Showing Up Is Half the Battle: The Impact of Telehealth on Psychiatric Appointment Attendance for Hospital-Based Intensive Outpatient Services During COVID-19.

Introduction: The COVID-19 pandemic accelerated telehealth to deliver psychiatric services. Continuation of psychiatric services for individuals with high clinical acuity was critical. This study examined attendance to rapidly deployed telehealth services for psychiatrically high-risk individuals receiving intensive outpatient program (IOP), primarily group-based psychotherapy services for adults and adolescents by race/ethnicity, insurance, and clinical treatment program within a large hospital-based outpatient psychiatric setting. Methods: Chi-square tests compared whether attendance rates for telehealth versus in-person IOP services varied by population group, race, insurance, and clinical program, using observational data of adolescent and adult patients treated between October 1, 2019, and July 31, 2020. Results: Appointment attendance increased for telehealth versus in-person services for adolescents (χ2 (df = 1) = 27.49, p < 0.0001) and adults (χ2 (df = 1) = 434.37, p < 0.0001). For adults, increased appointment attendance for telehealth was observed across insurance type (Medicaid: +11.5%; Medicare: +13.79%; Commercial: +6.94%), race/ethnicity (+6.23% to +15.76% across groups), and for IOP groups across all five diagnostic treatment programs (between 7.59% and 15.9% increases across groups). Adolescent results were mixed; increased appointment attendance for telehealth was observed among commercially insured youth (+7.11%), but no differences were observed for Medicaid-insured youth. Non-Hispanic white youth had increased attendance for telehealth (+8.38%) and no differences were observed for non-Hispanic black youth. Decreases were found in telehealth attendance for Hispanic/Latinx youth (-13.49%). Discussion: Rapidly deployed telehealth increased attendance to intensive services for psychiatrically high-risk individuals, particularly among adults and for adolescents with commercial insurance and non-Hispanic white youth. Trends among racial/ethnic and Medicaid-insured youth warrant further investigation regarding the potential for special challenges or vulnerabilities and advocacy needs. Findings highlight telehealth as an important tool in supporting availability of services for individuals with high levels of psychiatric acuity, particularly for group-based services, during the pandemic.

Investigation of salicylate hepatic responses in comparison with chemical analogues of the drug.

Anti-hyperglycaemic effects of the hydroxybenzoic acid salicylate might stem from effects of the drug on mitochondrial uncoupling, activation of AMP-activated protein kinase, and inhibition of NF-κB signalling. Here, we have gauged the contribution of these effects to control of hepatocyte glucose production, comparing salicylate with inactive hydroxybenzoic acid analogues of the drug. In rat H4IIE hepatoma cells, salicylate was the only drug tested that activated AMPK. Salicylate also reduced mTOR signalling, but this property was observed widely among the analogues. In a sub-panel of analogues, salicylate alone reduced promoter activity of the key gluconeogenic enzyme glucose 6-phosphatase and suppressed basal glucose production in mouse primary hepatocytes. Both salicylate and 2,6 dihydroxybenzoic acid suppressed TNFα-induced IκB degradation, and in genetic knockout experiments, we found that the effect of salicylate on IκB degradation was AMPK-independent. Previous data also identified AMPK-independent regulation of glucose but we found that direct inhibition of neither NF-κB nor mTOR signalling suppressed glucose production, suggesting that other factors besides these cell signalling pathways may need to be considered to account for this response to salicylate. We found, for example, that H4IIE cells were exquisitely sensitive to uncoupling with modest doses of salicylate, which occurred on a similar time course to another anti-hyperglycaemic uncoupling agent 2,4-dinitrophenol, while there was no discernible effect at all of two salicylate analogues which are not anti-hyperglycaemic. This finding supports much earlier literature suggesting that salicylates exert anti-hyperglycaemic effects at least in part through uncoupling.

Using the red/yellow/green discharge tool to improve the timeliness of hospital discharges.

