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1.
J Thromb Thrombolysis ; 57(4): 658-667, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38393675

RESUMO

DOACs have emerged as first-line treatment in most cancer-associated thrombosis (CAT), representing a paradigm shift in its management. However, CAT management remains challenging and requires careful risk-benefit considerations. A retrospective analysis of CAT presentations to a tertiary referral centre from January 2011 to December 2020. Outcomes in CAT patients were compared to VTE patients without malignancy. Subgroup analysis was also conducted for CAT according to anticoagulation type. 514 CAT cases from 491 patients were identified from 3230 total VTE cases. CAT patients had higher rates of major VTE (PE and/or proximal DVT) compared to patients without malignancy (78.4% vs. 66.8%, p < 0.001). CAT patients also had higher rates of VTE recurrence (HR 1.66, 95%CI 1.23-2.26), major bleeding (HR 3.41, 95%CI 2.36-4.93), VTE-related mortality (HR 2.59, 95%CI 1.46-4.62) and bleeding-related mortality (HR 2.66, 95%CI 1.05-6.73). There were no significant differences in rates of VTE recurrence, major bleeding, VTE-related mortality or fatal bleeding between CAT patients treated with DOACs, enoxaparin or warfarin. In the subgroup of CAT treated with DOACs, there was no significant difference in rates of GI bleeding compared to the enoxaparin subgroup (HR 0.17, 95%CI 0.02-1.26). CAT was associated with a larger clot burden and higher rates of VTE recurrence, major bleeding and mortality compared to VTE patients without malignancy in this large real-world study. This study demonstrated no significant differences in complication rates for CAT patients treated with DOACs over enoxaparin, suggesting that DOACs can be safely used in most cases of CAT.


Assuntos
Neoplasias , Trombose , Tromboembolia Venosa , Humanos , Anticoagulantes/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Enoxaparina/uso terapêutico , Estudos Retrospectivos , Hemorragia/induzido quimicamente , Trombose/tratamento farmacológico , Resultado do Tratamento , Neoplasias/complicações , Administração Oral
3.
Radiol Artif Intell ; 5(3): e220079, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37293345

RESUMO

Purpose: To explore the impact of different user interfaces (UIs) for artificial intelligence (AI) outputs on radiologist performance and user preference in detecting lung nodules and masses on chest radiographs. Materials and Methods: A retrospective paired-reader study with a 4-week washout period was used to evaluate three different AI UIs compared with no AI output. Ten radiologists (eight radiology attending physicians and two trainees) evaluated 140 chest radiographs (81 with histologically confirmed nodules and 59 confirmed as normal with CT), with either no AI or one of three UI outputs: (a) text-only, (b) combined AI confidence score and text, or (c) combined text, AI confidence score, and image overlay. Areas under the receiver operating characteristic curve were calculated to compare radiologist diagnostic performance with each UI with their diagnostic performance without AI. Radiologists reported their UI preference. Results: The area under the receiver operating characteristic curve improved when radiologists used the text-only output compared with no AI (0.87 vs 0.82; P < .001). There was no difference in performance for the combined text and AI confidence score output compared with no AI (0.77 vs 0.82; P = .46) and for the combined text, AI confidence score, and image overlay output compared with no AI (0.80 vs 0.82; P = .66). Eight of the 10 radiologists (80%) preferred the combined text, AI confidence score, and image overlay output over the other two interfaces. Conclusion: Text-only UI output significantly improved radiologist performance compared with no AI in the detection of lung nodules and masses on chest radiographs, but user preference did not correspond with user performance.Keywords: Artificial Intelligence, Chest Radiograph, Conventional Radiography, Lung Nodule, Mass Detection© RSNA, 2023.

