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1.
Epilepsia ; 65(7): 2017-2029, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38776170

RESUMO

OBJECTIVE: This study was undertaken to assess the utility of the Ages and Stages Questionnaire-3rd Edition (ASQ-3) and the Vineland Adaptive Behavior Scales-2nd Edition (VABS-II) as neurodevelopmental screening tools for infants exposed to antiseizure medications in utero, and to examine their suitability for use in large-population signal generation initiatives. METHODS: Participants were women with epilepsy who were recruited from 21 hospitals in England and Northern Ireland during pregnancy between 2014 and 2016. Offspring were assessed at 24 months old using the Bayley Scales of Infant Development-3rd Edition (BSID-III), the VABS-II, and the ASQ-3 (n = 223). The sensitivity and specificity of the ASQ-3 and VABS-II to identify developmental delay at 24 months were examined, using the BSID-III to define cases. RESULTS: The ASQ-3 identified 65 children (29.1%) as at risk of developmental delay at 24 months using standard referral criteria. Using a categorical approach and standard referral criteria to identify delay in the ASQ-3 and BSID-III at 24 months, the ASQ-3 showed excellent sensitivity (90.9%) and moderate specificity (74.1%). Utilizing different cut-points resulted in improved properties and may be preferred in certain contexts. The VABS-II exhibited the strongest psychometric properties when borderline impairment (>1 SD below the mean) was compared to BSID-III referral data (sensitivity = 100.0%, specificity = 96.6%). SIGNIFICANCE: Both the ASQ-3 and VABS-II have good psychometric properties in a sample of children exposed to antiseizure medications when the purpose is the identification of at-risk groups. These findings identify the ASQ-3 as a measure that could be used effectively as part of a tiered surveillance system for teratogenic exposure by identifying a subset of individuals for more detailed investigations. Although the VABS-II has excellent psychometric properties, it is more labor-intensive for both the research team and participants and is available in fewer languages than the ASQ-3.


Assuntos
Anticonvulsivantes , Deficiências do Desenvolvimento , Epilepsia , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Inquéritos e Questionários , Deficiências do Desenvolvimento/induzido quimicamente , Deficiências do Desenvolvimento/diagnóstico , Pré-Escolar , Epilepsia/tratamento farmacológico , Masculino , Lactente , Pais , Adulto , Complicações na Gravidez/tratamento farmacológico , Sensibilidade e Especificidade , Desenvolvimento Infantil/efeitos dos fármacos
2.
Eur Arch Otorhinolaryngol ; 281(4): 1835-1841, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38189967

RESUMO

PURPOSE: This study aimed to evaluate the utility of large language model (LLM) artificial intelligence tools, Chat Generative Pre-Trained Transformer (ChatGPT) versions 3.5 and 4, in managing complex otolaryngological clinical scenarios, specifically for the multidisciplinary management of odontogenic sinusitis (ODS). METHODS: A prospective, structured multidisciplinary specialist evaluation was conducted using five ad hoc designed ODS-related clinical scenarios. LLM responses to these scenarios were critically reviewed by a multidisciplinary panel of eight specialist evaluators (2 ODS experts, 2 rhinologists, 2 general otolaryngologists, and 2 maxillofacial surgeons). Based on the level of disagreement from panel members, a Total Disagreement Score (TDS) was calculated for each LLM response, and TDS comparisons were made between ChatGPT3.5 and ChatGPT4, as well as between different evaluators. RESULTS: While disagreement to some degree was demonstrated in 73/80 evaluator reviews of LLMs' responses, TDSs were significantly lower for ChatGPT4 compared to ChatGPT3.5. Highest TDSs were found in the case of complicated ODS with orbital abscess, presumably due to increased case complexity with dental, rhinologic, and orbital factors affecting diagnostic and therapeutic options. There were no statistically significant differences in TDSs between evaluators' specialties, though ODS experts and maxillofacial surgeons tended to assign higher TDSs. CONCLUSIONS: LLMs like ChatGPT, especially newer versions, showed potential for complimenting evidence-based clinical decision-making, but substantial disagreement was still demonstrated between LLMs and clinical specialists across most case examples, suggesting they are not yet optimal in aiding clinical management decisions. Future studies will be important to analyze LLMs' performance as they evolve over time.


