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BACKGROUND: The rapid growth of social media as an information channel has made it possible to quickly spread inaccurate or false vaccine information, thus creating obstacles for vaccine promotion. OBJECTIVE: The aim of this study is to develop and evaluate an intelligent automated protocol for identifying and classifying human papillomavirus (HPV) vaccine misinformation on social media using machine learning (ML)-based methods. METHODS: Reddit posts (from 2007 to 2017, N=28,121) that contained keywords related to HPV vaccination were compiled. A random subset (2200/28,121, 7.82%) was manually labeled for misinformation and served as the gold standard corpus for evaluation. A total of 5 ML-based algorithms, including a support vector machine, logistic regression, extremely randomized trees, a convolutional neural network, and a recurrent neural network designed to identify vaccine misinformation, were evaluated for identification performance. Topic modeling was applied to identify the major categories associated with HPV vaccine misinformation. RESULTS: A convolutional neural network model achieved the highest area under the receiver operating characteristic curve of 0.7943. Of the 28,121 Reddit posts, 7207 (25.63%) were classified as vaccine misinformation, with discussions about general safety issues identified as the leading type of misinformed posts (2666/7207, 36.99%). CONCLUSIONS: ML-based approaches are effective in the identification and classification of HPV vaccine misinformation on Reddit and may be generalizable to other social media platforms. ML-based methods may provide the capacity and utility to meet the challenge involved in intelligent automated monitoring and classification of public health misinformation on social media platforms. The timely identification of vaccine misinformation on the internet is the first step in misinformation correction and vaccine promotion.
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Vacinas contra Papillomavirus , Mídias Sociais , Comunicação , Humanos , Aprendizado de Máquina , Saúde PúblicaRESUMO
BACKGROUND: Social media platforms such as YouTube are hotbeds for the spread of misinformation about vaccines. OBJECTIVE: The aim of this study was to explore how individuals are exposed to antivaccine misinformation on YouTube based on whether they start their viewing from a keyword-based search or from antivaccine seed videos. METHODS: Four networks of videos based on YouTube recommendations were collected in November 2019. Two search networks were created from provaccine and antivaccine keywords to resemble goal-oriented browsing. Two seed networks were constructed from conspiracy and antivaccine expert seed videos to resemble direct navigation. Video contents and network structures were analyzed using the network exposure model. RESULTS: Viewers are more likely to encounter antivaccine videos through direct navigation starting from an antivaccine video than through goal-oriented browsing. In the two seed networks, provaccine videos, antivaccine videos, and videos containing health misinformation were all found to be more likely to lead to more antivaccine videos. CONCLUSIONS: YouTube has boosted the search rankings of provaccine videos to combat the influence of antivaccine information. However, when viewers are directed to antivaccine videos on YouTube from another site, the recommendation algorithm is still likely to expose them to additional antivaccine information.
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Comunicação , Disseminação de Informação/métodos , Mídias Sociais/normas , Vacinas/uso terapêutico , Algoritmos , HumanosRESUMO
The human papillomavirus (HPV) vaccine protects adolescents and young adults from 9 high-risk HPV virus types that cause 90% of cervical and anal cancers and 70% of oropharyngeal cancers. This study extends our previous research analyzing online content concerning the HPV vaccination in social media platforms used by young adults, in which we used Pathfinder network scaling and methods of distributional semantics to characterize differences in knowledge organization reflected in consumer- and expert-generated online content. The current study extends this approach to evaluate HPV vaccine perceptions among young adults who populate Reddit, a major social media platform. We derived Pathfinder networks from estimates of semantic relatedness obtained by learning word embeddings from Reddit posts and compared these to networks derived from human expert estimation of the relationship between key concepts. Results revealed that users of Reddit, predominantly comprising young adults in the vaccine catch up age-group 18 through 26 years of age, perceived the HPV vaccine domain from a virus-framed perspective that could impact their lifestyle choices and that their awareness of the HPV vaccine for cancer prevention is also lacking. Further differences in knowledge structures were elucidated, with implications for future health communication initiatives.