4.
West J Emerg Med ; 24(2): 236-242, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36976598

RESUMO

INTRODUCTION: Medications for addiction treatment (MAT) are the evidence-based standard of care for treatment of opioid use disorder (OUD), but stigma continues to surround their use. We conducted an exploratory study to characterize perceptions of different types of MAT among people who use drugs. METHODS: We conducted this qualitative study in adults with a history of non-medical opioid use who presented to an emergency department for complications of OUD. A semi-structured interview that explored knowledge, perceptions, and attitudes toward MAT was administered, and applied thematic analysis conducted. RESULTS: We enrolled 20 adults. All participants had prior experience with MAT. Among participants indicating a preferred treatment modality, buprenorphine was the commonly favored agent. Previous experience with prolonged withdrawal symptoms upon MAT discontinuation and the perception of "trading one drug for another" were common reasons for reluctance to engage in agonist or partial-agonist therapy. While some participants preferred treatment with naltrexone, others were unwilling to initiate antagonist therapy due to fear of precipitated withdrawal. Most participants strongly considered the aversive nature of MAT discontinuation as a barrier to initiating treatment. Participants overall viewed MAT positively, but many had strong preferences for a particular agent. CONCLUSION: The anticipation of withdrawal symptoms during initiation and cessation of treatment affected willingness to engage in a specific therapy. Future educational materials for people who use drugs may focus on comparisons of respective benefits and drawbacks of agonists, partial agonists, and antagonists. Emergency clinicians must be prepared to answer questions about MAT discontinuation to effectively engage patients with OUD.


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Síndrome de Abstinência a Substâncias , Adulto , Humanos , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Buprenorfina/uso terapêutico , Serviço Hospitalar de Emergência , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Analgésicos Opioides/uso terapêutico
5.
J Thromb Thrombolysis ; 55(2): 304-311, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36526867

RESUMO

Obesity is a known risk factor for venous thromboembolism (VTE) and poses a unique set of challenges in anticoagulation management. We report a 10-year experience of VTE management in morbidly obese patients. We conducted a retrospective analysis of VTE presentations to Northern Health, Victoria, Australia, from January 2011 to December 2020, with median follow-up of 44 months. Morbidly obese patients (defined as weighing > 120 kg) were compared to those ≤ 120 kg. Patients with active malignancy were excluded. 194 VTE cases with weight > 120 kg were compared to 2168 cases weighing ≤ 120 kg. Patients > 120 kg were more likely to present with unprovoked VTE (59.3% vs. 45.2%, p < 0.001) and major VTE (74.7% vs. 67.4%, p = 0.028). Overall, patients > 120 kg were more likely to develop VTE recurrence after anticoagulation cessation (7.80 vs. 3.92 per 100-patient-years, HR 1.97, 95%CI 1.29-3.00), while there were no significant differences in major bleeding or 30-day all-cause mortality. There were no significant differences in outcomes in patients > 120 kg treated with warfarin compared to direct oral anticoagulants (DOAC), or when comparing those treated with an uncapped (1 mg/kg BD) vs. capped (< 1 mg/kg) enoxaparin dosing regimen. Morbid obesity is associated with increased clot burden at presentation and VTE recurrence following anticoagulation cessation, without significant differences in bleeding compared to those ≤ 120 kg. There were no significant differences in morbidly obese patients' outcomes when treated with warfarin or DOAC, or when treated with an uncapped or capped enoxaparin dosing strategy. Larger randomised controlled trials evaluating the safety of DOACs and different enoxaparin dosing strategies in patients > 120 kg are warranted.


Assuntos
Obesidade Mórbida , Tromboembolia Venosa , Humanos , Varfarina/uso terapêutico , Anticoagulantes/efeitos adversos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/complicações , Enoxaparina , Obesidade Mórbida/complicações , Estudos Retrospectivos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Administração Oral
6.
Intern Med J ; 53(7): 1163-1169, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-35762150

