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Evidence in oncology. The Janeway lecture 2000.

PURPOSE: The purpose of this address is to evaluate the types of evidence that have fashioned clinical decision making in oncology over the past century and to determine the appropriate weighting of evidence at the start of a new century in the shaping of patient care, clinical research, and health policy. METHODS: Three separate analytic approaches were used: (1) a review of publications that altered medical practice, (2) a consideration of the misperception that little progress has been made by looking at the relationship between 5-year survival rates and national mortality rates, (3) an evaluation of the quality of data from clinical trials. RESULTS: Published reports suggest that res ipsa loquitur was the dominant mindset of researchers in the first half century and continuing into the second half century. However, recognition of the scarcity of dramatic improvements in outcome and the possibility of incremental improvements led to the mounting of prospective randomized comparative trials that could identify such incremental improvements. Findings from these trials have profoundly altered patient care in the past quarter century. Data suggest that there is a sequence of events-increased survival rates in patients at research institutions followed by significant increases in survival rates nationally-followed by a reduction in annual mortality rates that do reflect improvements in treatment. Phase III comparative clinical trials yield the highest quality data in oncology. Meta-analysis of such data may be useful, but the most compelling data that alter medical practice come either from comparative clinical trials showing such significant differences in results as to necessitate their early termination on ethical grounds or from replicated phase III trials. DISCUSSION: The nature of evidence influencing clinical practice and research has changed greatly in the past century. Although res ipsa loquitur still pervades the thinking of some oncologists, recognition of the incremental nature of progress is now the more dominant force in contemporary oncologic research. In addition, as molecular targets become the focus of therapeutic efforts, it will be especially important to proceed as quickly as possible to phase III comparative trials rather than to phase II studies.

Clinical Trials as Topic↗
PubMed2001

2001 ASPET Otto Krayer Award Lecture. Molecular targets for antiviral agents.

There are a number of virus-specific processes within the virus replicative cycle or virus-infected cell that have proven to be attractive targets for chemotherapeutic intervention, i.e., virus adsorption and entry into the cells, reverse (RNA --> DNA) transcription, viral DNA polymerization, and cellular enzymatic reactions that are associated with viral DNA and RNA synthesis and viral mRNA maturation (i.e., methylation). A variety of chemotherapeutic agents, both nucleoside (and nucleotide) and non-nucleoside entities, have been identified that specifically interact with these viral targets, that selectively inhibit virus replication, and that are either used or considered for clinical use in the treatment of virus infections in humans. Their indications encompass virtually all major human viral pathogens, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), human papilloma virus (HPV), orthomyxoviruses (influenza A and B), paramyxoviruses [e.g., respiratory syncytial virus (RSV)] and hemorrhagic fever viruses (such as Ebola virus).

Adenosylhomocysteinase↗
PubMed2001

The Hubert de Watteville Memorial Lecture. Imagine a world where motherhood is safe for all women--you can help make it happen.

The neglected tragedy of maternal mortality is a health scandal of our time. Motherhood can be made safe for all women and obstetricians have a global social responsibility to make it happen. Ten propositions are outlined: safe motherhood is to be recognized as a woman's human right; a woman's life is to be considered worth saving; life-saving emergency obstetric care is to made accessible to all women when they need it; all deliveries are to be attended by skilled birth attendants; all pregnant women are to have access to prenatal care; motherhood must be a voluntary woman's choice; making motherhood safe for all women is to be an international commitment; lack of resources in developing countries is not to be accepted as an excuse for inaction; women, North and South should mobilize for women's right to life; and our profession should act without national frontiers. The challenge is great, but so also is the reward.

Female↗
PubMed2001

Conrad Berens Lecture. Chronic cicatricial conjunctivitis.

PURPOSE: To describe the spectrum of problems that can result in chronic cicatricial conjunctivitis, and acquaint the reader with strategies for definitively establishing a diagnosis and instituting treatment. METHODS: Case studies, with emphasis on extensive general medical history taking, ocular and general physical examination, laboratory testing, and biopsy of inflamed conjunctiva. RESULTS: Chronic cicatricial conjunctivitis can be grouped into the classic broad categories of infectious, malignant, traumatic, autoimmune, and miscellaneous. Mismanagement and poor outcomes may occur as a consequence of misdiagnosis of the underlying etiology. Arriving at the correct diagnosis and choosing the best therapy will generally require a systematic and multi-disciplinary approach. CONCLUSIONS: The elements that are most helpful in achieving the goal of specific etiologic diagnosis of chronic cicatrizing conjunctivitis include exhaustive history and review of systems elicitation, detailed ocular examination, careful extraocular examination, and immunohistopathologic study of biopsied inflamed conjunctiva.

Chronic Disease↗