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Conhecimentos, Atitudes e Prática em Saúde , Vacinas contra Papillomavirus/genética , Semântica , Criança , Feminino , Humanos , MasculinoRESUMO
Safe use of immune checkpoint blockade in patients with cancer and autoimmune disorders requires a better understanding of the pathophysiology of immunologic activation. We describe the immune correlates of reactivation of granulomatosis with polyangiitis (GPA)-an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis-in a patient with metastatic urothelial carcinoma treated with pembrolizumab. After PD-1 blockade, an inflammatory pulmonary nodule demonstrated a granulomatous, CD4+ T-cell infiltrate, correlating with increased CD4+ and CD8+ naïve memory cells in the peripheral blood without changes in other immune checkpoint receptors. Placed within the context of the existing literature on GPA and disease control, our findings suggest a key role for PD-1 in GPA self-tolerance and that selective strategies for immunotherapy may be needed in patients with certain autoimmune disorders. We further summarize the current literature regarding reactivation of autoimmune disorders in patients undergoing immune checkpoint blockade, as well as potential immunosuppressive strategies to minimize the risks of further vasculitic reactivation upon rechallenge with anti-PD-1 blockade. KEY POINTS: Nonspecific imaging findings in patients with cancer and rheumatological disorders may require biopsy to distinguish underlying pathology.Patients with rheumatologic disorders have increased risk of reactivation with PD-(L)1 immune checkpoint blockade, requiring assessment of disease status before starting treatment.Further study is needed to evaluate the efficacy of treatment regimens in preventing and controlling disease reactivation.
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Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma de Células de Transição/diagnóstico , Granulomatose com Poliangiite/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Adrenalectomia , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/imunologia , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/métodos , Cistectomia , Diagnóstico Diferencial , Granulomatose com Poliangiite/induzido quimicamente , Granulomatose com Poliangiite/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/imunologia , Neoplasia Endócrina Múltipla Tipo 2a/terapia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/imunologia , Nefroureterectomia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Prostatectomia , Exacerbação dos Sintomas , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/imunologiaRESUMO
Peripheral blood mononuclear cells (PBMCs) are essential to the study of autoimmune, infectious, parasitic diseases, and cancer. In the rapidly growing field of cancer immunology, cellular phenotyping provides critical information about patient responses to treatments and treatment efficacies. Notably, the evaluation of T cell based therapies relies on the isolation of highly viable CD3+ T cell, CD4+ Helper T cell, and CD8+ Cytotoxic T cell populations before and during patient treatments. Cryopreservation of PBMC populations allows researchers to thaw and characterize clinical samples by flow cytometry, mass cytometry, sequencing, etc. in a high-throughput manner and in batches. Therefore, it is important to separate and bank an abundance of robust circulating immune cells. Here, we report our internal protocols for the high-quality separation, banking, and thawing of clinically relevant PBMC populations. We present quality control data from 11 melanoma patients and characterize their CD3+, CD4+, and CD8+ T cells by 4-color flow cytometry.
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Bancos de Espécimes Biológicos/normas , Separação Celular/métodos , Leucócitos Mononucleares/patologia , Melanoma/sangue , Melanoma/patologia , Controle de Qualidade , Contagem de Células , Sobrevivência Celular , Humanos , Imunofenotipagem , Estadiamento de NeoplasiasRESUMO
This study demonstrates the use of distributed vector representations and Pathfinder Network Scaling (PFNETS) to represent online vaccine content created by health experts and by laypeople. By analyzing a target audience's conceptualization of a topic, domain experts can develop targeted interventions to improve the basic health knowledge of consumers. The underlying assumption is that the content created by different groups reflects the mental organization of their knowledge. Applying automated text analysis to this content may elucidate differences between the knowledge structures of laypeople (heath consumers) and professionals (health experts). This paper utilizes vaccine information generated by laypeople and health experts to investigate the utility of this approach. We used an established technique from cognitive psychology, Pathfinder Network Scaling to infer the structure of the associational networks between concepts learned from online content using methods of distributional semantics. In doing so, we extend the original application of PFNETS to infer knowledge structures from individual participants, to infer the prevailing knowledge structures within communities of content authors. The resulting graphs reveal opportunities for public health and vaccination education experts to improve communication and intervention efforts directed towards health consumers. Our efforts demonstrate the feasibility of using an automated procedure to examine the manifestation of conceptual models within large bodies of free text, revealing evidence of conflicting understanding of vaccine concepts among health consumers as compared with health experts. Additionally, this study provides insight into the differences between consumer and expert abstraction of domain knowledge, revealing vaccine-related knowledge gaps that suggest opportunities to improve provider-patient communication.