RESUMO

BACKGROUND: Magnetic Resonance Imaging is used for evaluation of bone in Gaucher disease (GD), but a widely available quantitative scoring method remains elusive. AIMS: The study purpose was to assess the reproducibility of the LiverLab tool for assessing bone marrow fat fraction (FF) and determine whether it could differentiate GD patients from healthy subjects. METHODS: Ten healthy volunteers and 18 GD patients were prospectively recruited. FF was calculated at L3, L4 and L5. GD patient bone marrow burden (BMB) score assessed by one observer. Inter and intra-rater agreement assessed with Bland-Altman data plots. Differences in FF between healthy volunteers versus GD patients and between subjects treated versus not treated assessed using two-sample t-tests. In GD patients, the relationship between FF, BMB and glucosylsphingosine was determined using the Pearson's correlation coefficient. RESULTS: Healthy volunteer mean FF was 0.36, standard deviation (SD) 0.10 (range 0.20-0.57). Intra and inter-rater SD were both 0.02. GD patient mean FF was 0.40, SD 0.13 (range 0.09-0.57). No statistical difference was shown between healthy volunteers and GD patients (P = 0.447) or between GD patients whether on enzyme replacement therapy or not (P = 0.090). No significant correlation between mean FF and total BMB (r = -0.525, P = 0.253) or between FF and glucosylsphingosine levels (r = 0.287, P = 0.248). CONCLUSION: Excellent reproducibility of LiverLab FF measurements across studies and observers is comparable to Dixon quantitative chemical shift imaging (QCSI). Lack of statistical difference between GD patients and controls may be explained by limited patient numbers, active treatment or mild disease severity in untreated patients.


Assuntos
Medula Óssea , Doença de Gaucher , Humanos , Adulto , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Doença de Gaucher/diagnóstico por imagem , Doença de Gaucher/terapia , Voluntários Saudáveis , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , Voluntários
7.
J Thromb Thrombolysis ; 55(1): 32-41, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35908244

RESUMO

Assessing the risk of recurrent venous thromboembolism (VTE), particularly when patients are anticoagulated, remains a major challenge largely due to the lack of biomarkers. Blood was sampled from adult VTE patients recruited between January 2018 and September 2020, while receiving therapeutic anticoagulation. Results were compared to 144 healthy subjects (34.7% male, median age 42 years). Overall haemostatic potential (OHP) assay, a spectrophotometric assay, was performed on platelet-poor plasma, in which fibrin formation (triggered by small amounts of thrombin (overall coagulation potential, OCP)) and fibrinolysis (by the addition of thrombin and tissue plasminogen activator (OHP)) are simultaneously measured. Results were obtained from 196 patients (52.6% male, mean age 57.1 years). Compared to healthy subjects, VTE patients displayed significantly higher OCP (39.6 vs 34.5 units, p < 0.001) and OHP (9.3 vs 6.4 units, p < 0.001) as well as lower overall fibrinolytic potential (75.6 v s81.1%, p < 0.001). All 16 VTE recurrences, including 11 unprovoked, occurred above an OCP cut-off of 40th percentile (recurrence rate 4.32/100 patient-years (100PY), 95% confidence interval (CI) 2.39-7.80, p = 0.002). Of 97 patients who subsequently discontinued anticoagulation, all unprovoked VTE recurrences (n = 9) occurred above the 40th OCP percentile (recurrence rate 9.10/100PY, 95% CI 4.74-17.49, p = 0.005) and the 40th OHP percentile (recurrence rate 8.46/100PY, 95% CI 4.40-16.25, p = 0.009). Our pilot study demonstrates that the OHP assay can detect a hypercoagulable and hypofibrinolytic state in anticoagulated VTE patients and may be able to risk stratify VTE recurrence, allowing for more individualised decision on long-term anticoagulation. Further larger prospective studies are required.


Assuntos
Hemostáticos , Tromboembolia Venosa , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Hemostáticos/uso terapêutico , Trombina , Projetos Piloto , Fatores de Risco , Anticoagulantes/uso terapêutico , Recidiva
8.
Thromb Res ; 219: 112-120, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36162254

