplankton.


Asunto(s)
Simulación por Computador , Ecosistema , Conceptos Matemáticos , Modelos Biológicos , Fitoplancton , Dinámica Poblacional , Fitoplancton/fisiología , Fitoplancton/crecimiento & desarrollo , Dinámica Poblacional/estadística & datos numéricos , Biodiversidad
11.
Drug Alcohol Depend ; 257: 111257, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38493565

RESUMEN

OBJECTIVE: Relighting, i.e., extinguishing, saving, and later relighting and smoking unfinished cigarettes, appears prevalent, may be associated with nicotine dependence and negative health outcomes, yet is poorly understood. We estimate the prevalence, frequency, correlates of, and reasons for, cigarette relighting. METHODS: Survey respondents (n=676) were 18-45-year-old US-based Amazon Mechanical Turk (MTurk) participants who smoked cigarettes every/some days. Items assessed frequency of and reasons for relighting. Reported smoking sessions per day were compared to calculations based on reported cigarettes per day (CPD) and relighting frequency. RESULTS: Seventy-two percent of those who smoked reported relighting cigarettes. Reasons included not having time to finish (77%), not feeling like finishing (75%), saving money or avoiding wasting (70%), and making cigarettes last longer (59%). Nearly half (44%) relight to cut down and 34% to reduce harm. Hispanic (OR=1.73, CI:1.03-2.91) and non-Hispanic Black respondents (OR= 2.23, CI:1.20-4.10) had higher odds of relighting than others, as did those who smoke within 30minutes of waking (OR=2.45, CI:1.33-4.52) or wake up at night to smoke (OR=2.40, CI:1.68-3.44) (all ps <0.05). Respondents demonstrated low consistency in reporting the number of times they smoke (first-lit and relit) compared to calculations based on CPD and relighting frequency. CONCLUSIONS: Relighting is associated with race, ethnicity, nicotine dependence, and is often done to save money, cut down smoking, and reduce harm. Among those who relight, "smoking session" frequency seemed to be underestimated. Single item smoking frequency measures may not be ideal for individuals who smoke and relight.


Asunto(s)
Cese del Hábito de Fumar , Productos de Tabaco , Tabaquismo , Adolescente , Adulto , Humanos , Persona de Mediana Edad , Adulto Joven , Hispánicos o Latinos , Encuestas y Cuestionarios , Tabaquismo/epidemiología , Negro o Afroamericano
12.
Expert Opin Drug Saf ; 23(4): 469-476, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38462751

RESUMEN

BACKGROUND: Shorter regimens for drug-resistant tuberculosis (DR-TB) have non-inferior efficacy compared with longer regimens, but QT prolongation is a concern. T-wave morphology abnormalities may be a predictor of QT prolongation. RESEARCH DESIGN AND METHODS: STREAM Stage 1 was a randomized controlled trial in rifampicin-resistant TB, comparing short and long regimens. All participants had regular ECGs. QT/QTcF prolongation (≥500 ms or increase in ≥60 ms from baseline) was more common on the short regimen which contained high-dose moxifloxacin and clofazimine. Blinded ECGs were selected from the baseline, early (weeks 1-4), and late (weeks 12-36) time points. T-wave morphology was categorized as normal or abnormal (notched, asymmetric, flat-wave, flat peak, or broad). Differences between groups were assessed using Chi-Square tests (paired/unpaired, as appropriate). RESULTS: Two-hundred participants with available ECGs at relevant times were analyzed (QT prolongation group n = 82; non-prolongation group n = 118). At baseline, 23% (45/200) of participants displayed abnormal T-waves, increasing to 45% (90/200, p < 0.001) at the late time point. Abnormalities were more common in participants allocated the Short regimen (75/117, 64%) than the Long (14/38, 36.8%, p = 0.003); these occurred prior to QT/QTcF ≥500 ms in 53% of the participants (Long 2/5; Short 14/25). CONCLUSIONS: T-wave abnormalities may help identify patients at risk of QT prolongation on DR-TB treatment. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02409290). Current Controlled Trial number, ISRCTN78372190.


Asunto(s)
Síndrome de QT Prolongado , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Arritmias Cardíacas/inducido químicamente , Electrocardiografía , Síndrome de QT Prolongado/inducido químicamente , Moxifloxacino/efectos adversos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico
13.
Headache ; 64(4): 374-379, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38523478

