Lesion and neuroimaging studies indicate that the insula mediates motor aspects of speech production, specifically, articulatory control. Although it has direct connections to Broca's area, the canonical speech production region, the insula is also broadly connected with other speech and language centres, and may play a role in coordinating higher-order cognitive aspects of speech and language production. The extent of the insula's involvement in speech and language processing was assessed using the Activation Likelihood Estimate (ALE) method. Meta-analyses of 42 fMRI studies with healthy adults were performed, comparing insula activation during performance of language (expressive and receptive) and speech (production and perception) tasks. Both tasks activated bilateral anterior insulae. However, speech perception tasks preferentially activated the left dorsal mid-insula, whereas expressive language tasks activated left ventral mid-insula. Results suggest distinct regions of the mid-insula play different roles in speech and language processing.

BACKGROUND The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations to third-party payer systems, physicians, and patients. OBJECTIVE Develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as first-line therapy in metastatic melanoma while accounting for differential effectiveness in PD-L1 positive and negative patients. METHODS A three-state Markov model (‘PD-L1 positive stable disease’, ‘PD-L1 negative stable disease’, and ‘Progression and/or Death’) was developed using a US societal perspective with a lifetime time horizon of 14.5 years. Transition probabilities were calculated from progression-free survival data reported in the CheckMate-067 trial. Costs were expressed in 2015 US dollars and were determined using national sources. Adverse event (AE) management was determined using immune-related AE (irAE) data from CheckMate-067, irAE management guides for nivolumab and ipilimumab, and treatment guidelines. Utilities were obtained from published literature, using melanoma-specific studies when available, and were weighted based on incidence and duration of irAEs. Base case, one-way sensitivity, and probabilistic sensitivity analyses were conducted. RESULTS Nivolumab-ipilimumab combination therapy is not the cost effective choice ($454,092 per progression-free quality-adjusted-life-year [PFQALY]) compared to nivolumab monotherapy in our base case analysis at a willingness-to-pay threshold of $100,000/PFQALY. Both combination therapy and nivolumab monotherapy were cost-effective choices compared to ipilimumab monotherapy. PD-L1 positive status, utility of nivolumab and combination therapy, and medication costs contributed the most uncertainty to the model. In a population of 100% PD-L1 negative patients, nivolumab was still the optimal treatment but combination therapy had an improved ICER of $295,903/PFQALY. Combination therapy became dominated by nivolumab when 68% of the sample was PD-L1 positive. In addition, the cost of ipilimumab would have to decrease to <$21,555 per dose for combination therapy to have an ICER <$100,000/PFQALY, and to <$19,151 (a 42% reduction) to be more cost-effective than nivolumab monotherapy. CONCLUSIONS Nivolumab-ipilimumab combination therapy is not cost-effective compared to nivolumab monotherapy, which is the most cost-effective option. Professionals in managed care settings should consider the pharmacoeconomic implications of these new immunotherapies as they make value-based formulary decisions and future cost-effectiveness studies are completed.

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OBJECTIVES To identify participants living at home and to estimate the risk of their transition into an institutional setting. DESIGN Prospective cohort study from the National Health and Aging Trends Study (NHATS), a nationally representative survey of US adults aged 65 and older. SETTING US national sample. PARTICIPANTS A total of 4712 NHATS participants were living at home in 2011. Residential transitions were described every year through 2017. MEASUREMENTS The primary outcome was transition time into an institutional setting. Primary predictors were social support factors (living spouse, lives with others, presence of social network, and participation in social activities). Covariates included age, sex, race, cognitive status, functional disability, multimorbidity, and Medicaid enrollment. A Fine and Gray hazards model estimated the risk of transition into an institutional setting, with death before institutionalization considered a competing risk. RESULTS In 2011, 4712 NHATS participants were living at home (78 ± 8 y; 57% female; 80% white; 10% probable dementia; 7% with three or more activities of daily living disabilities). By 2017, 58% remained at home, 17% had either transitioned to an institution or died in an institution, and 25% died before institutionalization. In multivariable analyses that adjusted for age, sex, race, cognitive status, functional disability, multimorbidity, and Medicaid enrollment, participants were more likely to move out of the home into an institution if they had no social network (0 vs three or more people; subhazard ratio [sHR] = 1.8; 95% confidence interval [CI] = 1.2–2.5; P = .003) or lived alone (sHR = 1.9; 95% CI = 1.6–2.2; P < .0001). Older adults who enjoyed going to the movies, dinner, or the casino and visiting family or friends had a lower probability of institutionalization compared with participants who did not enjoy these activities or did not visit family or friends (adjusted sHR = .7; 95% CI = .6–.9; adjusted sHR = .7; 95% CI = .6–.9, respectively). CONCLUSION Policy initiatives should target older adults with limited social support to reduce the risk of moving from home into an institution. J Am Geriatr Soc 67:2622–2627, 2019

33. The first rounds of coronavirus relief didn't include primary caregivers: these lawmakers want to change that. Time.