RESUMO

BACKGROUND: The introduction of direct oral anticoagulants (DOAC) has resulted in a paradigm shift in the management of venous thromboembolism (VTE). We evaluate the impact of the transition to DOAC, over the last decade, on overall VTE clinical outcomes including in first unprovoked major VTEs. METHOD: A retrospective analysis of all VTE admissions in non-cancer patients from January 2011 to December 2020 at Northern Health, Victoria, Australia. "Warfarin era" included events that occurred between January 2011 and December 2014 and "DOAC era" from January 2016. RESULTS: There were 2687 cases involving 2508 patients (45.9 % males; median age 63 years). 98 % were symptomatic and 1261 events (47 %) were unprovoked. 1003 events occurred during the warfarin era (79 % warfarin, 6 % DOAC) and 1479 during the DOAC era (18 % warfarin, 70 % DOAC). While recurrent thrombosis during the acute phase of treatment was comparable, there were fewer recurrences during the long-term preventative phase of treatment in the DOAC era compared to warfarin era (HR 0.602, 95 % CI: 0.393-0.924, p0.020). Clinically significant bleeding events were lower in the DOAC era (HR 0.623, 95 % CI: 0.395-0.985, p = 0.043). A subanalysis of first unprovoked major VTE events (n = 602) demonstrated a significant reduction in recurrent VTE during the long-term preventative phase of treatment in the DOAC era (HR 0.296, 95 % CI: 0.097-0.901, p = 0.032) with no difference in clinically significantly bleeding rates (HR 0.529, 95 % CI 0.219-1.280, p = 0.158) between the eras. CONCLUSION: Treatment outcomes for VTE appear to have improved over time with reduced rate of thrombotic and clinically significant bleeding complications in the DOAC era.


Assuntos
Tromboembolia Venosa , Varfarina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Administração Oral , Anticoagulantes/efeitos adversos , Hemorragia/tratamento farmacológico , Estudos Retrospectivos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Varfarina/efeitos adversos
9.
Clin Endocrinol (Oxf) ; 97(1): 124-129, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35508893

RESUMO

BACKGROUND: The modern era of radioiodine (I-131) theranostics for metastatic differentiated thyroid cancer requires us to rationalize the role of traditional empiric prescription in nonmalignant thyroid disease. We currently practice empiric I-131 prescription for treatment of hyperthyroidism. This study aims to assess outcomes after treatment of hyperthyroidism by empiric I-131 prescription at our centre, evaluate factors that impact on outcomes and prescribing practice, and gain insight into whether there is a place for theranostically-guided prescription in hyperthyroidism. PATIENTS AND METHODS: A retrospective review was undertaken of all patients with Graves' disease, toxic multinodular goitre (MNG) and toxic adenoma treated with I-131 between 2016 and 2021. Associations between clinical or scintigraphic variables and remission (euthyroid or hypothyroid) or persistence of hyperthyroidism at follow-up were performed using standard t test as well as Pearson's product correlation. RESULTS: Of 146 patients with a mean follow-up of 13.6 months, 80.8% achieved remission of hyperthyroidism. This was highest in toxic nodules (90.1%), compared with Graves' disease (73.8%) and toxic MNG (75.5%). In patients with Graves' disease, higher administered activity was associated with remission (p = .035). There was a weak inverse correlation between the Tc-99m pertechnetate uptake vs prescribed activity in Graves' disease (r = -0.33; p = .009). Only one patient (0.7%) had an I-131 induced flare of thyrotoxicosis. CONCLUSION: Traditional empiric I-131 prescription is a safe and effective treatment of hyperthyroidism and suitable for most patients. However, there may be a role for personalized I-131 prescription by theranostic guidance in selected patients with high thyroid hyperactivity.


Assuntos
Bócio Nodular , Doença de Graves , Hipertireoidismo , Doença de Graves/complicações , Humanos , Hipertireoidismo/complicações , Hipertireoidismo/tratamento farmacológico , Hipertireoidismo/radioterapia , Radioisótopos do Iodo/uso terapêutico , Medicina de Precisão
10.
J Med Imaging Radiat Oncol ; 66(6): 755-760, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34612025

