Process, resource and success factors associated with chimeric antigen receptor T-cell therapy for multiple myeloma.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy represents a new frontier in multiple myeloma. It is important to understand critical success factors (CSFs) that may optimize its use in this therapeutic area. Methods: We estimated the CAR-T process using time-driven activity-based costing. Information was obtained through interviews at four US oncology centers and with payer representatives, and through publicly available data. Results: The CAR-T process comprises 13 steps which take 177 days; it was estimated to include 46 professionals and ten care settings. CSFs included proactive collaboration, streamlined reimbursement and CAR-T administration in alternative settings when possible. Implementing CSFs may reduce episode time and costs by 14.4 and 13.2%, respectively. Conclusion: Our research provides a blueprint for improving efficiencies in CAR-T therapy, thereby increasing its sustainability for multiple myeloma.

Patients with multiple myeloma can now be treated with chimeric antigen receptor T-cell (CAR-T) therapy. We studied how CAR-T therapy is used for multiple myeloma. We also studied things that could help make this therapy easier for doctors to use. The CAR-T process takes 13 steps and 177 days. It begins with the choice to use the therapy and ends about 100 days after it is used. The process uses 46 different healthcare professionals and ten different locations. We found several possible changes that can improve this process. Of these changes, three stand out. First, improved teamwork between members of the care team can help them prepare for and resolve possible problems. Second, reducing insurance red tape will make it easier to provide CAR-T therapy to patients. Third, allowing use of CAR-T therapy in places other than hospitals can help more patients receive this therapy. If applied, these three things may lower the time needed to treat patients by 14.4% and may reduce costs by 13.2%.

Hearing loss and cognitive effort in older adults' report accuracy for verbal materials.

BACKGROUND: In addition to declines in auditory acuity, adult aging is often also accompanied by reduced cognitive efficiency, most notably in working memory resources and a general slowing in a number of perceptual and cognitive domains. Effectiveness of speech comprehension by older adults reflects a balance between these declines and the relative preservation in healthy aging of linguistic knowledge and the procedural rules for its application. PURPOSE: To examine effects of hearing acuity in older adults on intelligibility functions for sentences that varied in two degrees of syntactic complexity, with their concomitant demands on older adults' working memory resources. RESEARCH DESIGN: Stimuli consisted of monosyllabic words presented in isolation, and nine-word sentences that varied in syntactic complexity. Two sentence types were employed: sentences with a subject-relative clause structure, and more syntactically complex sentences in which meaning was expressed with an object-relative clause structure. The stimuli were presented initially below the level of audibility and then increased in loudness in 2 dB increments until the single-word stimuli and all nine words of the sentence stimuli could be correctly reported. STUDY SAMPLE: Participants were 16 older adults with good hearing acuity for their ages, 16 age-matched adults with mild-to-moderate hearing loss, and 16 young adults with age-normal hearing. RESULTS: Along with confirming better report accuracy for the words of meaningful sentences than for words heard in isolation, performance curves for the sentence stimuli showed a significant effect of syntactic complexity. This took the form of older adults having poorer report accuracy at any given loudness level for sentences with greater syntactic complexity. This general effect of syntactic complexity on perceptual report accuracy was further exacerbated by age and hearing loss. CONCLUSIONS: Age-limited working memory resources are impacted both by the resource demands required for comprehension of syntactically complex sentences and by effortful listening attendant to hearing loss.

Perception of alternated speech operates similarly in young and older adults with age-normal hearing.

When speech is rapidly alternated between the two ears, intelligibility declines as the rate of alternation approaches 3 to 5 switching cycles per second, and then, paradoxically, returns to a good level beyond that point. We tested intelligibility when shadowing was used as a response measure (Experiment 1), when recall was used as a response measure (Experiment 2), and when time-compression was used to vary the speech rate of the presented materials (Experiment 3). In spite of claims that older adults are generally slower in switching attention, younger and older adults did not differ in the critical alternation rates producing minimal intelligibility. We suggest that the point of minimal intelligibility in alternated speech reflects an interaction between (1) the rate of disruption induced by breaking the speech stream between two sound sources, (2) the amount of contextual information per ear, and (3) the size of the silent gaps separating the speech elements that must be perceptually bridged.

Hearing loss and perceptual effort: downstream effects on older adults' memory for speech.

A group of older adults with good hearing and a group with mild-to-moderate hearing loss were tested for recall of the final three words heard in a running memory task. Near perfect recall of the final words of the three-word sets by both good- and poor-hearing participants allowed the inference that all three words had been correctly identified. Nevertheless, the poor-hearing group recalled significantly fewer of the nonfinal words than did the better hearing group. This was true even though both groups were matched for age, education, and verbal ability. Results were taken as support for an effortfulness hypothesis: the notion that the extra effort that a hearing-impaired listener must expend to achieve perceptual success comes at the cost of processing resources that might otherwise be available for encoding the speech content in memory.

Differential and history-dependent modulation of a stretch receptor in the stomatogastric system of the crab, Cancer borealis.

Neuromodulators can modify the magnitude and kinetics of the response of a sensory neuron to a stimulus. Six neuroactive substances modified the activity of the gastropyloric receptor 2 (GPR2) neuron of the stomatogastric nervous system (STNS) of the crab Cancer borealis during muscle stretch. Stretches were applied to the gastric mill 9 (gm9) and the cardio-pyloric valve 3a (cpv3a) muscles. SDRNFLRFamide and dopamine had excitatory effects on GPR2. Serotonin, GABA, and the peptide allatostatin-3 (AST) decreased GPR2 firing during stretch. Moreover, SDRNFLRFamide and TNRNFLRFamide increased the unstimulated spontaneous firing rate, whereas AST and GABA decreased it. The actions of AST and GABA were amplitude- and history-dependent. In fully recovered preparations, AST and GABA decreased the response to small-amplitude stretches proportionally more than to those evoked by large-amplitude stretches. For large-amplitude stretches, the effects of AST and GABA were more pronounced as the number of recent stretches increased. The modulators that affected the stretch-induced GPR2 firing rate were also tested when the neuron was operating in a bursting mode of activity. Application of SDRNFLRFamide increased the bursting frequency transiently, whereas high concentrations of serotonin, AST, and GABA abolished bursting altogether. Together these data demonstrate that the effects of neuromodulators depend on the previous activity and current state of the sensory neuron.