BACKGROUND: As part of Yale-New Haven Hospital (Connecticut)'s Safe Patient Flow Initiative, the physician leadership developed the Red/Yellow/Green (RYG) Discharge Tool, an electronic medical record-based prompt to identify likelihood of patients' next-day discharge: green (very likely), yellow (possibly), and red (unlikely). The tool's purpose was to enhance communication with nursing/care coordination and trigger earlier discharge steps for patients identified as "green" or "yellow." METHODS: Data on discharge assignments, discharge dates/ times, and team designation were collected for all adult medicine patients discharged in October-December 2009 (Study Period 1) and October-December 2011 (Study Period 2), between which the tool's placement changed from the sign-out note to the daily progress note. RESULTS: In Study Period 1, 75.9% of the patients had discharge assignments, compared with 90.8% in Period 2 (p < .001). The overall 11 A.M. discharge rate improved from 10.4% to 21.2% from 2007 to 2011. "Green" patients were more likely to be discharged before 11 A.M. than "yellow" or "red" patients (p < .001). Patients with RYG assignments discharged by 11 A.M. had a lower length of stay than those without assignments and did not have an associated increased risk of readmission. Discharge prediction accuracy worsened after the change in placement, decreasing from 75.1% to 59.1% for "green" patients (p < .001), and from 34.5% to 29.2% (p < .001) for "yellow" patients. In both periods, hospitalists were more accurate than house staff in discharge predictions, suggesting that education and/or experience may contribute to discharge assignment. CONCLUSIONS: The RYG Discharge Tool helped facilitate earlier discharges, but accuracy depends on placement in daily work flow and experience.

The safe patient flow initiative: a collaborative quality improvement journey at Yale-New Haven Hospital.

BACKGROUND: Yale-New Haven Hospital (YNHH) began a successful journey to achieve safe patient flow in fiscal year (FY) 2008 (October 1, 2007-September 30, 2008). The 966-bed (now 1,541-bed) academic medical center faced several challenges, including overcrowding in the Adult Emergency Department (ED); delays in the postanesthesia care unit, which affected the flow of patients through the operating rooms; pinched capacity during the central part of the day; and a lack of interdependent institutionwide coordination of patients. METHODS: The Safe Patient Flow Steering Committee oversaw improvement efforts, most of which were implemented in FY 2009 (October 2008-September 2009), through a cascade of operational meetings. Process changes were made in various departments, such as the Adult ED, Physicians/Providers, and the Bed Management Department. Organizationwide method changes involved standardizing the discharge process, using status boards for visual control, and improving accuracy and timeliness of data entry. RESULTS: Between FY 2008 and FY 2011, YNHH experienced an 84% improvement in discharges by 11:00 A.M. The average length of stay decreased from 5.23 to 5.05 days, thereby accommodating an additional 45 inpatients on a daily basis, contributing to YNHH's positive operating margin amid increasing volume and overall decreasing inpatient length of stay. CONCLUSIONS: YNHH improved clinical, operational, and financial outcomes by embracing five key components of demand capacity management: real-time communication, inter/intradepartmental and interdisciplinary collaboration, staff empowerment, standardization of best practices, and institutional memory.

Emergency conversion to telehealth in hospital-based psychiatric outpatient services: Strategy and early observations.

Balancing public health physical distancing guidelines and the need to provide critical mental health services for risky and psychiatrically complex patient populations without disruption, many systems swiftly pivoted to telehealth to provide care during COVID-19. Leveraging technology, Yale New Haven Psychiatric Hospital's ambulatory services designed and deployed virtual intensive outpatient (IOP) and outpatient (OP) group-based services rapidly. Strategies for rapid deployment of group-based services, including action steps transitioning to telehealth, clinical protocols, and remote workforce training, early observations and challenges to implementation are described as helpful tools for clinical settings with similar needs to prevent infectious spread while addressing the mental health needs of patients.

Metformin selectively targets redox control of complex I energy transduction.