RESUMO

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has infected over 215 million individuals worldwide. Chest radiographs (CXR) and computed tomography (CT) have assisted with diagnosis and assessment of COVID-19. Previous reports have described peripheral and lower zone predominant opacities on chest radiographs. Whilst the most common patterns on CT are bilateral, peripheral basal predominant ground glass opacities (Wong et al., Radiology, 296, 2020, E72; Karimian and Azami, Pol J Radiol, 86, 2021, e31). This study describes the imaging findings in an Australian tertiary hospital population. METHODS: COVID-PCR-positive patients who had chest imaging (CXR, CT and ventilation perfusion (V/Q) scans) from January 2020 to August 2020 were included. Distribution, location and pattern of involvement was recorded. Evaluation of the assessors was performed using Fleiss Kappa calculations for review of radiographic findings and qualitative analysis of CT findings. RESULTS: A total of 681 studies (616 CXRs, 59 CTs, 6 V/Q) from 181 patients were reviewed. The most common chest radiograph finding was bilateral lower lobe predominant diffuse opacification and most common CT pattern being ground glass opacities. Of the CT imaging, 33 were CT Pulmonary Angiograms of which five demonstrated acute pulmonary emboli. There was good inter-rater agreement between radiologists in assessment of imaging appearances on CXR (kappa 0.29-0.73) and CT studies. CONCLUSION: A review of imaging in an Australian tertiary hospital demonstrates similar patterns of COVID-19 infection on chest X-ray and CT imaging when compared to the international population.


Assuntos
COVID-19 , Austrália , COVID-19/diagnóstico por imagem , Teste para COVID-19 , Humanos , Centros de Atenção Terciária , Tomografia Computadorizada por Raios X
11.
Elife ; 102021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34409939

RESUMO

NmMetQ is a substrate-binding protein (SBP) from Neisseria meningitidis that has been identified as a surface-exposed candidate antigen for meningococcal vaccines. However, this location for NmMetQ challenges the prevailing view that SBPs in Gram-negative bacteria are localized to the periplasmic space to promote interaction with their cognate ABC transporter embedded in the bacterial inner membrane. To elucidate the roles of NmMetQ, we characterized NmMetQ with and without its cognate ABC transporter (NmMetNI). Here, we show that NmMetQ is a lipoprotein (lipo-NmMetQ) that binds multiple methionine analogs and stimulates the ATPase activity of NmMetNI. Using single-particle electron cryo-microscopy, we determined the structures of NmMetNI in the presence and absence of lipo-NmMetQ. Based on our data, we propose that NmMetQ tethers to membranes via a lipid anchor and has dual function and localization, playing a role in NmMetNI-mediated transport at the inner membrane and moonlighting on the bacterial surface.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Proteínas de Bactérias/metabolismo , Lipoproteínas/metabolismo , Metionina/metabolismo , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Microscopia Crioeletrônica , Lipoproteínas/química , Lipoproteínas/genética , Neisseria meningitidis/metabolismo , Periplasma , Ligação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína
12.
medRxiv ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34401892

RESUMO

In comparison to the general patient population, trauma patients show higher level detections of bloodborne infectious diseases, such as Hepatitis and Human Immunodeficiency Virus. In comparison to bloodborne pathogens, the prevalence of respiratory infections such as SARS-CoV-2 and how that relates with other variables, such as drug usage and trauma type, is currently unknown in trauma populations. Here, we evaluated SARS-CoV-2 seropositivity and antibody isotype profile in 2,542 trauma patients from six Level-1 trauma centers between April and October of 2020 during the first wave of the COVID-19 pandemic. We found that the seroprevalence in trauma victims 18-44 years old (9.79%, 95% confidence interval/CI: 8.33 - 11.47) was much higher in comparison to older patients (45-69 years old: 6.03%, 4.59-5.88; 70+ years old: 4.33%, 2.54 - 7.20). Black/African American (9.54%, 7.77 - 11.65) and Hispanic/Latino patients (14.95%, 11.80 - 18.75) also had higher seroprevalence in comparison, respectively, to White (5.72%, 4.62 - 7.05) and Non-Latino patients (6.55%, 5.57 - 7.69). More than half (55.54%) of those tested for drug toxicology had at least one drug present in their system. Those that tested positive for narcotics or sedatives had a significant negative correlation with seropositivity, while those on anti-depressants trended positive. These findings represent an important consideration for both the patients and first responders that treat trauma patients facing potential risk of respiratory infectious diseases like SARS-CoV-2.