RESUMEN

OBJECTIVE: To assess for improvement in comfort in participating in advocacy for migraine and headache disorders and knowledge needed for successful advocacy. BACKGROUND: The Advocacy Connection Team (ACT)-Now program is an educational program offered through Miles for Migraine, a non-profit advocacy organization. It is designed to teach headache fellows and patients advocacy skills. METHODS: In a cross-sectional pre-test-post-test design, the 2021 ACT-Now cohort of 98 participants were administered a set of 11 pre-course survey questions identifying their role (healthcare provider/headache fellow or patient/caregiver), baseline knowledge of migraine-related disability and stigma, and baseline engagement and comfort with advocating. The post-course survey questions were the same as the pre-course questions, with the addition of one question assessing knowledge of migraine-related disability, additional questions addressing comfort levels advocating with insurance and policymakers, as well as creating an advocacy plan. RESULTS: For the pre-course survey, 69 participants responded and for the post-course survey, 40 participants responded. Compared to the pre-course survey, participants were able to correctly identify epidemiological data about migraine following the ACT-Now course (pre-course 46% correct, post-course 58% correct, p = 0.263). There was also an increase in the comfort level of participants in advocacy activities, including the creation of an advocacy action plan (pre-course 23% were "very comfortable" advocating, post-course 63%, p < 0.05). CONCLUSION: These results demonstrate that ACT-Now is effective at improving advocacy skills in a mixed cohort of patients and headache fellows, giving them the skills to create advocacy plans and engage with other patients and physicians, payers, and policymakers to create a more understanding, equitable and compassionate world for persons with migraine and other headache diseases.


Asunto(s)
Trastornos Migrañosos , Defensa del Paciente , Humanos , Defensa del Paciente/educación , Estudios Transversales , Femenino , Masculino , Trastornos Migrañosos/terapia , Adulto , Cuidadores/educación , Persona de Mediana Edad , Trastornos de Cefalalgia/terapia , Becas , Conocimientos, Actitudes y Práctica en Salud
14.
Handb Clin Neurol ; 199: 67-86, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38307673

RESUMEN

Migraine headache is highly prevalent and the most common neurologic disorder, affecting one billion people worldwide. It is also the most disabling condition in people under 50, with a huge impact on working ability, family, and social life. Access to effective preventive medication is important and may be considered if the patient has 6 or more migraine days per month, ineffective abortive agents, or disability on 2 or more days per month. Propranolol, metoprolol, candesartan, topiramate, divalproex, lisinopril, amitriptyline, and venlafaxine have the strongest evidence to support for use. Flunarizine and pizotifen may also be effective. Selection of preventive treatments is based on individual characteristics, comorbid conditions, efficacy, contraindications, side effects, cost, compliance, and drug. An adequate trial of migraine prophylaxis is usually 2 months at the target dose, and it is always important to re-evaluate indication for prophylactic use after a period of time.


Asunto(s)
Trastornos Migrañosos , Humanos , Administración Oral , Amitriptilina/uso terapéutico , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/prevención & control , Propranolol/uso terapéutico , Ácido Valproico/uso terapéutico
16.
BMC Psychol ; 12(1): 97, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38409094

RESUMEN

BACKGROUND: Affect can influence people's perceptions, decisions, and the way they make sense of an experience. Some studies show that having one's cell phone removed will lead to negative emotional reactions, while others have found no significant impact on how we feel. In this paper we investigate the impact of cell phone possession and removal on participant's affective state. METHODS: We use a randomized double-blind procedure to examine whether cell phone removal enhances negativity, promotes positivity, or is emotionally inconsequential. We measure affect using a PANAS self-report scale as well as a less transparent temporal-estimation procedure. RESULTS: Our findings suggest that cell phone possession or removal has no influence on a person's affective state. CONCLUSIONS: Measured through both the PANAS self-report scale and temporal estimation task, affect remained consistent regardless of cell phone possession. These results suggest that cell phones may not carry the emotional weight often attributed to them. This finding challenges a common theme revolving around the negative emotional impact of cell phones and technology. Consequently, these findings may have important implications for the generally perceived notion that cell phones are having a negative effect on people's emotions.


Asunto(s)
Teléfono Celular , Felicidad , Humanos , Método Doble Ciego , Emociones , Autoinforme
17.
JCEM Case Rep ; 2(2): luae007, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38283727
18.
Heart Rhythm ; 21(6): 903-910, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38218330

RESUMEN

BACKGROUND: Genetic testing in the inherited arrhythmia clinic informs risk stratification, clinical management, and family screening. Periodic review of variant classification is recommended as supporting evidence accrues over time. However, there is limited reporting of real-world data on the frequency and impact of variant reclassification. OBJECTIVE: The purpose of this study was to determine the burden of variant reclassification in our inherited arrhythmia clinic and the impact on clinical management. METHODS: Genetic testing reports for patients referred to our clinic from 2004-2020 were reviewed. Reported variants were reinvestigated using ClinVar, VarSome, and a literature review. Classification was updated using the American College of Medical Genetics and Genomics (ACMG) criteria and tested for association with arrhythmic events and modification of medical management. RESULTS: We identified 517 patients (median age 37 years) who underwent gene panel testing. A variant of uncertain significance (VUS) was reported for 94 patients (18.2%) and more commonly identified when using large gene panels (P <.001). A total of 28 of 87 unique VUSs (32.2%) were reclassified to pathogenic/likely pathogenic (n = 11) or benign/likely benign (n = 17). Of 138 originally reported pathogenic variants, 7 (5.1%) lacked support using ACMG criteria. Variant reclassification was not associated with arrhythmic events; however, it did impact genotype-specific counseling and future therapeutic options. CONCLUSION: In our large real-world patient cohort, we identify a clinically important proportion of both pathogenic variants and VUSs with evidence for reclassification. These findings highlight the need for informed pretest counseling, a regular structured review of variants reported in genetic testing, and the potential benefits to patients for supporting genotype-guided therapy.