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Participação da Comunidade , Sistemas On-Line , Vacinas , Automação , HumanosRESUMO
BACKGROUND: Tanning accelerators are topical products used by indoor tanners to augment and hasten the tanning process. These products contain tyrosine, psoralens, and/or other chemicals. OBJECTIVE: We sought to better define the population using accelerators, identify predictors of their use, and describe any related adverse effects. METHODS: This cross-sectional study surveyed 200 indoor tanners about their tanning practices and accelerator use. Primary analysis compared accelerator users with nonusers with respect to questionnaire variables. Descriptive statistics and χ(2) contingency tables were applied to identify statistically significant variables. RESULTS: Of respondents, 53% used accelerators; 97% were female and 3% were male with a median age of 22 years (range: 19-67). Users were more likely to spray tan, tan frequently, and be addicted to tanning. Acne and rashes were more common in accelerator users. Adverse reactions to accelerators prevented their further use 31% of the time. LIMITATIONS: A limited adult population was evaluated; exact accelerator ingredients were not examined. CONCLUSIONS: Tanning accelerator users are high-risk indoor tanners who tan more frequently and who are more likely addicted to tanning. Acne and rashes are more common with these products and act as only mild deterrents to continued use. Additional research should investigate accelerators' longer-term health effects.
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Cosméticos/efeitos adversos , Banho de Sol , Raios Ultravioleta , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Banho de Sol/estatística & dados numéricos , Adulto JovemRESUMO
OBJECTIVES: Immunization forecasting systems evaluate patient vaccination histories and recommend the dates and vaccines that should be administered. We described the conceptualization, development, implementation, and distribution of a novel immunization forecaster, the Texas Children's Hospital (TCH) Forecaster. METHODS: In 2007, TCH convened an internal expert team that included a pediatrician, immunization nurse, software engineer, and immunization subject matter experts to develop the TCH Forecaster. Our team developed the design of the model, wrote the software, populated the Excel tables, integrated the software, and tested the Forecaster. We created a table of rules that contained each vaccine's recommendations, minimum ages and intervals, and contraindications, which served as the basis for the TCH Forecaster. RESULTS: We created 15 vaccine tables that incorporated 79 unique dose states and 84 vaccine types to operationalize the entire United States recommended immunization schedule. The TCH Forecaster was implemented throughout the TCH system, the Indian Health Service, and the Virginia Department of Health. The TCH Forecast Tester is currently being used nationally. CONCLUSIONS: Immunization forecasting systems might positively affect adherence to vaccine recommendations. Efforts to support health care provider utilization of immunization forecasting systems and to evaluate their impact on patient care are needed.
