All Publications


  • Analysis of Female Enrollment and Participant Sex by Burden of Disease in US Clinical Trials Between 2000 and 2020. JAMA network open Steinberg, J. R., Turner, B. E., Weeks, B. T., Magnani, C. J., Wong, B. O., Rodriguez, F., Yee, L. M., Cullen, M. R. 2021; 4 (6): e2113749

    Abstract

    Importance: Although female representation has increased in clinical trials, little is known about how clinical trial representation compares with burden of disease or is associated with clinical trial features, including disease category.Objective: To describe the rate of sex reporting (ie, the presence of clinical trial data according to sex), compare the female burden of disease with the female proportion of clinical trial enrollees, and investigate the associations of disease category and clinical trial features with the female proportion of clinical trial enrollees.Design, Setting, and Participants: This cross-sectional study included descriptive analyses and logistic and generalized linear regression analyses with a logit link. Data were downloaded from the Aggregate Analysis of ClinicalTrials.gov database for all studies registered between March 1, 2000, and March 9, 2020. Enrollment was compared with data from the 2016 Global Burden of Disease database. Of 328 452 clinical trials, 70 095 were excluded because they had noninterventional designs, 167 936 because they had recruitment sites outside the US, 69 084 because they had no reported results, 1003 because they received primary funding from the US military, and 314 because they had unclear sex categories. A total of 20 020 interventional studies enrolling approximately5.11 million participants met inclusion criteria and were divided into those with and without data on participant sex.Exposures: The primary exposure variable was clinical trial disease category. Secondary exposure variables included funding, study design, and study phase.Main Outcomes and Measures: Sex reporting and female proportion of participants in clinical trials.Results: Among 20 020 clinical trials from 2000 to 2020, 19 866 studies (99.2%) reported sex, and 154 studies (0.8%) did not. Clinical trials in the fields of oncology (46% of disability-adjusted life-years [DALYs]; 43% of participants), neurology (56% of DALYs; 53% of participants), immunology (49% of DALYs; 46% of participants), and nephrology (45% of DALYs; 42% of participants) had the lowest female representation relative to corresponding DALYs. Male participants were underrepresented in 8 disease categories, with the greatest disparity in clinical trials of musculoskeletal disease and trauma (11.3% difference between representation and proportion of DALYs). Clinical trials of preventive interventions were associated with greater female enrollment (adjusted relative difference, 8.48%; 95% CI, 3.77%-13.00%). Clinical trials in cardiology (adjusted relative difference, -18.68%; 95% CI, -22.87% to -14.47%) and pediatrics (adjusted relative difference, -20.47%; 95% CI, -25.77% to -15.16%) had the greatest negative association with female enrollment.Conclusions and Relevance: In this study, sex differences in clinical trials varied by clinical trial disease category, with male and female participants underrepresented in different medical fields. Although sex equity has progressed, these findings suggest that sex bias in clinical trials persists within medical fields, with negative consequences for the health of all individuals.

    View details for DOI 10.1001/jamanetworkopen.2021.13749

    View details for PubMedID 34143192

  • The surgical oncology clinical trial landscape: A cross-sectional analysis of ClinicalTrials.gov from 2008-2020. Perera, N. D., Turner, B. E., Shen, J. Z., Wong, B. O., Litt, H. K., Stavins, M. A., Bellomo, T. R., Saleki, M., Bell, A., Ionescu, R., Shyu, M., Wang, M. M., Tao, J., Sarsour, N., O'Keefe, R. M., Takasugi, J. M., Steinberg, J. R., King, R., Mahipal, A., Wren, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2021
  • Cancer Care during Covid-19: A multi-institutional qualitative study on physician and patient perspectives on telemedicine. Wong, B. O., Aslakson, R., Holdsworth, L. M., Siden, R., Tabor, H., Verano, M., Schapira, L. LIPPINCOTT WILLIAMS & WILKINS. 2021
  • More than Conveying Information: Informed Consent as Speech Act. The American journal of bioethics : AJOB Wong, B. O., Batten, J. N., Blythe, J. A., Magnus, D. C. 2021; 21 (5): 1–3