Assuntos
Inteligência Artificial , Sinusite , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes , Idioma
3.
Epilepsia ; 64(9): 2454-2471, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37403560

RESUMO

OBJECTIVE: Despite widespread monotherapy use of lamotrigine or levetiracetam during pregnancy, prospectively collected, blinded child development data are still limited. The NaME (Neurodevelopment of Babies Born to Mothers With Epilepsy) Study prospectively recruited a new cohort of women with epilepsy and their offspring for longitudinal follow-up. METHODS: Pregnant women of <21 weeks gestation (n = 401) were recruited from 21 hospitals in the UK. Data collection occurred during pregnancy (recruitment, trimester 3) and at 12 and 24 months of age. The primary outcome was blinded assessment of infant cognitive, language, and motor development on the Bayley Scales of Infant and Toddler Development (3rd edition) at 24 months of age with supplementary parent reporting on the Vinelands Adaptive Behavior Scales (2nd edition). RESULTS: There were 394 live births, with 277 children (70%) completing the Bayley assessment at 24 months. There was no evidence of an association of prenatal exposure to monotherapy lamotrigine (-.74, SE = 2.9, 95% confidence interval [CI] = -6.5 to 5.0, p = .80) or levetiracetam (-1.57, SE = 3.1, 95% CI = -4.6 to 7.7, p = .62) with poorer infant cognition, following adjustment for other maternal and child factors in comparison to nonexposed children. Similar results were observed for language and motor scores. There was no evidence of an association between increasing doses of either lamotrigine or levetiracetam. Nor was there evidence that higher dose folic acid supplementation (≥5 mg/day) or convulsive seizure exposure was associated with child development scores. Continued infant exposure to antiseizure medications through breast milk was not associated with poorer outcomes, but the number of women breastfeeding beyond 3 months was low. SIGNIFICANCE: These data are reassuring for infant development following in utero exposure to monotherapy lamotrigine or levetiracetam, but child development is dynamic, and future follow-up is required to rule out later emerging effects.


Assuntos
Epilepsia , Efeitos Tardios da Exposição Pré-Natal , Lactente , Humanos , Feminino , Gravidez , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Levetiracetam/farmacologia , Mães , Estudos Prospectivos , Epilepsia/tratamento farmacológico , Anticonvulsivantes/efeitos adversos , Desenvolvimento Infantil , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
4.
Am J Otolaryngol ; 44(4): 103921, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37187016

RESUMO

BACKGROUND: Multidisciplinary collaboration is essential for effective odontogenic sinusitis (ODS) management. One point of debate has been the optimal timing of primary dental treatment and endoscopic sinus surgery (ESS), but differences in time to completion of these treatment pathways have not been studied. METHODS: A retrospective cohort study was conducted on ODS patients from 2015 to 2022. Demographic and clinical variables were recorded, and various durations of time were analyzed from rhinologic consultation through treatment completion. Resolution of sinusitis symptoms and purulence on endoscopy was also recorded. RESULTS: Eighty-nine ODS patients were analyzed (47.2 % male, median 59 years-old). Of the 89 ODS patients, 56 had treatable dental pathology, and 33 had no treatable dental pathology. Median time to treatment completion for all patients was 103 days. Of 56 ODS patients with treatable dental pathology, 33 had primary dental treatment, and 27 (81 %) required secondary ESS. In patients who underwent primary dental treatment followed by ESS, median time from initial evaluation to treatment completion was 236.0 days. If ESS was pursued primarily followed by dental treatment, median time from initial evaluation to treatment completion was 112.0 days, which was significantly shorter than if dental treatment was pursued primarily (p = 0.002). Overall symptomatic and endoscopic resolution was 97.8 %. CONCLUSIONS: After dental and sinus surgical treatment, ODS patients experienced 97.8 % resolution of symptoms and purulence on endoscopy. In patients with ODS due to treatable dental pathology, primary ESS followed by dental treatment resulted in a shorter overall treatment duration than primary dental treatment followed by ESS.