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Sistemas de Gerenciamento de Base de Dados , Previsões/métodos , Hospitais Pediátricos , Programas de Imunização/organização & administração , Criança , Pré-Escolar , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Esquemas de Imunização , Lactente , Recém-Nascido , Masculino , Sistemas Computadorizados de Registros Médicos , Modelos Organizacionais , Sistemas de Alerta , Design de Software , TexasRESUMO
OBJECTIVES: Data on US caregiver perceptions on coronavirus disease 2019 (COVID-19) and COVID-19 vaccination are limited. We identified trends in and associations with COVID-19 vaccine hesitancy in caregivers of hospitalized children. METHODS: Cross-sectional surveys on pediatric COVID-19 disease and vaccine attitudes, behaviors, and beliefs were administered across study years (December 8, 2020-April 5, 2021, November 30, 2021-March 15, 2022, and October 26, 2022-March 15, 2023). English and Spanish-speaking caregivers of hospitalized children ages 6 months to 11 years were included. General vaccine hesitancy was assessed using the Parent Attitudes about Childhood Vaccines survey. RESULTS: Of 1268 caregivers from diverse backgrounds, one-third vaccinated or intended to vaccinate their child. Half endorsed fear of their child receiving the COVID-19 vaccine and were concerned the vaccine was new. Over time, more believed "the COVID-19 vaccine does not work" and fewer agreed "children who are otherwise healthy can die from COVID-19." Study season (2022-2023), older child age, higher income, child receipt of influenza vaccine, caregiver receipt of COVID-19 vaccine, and not being worried about vaccine novelty were positively associated with child vaccination. Intent to vaccinate was negatively associated with study season (2022-2023), Parent Attitudes about Childhood Vaccines score ≥50, lack of child influenza and caregiver COVID-19 vaccination, lack of fear of their child "getting COVID-19" and being "worried that the COVID-19 vaccine is new." The majority who intended to vaccinate were willing to immunize before discharge. CONCLUSIONS: Vaccine novelty and perceived lack of need were associated with refusal. Caregiver COVID-19 and child influenza vaccine acceptance were positively associated with COVID-19 vaccine acceptance. The inpatient setting offers the opportunity to improve vaccine uptake.
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CRISPR therapy for hematological disease has proven effective for transplant dependent beta thalassemia and sickle cell anemia, with additional disease targets in sight. The success of these therapies relies on high rates of CRISPR-induced double strand DNA breaks in hematopoietic stem and progenitor cells (HSPC). To achieve these levels, CRISPR complexes are typically delivered by electroporation ex vivo which is toxic to HSPCs. HSPCs are then cultured in stimulating conditions that promote error-prone DNA repair, requiring conditioning with chemotherapy to facilitate engraftment after reinfusion. In vivo delivery by nanocarriers of CRISPR gene editing tools has the potential to mitigate this complexity and toxicity and make this revolutionary therapy globally available. To achieve in vivo delivery, the inherent restriction factors against oligonucleotide delivery into HSPCs, that make ex vivo manipulation including electroporation and stimulation essential, must be overcome. To this end, our group developed a CRISPR carrying gold nanoparticle (CRISPR-AuNP) capable of delivering either Cas9 or Cas12a CRISPRs as ribonucleoprotein complexes (RNP) without compromising HSPC fitness. However, the most commonly used CRISPR, Cas9, demonstrated inconsistent activity in this delivery system, with lower activity relative to Cas12a. Investigation of Cas9 RNP biophysics relative to Cas12a revealed duplex RNA instability during the initial loading onto Au cores, resulting in undetectable Cas9 loading to the particle surface. Here we demonstrate preformation of RNP before loading, coupled with optimization of the loading chemistry and conditions, resulted in 39.6 ± 7.0 Cas9 RNP/AuNP without compromising RNP activity in both in vitro assays and primary human HSPC. The same alterations improved Cas12a RNP/AuNP loading 10-fold over previously reported levels. To achieve particle stability, the reported polyethyleneimine outer coating was altered to include PEGylation and the resulting 2nd generation CRISPR-AuNP demonstrates favorable nanoformulation characteristics for in vivo administration, with a hydrophilic, more neutral nanoparticle surface. Direct treatment of HSPC in vitro showed 72.5 ± 7.37% uptake of 2nd generation CRISPR-AuNP in primary human HSPC, but with endosomal accumulation and low rates of gene editing consistent with low levels of endosomal escape.
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In this paper, we explore the benefits of storytelling in health communication and, in particular, immunization education. During the mid-20th century polio epidemic, both personal stories and scientific information abounded in the media. However, as rates of vaccine-preventable diseases declined, narratives about the dangers of such diseases faded as did the public fear of them. Meanwhile, anti-vaccine advocates flooded the media and Internet with stories of injured children and tied those injuries, such as autism, to vaccines. Medical experts often counter anti-vaccine concerns with scientific information which can fail to persuade parents. Furthermore, evidence suggests that many people misunderstand quantitative information resulting in a misinterpretation of risk. Compared to scientific information, stories relate life lessons and values. They are effective because they are memorable and relatable. Evidence also suggests that storytelling can effectively improve health knowledge and behaviors. Inspired by In Harm's Way--True Stories of Uninsured Texas Children by the Children's Defense Fund and Faces of Influenza by the American Lung Association, we published Vaccine-Preventable Disease: The Forgotten Story, a collection of photographs and personal stories of families affected by vaccine-preventable diseases. We have found that the stories included in our booklet capture all the benefits of storytelling. Given the many benefits of storytelling, providers should strive to include stories along with medical facts in their daily practice.