13.
West J Emerg Med ; 22(2): 339-345, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33856321

RESUMO

INTRODUCTION: Bystander naloxone distribution is an important component of public health initiatives to decrease opioid-related deaths. While there is evidence supporting naloxone distribution programs, the effects of increasing naloxone availability on the behavior of people who use drugs have not been adequately delineated. In this study we sought to 1) evaluate whether individuals' drug use patterns have changed due to naloxone availability; and 2) explore individuals' knowledge of, access to, experiences with, and perceptions of naloxone. METHODS: We conducted a pilot study of adults presenting to the emergency department whose medical history included non-medical opioid use. Semi-structured interviews were conducted with participants and thematic analysis was used to code and analyze interview transcripts. RESULTS: Ten participants completed the study. All were aware of naloxone by brand name (Narcan) and had been trained in its use, and all but one had either currently or previously possessed a kit. Barriers to naloxone administration included fear of legal repercussions, not having it available, and a desire to avoid interrupting another user's "high." Of the eight participants who reported being revived with naloxone at least once during their lifetime, all described experiencing a noxious physical response and expressed a desire to avoid receiving it again. Furthermore, participants did not report increasing their use of opioids when naloxone was available. CONCLUSIONS: Participants were accepting of and knowledgeable about naloxone, and were willing to administer naloxone to save a life. Participants tended to use opioids more cautiously when naloxone was present due to fears of experiencing precipitated withdrawal. This study provides preliminary evidence countering the unsubstantiated narrative that increased naloxone availability begets more high-risk opioid use and further supports increasing naloxone access.


Assuntos
Overdose de Drogas/prevenção & controle , Usuários de Drogas/psicologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Naloxona/uso terapêutico , Transtornos Relacionados ao Uso de Opioides , Adulto , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/psicologia , Transtornos Relacionados ao Uso de Opioides/terapia , Projetos Piloto
14.
Front Immunol ; 12: 653710, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33912179

RESUMO

Antiseizure medications (ASMs) are frequently implicated in T cell-mediated drug hypersensitivity reactions and cause skin tropic pathologies that range in severity from mild rashes to life-threatening systemic syndromes. During the acute stages of the more severe manifestations of these reactions, drug responsive proinflammatory CD8+ T cells display classical features of Th1 cytokine production (e.g. IFNγ) and cytolysis (e.g. granzyme B, perforin). These T cells may be found locally at the site of pathology (e.g. blister cells/fluid), as well as systemically (e.g. blood, organs). What is less understood are the long-lived immunological effects of the memory T cell pool following T cell-mediated drug hypersensitivity reactions. In this study, we examine the ASM carbamazepine (CBZ) and the CBZ-reactive memory T cell pool in patients who have a history of either Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) from 3-to-20 years following their initial adverse reaction. We show that in vitro drug restimulation of CBZ-reactive CD8+ T cells results in a proinflammatory profile and produces a mainly focused, yet private, T cell receptor (TCR) usage amongst human leukocyte antigen (HLA)-B*15:02-positive SJS or TEN patients. Additionally, we show that expression of these CBZ-reactive TCRs in a reporter cell line, lacking endogenous αßTCR, recapitulates the features of TCR activation reported for ASM-treated T cell lines/clones, providing a useful tool for further functional validations. Finally, we conduct a comprehensive evaluation of the HLA-B*15:02 immunopeptidome following ASM (or a metabolite) treatment of a HLA-B*15:02-positive B-lymphoblastoid cell line (C1R.B*15:02) and minor perturbation of the peptide repertoire. Collectively, this study shows that the CBZ-reactive T cells characterized require both the drug and HLA-B*15:02 for activation and that reactivation of memory T cells from blood results in a focused private TCR profile in patients with resolved disease.