Assuntos
Sinusite Maxilar , Rinite , Sinusite , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Sinusite Maxilar/etiologia , Sinusite Maxilar/cirurgia , Estudos Retrospectivos , Sinusite/complicações , Sinusite/terapia , Endoscopia/métodos , Fatores de Tempo , Doença Crônica
5.
Semin Neurol ; 42(5): 679-692, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36513097

RESUMO

Over the last 50 years there has been a significant increase in our understanding of the issues faced by women with epilepsy, in both planning and undertaking pregnancy. The risks of teratogenicity associated with antiseizure medications have emerged slowly. The major pregnancy registers have substantially contributed to our knowledge about teratogenic risk associated with the commonly used antiseizure medications. However, there are substantial gaps in our knowledge about the potential risks associated with many third-generation drugs. The remit of the pregnancy registers and the wider research focus has moved beyond anatomical major congenital malformations. Increasingly neurodevelopmental and behavioral abnormalities have been investigated after in utero exposure to antiseizure medications. Public health approaches can help reduce the risk of teratogenicity. However, neurologists still have a vital role in reducing the risk of teratogenicity at an individual level for women attending their clinic. They also have responsibility to ensure that women with epilepsy are aware of the rationale for the different available options.


Assuntos
Anticonvulsivantes , Epilepsia , Gravidez , Feminino , Humanos , Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Teratogênicos
6.
Vet Radiol Ultrasound ; 63 Suppl 1: 897-902, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36514227

RESUMO

Evidence-based medicine, outcomes management, and multidisciplinary systems are laying the foundation for radiology on the cusp of a new day. Environmental and operational forces coupled with technological advancements are redefining the veterinary radiologist of tomorrow. In the past several years, veterinary image volumes have exploded, and the scale of hardware and software required to support it seems boundless. The most dynamic trend within veterinary radiology is implementing digital information systems such as PACS, RIS, PIMS, and Voice Recognition systems. While the digitization of radiography imaging has significantly improved the workflow of the veterinary radiology assistant and radiologist, tedious, redundant tasks are abundant and mind-numbing. They can lead to errors with a significant impact on patient care.  Today, these boring and repetitious tasks continue to bog down patient throughput and workflow. Artificial intelligence, particularly machine learning, shows much promise to rocket the workflow and veterinary clinical imaging into a new day where the AI management of mundane tasks allows for efficiency so the radiologist can better concentrate on the quality of patient care. In this article, we briefly discuss the major subsets of artificial intelligence (AI) workflow for the radiologist and veterinary radiology assistant including image acquisition, segmentation and mensuration, rotation and hanging protocol, detection and prioritization, monitoring and registration of lesions, implementation of these subsets, and the ethics of utilizing AI in veterinary medicine.


Assuntos
Inteligência Artificial , Radiologia , Animais , Radiologistas , Software , Fluxo de Trabalho
7.
Pract Neurol ; 22(2): 98-106, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34887343

RESUMO

Pregnancy is a time of physical, physiological and psychological challenge. For women with epilepsy, as well as its potential for joy and fulfilment, pregnancy may bring additional risks and difficulties. Clinicians must anticipate and prevent these complications, ensuring that pregnancy, delivery and motherhood proceed without obstetric or medical complications, using available evidence to balance individual risks of undertreatment and overtreatment. Here we review epilepsy management in pregnancy, identifying some of the known effects of epilepsy and its treatment on gestation, fetal malformation, delivery, and neurocognitive and behavioural development. We outline strategies to reduce obstetric and fetal complications in women with epilepsy, while recognising the sometimes competing need to maintain or improve seizure control. We reinforce the importance of identifying those at highest risk, who may require additional measures or safeguards.