Many guanide-containing drugs are antihyperglycaemic but most exhibit toxicity, to the extent that only the biguanide metformin has enjoyed sustained clinical use. Here, we have isolated unique mitochondrial redox control properties of metformin that are likely to account for this difference. In primary hepatocytes and H4IIE hepatoma cells we found that antihyperglycaemic diguanides DG5-DG10 and the biguanide phenformin were up to 1000-fold more potent than metformin on cell signalling responses, gluconeogenic promoter expression and hepatocyte glucose production. Each drug inhibited cellular oxygen consumption similarly but there were marked differences in other respects. All diguanides and phenformin but not metformin inhibited NADH oxidation in submitochondrial particles, indicative of complex I inhibition, which also corresponded closely with dehydrogenase activity in living cells measured by WST-1. Consistent with these findings, in isolated mitochondria, DG8 but not metformin caused the NADH/NAD+ couple to become more reduced over time and mitochondrial deterioration ensued, suggesting direct inhibition of complex I and mitochondrial toxicity of DG8. In contrast, metformin exerted a selective oxidation of the mitochondrial NADH/NAD+ couple, without triggering mitochondrial deterioration. Together, our results suggest that metformin suppresses energy transduction by selectively inducing a state in complex I where redox and proton transfer domains are no longer efficiently coupled.

Cellular responses to the metal-binding properties of metformin.

In recent decades, the antihyperglycemic biguanide metformin has been used extensively in the treatment of type 2 diabetes, despite continuing uncertainty over its direct target. In this article, using two independent approaches, we demonstrate that cellular actions of metformin are disrupted by interference with its metal-binding properties, which have been known for over a century but little studied by biologists. We demonstrate that copper sequestration opposes known actions of metformin not only on AMP-activated protein kinase (AMPK)-dependent signaling, but also on S6 protein phosphorylation. Biguanide/metal interactions are stabilized by extensive π-electron delocalization and by investigating analogs of metformin; we provide evidence that this intrinsic property enables biguanides to regulate AMPK, glucose production, gluconeogenic gene expression, mitochondrial respiration, and mitochondrial copper binding. In contrast, regulation of S6 phosphorylation is prevented only by direct modification of the metal-liganding groups of the biguanide structure, supporting recent data that AMPK and S6 phosphorylation are regulated independently by biguanides. Additional studies with pioglitazone suggest that mitochondrial copper is targeted by both of these clinically important drugs. Together, these results suggest that cellular effects of biguanides depend on their metal-binding properties. This link may illuminate a better understanding of the molecular mechanisms enabling antihyperglycemic drug action.

Residual effects of lovastatin and simvastatin on urinary mevalonate excretions in patients with familial hypercholesterolemia.

3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitors are widely used to decrease plasma cholesterol levels in patients with heterozygous familial hypercholesterolemia (FH) who are at increased risk of premature coronary artery disease. Tissue-culture and animal studies have indicated that administration of HMG CoA reductase inhibitors (eg, lovastatin, simvastatin, etc) induces a compensatory increase in the activity of HMG CoA reductase, both by increasing its synthesis and decreasing catabolism. To determine in human subjects whether cessation of therapy with this class of drugs leads to induction of HMG CoA reductase activity and above-normal rates of cholesterol biosynthesis, we measured urinary concentrations of mevalonic acid (an indicator of cholesterol biosynthesis) after the cessation of therapy with lovastatin and simvastatin (80 mg/day) in patients with heterozygous FH. Plasma concentrations of LDL increased promptly on discontinuation of reductase inhibitor therapy but did not increase above pretreatment levels at any point after drug discontinuation. Similarly, the 24-hour urinary excretion of mevalonic acid was reduced during treatment with lovastatin or simvastatin and increased promptly on discontinuation of drug but did not increase to levels exceeding those found at baseline when the patients were receiving dietary therapy only. We conclude that cessation of treatment with HMG CoA reductase inhibitors in patients with FH does not result in a rebound increase in cholesterol biosynthesis and that no rebound overshoot occurs in plasma concentrations of low-density-lipoprotein cholesterol.