Assuntos
Anticonvulsivantes/efeitos adversos , Linfócitos T CD8-Positivos/imunologia , Carbamazepina/efeitos adversos , Seleção Clonal Mediada por Antígeno/efeitos dos fármacos , Síndrome de Stevens-Johnson/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Seleção Clonal Mediada por Antígeno/genética , Feminino , Antígeno HLA-B15/análise , Antígeno HLA-B15/metabolismo , Voluntários Saudáveis , Humanos , Memória Imunológica/efeitos dos fármacos , Masculino , Peptídeos/análise , Peptídeos/metabolismo , Cultura Primária de Células , Proteômica , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Síndrome de Stevens-Johnson/sangue
15.
Front Pediatr ; 9: 649775, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748051

RESUMO

The incidence of neonatal varicella has decreased dramatically since the introduction of the varicella vaccination. Although the varicella zoster virus is often associated with a mild infection, it may cause severe morbidity and mortality, particularly in the neonatal period and immunocompromised hosts. We report a case of neonatal varicella acquired from maternal zoster in a mother on biological immunosuppressive therapy. Following the diagnosis, the baby improved on antiviral therapy without any neurological sequelae. This case highlights the limited published data on neonatal varicella following herpes zoster reactivation to inform practice. This includes the role of varicella zoster immunoglobulin in neonates exposed to maternal zoster, the degree of trans-placental immunity and optimum antiviral dosing and duration.

16.
Asia Pac Allergy ; 11(1): e1, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33604271

RESUMO

BACKGROUND: Adrenaline autoinjectors (AAInj) facilitates early administration of adrenaline and remains the first-line treatment for anaphylaxis. However, only a minority of anaphylaxis survivors in Hong Kong are prescribed AAInj and formal guidance do not exist. International anaphylaxis guidelines have been largely based on Western studies, which may not be as relevant for non-Western populations. OBJECTIVE: To formulate a set of consensus statements on the prescription of AAInj in Hong Kong. METHODS: Consensus statements were formulated by the Hong Kong Anaphylaxis Consortium by the Delphi method. Agreement was defined as greater than or equal to 80% consensus. Subgroup analysis was performed to investigate differences between allergy and emergency medicine physicians. RESULTS: A total of 7 statements met criteria for consensus with good overall agreement between allergy and emergency medicine physicians. AAInj should be used as first-line treatment and prescribed for all patients at risk of anaphylaxis. This should be prescribed prior to discharge from the Accident and Emergency Department together with an immediate referral to an allergy center. The decision for prescribing AAInj should be based on the severity of previous reactions; including objective signs of respiratory involvement, objective signs of cardiovascular involvement and multiorgan involvement (regardless of severity). Patient demographics and comorbidities, specifically history of asthma or chronic obstructive pulmonary disease, should also be considered. Patients deemed eligible for AAInj should be offered avoidance advice and prescribed one AAInj while awaiting review by allergists. AAInj technique should be demonstrated by a healthcare professional or instruction video, and a return demonstration by the patient is required. The patient should also be counseled that the decision on the continued need of AAInj prescription in the long-term should be reviewed by an allergist. CONCLUSION: Consensus statements support the prescription of AAInj by front-line physicians with subsequent allergist review when treating patients at risk of anaphylaxis in Hong Kong.

17.
Pediatr Emerg Care ; 37(9): e579-e580, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30789871

RESUMO

ABSTRACT: We report the case of a young adult who became unresponsive after insufflating what he believed to be "crushed Xanax." Naloxone was administered, reversing his altered mental status and respiratory depression. Clinicians suspected opioid toxicity; however, the patient adamantly denied opioid use. Because of unclear etiology of his symptoms, blood and urine specimens were obtained. A urine specimen was split and then submitted for a clinical comprehensive drug screen using gas chromatography-mass spectrometry. The blood specimen and the remaining urine specimen were sent to a reference laboratory for analysis using liquid chromatography quadrupole time-of-flight mass spectrometry and liquid chromatography tandem mass spectrometry. The standard, clinical gas chromatography-mass spectrometry urine drug testing procedure only detected caffeine; however, analysis by liquid chromatography quadrupole time-of-flight mass spectrometry and liquid chromatography tandem mass spectrometry confirmed the presence of U-47700 (a high-potency clandestine opioid) and its metabolites in the urine and blood. These findings implicate U-47700 as the agent responsible for the patient's signs of opioid toxicity. In this case, a young adult intending to use alprazolam encountered U-47700 with life-threatening effect. Clinicians must remain vigilant for symptoms consistent with opioid overdose, especially with increasing prevalence of counterfeit drugs containing clandestine opioids. Clinicians must also consider obtaining specimens for appropriate analytical testing to improve surveillance and facilitate public health interventions.