Assuntos
Epilepsia , Complicações na Gravidez , Anticonvulsivantes/uso terapêutico , Epilepsia/complicações , Epilepsia/diagnóstico , Epilepsia/terapia , Feminino , Humanos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/terapia , Convulsões/complicações
8.
Ann Neurol ; 87(6): 897-906, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32215971

RESUMO

OBJECTIVE: The mechanisms by which antiepileptic drugs (AEDs) cause birth defects (BDs) are unknown. Data suggest that AED-induced BDs may result from a genome-wide increase of de novo variants in the embryo, a mechanism that we investigated. METHODS: Whole exome sequencing data from child-parent trios were interrogated for de novo single-nucleotide variants/indels (dnSNVs/indels) and de novo copy number variants (dnCNVs). Generalized linear models were applied to assess de novo variant burdens in children exposed prenatally to AEDs (AED-exposed children) versus children without BDs not exposed prenatally to AEDs (AED-unexposed unaffected children), and AED-exposed children with BDs versus those without BDs, adjusting for confounders. Fisher exact test was used to compare categorical data. RESULTS: Sixty-seven child-parent trios were included: 10 with AED-exposed children with BDs, 46 with AED-exposed unaffected children, and 11 with AED-unexposed unaffected children. The dnSNV/indel burden did not differ between AED-exposed children and AED-unexposed unaffected children (median dnSNV/indel number/child [range] = 3 [0-7] vs 3 [1-5], p = 0.50). Among AED-exposed children, there were no significant differences between those with BDs and those unaffected. Likely deleterious dnSNVs/indels were detected in 9 of 67 (13%) children, none of whom had BDs. The proportion of cases harboring likely deleterious dnSNVs/indels did not differ significantly between AED-unexposed and AED-exposed children. The dnCNV burden was not associated with AED exposure or birth outcome. INTERPRETATION: Our study indicates that prenatal AED exposure does not increase the burden of de novo variants, and that this mechanism is not a major contributor to AED-induced BDs. These results can be incorporated in routine patient counseling. ANN NEUROL 2020;87:897-906.


Assuntos
Anormalidades Induzidas por Medicamentos/genética , Anticonvulsivantes/efeitos adversos , Carga Genética , Variação Genética/genética , Teratogênicos , Anormalidades Induzidas por Medicamentos/epidemiologia , Adulto , DNA/genética , Variações do Número de Cópias de DNA/genética , Exoma/genética , Feminino , Humanos , Recém-Nascido , Masculino , Idade Paterna , Polimorfismo de Nucleotídeo Único/genética , Gravidez
9.
Am J Otolaryngol ; 42(4): 102931, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33550027

RESUMO

PURPOSE: Empty nose syndrome (ENS) is characterized by nasal dryness, crusting, and paradoxical nasal obstruction most commonly after inferior turbinate resection. ENS has also been reported to occur after middle turbinate resection (MTR), and concern for causing ENS is a possible reason surgeons preserve the MT during endoscopic sinus surgery (ESS). The objective was to determine whether MTR during ESS led to ENS. MATERIALS AND METHODS: This was a prospective case series of 95 consecutive patients that underwent bilateral subtotal MTR during ESS with either Draf IIB or Draf III frontal sinusotomies, for chronic rhinosinusitis with or without nasal polyps, and frontal sinus inverted papillomas. Demographic data and postoperative Empty Nose Syndrome 6-item Questionnaire (ENS6Q) scores were obtained. Nasal crusting was also documented on last postoperative nasal endoscopy. RESULTS: Pathologies included chronic rhinosinusitis with nasal polyps (69), without nasal polyps (12), and inverted papillomas (14). Fifty-six patients underwent subtotal MTRs during ESS with Draf IIB, and 39 with Draf III. Mean follow-up was 19.4 months (range 12-49). Mean postoperative ENS6Q score was 2.1. Only 2.1% had ENS6Q scores ≥ 11, and 6.3% had nasal crusting at last follow-up. None of the patients with ENS6Q scores ≥ 11 had nasal crusting at last follow-up. There were no significant differences in outcomes between ages, genders, surgery types, or pathologies. CONCLUSIONS: Patients who underwent bilateral subtotal MTR during ESS were unlikely to develop ENS by at least 1 year postoperatively, based on patients rarely experiencing ENS6Q scores ≥ 11 or persistent nasal crusting.