    View details for DOI 10.1080/15265161.2021.1912513

    View details for PubMedID 33945426

  • Recognizing the Role of Language in the Hidden Curriculum of Undergraduate Medical Education: Implications for Equity in Medical Training. Academic medicine : journal of the Association of American Medical Colleges Wong, B. O., Blythe, J. A., Batten, J. N., Turner, B. E., Lau, J. N., Hosamani, P. n., Hanks, W. F., Magnus, D. n. 2020

    Abstract

    Medical education involves a transition from "outsider" to "insider" status, which entails both rigorous formal training and an inculturation of values and norms via a "hidden curriculum." Within this transition, the ability to "talk the talk" designates an individual as an insider, and learning to talk this talk is a key component of professional socialization. This article uses the framework of "patterns of medical language" to explore the role of language in the hidden curriculum of medical education, exploring how students must learn to recognize and participate fluently within patterns of medical language in order to be acknowledged and evaluated as competent trainees. The authors illustrate this by reframing the objectives for medical education which are outlined by the Association of American Medical Colleges as a series of overlapping patterns of medical language which students are expected to master before residency. We propose that many of these patterns of medical language are learned through trial-and-error, taught via a hidden curriculum rather than through explicit instruction. Medical students come from increasingly diverse backgrounds and therefore begin medical training further from or closer to insider status. Thus, evaluative practices based on patterns of medical language, which are not explicitly taught, may exacerbate and perpetuate existing inequities in medical education. This article aims to bring awareness to the importance of medical language within the hidden curriculum of medical education, to the role of medical language as a marker of "insider" status, and to the centrality of medical language in evaluative practices. We conclude by offering possible approaches to ameliorate the inequities that may exist due to current evaluative practices, and call for further discussion and innovation to explicitly address the role of language in the hidden curriculum of medical education.

    View details for DOI 10.1097/ACM.0000000000003657

    View details for PubMedID 32769473

  • Changes in epidemiological profiles of AIDS in China: a systematic analysis Chen, X., Wang, R., Zhang, Y., Hu, T., Sun, X., Wong, B. O. ELSEVIER SCIENCE INC. 2019: 8
  • Treatability Statements in Serious Illness: The Gap Between What is Said and What is Heard CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS Batten, J. N., Wong, B. O., Hanks, W. F., Magnus, D. C. 2019; 28 (3): 394–404

    Abstract

    Empirical work has shown that patients and physicians have markedly divergent understandings of treatability statements (e.g., "This is a treatable condition," "We have treatments for your loved one") in the context of serious illness. Patients often understand treatability statements as conveying good news for prognosis and quality of life. In contrast, physicians often do not intend treatability statements to convey improvement in prognosis or quality of life, but merely that a treatment is available. Similarly, patients often understand treatability statements as conveying encouragement to hope and pursue further treatment, though this may not be intended by physicians. This radical divergence in understandings may lead to severe miscommunication. This paper seeks to better understand this divergence through linguistic theory-in particular, H.P. Grice's notion of conversational implicature. This theoretical approach reveals three levels of meaning of treatability statements: (1) the literal meaning, (2) the physician's intended meaning, and (3) the patient's received meaning. The divergence between the physician's intended meaning and the patient's received meaning can be understood to arise from the lack of shared experience between physicians and patients, and the differing assumptions that each party makes about conversations. This divergence in meaning raises new and largely unidentified challenges to informed consent and shared decision making in the context of serious illness, which indicates a need for further empirical research in this area.

