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1.
Cell ; 185(17): 3073-3078, 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-35985283

RESUMO

Many organizations persist in working with others that engage in known, remediable structural discrimination. We name this practice interorganizational structural discrimination (ISD) and argue it is a pivotal contributor to inequities in science and medicine. We urge organizations to leverage their relationships and demand progress from collaborators.

2.
Mol Psychiatry ; 29(8): 2335-2345, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38486050

RESUMO

Efforts to develop an individualized treatment rule (ITR) to optimize major depressive disorder (MDD) treatment with antidepressant medication (ADM), psychotherapy, or combined ADM-psychotherapy have been hampered by small samples, small predictor sets, and suboptimal analysis methods. Analyses of large administrative databases designed to approximate experiments followed iteratively by pragmatic trials hold promise for resolving these problems. The current report presents a proof-of-concept study using electronic health records (EHR) of n = 43,470 outpatients beginning MDD treatment in Veterans Health Administration Primary Care Mental Health Integration (PC-MHI) clinics, which offer access not only to ADMs but also psychotherapy and combined ADM-psychotherapy. EHR and geospatial databases were used to generate an extensive baseline predictor set (5,865 variables). The outcome was a composite measure of at least one serious negative event (suicide attempt, psychiatric emergency department visit, psychiatric hospitalization, suicide death) over the next 12 months. Best-practices methods were used to adjust for nonrandom treatment assignment and to estimate a preliminary ITR in a 70% training sample and to evaluate the ITR in the 30% test sample. Statistically significant aggregate variation was found in overall probability of the outcome related to baseline predictors (AU-ROC = 0.68, S.E. = 0.01), with test sample outcome prevalence of 32.6% among the 5% of patients having highest predicted risk compared to 7.1% in the remainder of the test sample. The ITR found that psychotherapy-only was the optimal treatment for 56.0% of patients (roughly 20% lower risk of the outcome than if receiving one of the other treatments) and that treatment type was unrelated to outcome risk among other patients. Change in aggregate treatment costs of implementing this ITR would be negligible, as 16.1% fewer patients would be prescribed ADMs and 2.9% more would receive psychotherapy. A pragmatic trial would be needed to confirm the accuracy of the ITR.


Assuntos
Antidepressivos , Transtorno Depressivo Maior , Registros Eletrônicos de Saúde , Medicina de Precisão , Psicoterapia , Veteranos , Humanos , Transtorno Depressivo Maior/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Psicoterapia/métodos , Antidepressivos/uso terapêutico , Adulto , Medicina de Precisão/métodos , Estados Unidos , Resultado do Tratamento , United States Department of Veterans Affairs , Idoso , Tentativa de Suicídio
3.
Artigo em Inglês | MEDLINE | ID: mdl-39241910

RESUMO

Leadless pacemakers have demonstrated potential as a transvenous pacing option in Adult Congenital Heart Disease patients. Aveir™ single-chamber (VR) leadless pacemakers have demonstrated safety in patients without congenital heart disease in a dual chamber approach. We present a case of dual-chamber pacing using the Aveir dual-chamber (DR) leadless pacemaker in a patient with repaired dextro-transposition of the great arteries with ventricular septal defect (VSD) surgical closure. A 26-year-old male patient with a history of transposition of the great arteries status post arterial switch and VSD repair neonatally had complicated second degree atrioventricular block and sinus node dysfunction necessitating pacemaker placement. Epicardial single-chamber ventricular pacemaker was placed neonatally, which was switched to dual-chamber pacemaker at age 17 due to malfunction. Recent fracture of pacemaker leads led to implantation of new dual chamber leadless pacemaker. Removal of previous pacemaker leads via mechanical extraction occurred and implantation of Aveir DR leadless pacemaker was performed under anesthesia via right femoral vein access without complication. Follow-up demonstrated Aveir VR threshold of 1.0V@0.2 ms, R-wave of 8.9mV, impedance of 490Ω, and the Aveir AR threshold of 0.75V@0.2 ms, P-wave of 3.7mV, and impedance of 400Ω. This case demonstrates safety and efficacy of dual chamber leadless pacemaker implantation in an ACHD patient.