Assuntos
Analgésicos Opioides , Overdose de Drogas , Alprazolam , Benzamidas , Overdose de Drogas/diagnóstico , Humanos , Masculino , Adulto Jovem
18.
J Med Toxicol ; 16(4): 405-415, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32253630

RESUMO

INTRODUCTION: Emergency department (ED)-based naloxone distribution programs are a widespread harm reduction strategy. However, data describing the community penetrance of naloxone distributed from these programs are lacking. This study gauges acceptance of naloxone use and monitoring technology among people who use drugs (PWUD), and explores the use of real-time location systems (RTLS) in monitoring naloxone movements. METHODS: A prospective observational study was conducted on a convenience sample of individuals (N = 30) presenting to a tertiary-care academic medical center ED for an opioid-related complaint. A naloxone kit equipped with a low-energy Bluetooth (BLE) tracking system was employed to detect movement of naloxone off the hospital campus as a proxy for community penetrance, followed by a qualitative interview to gauge participant acceptance of naloxone use and monitoring technology. RESULTS: Detection of BLE signals verified transit of 24 distributed naloxone kits off our hospital campus. Three participants whose BLE signals were not captured reported taking their kits with them following discharge, suggesting technological errors occurred; another three participants were lost to follow-up. Qualitative interviews demonstrated that participants accepted ED-based naloxone distribution programs and passive tracking technologies, but revealed concerns regarding hypothetical continuous monitoring systems and problematic interactions with first responders and law enforcement personnel. CONCLUSIONS: Based on acquired BLE signals, 80% of dispensed naloxone kits left the hospital campus. Use of RTLS to passively geolocate naloxone rescue kits is feasible, but detection can be adversely affected by technological errors. PWUD are amenable to transient monitoring technologies but identified barriers to implementation.


Assuntos
Overdose de Drogas/tratamento farmacológico , Serviço Hospitalar de Emergência , Sistemas de Informação Geográfica , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Epidemia de Opioides , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Tecnologia sem Fio , Adulto , Feminino , Redução do Dano , Humanos , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos
19.
Proc Annu Hawaii Int Conf Syst Sci ; 2020: 3488-3496, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32015694

RESUMO

The opioid epidemic is a growing public health emergency in the United States, with deaths from opioid overdose having increased five-fold since 1999. Emergency departments (EDs) are the primary sites of medical care after near-fatal opioid overdose but are poorly equipped to provide adequate substance use treatment planning prior to discharge. In many underserved locales, limited access to clinicians trained in addiction medicine and behavioral health exacerbates this disparity. In an effort to improve post-overdose care in the ED, we developed a telemedicine protocol to facilitate timely access to substance use disorder evaluations. In this paper, we describe the conception and refinement of the telemedicine program, our experience with the first 20 participants, and potential implications of the platform on health disparities for individuals with opioid use disorder.

20.
Curr Addict Rep ; 7(3): 291-300, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33738178

RESUMO

PURPOSE OF REVIEW: The goal of this scoping review is to evaluate the advances in wearable and other wireless mobile health (mHealth) technologies in the treatment of substance use disorders. RECENT FINDINGS: There are a variety of wireless technologies under investigation for the treatment of substance use disorder. Wearable sensors are the most commonly used technology. They can be used to decrease heavy substance use, mitigate factors related to relapse, and monitor for overdose. New technologies pose distinct advantages over traditional therapies by increasing geographic availability and continuously providing feedback and monitoring while remaining relatively non-invasive. SUMMARY: Wearable and novel technologies are important to the evolving landscape of substance use treatment. As technologies continue to develop and show efficacy, they should be incorporated into multifactorial treatment plans.

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