    View details for DOI 10.1017/S096318011900029X

    View details for Web of Science ID 000477671000003

    View details for PubMedID 31368425

  • Response to Commentaries: When "Everyday Language" Contributes to Miscommunication in Serious Illness CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS Batten, J. N., Wong, B. O., Magnus, D. C. 2019; 28 (3): 433–38

    View details for DOI 10.1017/S0963180119000355

    View details for Web of Science ID 000477671000009

    View details for PubMedID 31298189

  • We Convey More Than We (Literally) Say. The American journal of bioethics : AJOB Batten, J. N., Wong, B. O., Hanks, W. F., Magnus, D. 2018; 18 (9): 1–3

    View details for PubMedID 30265601

  • The vicious circle of patient-physician mistrust in China: health professionals' perspectives, institutional conflict of interest, and building trust through medical professionalism DEVELOPING WORLD BIOETHICS Nie, J., Cheng, Y., Zou, X., Gong, N., Tucker, J. D., Wong, B., Kleinman, A. 2018; 18 (1): 26–36

    Abstract

    To investigate the phenomenon of patient-physician mistrust in China, a qualitative study involving 107 physicians, nurses and health officials in Guangdong Province, southern China, was conducted through semi-structured interviews and focus groups. In this paper we report the key findings of the empirical study and argue for the essential role of medical professionalism in rebuilding patient-physician trust. Health professionals are trapped in a vicious circle of mistrust. Mistrust (particularly physicians' distrust of patients and their relatives) leads to increased levels of fear and self-protection by doctors which exacerbate difficulties in communication; in turn, this increases physician workloads, adding to a strong sense of injustice and victimization. These factors produce poorer healthcare outcomes and increasingly discontented and angry patients, escalate conflicts and disputes, and result in negative media coverage, all these ultimately contributing to even greater levels of mistrust. The vicious circle indicates not only the crisis of patient-physician relationship but the crisis of medicine as a profession and institution. Underlying the circle is the inherent conflict of interest in the healthcare system by which health professionals and hospitals have become profit-driven. This institutional conflict of interest seriously compromises the fundamental principle of medical professionalism-the primacy of patient welfare-as well as the traditional Chinese ideal of "medicine as the art of humanity". Patient trust can be restored through rectifying this institutional conflict of interest and promoting medical professionalism via a series of recommended practical measures.

    View details for DOI 10.1111/dewb.12170

    View details for Web of Science ID 000426847900005

    View details for PubMedID 28922547

  • Rebuilding patient-physician trust in China, developing a trust-oriented bioethics DEVELOPING WORLD BIOETHICS Nie, J., Tucker, J. D., Zhu, W., Cheng, Y., Wong, B., Kleinman, A. 2018; 18 (1): 4–6

    View details for DOI 10.1111/dewb.12172

    View details for Web of Science ID 000426847900002

    View details for PubMedID 28922586

  • Rebuilding patient-physician trust in China. Lancet (London, England) Tucker, J. D., Wong, B. n., Nie, J. B., Kleinman, A. n. 2016; 388 (10046): 755

    View details for PubMedID 27560268

  • Patient-physician mistrust and violence against physicians in Guangdong Province, China: a qualitative study. BMJ open Tucker, J. D., Cheng, Y. n., Wong, B. n., Gong, N. n., Nie, J. B., Zhu, W. n., McLaughlin, M. M., Xie, R. n., Deng, Y. n., Huang, M. n., Wong, W. C., Lan, P. n., Liu, H. n., Miao, W. n., Kleinman, A. n. 2015; 5 (10): e008221

    Abstract

    To better understand the origins, manifestations and current policy responses to patient-physician mistrust in China.Qualitative study using in-depth interviews focused on personal experiences of patient-physician mistrust and trust.Guangdong Province, China.One hundred and sixty patients, patient family members, physicians, nurses and hospital administrators at seven hospitals varying in type, geography and stages of achieving goals of health reform. These interviews included purposive selection of individuals who had experienced both trustful and mistrustful patient-physician relationships.One of the most prominent forces driving patient-physician mistrust was a patient perception of injustice within the medical sphere, related to profit mongering, knowledge imbalances and physician conflicts of interest. Individual physicians, departments and hospitals were explicitly incentivised to generate revenue without evaluation of caregiving. Physicians did not receive training in negotiating medical disputes or humanistic principles that underpin caregiving. Patient-physician mistrust precipitated medical disputes leading to the following outcomes: non-resolution with patient resentment towards physicians; violent resolution such as physical and verbal attacks against physicians; and non-violent resolution such as hospital-mediated dispute resolution. Policy responses to violence included increased hospital security forces, which inadvertently fuelled mistrust. Instead of encouraging communication that facilitated resolution, medical disputes sometimes ignited a vicious cycle leading to mob violence. However, patient-physician interactions at one hospital that has implemented a primary care model embodying health reform goals showed improved patient-physician trust.The blind pursuit of financial profits at a systems level has eroded patient-physician trust in China. Restructuring incentives, reforming medical education and promoting caregiving are pathways towards restoring trust. Assessing and valuing the quality of caregiving is essential for transitioning away from entrenched profit-focused models. Moral, in addition to regulatory and legal, responses are urgently needed to restore trust.