4.
Psychol Med ; 53(8): 3591-3600, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35144713

RESUMO

BACKGROUND: Fewer than half of patients with major depressive disorder (MDD) respond to psychotherapy. Pre-emptively informing patients of their likelihood of responding could be useful as part of a patient-centered treatment decision-support plan. METHODS: This prospective observational study examined a national sample of 807 patients beginning psychotherapy for MDD at the Veterans Health Administration. Patients completed a self-report survey at baseline and 3-months follow-up (data collected 2018-2020). We developed a machine learning (ML) model to predict psychotherapy response at 3 months using baseline survey, administrative, and geospatial variables in a 70% training sample. Model performance was then evaluated in the 30% test sample. RESULTS: 32.0% of patients responded to treatment after 3 months. The best ML model had an AUC (SE) of 0.652 (0.038) in the test sample. Among the one-third of patients ranked by the model as most likely to respond, 50.0% in the test sample responded to psychotherapy. In comparison, among the remaining two-thirds of patients, <25% responded to psychotherapy. The model selected 43 predictors, of which nearly all were self-report variables. CONCLUSIONS: Patients with MDD could pre-emptively be informed of their likelihood of responding to psychotherapy using a prediction tool based on self-report data. This tool could meaningfully help patients and providers in shared decision-making, although parallel information about the likelihood of responding to alternative treatments would be needed to inform decision-making across multiple treatments.


Assuntos
Transtorno Depressivo Maior , Veteranos , Humanos , Transtorno Depressivo Maior/terapia , Depressão/terapia , Resultado do Tratamento , Psicoterapia
5.
Psychol Med ; 53(11): 5001-5011, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37650342

RESUMO

BACKGROUND: Only a limited number of patients with major depressive disorder (MDD) respond to a first course of antidepressant medication (ADM). We investigated the feasibility of creating a baseline model to determine which of these would be among patients beginning ADM treatment in the US Veterans Health Administration (VHA). METHODS: A 2018-2020 national sample of n = 660 VHA patients receiving ADM treatment for MDD completed an extensive baseline self-report assessment near the beginning of treatment and a 3-month self-report follow-up assessment. Using baseline self-report data along with administrative and geospatial data, an ensemble machine learning method was used to develop a model for 3-month treatment response defined by the Quick Inventory of Depression Symptomatology Self-Report and a modified Sheehan Disability Scale. The model was developed in a 70% training sample and tested in the remaining 30% test sample. RESULTS: In total, 35.7% of patients responded to treatment. The prediction model had an area under the ROC curve (s.e.) of 0.66 (0.04) in the test sample. A strong gradient in probability (s.e.) of treatment response was found across three subsamples of the test sample using training sample thresholds for high [45.6% (5.5)], intermediate [34.5% (7.6)], and low [11.1% (4.9)] probabilities of response. Baseline symptom severity, comorbidity, treatment characteristics (expectations, history, and aspects of current treatment), and protective/resilience factors were the most important predictors. CONCLUSIONS: Although these results are promising, parallel models to predict response to alternative treatments based on data collected before initiating treatment would be needed for such models to help guide treatment selection.


Assuntos
Transtorno Depressivo Maior , Veteranos , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Depressão , Antidepressivos/uso terapêutico , Aprendizado de Máquina
6.
J Gen Intern Med ; 37(13): 3235-3241, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-34613577