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Atenção à Saúde/métodos , Educação em Saúde/métodos , Controle de Infecções/métodos , Meios de Comunicação de Massa , Vacinação , Humanos , Estados UnidosRESUMO
Opioids are among the most effective analgesics for the management of pain in the acute phase of a spinal cord injury (SCI), and approximately 80% of patients are treated with morphine in the first 24 h following SCI. We have found that morphine treatment in the first 7 days after SCI increases symptoms of pain at 42 days post-injury and undermines the recovery of locomotor function in a rodent model. Prior research has implicated microglia/macrophages in opioid-induced hyperalgesia and the development of neuropathic pain. We hypothesized that glial activation may also underlie the development of morphine-induced pain and cell death after SCI. Supporting this hypothesis, our previous studies found that intrathecal and intravenous morphine increase the number of activated microglia and macrophages present at the spinal lesion site, and that the adverse effects of intrathecal morphine can be blocked with intrathecal minocycline. Recognizing that the cellular expression of opioid receptors, and the intracellular signaling pathways engaged, can change with repeated administration of opioids, the current study tested whether minocycline was also protective with repeated intravenous morphine administration, more closely simulating clinical treatment. Using a rat model of SCI, we co-administered intravenous morphine and intrathecal minocycline for the first 7 days post injury and monitored sensory and locomotor recovery. Contrary to our hypothesis and previous findings with intrathecal morphine, we found that minocycline did not prevent the negative effects of morphine. Surprisingly, we also found that intrathecal minocycline alone is detrimental for locomotor recovery after SCI. Using ex vivo cell cultures, we investigated how minocycline and morphine altered microglia/macrophage function. Commensurate with published studies, we found that minocycline blocked the effects of morphine on the release of pro-inflammatory cytokines but, like morphine, it increased glial phagocytosis. While phagocytosis is critical for the removal of cellular and extracellular debris at the spinal injury site, increased phagocytosis after injury has been linked to the clearance of stressed but viable neurons and protracted inflammation. In sum, our data suggest that both morphine and minocycline alter the acute immune response, and reduce locomotor recovery after SCI.
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Neuralgia , Traumatismos da Medula Espinal , Ratos , Animais , Morfina , Minociclina/uso terapêutico , Recuperação de Função Fisiológica , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Analgésicos Opioides , Neuralgia/metabolismo , Medula Espinal/patologiaRESUMO
Immediately following spinal cord injury (SCI) patients experience pain associated with injury to the spinal cord and nerves as well as with accompanying peripheral injuries. This pain is usually treated with opioids, and most commonly with morphine. However, in a rodent model we have shown that, irrespective of the route of administration, morphine administered in the acute phase of SCI undermines long-term locomotor recovery. Our previous data suggest that activation of kappa opioid receptors (KORs) mediates these negative effects. Blocking KORs with norbinaltorphimine (norBNI), prior to a single dose of epidural morphine, prevented the morphine-induced attenuation of locomotor recovery. Because numerous cellular changes occur with chronic opioid administration compared with a single dose, the current study tested whether norBNI was also effective in a more clinically relevant paradigm of repeated, intravenous morphine administration after SCI. We hypothesized that blocking KOR activation during repeated, intravenous morphine administration would also protect recovery. Supporting this hypothesis, we found that blocking KOR activation in young, male rats prevented the negative effects of morphine on locomotor recovery, although neither norBNI nor morphine had an effect on long-term pain at the doses used. We also found that norBNI treatment blocked the adverse effects of morphine on lesion size. These data suggest that a KOR antagonist given in conjunction with morphine may provide a clinical strategy for effective analgesia without compromising locomotor recovery after SCI.
