The frequency of use of unconventional therapy in the United States is far higher than previously reported. Medical doctors should ask about their patients' use of unconventional therapy whenever they obtain a medical history.

Generating the appropriate protonation states of drug-like molecules in solution is important for success in both ligand- and structure-based virtual screening. Screening collections of millions of compounds requires a method for determining tautomers and their energies that is sufficiently rapid, accurate, and comprehensive. To maximise enrichment, the lowest energy tautomers must be determined from heterogeneous input, without over-enumerating unfavourable states. While computationally expensive, the density functional theory (DFT) method M06-2X/aug-cc-pVTZ(-f) [PB-SCRF] provides accurate energies for enumerated model tautomeric systems. The empirical Hammett-Taft methodology can very rapidly extrapolate substituent effects from model systems to drug-like molecules via the relationship between pK(T) and pK(a). Combining the two complementary approaches transforms the tautomer problem from a scientific challenge to one of engineering scale-up, and avoids issues that arise due to the very limited number of measured pK(T) values, especially for the complicated heterocycles often favoured by medicinal chemists for their novelty and versatility. Several hundreds of pre-calculated tautomer energies and substituent pK(a) effects are tabulated in databases for use in structural adjustment by the program Epik, which treats tautomers as a subset of the larger problem of the protonation states in aqueous ensembles and their energy penalties. Accuracy and coverage is continually improved and expanded by parameterizing new systems of interest using DFT and experimental data. Recommendations are made for how to best incorporate tautomers in molecular design and virtual screening workflows.

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Physicians often underestimate or fail to recognize functional disabilities that are reported by their patients. They overstate functional impairment to a lesser degree. Because these discrepancies may adversely affect patient care and well-being, medical educators and clinicians should pay more attention to the assessment of patient function.