RESUMO

BACKGROUND: Physician responsiveness to patient preferences for depression treatment may improve treatment adherence and clinical outcomes. OBJECTIVE: To examine associations of patient treatment preferences with types of depression treatment received and treatment adherence among Veterans initiating depression treatment. DESIGN: Patient self-report surveys at treatment initiation linked to medical records. SETTING: Veterans Health Administration (VA) clinics nationally, 2018-2020. PARTICIPANTS: A total of 2582 patients (76.7% male, mean age 48.7 years, 62.3% Non-Hispanic White) MAIN MEASURES: Patient self-reported preferences for medication and psychotherapy on 0-10 self-anchoring visual analog scales (0="completely unwilling"; 10="completely willing"). Treatment receipt and adherence (refilling medications; attending 3+ psychotherapy sessions) over 3 months. Logistic regression models controlled for socio-demographics and geographic variables. KEY RESULTS: More patients reported strong preferences (10/10) for psychotherapy than medication (51.2% versus 36.7%, McNemar χ21=175.3, p<0.001). A total of 32.1% of patients who preferred (7-10/10) medication and 21.8% who preferred psychotherapy did not receive these treatments. Patients who strongly preferred medication were substantially more likely to receive medication than those who had strong negative preferences (odds ratios [OR]=17.5; 95% confidence interval [CI]=12.5-24.5). Compared with patients who had strong negative psychotherapy preferences, those with strong psychotherapy preferences were about twice as likely to receive psychotherapy (OR=1.9; 95% CI=1.0-3.5). Patients who strongly preferred psychotherapy were more likely to adhere to psychotherapy than those with strong negative preferences (OR=3.3; 95% CI=1.4-7.4). Treatment preferences were not associated with medication or combined treatment adherence. Patients in primary care settings had lower odds of receiving (but not adhering to) psychotherapy than patients in specialty mental health settings. Depression severity was not associated with treatment receipt or adherence. CONCLUSIONS: Mismatches between treatment preferences and treatment type received were common and associated with worse treatment adherence for psychotherapy. Future research could examine ways to decrease mismatch between patient preferences and treatments received and potential effects on patient outcomes.


Assuntos
Veteranos , Depressão/epidemiologia , Depressão/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Preferência do Paciente/psicologia , Psicoterapia , Veteranos/psicologia , Saúde dos Veteranos
7.
J Gastroenterol Hepatol ; 36(4): 873-884, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32632941

RESUMO

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third most common cause of cancer-related death. Long-term prognosis remains poor with treatment options frequently limited by advanced tumor stage, tumor location, or underlying liver dysfunction. Stereotactic ablative body radiotherapy (SABR) utilizes technological advances to deliver highly precise, tumoricidal doses of radiation. There is an emerging body of literature on SABR in HCC demonstrating high rates of local control in the order of 80-90% at 3 years. SABR is associated with a low risk of radiation-induced liver disease or decompensation in appropriately selected HCC patients with compensated liver function and is now being incorporated into guidelines as an additional treatment option. This review outlines the emerging role of SABR in the multidisciplinary management of HCC and summarizes the current evidence for its use as an alternative ablative option for early-stage disease, as a bridge to transplant, and as palliation for advanced-stage disease. We outline specific considerations regarding patient selection, toxicities, and response assessment. Finally, we compare current international guidelines and recommendations for the use of SABR and summarize ongoing studies.


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Radiocirurgia/métodos , Carcinoma Hepatocelular/patologia , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Estadiamento de Neoplasias , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Radiocirurgia/efeitos adversos , Dosagem Radioterapêutica
8.
Int J Cancer ; 146(8): 2305-2314, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31950498

RESUMO

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated "risk of bias" tool to assess study quality. Four separate Phase I-II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5-34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I-III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno CTLA-4/antagonistas & inibidores , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/imunologia , Antígeno CTLA-4/imunologia , Quimiorradioterapia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Nivolumabe/administração & dosagem , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/imunologia
9.
J Head Trauma Rehabil ; 35(1): 14-26, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31306300

RESUMO

OBJECTIVE: To estimate associations of lifetime traumatic brain injury (TBI) characteristics with prospective suicide attempt among US Army soldiers. METHOD: The Army STARRS (Study to Assess Risk and Resilience in Servicemembers) Pre/Post Deployment Study surveyed 3 Brigade Combat Teams that were deployed to Afghanistan in 2012. Lifetime TBI and past-month postconcussive/post-TBI symptoms were evaluated at predeployment baseline. Recency and number of TBIs were quantified, and TBI severity was classified on the basis of reports of alteration/loss of consciousness and memory lapse. Suicide attempt data came from administrative records and surveys administered after return from deployment. Logistic regression models estimated associations of TBI characteristics with prospective suicide attempt among baseline respondents who were deployed (n = 7677), adjusting for other risk factors including lifetime mental disorder. RESULTS: One hundred three soldiers made a suicide attempt over a median follow-up period of 30 months (weighted prevalence = 1.31% [0.14%]). In the final model estimating joint associations of TBI severity/recency and past-month postconcussive/post-TBI symptoms, only postconcussive/post-TBI symptoms were associated with a higher risk of suicide attempt (per standard score increase: AOR [adjusted odds ratio] = 1.31; 95% CI, 1.05-1.63; P = .012). CONCLUSIONS: Among the lifetime TBI characteristics evaluated at predeployment baseline, only past-month postconcussive/post-TBI symptoms were prospectively associated with an increased risk of suicide attempt following deployment. Detection of postconcussive/post-TBI symptoms could facilitate targeting of Army suicide prevention programs.