Assuntos
Endoscopia/efeitos adversos , Endoscopia/métodos , Obstrução Nasal/etiologia , Procedimentos Cirúrgicos Otorrinolaringológicos/efeitos adversos , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Complicações Pós-Operatórias/etiologia , Rinite/cirurgia , Sinusite/cirurgia , Conchas Nasais/cirurgia , Adulto , Idoso , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Obstrução Nasal/epidemiologia , Pólipos Nasais/complicações , Pólipos Nasais/cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Rinite/complicações , Sinusite/complicações , Inquéritos e Questionários , Síndrome , Fatores de Tempo
10.
Am J Otolaryngol ; 42(3): 102925, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33486208

RESUMO

PURPOSE: Endodontic disease is one of the most common causes of bacterial odontogenic sinusitis (ODS). Diagnosing ODS of endodontic origin involves otolaryngologists confirming sinusitis, and dental specialists confirming endodontic sources. The purpose of this study was to conduct a multidisciplinary literature review to highlight clinical and microbiological features of ODS, and the most optimal diagnostic modalities to confirm endodontic disease. METHODS: An extensive review of both medical and dental literature was performed by rhinologists, endodontists, and an infectious disease specialist. Frequencies of various clinical and microbiological features from ODS studies were collected, and averages were calculated. Different endodontic testing and imaging modalities were also evaluated on their abilities to confirm endodontic disease. RESULTS: ODS patients most often present with unilateral sinonasal symptoms for over 3 months, purulence on nasal endoscopy, and overt dental pathology on computed tomography (CT). Subjective foul smell, and maxillary sinus cultures demonstrating anaerobes and α-streptococci (viridans group) may be more specific to ODS. For endodontic evaluations, cold pulp testing and cone-beam CT imaging are most optimal for confirming pulpal and periapical disease. CONCLUSION: Diagnosing ODS requires collaboration between otolaryngologists and dental specialists. Clinicians should suspect ODS when patients present with unilateral sinonasal symptoms, especially foul smell. Patients will generally have purulent drainage on nasal endoscopy, and both sinus opacification and overt dental pathology on CT. However, some patients will have subtle or absent dental pathology on CT. For suspected endodontic disease, endodontists should be consulted for at least cold pulp testing, and ideally cone-beam CT.


Assuntos
Infecções Bacterianas , Sinusite Maxilar/diagnóstico , Sinusite Maxilar/microbiologia , Pulpite/diagnóstico , Pulpite/microbiologia , Adulto , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Estreptococos Viridans/isolamento & purificação , Estreptococos Viridans/patogenicidade
11.
Eur Arch Otorhinolaryngol ; 278(10): 3857-3865, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33609178

RESUMO

PURPOSE: Odontogenic sinusitis (ODS) is underrepresented in the literature compared to other forms of rhinosinusitis, specifically in sinusitis guidelines and position statements. ODS publication characteristics could help explain why ODS has received less attention in sinusitis guidelines and position statements. The purpose of this study was to explore trends in the quantity and quality of ODS studies over 3 decades from 1990 to 2019. METHODS: A systematic review was performed to identify all ODS studies from 1990 to 2019. The following variables from all ODS studies were compared between and across the 3 decades: authors' specialties, journal specialties, authors' geographic origins (continents), study topics, study designs, and evidence levels. RESULTS: From 1990 to 2019, there were 254 ODS studies that met inclusion criteria. Numbers of publications increased each decade, with 161 being published from 2010 to 2019. Otolaryngologists and dental authors published over 75% of ODS studies each decade, with 60-75% of ODS articles being published in otolaryngology or dental journals. European and Asian authors published the most ODS studies each decade. Overall, 92-100% of ODS publications per decade were level 4 and 5 evidence, with no significant changes between or across decades. CONCLUSION: While numbers of ODS publications increased each decade from 1990 to 2019, evidence levels remained low without significant changes over time. Otolaryngologists and dental authors published the majority of ODS studies each decade, with a minority of these studies being multidisciplinary. More ODS studies are needed across all aspects of the condition, and future projects would benefit from improved study designs and multidisciplinary collaboration.


