Abstract
The “bench to bedside” (BTB) paradigm of translational medicine (TM) assumes that medical progress emanates from basic science discoveries transforming clinical therapeutic models. However, a recent report found that most published medical research is false due, among other factors, to small samples, inherent bias and inappropriate statistical applications. Translation-blocking factors include the validity (or lack thereof) of the underlying pathophysiological constructs and related therapeutic paradigms and adherence to faulty traditional beliefs. Empirical discoveries have also led to major therapeutic advances, but scientific dogma has retrospectively retranslated these into the BTB paradigm. A review of the history of intravenous (I.V.) and oral therapy for cholera and NDDs illustrates some fallacies of the BTB model and highlights pitfalls blocking translational and transformative progress, and retro-translational factors, including programmatic modifications of therapeutic advances contradicting therapeutic paradigms and medical economic factors promoting more expensive and profitable medical applications inaccessible to resource-limited environments.
Highlights
The intravenous (I.V.) and oral treatment of cholera and non-cholera dehydrating diarrheas (NDDs) provide insights into translational medicine, spanning the period from the birth of clinical laboratory science in 1831 [1] to the development of modern oral rehydration and maintenance therapy (ORT) in 1967–1968 [2], which, in terms of saving lives, has been hailed as perhaps the most important translational advance of the last century [3].A translational medical advance rests upon three foundations: a valid causative paradigm derived from a correct understanding of disease pathophysiology, a valid therapeutic paradigm for correcting the pathophysiologic disorder, and a clinically effective methodology for delivering the treatment to provide a therapeutically beneficial or life-saving outcome
Treatments converging towards the modern case fatality rate (CFR) of less than 1% provide a key marker of translational progress, achieved by the timely replacement of diarrheal water and electrolyte losses with matching volumes of I.V. or absorbable oral solutions of similar electrolyte composition
The two reports concluded that “further investigation of the role [of oral solutions] was warranted but cautioned that intravenous solutions remain the mainstay of the successful treatment of cholera” [120], and “The results suggest that oral glucose therapy could be of value in the treatment of cholera and that the requirement for expensive and scarce I.V. fluids may be reduced thereby” [121]
Summary
The intravenous (I.V.) and oral treatment of cholera and non-cholera dehydrating diarrheas (NDDs) provide insights into translational medicine, spanning the period from the birth of clinical laboratory science (the “bench”) in 1831 [1] to the development of modern oral rehydration and maintenance therapy (ORT) in 1967–1968 (the “bedside”) [2], which, in terms of saving lives, has been hailed as perhaps the most important translational advance of the last century [3]. A translational medical advance rests upon three foundations: a valid causative paradigm derived from a correct understanding of disease pathophysiology, a valid therapeutic paradigm for correcting the pathophysiologic disorder, and a clinically effective (and safe) methodology for delivering the treatment to provide a therapeutically beneficial or life-saving outcome. In the case of intravenous (I.V.) and oral therapy (ORT) for cholera, the gap of 127 years from the first correct pathophysiologic and partial therapeutic paradigms for cholera (1831) to the 1960 s development of effective and safe treatment methods, and its application to NDD therapy, implies that a more nuanced understanding of transitional medicine is needed, based on historical review of the phases of translation
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