Assuntos
Lesões Encefálicas Traumáticas/psicologia , Militares/psicologia , Tentativa de Suicídio/estatística & dados numéricos , Adulto , Campanha Afegã de 2001- , Feminino , Humanos , Masculino , Destacamento Militar , Estudos Prospectivos , Fatores Socioeconômicos , Estados Unidos , Adulto Jovem
10.
Soc Psychiatry Psychiatr Epidemiol ; 53(3): 279-288, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29340781

RESUMO

PURPOSE: The primary aims are to (1) obtain representative prevalence estimates of suicidal thoughts and behaviors (STB) among college students worldwide and (2) investigate whether STB is related to matriculation to and attrition from college. METHODS: Data from the WHO World Mental Health Surveys were analyzed, which include face-to-face interviews with 5750 young adults aged 18-22 spanning 21 countries (weighted mean response rate = 71.4%). Standardized STB prevalence estimates were calculated for four well-defined groups of same-aged peers: college students, college attriters (i.e., dropouts), secondary school graduates who never entered college, and secondary school non-graduates. Logistic regression assessed the association between STB and college entrance as well as attrition from college. RESULTS: Twelve-month STB in college students was 1.9%, a rate significantly lower than same-aged peers not in college (3.4%; OR 0.5; p < 0.01). Lifetime prevalence of STB with onset prior to age 18 among college entrants (i.e., college students or attriters) was 7.2%, a rate significantly lower than among non-college attenders (i.e., secondary school graduates or non-graduates; 8.2%; OR 0.7; p = 0.03). Pre-matriculation onset STB (but not post-matriculation onset STB) increased the odds of college attrition (OR 1.7; p < 0.01). CONCLUSION: STB with onset prior to age 18 is associated with reduced likelihood of college entrance as well as greater attrition from college. Future prospective research should investigate the causality of these associations and determine whether targeting onset and persistence of childhood-adolescent onset STB leads to improved educational attainment.


Assuntos
Grupo Associado , Estudantes/estatística & dados numéricos , Ideação Suicida , Tentativa de Suicídio/estatística & dados numéricos , Adolescente , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Prevalência , Estudantes/psicologia , Tentativa de Suicídio/psicologia , Universidades , Organização Mundial da Saúde , Adulto Jovem
11.
Br J Psychiatry ; 211(5): 280-288, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28935660

RESUMO

BackgroundAlthough childhood adversities are known to predict increased risk of post-traumatic stress disorder (PTSD) after traumatic experiences, it is unclear whether this association varies by childhood adversity or traumatic experience types or by age.AimsTo examine variation in associations of childhood adversities with PTSD according to childhood adversity types, traumatic experience types and life-course stage.MethodEpidemiological data were analysed from the World Mental Health Surveys (n = 27 017).ResultsFour childhood adversities (physical and sexual abuse, neglect, parent psychopathology) were associated with similarly increased odds of PTSD following traumatic experiences (odds ratio (OR) = 1.8), whereas the other eight childhood adversities assessed did not predict PTSD. Childhood adversity-PTSD associations did not vary across traumatic experience types, but were stronger in childhood-adolescence and early-middle adulthood than later adulthood.ConclusionsChildhood adversities are differentially associated with PTSD, with the strongest associations in childhood-adolescence and early-middle adulthood. Consistency of associations across traumatic experience types suggests that childhood adversities are associated with generalised vulnerability to PTSD following traumatic experiences.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância/estatística & dados numéricos , Filho de Pais com Deficiência/estatística & dados numéricos , Saúde Mental/estatística & dados numéricos , Trauma Psicológico/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Sobreviventes Adultos de Maus-Tratos Infantis/estatística & dados numéricos , Fatores Etários , Saúde Global/estatística & dados numéricos , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos
13.
ANZ J Surg ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946707