Assuntos
Sinusite Maxilar , Otolaringologia , Sinusite , Humanos , Otorrinolaringologistas , Projetos de Pesquisa , Sinusite/complicações , Sinusite/epidemiologia
12.
Clin Otolaryngol ; 46(1): 52-59, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979035

RESUMO

INTRODUCTION: Allergic rhinitis (AR) is a common inflammatory condition of the nasal mucosa affecting approximately 20% of the population worldwide. Current therapies include intranasal antihistamines, corticosteroids, subcutaneous and sublingual immunotherapy (SLIT). This review and meta-analysis assess the efficacy of SLIT in the management of grass pollen-induced AR in adults. METHODS: Ovid EMBASE, Ovid EBM Reviews, Cochrane Central Register of Controlled Trials, Ovid MedLine and PubMed were searched using the following terms: 'sublingual immunotherapy', 'SLIT', 'rhinitis', 'allergic rhinitis', 'rhinosinusitis' and 'rhino-conjunctivitis'. All included studies were double-blind, placebo-controlled and randomised trials. Primary outcome was symptom score and secondary outcome included quality of life and safety profile. Meta-analysis of symptom improvement was carried out. RESULTS: Six studies were identified with 979 subjects randomly allocated to SLIT and 992 to a placebo control. All studies reported an improvement in symptoms with SLIT, with five reaching statistical significance (P < .05). Four studies reported statistically significant improvement in quality of life (P < .05). Oral pruritus was the most common adverse event reported. The overall risk of bias was high in 50% of the studies. CONCLUSIONS: Sublingual immunotherapy was a safe and effective treatment for grass pollen-induced AR in adults, and therefore, consideration should be given to its use for moderate-to-severe disease in the UK-wide population.


Assuntos
Rinite Alérgica/terapia , Imunoterapia Sublingual , Adolescente , Adulto , Idoso , Alérgenos , Humanos , Pessoa de Meia-Idade , Pólen , Rinite Alérgica/diagnóstico , Rinite Alérgica/etiologia , Adulto Jovem
13.
Emerg Infect Dis ; 26(11): 2586-2590, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33079040

RESUMO

The Federal Select Agent Program dictates that all research entities in the United States must rigorously assess laboratory protocols to sterilize samples being removed from containment areas. We validated procedures using sterile filtration and methanol to remove the following select agents: Francisella tularensis, Burkholderia pseudomallei, B. mallei, Yersinia pestis, and Bacillus anthracis. We validated methanol treatment for B. pseudomallei. These validations reaffirm safety protocols that enable researchers to keep samples sufficiently intact when samples are transferred between laboratories.


Assuntos
Contenção de Riscos Biológicos/normas , Laboratórios/normas , Bacillus anthracis , Burkholderia mallei , Burkholderia pseudomallei , Francisella tularensis , Esterilização , Yersinia pestis
14.
Mol Biol Rep ; 47(7): 5127-5136, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32583282

RESUMO

Common sequence variations in the VRK2 gene contribute to genetic risk for various psychiatric diseases including schizophrenia and major depressive disorder. Despite the clear importance of studying the regulation and function of VRK2 for understanding the causes of these diseases, the organisation and expression of the gene remain poorly characterised. Using reverse-transcriptase-PCR, we have amplifed exons of Vrk2 mRNA from regions of mouse brain, and from different cell classes comprising neurones, astrocytes and microglial cells. We find that Vrk2 mRNA is expressed in all cell types, and that the splicing of the mouse Vrk2 gene is much more complex than previously appreciated. In addition to the predicted alternative splicing (absence/presence) of the penultimate 3 prime exon, we also detected a variety of 5 prime structures, including two novel exons spanning the first characterised exon (exon 1), which we term exons 1a and 1b. While expressed in neurones and astrocytes, exon 1b was not expressed in microglial cells. Expression of transcripts containing exon 1a in microglia was increased by immune stimulation. An additional truncated transcript lacking 7 central exons was also identified. As with the human gene, the results confirm complex patterns of alternative splicing which are likely to be relevant for understanding the physiological and pathological function of the gene in the CNS.