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Morfina , Antagonistas de Entorpecentes , Receptores Opioides kappa , Traumatismos da Medula Espinal , Animais , Masculino , Ratos , Analgésicos Opioides/efeitos adversos , Morfina/efeitos adversos , Antagonistas de Entorpecentes/farmacologia , Dor , Ratos Sprague-Dawley , Receptores Opioides kappa/antagonistas & inibidores , Medula Espinal , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/induzido quimicamenteRESUMO
After spinal cord injury (SCI), 80% of individuals are diagnosed with osteopenia or osteoporosis. The dramatic loss of bone after SCI increases the potential for fractures 100-fold, with post-fracture complications occurring in 54% of cases. With the age of new SCI injuries increasing, we hypothesized that a SCI-induced reduction in weight bearing could further exacerbate age-induced bone loss. To test this, young (2-3 months) and old (20-30 months) male and female mice were given a moderate spinal contusion injury (T9-T10), and recovery was assessed for 28 days (BMS, rearing counts, distance traveled). Tibial trabecular bone volume was measured after 28 days with ex vivo microCT. While BMS scores did not differ across groups, older subjects travelled less in the open field and there was a decrease in rearing with age and SCI. As expected, aging decreased trabecular bone volume and cortical thickness in both old male and female mice. SCI alone also reduced trabecular bone volume in young mice, but did not have an additional effect beyond the age-dependent decrease in trabecular and cortical bone volume seen in both sexes. Interestingly, both rearing and total activity correlated with decreased bone volume. These data underscore the importance of load and use on bone mass. While partial weight-bearing does not stabilize/reverse bone loss in humans, our data suggest that therapies that simulate complete loading may be effective after SCI.
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BACKGROUND: The combination of antiangiogenic agents with immune checkpoint inhibitors could potentially overcome immune suppression driven by tumor angiogenesis. We report results from a phase IB study of ziv-aflibercept plus pembrolizumab in patients with advanced solid tumors. METHODS: This is a multicenter phase IB dose-escalation study of the combination of ziv-aflibercept (at 2-4 mg/kg) plus pembrolizumab (at 2 mg/kg) administered intravenously every 2 weeks with expansion cohorts in programmed cell death protein 1 (PD-1)/programmed death-ligand 1(PD-L1)-naïve melanoma, renal cell carcinoma (RCC), microsatellite stable colorectal cancer (CRC), and ovarian cancer. The primary objective was to determine maximum tolerated dose (MTD) and recommended dose of the combination. Secondary endpoints included overall response rate (ORR) and overall survival (OS). Exploratory objectives included correlation of clinical efficacy with tumor and peripheral immune population densities. RESULTS: Overall, 33 patients were enrolled during dose escalation (n=3) and dose expansion (n=30). No dose-limiting toxicities were reported in the initial dose level. Ziv-aflibercept 4 mg/kg plus pembrolizumab 2 mg/kg every 2 weeks was established as the MTD. Grade ≥3 adverse events occurred in 19/33 patients (58%), the most common being hypertension (36%) and proteinuria (18%). ORR in the dose-expansion cohort was 16.7% (5/30, 90% CI 7% to 32%). Complete responses occurred in melanoma (n=2); partial responses occurred in RCC (n=1), mesothelioma (n=1), and melanoma (n=1). Median OS was as follows: melanoma, not reached (NR); RCC, 15.7 months (90% CI 2.5 to 15.7); CRC, 3.3 months (90% CI 0.6 to 3.4); ovarian, 12.5 months (90% CI 3.8 to 13.6); other solid tumors, NR. Activated tumor-infiltrating CD8 T cells at baseline (CD8+PD1+), high CD40L expression, and increased peripheral memory CD8 T cells correlated with clinical response. CONCLUSION: The combination of ziv-aflibercept and pembrolizumab demonstrated an acceptable safety profile with antitumor activity in solid tumors. The combination is currently being studied in sarcoma and anti-PD-1-resistant melanoma. TRIAL REGISTRATION NUMBER: NCT02298959.