RESUMO

BACKGROUND: Advanced skull base malignancies are a heterogenous subset of head and neck cancers, and management is often complex. In recent times, there has been a paradigm shift in surgical technique and the advent of novel systemic options. Our goal was to analyse the long-term outcomes of a single quaternary head and neck and skull base service. METHODS: A retrospective review of 127 patients with advanced anterior skull base malignancies that were treated at our institution between 1999 and 2015 was performed. Multiple variables were investigated to assess their significance on 5 and 10-year outcomes. RESULTS: The mean age was 60.9 (± 12.6 SD). Sixty-four percent were males and 36% were females. Ninety percent of patients had T4 disease. Median survival time was 133 months. The 5-year overall survival (OS) was 66.2%, disease-specific survival (DSS) was 74.7%, and recurrence-free survival (RFS) was 65.0%. The 10-year OS was 55.1%, DSS was 72.1%, and RFS was 53.4%. Histological type and margin status significantly affected OS & DSS. CONCLUSION: Surgical management of advanced skull base tumours has evolved over the last few decades at our institution with acceptable survival outcomes and complication rates. Histological diagnosis and margin status are the main predictors of survival. The addition of neoadjuvant systemic agents in current trials may improve outcomes.

14.
Child Adolesc Psychiatr Clin N Am ; 33(1): 17-32, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37981333

RESUMO

Documented disparities have profoundly impacted the training and careers of physicians from socially and historically marginalized groups, including women, people with disabilities, people who identify with racial and ethnic minority groups, and the lesbian, gay, bisexual, transgender, and queer or questioning+ community. Professionalism is a core component of medical training and practice, yet a focus on workforce diversity, equity, and inclusion is often absent. This report aims to encourage the adoption of workforce diversity, equity, and inclusion as a crucial component of professionalism, with an emphasis on the field of psychiatry.


Assuntos
Profissionalismo , Psiquiatria , Humanos , Feminino , Etnicidade , Grupos Minoritários , Recursos Humanos
15.
Oral Oncol ; 150: 106687, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38262249

RESUMO

OBJECTIVES: The incidence of human papillomavirus positive oropharyngeal cancer (HPV+OPC) is increasing, and new biomarkers are required to better define prognostic groups and guide treatment. Infiltrating T cells have been well studied in head and neck cancer, however the presence and role of B cells and tertiary lymphoid structures (TLS) in the tumor microenvironment has not, even though the interplay between T and B cells is increasingly being recognised. MATERIALS AND METHODS: Using CD20 immunohistochemistry (IHC) to identify B cells and TLS in a cohort of 159 HPV + OPC patients, we semi-quantitatively scored abundance and location (intra-tumoral or stromal) and correlated findings with patient survival. RESULTS: 32% (51/157) of patients had high intra-tumoral (IT) abundance of CD20+ B cells (≥5%) and this was prognostic for improved overall survival (OS) with an adjusted hazard ratio (HR) of 0.2 (95 % CI 0.0-0.7, p = 0.014). We validated our results in an independent cohort comprising 171 HPV + OPC where 14% (23/171) were IT CD20+ high, again showing improved survival with an adjusted HR for OS of 0.2 (95 % CI 0.0-1.4, p = 0.003). Neither stromal abundance nor the presence of TLS were prognostic in either cohort. B cells were subtyped by multispectral IHC, identifying CD20+CD27+ cells, consistent with memory B cells, as the predominant subtype. Combined with validated biomarker CD103, a marker of tissue-resident memory T cells, IT CD20+ B cells abundance was able to prognostically stratify patients further. CONCLUSIONS: CD20+ B cell abundance has the potential to be used as a biomarker to identify good and poor prognosis HPV + OPC patients.