Assuntos
Processamento Alternativo , Encéfalo/metabolismo , Proteínas Serina-Treonina Quinases/genética , Animais , Encéfalo/citologia , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Neurônios/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo
15.
Am J Otolaryngol ; 41(6): 102635, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32653733

RESUMO

PURPOSE: Odontogenic sinusitis is underrepresented in sinusitis literature as well as in the otolaryngology teaching curriculum sponsored by the American Academy of Otolaryngology-Head and Neck Surgery. Otolaryngologists and residents in training may therefore have a decreased awareness of the condition. The objective of this study was to survey otolaryngology chief residents toward the ends of their training to determine how often they considered odontogenic sinusitis as a cause of unilateral sinus disease. MATERIALS AND METHODS: An online REDCap survey was conducted from December 2018 to January 2019. Online surveys were emailed to 119 Otolaryngology residency program directors in the United States of America, which were then forwarded to their chief residents. Surveys included 3 demographic and 4 clinical questions. Clinical questions included 3 computed tomography-based questions requiring either differential diagnoses or most likely diagnosis, and 1 question on residents' perceived prevalence of odontogenic sinusitis as a cause of unilateral sinus opacification. Answer choices were tabulated and compared based on geographic region and post-residency career plans. RESULTS: Of 293 chief residents emailed, 94 completed the survey (32.1%). While answer choices on imaging-based questions varied, odontogenic sinusitis was generally underrecognized. Approximately 70% of residents felt odontogenic sinusitis represented 0%-40% of unilateral sinus opacification. There were no statistically significant differences in answers based on geographic distribution or post-residency career plans. CONCLUSIONS: Otolaryngology chief residents recognized odontogenic sinusitis with variable accuracy on imaging, and generally underestimated its prevalence as a cause of unilateral sinus opacification. Efforts should be made to teach otolaryngology residents about odontogenic sinusitis.


Assuntos
Conscientização , Internato e Residência , Sinusite Maxilar , Otorrinolaringologistas/psicologia , Otolaringologia/educação , Diagnóstico Diferencial , Humanos , Sinusite Maxilar/complicações , Sinusite Maxilar/diagnóstico , Sinusite Maxilar/diagnóstico por imagem , Sistemas On-Line , Doenças dos Seios Paranasais/etiologia , Inquéritos e Questionários , Tomografia Computadorizada por Raios X , Estados Unidos
16.
Am J Otolaryngol ; 41(6): 102667, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32823039

RESUMO

PURPOSE: To determine the effect of intranasal Doyle splints on postoperative pain following septoplasty and inferior turbinate reduction (ITR). Changes in Nasal Obstruction Symptom Evaluation (NOSE) scores were also evaluated. MATERIALS AND METHODS: A prospective cohort study conducted from January 2017 to January 2019. Patients were recruited if they experienced nasal obstruction due to septal deviation and inferior turbinate hypertrophy, and failed a one-month trial of intranasal corticosteroids. All patients underwent septoplasty with ITR, and either had Doyle splints or no splints placed. Patients were prescribed hydrocodone-acetaminophen 5-325 mg and asked to keep a daily log of pain medication use and visual analog scale (VAS) scores. Pain logs and NOSE scores were compared between patients who had splints versus patients who had no splints placed after septoplasty and ITR over the first postoperative week. NOSE scores were also collected at every postoperative visit (1 week, 1 month, and 6 months). RESULTS: Fifty-seven patients were enrolled (37 splints, 20 no-splints). The median postoperative pain VAS score was 3.0 (interquartile range [IQR] 2.0-5.0) for the splint group and 4.0 (IQR 2.0-5.0) for the no-splint group (P = 0.906). The median postoperative pain medication requirement in morphine equivalents at the first postoperative visit was 5.4 mg/day (IQR 2.0-13.3) for the splint group and 8.4 mg/day (IQR 1.8-15.3) for the no-splint group (P = 0.833). CONCLUSIONS: There were no statistically significant differences in postoperative pain VAS scores or pain medication use between the two groups. All patients experienced significant reductions in NOSE scores postoperatively.