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Carcinoma de Células Renais , Neoplasias Renais , Melanoma , Anticorpos Monoclonais Humanizados , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Masculino , Melanoma/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de FusãoRESUMO
BACKGROUND: Biomarkers predicting second-generation novel hormonal therapy (NHT) benefit relative to taxanes are critical for optimized treatment decisions for metastatic castration-resistant prostate cancer (mCRPC) patients. These associations have not been reported simultaneously for common mCRPC genomic biomarkers. OBJECTIVE: To evaluate predictive associations of common genomic aberrations in mCRPC using an established comprehensive genomic profiling (CGP) system. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study used data from a deidentified US-based clinicogenomic database comprising patients treated in routine clinical practice between 2011 and 2020, evaluated with Foundation Medicine CGP in tissue biopsies obtained around the time of treatment decision. The main cohort included 180 NHT and 179 taxane lines of therapy (LOTs) from 308 unique patients. The sequential cohort comprised a subset of the main cohort NHT LOTs immediately followed by taxane from 55 unique patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prostate-specific antigen (PSA) response, time to next treatment (TTNT), and overall survival (OS) were assessed. Main cohort analyses were adjusted for known treatment assignment biases via inverse probability of treatment weighting (IPTW) in treatment interaction models. RESULTS AND LIMITATIONS: In the main cohort, patients with AR amplification (ARamp) or PTEN aberrations (PTENalt) had worse relative PSA response on NHT versus taxanes compared with patients without. Patients with ARamp, PTENalt, or RB1 aberrations (RB1alt) also had worse relative TTNT and OS on NHT but not on taxanes. In multivariable models for TTNT and OS adjusted via IPTW, ARamp, PTENalt, and RB1alt were shown as poor prognostic factors overall and demonstrated significant treatment interactions, indicating reduced hazards of therapy switch and death on taxanes versus NHT. Consistent associations favoring increased benefit from subsequent taxane despite prior NHT treatment line were observed only for ARamp in the sequential cohort, in which very few patients had RB1alt for assessment. CONCLUSIONS: ARamp status is a candidate biomarker to predict poor effectiveness of NHT relative to taxanes in mCRPC in scenarios where both options are considered. PATIENT SUMMARY: Specific alterations in the DNA of tumors may assist in choosing between novel oral hormonal therapies and standard chemotherapy in advanced prostate cancer patients.
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Neoplasias de Próstata Resistentes à Castração , Biomarcadores Tumorais/genética , Humanos , Masculino , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Taxoides/uso terapêutico , Resultado do TratamentoRESUMO
Narratives can have a powerful impact on our health-related beliefs, attitudes, and behaviors. The human papillomavirus (HPV) vaccine can protect against human papillomavirus that leads to different types of cancers. However, HPV vaccination rates are low. This study explored the effectiveness of a narrative-based interactive game about the HPV vaccines as a method to communicate knowledge and perhaps create behavioral outcomes. We developed a serious storytelling game called Vaccination Vacation inspired by personal narratives of individuals who were impacted by the HPV. We tested the game using a randomized control study of 99 adult participants and compared the HPV knowledge and vaccine beliefs of the Gamer Group (who played the game, n = 44) and the Reader group (who read a vaccine information sheet, n = 55). We also evaluated the usability of the game. In addition to high usability, the interactive game slightly impacted the beliefs about the HPV vaccine over standard delivery of vaccine information, especially among those who never received the HPV vaccine. We also observed some gender-based differences in perception towards usability and the likelihood of frequently playing the game. A narrative-based game could bring positive changes to players' HPV-related health beliefs. The combination of more comprehensive HPV vaccine information with the narratives may produce a larger impact. Narrative-based games can be effectively used in other vaccine education interventions and warrant future research.