Assuntos
Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Prognóstico , Biomarcadores , Papillomavirus Humano , Microambiente Tumoral
16.
Front Oncol ; 14: 1419258, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39035738

RESUMO

Background: Programmed cell death ligand 1 (PD-L1) inhibitors have limited efficacy as monotherapy in patients with recurrent/metastatic (R/M) Human Papilloma Virus (HPV) oropharyngeal squamous cell carcinoma (OPSCC). A phase I study of the therapeutic HPV-16 DNA vaccine AMV002 in curatively treated patients with OPSCC demonstrated a measurable immune response against HPV while being associated with high safety and tolerability. This prospective phase Ib single centre pilot study aims to test the safety and tolerability of combined PD-L1 inhibitor, Durvalumab, with AMV002 in 12 patients with recurrent OPSCC. Methods: Participants had evidence of R/M HPV-associated OPSCC. They received three intradermal administrations of AMV002 with Durvalumab followed by Durvalumab maintenance. Safety and tolerability data was the primary endpoint. The study was conducted with ethical approval (HREC/2018/QMS/47293) in Brisbane, Australia. Findings: The most common adverse event (AE) related to vaccine administration was erythema at the injection site. There were no grade 3 or 4 vaccine related AEs. There was one presumed immune-related grade 3 elevation in lipase secondary to Durvalumab with no intervention required. No patient ceased study due to treatment-related AEs. At week 16, objective response rate was 8% (N=1) and disease control rate was 17% (N=2). At a median follow up of 25.6 (20.0-26.6) months there was one long term complete response while all other participants developed progressive disease. Of the 11 evaluated patients, 9, (82%) had E6 and/or E7-specific T cell responses to the vaccine. Conclusion: The combination of AMV002 therapeutic HPV-16 vaccine and Durvalumab was found to be safe and well tolerated with no increased safety signals generated. T cell responses to vaccine were observed but further work will be required to improve efficacy.

17.
JAMA Psychiatry ; 81(2): 135-143, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37851457

RESUMO

Importance: Psychiatric hospitalization is the standard of care for patients presenting to an emergency department (ED) or urgent care (UC) with high suicide risk. However, the effect of hospitalization in reducing subsequent suicidal behaviors is poorly understood and likely heterogeneous. Objectives: To estimate the association of psychiatric hospitalization with subsequent suicidal behaviors using observational data and develop a preliminary predictive analytics individualized treatment rule accounting for heterogeneity in this association across patients. Design, Setting, and Participants: A machine learning analysis of retrospective data was conducted. All veterans presenting with suicidal ideation (SI) or suicide attempt (SA) from January 1, 2010, to December 31, 2015, were included. Data were analyzed from September 1, 2022, to March 10, 2023. Subgroups were defined by primary psychiatric diagnosis (nonaffective psychosis, bipolar disorder, major depressive disorder, and other) and suicidality (SI only, SA in past 2-7 days, and SA in past day). Models were trained in 70.0% of the training samples and tested in the remaining 30.0%. Exposures: Psychiatric hospitalization vs nonhospitalization. Main Outcomes and Measures: Fatal and nonfatal SAs within 12 months of ED/UC visits were identified in administrative records and the National Death Index. Baseline covariates were drawn from electronic health records and geospatial databases. Results: Of 196 610 visits (90.3% men; median [IQR] age, 53 [41-59] years), 71.5% resulted in hospitalization. The 12-month SA risk was 11.9% with hospitalization and 12.0% with nonhospitalization (difference, -0.1%; 95% CI, -0.4% to 0.2%). In patients with SI only or SA in the past 2 to 7 days, most hospitalization was not associated with subsequent SAs. For patients with SA in the past day, hospitalization was associated with risk reductions ranging from -6.9% to -9.6% across diagnoses. Accounting for heterogeneity, hospitalization was associated with reduced risk of subsequent SAs in 28.1% of the patients and increased risk in 24.0%. An individualized treatment rule based on these associations may reduce SAs by 16.0% and hospitalizations by 13.0% compared with current rates. Conclusions and Relevance: The findings of this study suggest that psychiatric hospitalization is associated with reduced average SA risk in the immediate aftermath of an SA but not after other recent SAs or SI only. Substantial heterogeneity exists in these associations across patients. An individualized treatment rule accounting for this heterogeneity could both reduce SAs and avert hospitalizations.