Assuntos
Obstrução Nasal/cirurgia , Septo Nasal/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Rinoplastia/efeitos adversos , Rinoplastia/métodos , Contenções/efeitos adversos , Conchas Nasais/cirurgia , Adulto , Estudos de Coortes , Feminino , Humanos , Hipertrofia , Masculino , Pessoa de Meia-Idade , Obstrução Nasal/diagnóstico , Obstrução Nasal/etiologia , Septo Nasal/patologia , Medição da Dor , Dor Pós-Operatória/diagnóstico , Estudos Prospectivos , Resultado do Tratamento , Conchas Nasais/patologia
19.
J Neurol Neurosurg Psychiatry ; 89(12): 1320-1323, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29661925

RESUMO

OBJECTIVES: After 20 years of data collection, pregnancy registers have informed prescribing practice. Various populations show trends for a reduction in valproate prescribing, which is associated with an increased risk of anatomical teratogenesis and neurodevelopmental effects in those exposed in utero. Our aim was to determine if any shifts in prescribing trends have occurred in the UK and Ireland Epilepsy and Pregnancy Register cohort and to assess if there had been any change in the overall major congenital malformation (MCM) rate over time. METHODS: The UK and Ireland Epilepsy and Pregnancy Register, a prospective, observational, registration and follow-up study established in 1996, was used to determine the changes in antiepileptic drugs (AEDs) utilised during pregnancy and the MCM rate between 1996 and 2016. Linear regression analysis was used to assess changes in AED utilisation, and Poisson regression was used for the analysis of trends in the MCM rates. RESULTS: Outcome data for 9247 pregnancies showed a stable percentage of monotherapy to polytherapy prescribing habits over time. After Bonferroni correction, statistically significant (p<0.003) changes were found in monotherapy prescribing with increases in lamotrigine and levetiracetam and decreases in valproate and carbamazepine use. Between 1996 and 2016, the total MCM rate showed a 2.1% reduction per year (incidence risk ratio 0.979 (95% CIs 0.956 to 1.002) but Poisson regression analysis showed that this was not statistically significant p=0.08). CONCLUSION: Significant changes are seen in the prescribing habits in this cohort over 20 years, but a statistically significant change in the MCM rate was not detected. This work should be replicated on a larger scale to determine if significant changes are occurring in the MCM rate, which would allow a robust economic estimate of the benefits of improvements in prescribing practice and the personal effect of such changes.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Anticonvulsivantes/efeitos adversos , Uso de Medicamentos/tendências , Resultado da Gravidez/epidemiologia , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Feminino , Humanos , Incidência , Irlanda/epidemiologia , Gravidez , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Reino Unido/epidemiologia
20.
Pract Neurol ; 18(4): 291-305, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29650639

RESUMO

Non-convulsive status epilepticus (NCSE) is an enigmatic condition with protean manifestations. It often goes unrecognised, leading to delays in its diagnosis and treatment. The principal reason for such delay is the failure to consider and request an electroencephalogram (EEG), although occasional presentations have no scalp or surface electroencephalographic correlate. In certain settings with limited EEG availability, particularly out-of-hours, clinicians should consider treating without an EEG. Patients need a careful risk-benefit analysis to assess the risks of neuronal damage and harm versus the risks of adverse effects from various intensities of therapeutic intervention. Specialists in EEG, intensive care or epilepsy are invaluable in the management of patients with possible NCSE.


Assuntos
Estado Epiléptico/fisiopatologia , Adulto , Diagnóstico Diferencial , Eletroencefalografia , Feminino , Humanos , Atividade Motora , Estado Epiléptico/diagnóstico
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