A Critical Reappraisal of the Bleeding Time.

Seminars in Thrombosis and Hemostasis (STH) celebrates 50 years of publishing in 2024. To celebrate this landmark event, STH is republishing some archival material. This manuscript represents the second most highly cited paper ever published in STH. The manuscript published without an abstract, and essentially represented a State of the Art Review on the bleeding time, a relatively invasive procedure that required an incision on the skin or earlobe of a patient, and timing how long it took for the incision to stop bleeding. The bleeding time test was first described in 1901 by the French physician Milian, who presented three studies of bleeding from stab wounds made in the fingertips of healthy and diseased subjects. In 1910, Duke observed the duration of bleeding from small incisions of the ear lobe, and pointed out that the duration of bleeding was increased in instances of reduced platelet counts. The test was subsequently repeatedly modified, and numerous variants of the test, including semiautomated methods, were described by several workers. The most frequently utilised test reflected one described by Ivy and coworkers, who shifted the location of the incision to the volar aspect of the forearm and applied a blood pressure cuff to the arm to maintain a standard venous pressure. The bleeding time has been proposed for use as a diagnostic test for platelet-related bleeding disorders, a measure of efficacy in various forms of therapy, and as a prognosticator of abnormal bleeding. The authors to the current review reevaluated the bleeding time literature using methods to assess the performance of the test in 1990, locating 862 printed documents that discussed the bleeding time, the majority in peer-reviewed professional journals. As this is a republication of archival material, transformed into a modern format, we apologise in advance for any errors introduced during this transformation.

Characteristics of orphan drug applications that fail to achieve marketing approval in the USA.

The US Orphan Drug Act has fostered the development of drugs for patients with rare diseases by granting 'orphan designations', although several orphan drugs for which a marketing application has been submitted to the FDA have failed to obtain approval. This study identified the clinical trial design, the level of experience of the sponsor and the level of interaction with the FDA to be associated with non-approval. Sponsors, therefore, should engage in dialogue with the FDA and thoughtfully design pivotal clinical trials in accordance with FDA guidance documents.

ICPC Multilingual Collaboratory: a Web- and Unicode-based system for distributed editing/translating/viewing of the multilingual International Classification of Primary Care.

The International Classification of Primary Care (ICPC) is a clinical classification containing 726 clinical concepts, available in over 20 languages, augmented by links to ICD-10 concepts. It is employed in clinical information systems in several European countries, Israel, Japan, and Australia. In translating ICPC, it has been challenging to manage the flow of multilingual information, maintain its quality, and optimize its portability, particularly in light of the numerous character encodings used to represent its content. The ICPC Multilingual Collaboratory (IMC) is a World Wide Web-based environment, created to allow the viewing, maintenance, and translation of ICPC content by a dispersed international editorial staff. Based upon open-source software, it represents ICPC content using the Unicode standard for character encoding. The system implements three interfaces to ICPC data: 1) a password-protected editorial interface which instantiates a hierarchical authority model and communication channels for review and control of content, including a means of up-loading new candidate translations; 2) an openly accessible read-only interface, with e-mail access to the editors (providing another level of content review); and, 3) a management interface for the system administrator. The completed system powerfully demonstrates the ability of the World Wide Web, open-source software, and Unicode to expedite and simplify international multilingual collaboration, even in a world in which Unicode support is incomplete on existing computing platforms.