Assuntos
Transtorno Depressivo Maior , Ideação Suicida , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Tentativa de Suicídio/psicologia , Hospitalização , Fatores de Risco
18.
Int J Methods Psychiatr Res ; 33(4): e70003, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39352173

RESUMO

BACKGROUND: The period after psychiatric hospital discharge is one of elevated risk for suicide-related behaviors (SRBs). Post-discharge clinical outreach, although potentially effective in preventing SRBs, would be more cost-effective if targeted at high-risk patients. To this end, a machine learning model was developed to predict post-discharge suicides among Veterans Health Administration (VHA) psychiatric inpatients and target a high-risk preventive intervention. METHODS: The Veterans Coordinated Community Care (3C) Study is a multicenter randomized controlled trial using this model to identify high-risk VHA psychiatric inpatients (n = 850) randomized with equal allocation to either the Coping Long Term with Active Suicide Program (CLASP) post-discharge clinical outreach intervention or treatment-as-usual (TAU). The primary outcome is SRBs over a 6-month follow-up. We will estimate average treatment effects adjusted for loss to follow-up and investigate the possibility of heterogeneity of treatment effects. RESULTS: Recruitment is underway and will end September 2024. Six-month follow-up will end and analysis will begin in Summer 2025. CONCLUSION: Results will provide information about the effectiveness of CLASP versus TAU in reducing post-discharge SRBs and provide guidance to VHA clinicians and policymakers about the implications of targeted use of CLASP among high-risk psychiatric inpatients in the months after hospital discharge. CLINICAL TRIALS REGISTRATION: ClinicalTrials.Gov identifier: NCT05272176 (https://www. CLINICALTRIALS: gov/ct2/show/NCT05272176).


Assuntos
Pacientes Internados , Alta do Paciente , Prevenção do Suicídio , Veteranos , Humanos , Estados Unidos , Transtornos Mentais/prevenção & controle , Transtornos Mentais/terapia , United States Department of Veterans Affairs , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Seguimentos
19.
JAMA Psychiatry ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39320863

RESUMO

Importance: The suicide rate of military servicemembers increases sharply after returning to civilian life. Identifying high-risk servicemembers before they leave service could help target preventive interventions. Objective: To develop a model based on administrative data for regular US Army soldiers that can predict suicides 1 to 120 months after leaving active service. Design, Setting, and Participants: In this prognostic study, a consolidated administrative database was created for all regular US Army soldiers who left service from 2010 through 2019. Machine learning models were trained to predict suicides over the next 1 to 120 months in a random 70% training sample. Validation was implemented in the remaining 30%. Data were analyzed from March 2023 through March 2024. Main outcome and measures: The outcome was suicide in the National Death Index. Predictors came from administrative records available before leaving service on sociodemographics, Army career characteristics, psychopathologic risk factors, indicators of physical health, social networks and supports, and stressors. Results: Of the 800 579 soldiers in the cohort (84.9% male; median [IQR] age at discharge, 26 [23-33] years), 2084 suicides had occurred as of December 31, 2019 (51.6 per 100 000 person-years). A lasso model assuming consistent slopes over time discriminated as well over all but the shortest risk horizons as more complex stacked generalization ensemble machine learning models. Test sample area under the receiver operating characteristic curve ranged from 0.87 (SE = 0.06) for suicides in the first month after leaving service to 0.72 (SE = 0.003) for suicides over 120 months. The 10% of soldiers with highest predicted risk accounted for between 30.7% (SE = 1.8) and 46.6% (SE = 6.6) of all suicides across horizons. Calibration was for the most part better for the lasso model than the super learner model (both estimated over 120-month horizons.) Net benefit of a model-informed prevention strategy was positive compared with intervene-with-all or intervene-with-none strategies over a range of plausible intervention thresholds. Sociodemographics, Army career characteristics, and psychopathologic risk factors were the most important classes of predictors. Conclusions and relevance: These results demonstrated that a model based on administrative variables available at the time of leaving active Army service can predict suicides with meaningful accuracy over the subsequent decade. However, final determination of cost-effectiveness would require information beyond the scope of this report about intervention content, costs, and effects over relevant horizons in relation to the monetary value placed on preventing suicides.

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