Asunto(s)
Arritmias Cardíacas , Pruebas Genéticas , Humanos , Pruebas Genéticas/métodos , Arritmias Cardíacas/genética , Arritmias Cardíacas/terapia , Femenino , Masculino , Adulto , Variación Genética , Predisposición Genética a la Enfermedad , Estudios Retrospectivos , Medición de Riesgo/métodos , Manejo de la Enfermedad
19.
J Neurosurg ; 140(2): 386-392, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37877973

RESUMEN

OBJECTIVE: Inferior petrosal sinus (IPS) sampling (IPSS) is a diagnostic procedure used to guide diagnostic localization of imaging-negative adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas. However, the efficacy of IPSS has been suboptimal at accurately lateralizing the adenoma, reducing surgical cure rates and leading to unintended pituitary dysfunction due to the added exploration. One rationale for the occasional imprecision is the existence of additional petrosal sinus collateral channels that connect the IPS bilaterally, which may lead to false localization results during sampling. The aim of this study was to explore a potential connection between normal anatomical variation in the angioarchitecture of the IPSs and the ACTH results obtained in subsequent IPSS tests. METHODS: A retrospective review was performed on all cases between 1998 and 2013 involving patients at a single institution who underwent IPSS for radiographically equivocal pituitary microadenomas. Cases were reviewed for tumor laterality noted on either operative or pathology reports, as well as the presence of angiographic evidence of cross-filling between the sinuses. In addition, ACTH levels from the right and left IPSs were documented at baseline and at 2, 5, and 10 minutes after corticotropin-releasing hormone (CRH) administration. A ratio of the change in ACTH levels measured at the time of maximal response (10 minutes) versus the levels measured at the initial response (2 minutes) was computed for each patient and compared between patients by their angiographic cross-filling status. RESULTS: There were 41 patients with a histopathologically confirmed right- or left-sided ACTH-secreting pituitary microadenoma who underwent preoperative IPSS. Among these patients, 28 (68%) showed angiographic evidence of cross-filling between the IPSs, and 13 showed no cross-filling. On average, ACTH levels increased by a factor of 3.91 ± 0.77 in the contralateral IPS in patients with angiographic cross-filling, compared with a factor increase of only 1.80 ± 0.27 in patients without cross-filling (p = 0.014). In comparison, ACTH levels increased by a factor of 2.01 ± 0.57 in the ipsilateral IPS in patients with cross-filling, and by 8.78 ± 7.30 in those without cross-filling (p = 0.373). CONCLUSIONS: The presence of angiographic cross-filling, suggestive of a greater degree of vascular channel networking between the right and left IPS, is a significant factor influencing the measured rates of change of ACTH in IPSS and may impact the specificity of this test to accurately determine microadenoma laterality in the preoperative setting.


Asunto(s)
Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Neoplasias Hipofisarias , Humanos , Hormona Adrenocorticotrópica , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico por imagen , Muestreo de Seno Petroso/métodos , Hormona Liberadora de Corticotropina , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/cirugía
20.
Emerg Med Australas ; 36(2): 213-220, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37899072

RESUMEN

OBJECTIVE: Youth mental health is a growing issue, which can be worsened by alcohol and other drug (AOD) use. The present study aimed to characterise the association of AOD use in youth presenting to an ED with a mental health crisis. METHODS: A retrospective observational study of paediatric patients presenting with mental health concerns to a tertiary ED in New Zealand in 2019-2020, with an examination of use of alcohol or other drugs before presentation. RESULTS: There were 842 ED presentations, made up of 491 unique individuals, examined from the 2-year period. Overdose (63.1%) was the most common reason for presentation, with 39.9% of overdoses involving prescription-only medications, 36.7% over-the-counter, and 20.0% a combination. Seventy-four (8.8%) presentations had documented use of alcohol or other drugs (excluding those taken in overdose) before arrival, with alcohol (51 presentations), followed by cannabis (19 presentations), being the most commonly recorded drugs used. Concurrent AOD use was not associated with any significant difference in triage, length of stay or admission status. CONCLUSION: In New Zealand, it is not legal to sell alcohol to persons under 18 years; however, this was the most commonly identified drug impacting on youth mental health presentations. There is a known association between alcohol use and adverse mental health symptoms; therefore, efforts to decrease access to alcohol in this age group must continue, and harm reduction interventions to reduce clinically significant overdoses recommended.


Asunto(s)
Sobredosis de Droga , Trastornos Relacionados con Sustancias , Humanos , Adolescente , Niño , Salud Mental , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/diagnóstico , Sobredosis de Droga/epidemiología , Estudios Retrospectivos , Servicio de Urgencia en Hospital
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