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Vaccine hesitancy remains a global health threat. Addressing parental vaccine hesitancy is essential to maintaining high vaccine coverage levels and preventing disease outbreaks; however, it is unknown if administering a vaccine hesitancy screening tool negatively impacts parental vaccine beliefs. We conducted a stratified randomized controlled trial in pediatric primary care practices. English-speaking parents ≥18 years of age seeking routine care for infants <3 months of age were eligible. Participants were randomized to receive 1 of 2 surveys - the Parent Attitudes about Childhood Vaccines (PACV) survey or a placebo survey. Six months after initial enrollment, all participants were asked to complete the PACV, regardless of initial randomization group. Our primary outcome was the proportion of hesitant to non-hesitant parents at 6-months between randomization groups. We examined associations between vaccine hesitancy and participant characteristics. We also evaluated the change in the proportion of vaccine-hesitant parents in the PACV group between baseline and 6-month follow up. We enrolled 1705 parents at baseline. At 6-month follow up, 819 parents completed the PACV (50.2% from PACV group vs. 54.1% from placebo group). The proportion of hesitant parents at 6 months did not differ between PACV and placebo groups (6.6% vs. 6.1%; p = .78) and the odds of hesitancy among PACV group participants was not higher than those in the placebo group (OR = 1.10; 95% CI: 0.63-1.93; p = .743). Race was the only characteristic significantly associated with vaccine hesitancy at 6-month follow up (p = .003). Overall, administration of the PACV did not trigger vaccine hesitancy in this study population.
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Vacinação , Vacinas , Criança , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Lactente , Pais , Aceitação pelo Paciente de Cuidados de SaúdeRESUMO
PURPOSE: This study assessed the economic impact of increased use of comprehensive genomic profiling (CGP) versus conventional testing strategies among patients with advanced non-small-cell lung cancer (aNSCLC) from a US commercial health plan perspective. METHODS: A decision analytic model was developed to estimate the incremental benefits and costs across testing methodologies (CGP v non-CGP), as well as across sample types (tissue-based and liquid-based), for patients with newly diagnosed aNSCLC. Model outcomes included total direct costs, testing costs, and per member per month budget impact. Secondary model outcomes included the number of patients needed to test with CGP to add 1 life-year, and the number of patients needed to test with CGP to treat one individual with a biomarker-matched therapy. RESULTS: In a hypothetical 2,000,000-member health plan, 790 members were estimated to have incident aNSCLC; 609 underwent molecular diagnostic testing with 122 (20%) tested with CGP (109 tissue-based and 13 liquid) in the base-case. An increase in CGP from 20% to 30% (an additional 61 patients tested with CGP) was associated with 3.11 additional life-years gained and a $0.01 in US dollars per member per month budget impact. Approximately 19.6 patients would need to be tested with CGP versus non-CGP to add one life-year and 5.9 patients would need to be tested with CGP to treat at least one patient with a biomarker-matched therapy. CONCLUSION: An increase in CGP from 20% to 30% among patients with aNSCLC undergoing molecular diagnostic testing was associated with modest budget impact, most of which was attributable to prolonged survival associated with increased use of more effective treatments.
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Orçamentos , Carcinoma Pulmonar de Células não Pequenas/economia , Carcinoma Pulmonar de Células não Pequenas/genética , Perfilação da Expressão Gênica , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/genética , Técnicas de Diagnóstico Molecular/economia , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
Parents of children with autism spectrum disorder (ASD) may be at greater risk for developing antivaccine beliefs that lead to vaccine delays and/or refusals for their children. We investigated current parental vaccine hesitancy, parents' beliefs about causes of children's developmental delays, and children's vaccination histories among parents of children with ASD or non-ASD developmental delays. Data were analyzed from 89/511 parents (17.4%) who completed the Parent Attitudes About Childhood Vaccines questionnaire and the Revised Illness Perception Questionnaire; 46.1% had childhood vaccination records available. Overall, 21/89 (23.6%, 95% confidence interval [CI]: 15.0-34.0) of parents were vaccine hesitant (ASD n = 19/21 [90.5%], non-ASD n = 2/21 [9.5%]). Parents of children with ASD were significantly more likely to agree with "toxins in vaccines" as a cause of their child's developmental delays (28.4% vs 5.0%, P = .034). The odds of being vaccine hesitant were 11.9 times (95% CI 2.9-48.0) greater among parents who agreed versus disagreed that toxins in vaccines caused their children's developmental delays. Rates of prior vaccine receipt did not differ between hesitant and nonhesitant groups.