Katherine Possin and colleagues report on the implementation, development, and early findings of the Care Ecosystem, an adaptive, personalized, and scalable dementia care program.

The processive ␤-strands and turns of a polypeptide parallel ␤-helix represent one of the topologically simplest ␤-sheet folds. The three subunits of the tailspike adhesin of phage P22 each contain 13 rungs of a parallel ␤-helix followed by an interdigitated section of triple-stranded ␤-helix. Long stacks of hydrophobic residues dominate the elongated buried core of these two ␤-helix domains and extend into the core of the contiguous triple ␤-prism domain. To test whether these side-chain stacks represent essential residues for driving the chain into the correct fold, each of three stacked phenylalanine residues within the buried core were substituted with less bulky amino acids. The mutant chains with alanine in place of phenylalanine were defective in intracellular folding. The chains accumulated exclusively in the aggregated inclusion body state regardless of temperature of folding. These severe folding defects indicate that the stacked phenylalanine residues are essential for correct parallel ␤-helix folding. Replacement of the same phenylalanine residues with valine or leucine also impaired folding in vivo, but with less severity. Mutants were also constructed in a second buried stack that extends into the intertwined triple-stranded ␤-helix and contiguous ␤-prism regions of the protein. These mutants exhibited severe defects in later stages of chain folding or assembly, accumulating as misfolded but soluble multimeric species. The results indicate that the formation of the buried hydrophobic stacks is critical for the correct folding of the parallel ␤-helix, triple-stranded ␤-helix, and ␤-prism domains in the tailspike protein.

No abstract

Introduction Potentially inappropriate medications (PIMs) cause adverse events and death. We evaluate the Care Ecosystem (CE) collaborative dementia care program on medication use among community‐dwelling persons living with dementia (PLWD). Methods Secondary analysis of a randomized clinical trial (RCT) comparing CE to usual care (UC) on changes in PIMs, over 12 months between March 2015 and May 2020. Secondary outcomes included change in number of medications, clinically relevant PIMs, and anti‐dementia medications. Results Of 804 PLWD, N = 490 had complete medication data. The CE resulted in significantly fewer PIMs compared to UC (−0.35; 95% CI, −0.49 to −0.20; P < 0.0001). Number needed to prevent an increase in 1 PIM was 3. Total medications, PIMs for dementia or cognitive impairment, CNS‐active PIMs, anticholinergics, benzodiazepines, and opioids were also fewer. Anti‐dementia medication regimens were modified more frequently. Conclusion The CE medication review intervention embedded in collaborative dementia care optimized medication use among PLWD. Highlights Compared to usual care (UC), the Care Ecosystem (CE) medication review intervention prevented increases in potentially inappropriate medications (PIMs). Use of anticholinergics, benzodiazepines, and opioids were significantly reduced, with a trend for antipsychotics. Anti‐dementia medications were adjusted more frequently. The CE medication review intervention embedded in collaborative dementia care optimized medication use.