    View details for PubMedID 26443652

    View details for PubMedCentralID PMC4606416

  • Dysfunction of dendritic cells in aged C57BL/6 mice leads to failure of natural killer cell activation and of tumor eradication PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Guo, Z., Tilburgs, T., Wong, B., Strominger, J. L. 2014; 111 (39): 14199–204

    Abstract

    The reciprocal activation of dendritic cells (DCs) and natural killer cells (NKs) plays a key role in both innate and adaptive immunity. The effect of aging on this cross-talk, a critical step in virus disease control and tumor immunology, has not been reported. Splenic DCs and NKs were purified from both young and old C57BL/6 mice and cocultured in the presence of polyinosinic:polycytidylic acid (poly I:C). The resulting activation of NKs was measured as expression of CD69 and secretion of IFN-γ. However, DCs from old mice could not activate NKs from either young or old mice in vitro or in vivo. In contrast, DCs from young mice efficiently activated NKs from both young and old mice. DCs from old mice were deficient in poly I:C-stimulated secretion of IL-15, IL-18, and IFN-α. Gene expression analysis revealed many other differences between DCs of old and young mice. Young mice strongly eradicated MHC class I-negative NK-sensitive RMA-S lymphoma mutant tumor cells, but old mice did not, in concert with the previous report that mousepox kills aged, but not young, C57BL/6 mice. Furthermore, a similar dysfunction of DC and its key role in NK activation was found in 27 out of 55 healthy human donors.

    View details for DOI 10.1073/pnas.1414780111

    View details for Web of Science ID 000342350200049

    View details for PubMedID 25225399

    View details for PubMedCentralID PMC4191753

  • Tumor-derived Variants of Epstein-Barr Virus Latent Membrane Protein 1 Induce Sustained Erk Activation and c-Fos JOURNAL OF BIOLOGICAL CHEMISTRY Vaysberg, M., Hatton, O., Lambert, S. L., Snow, A. L., Wong, B., Krams, S. M., Martinez, O. M. 2008; 283 (52): 36573-36585

    Abstract

    Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is a proven oncogene that is essential for transformation of human B cells by the virus. LMP1 induces constitutive activation of several signal transduction pathways involving nuclear factor kappaB, phosphatidylinositol 3-kinase/Akt, and the mitogen-activated protein kinases (MAPK) p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (Erk). Sequencing of LMP1 isolated from a panel of EBV+ B cell lymphomas identified three different variants of LMP1, each distinct from the B95.8 prototype isoform. All tumor variants of LMP1 as well as the B95.8 LMP1 isoform were able to induce rapid p38 phosphorylation as well as Akt and JNK activation. Additionally all variants showed similar ability to activate nuclear factor kappaB. In contrast, only tumor-derived LMP1 variants induced prolonged Erk activation and c-Fos expression. Sequence analysis revealed only two amino acids, 212 and 366, shared by the tumor variants but distinct from B95.8. Point mutation of either amino acids 212 (glycine to serine) or 366 (serine to threonine) from the B95.8 isoform to the tumor variant version of LMP1 was sufficient for gain of function characterized by sustained activation of Erk and subsequent c-Fos induction and binding to the AP1 site. Our results indicate that the enhanced ability of tumor-derived LMP1 to induce and stabilize the c-Fos oncogene can be localized to two amino acids in the C terminus of LMP1.

    View details for DOI 10.1074/jbc.M802968200

    View details for Web of Science ID 000261840500055

    View details for PubMedID 18986987

    View details for PubMedCentralID PMC2605991