Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial.

BACKGROUND: From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. METHODS: TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). FINDINGS: Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62-1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88-2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. INTERPRETATION: Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation. FUNDING: UK Medical Research Council, UK National Institute for Health Research Cambridge Biomedical Research Centre, Eli Lilly and Company, Alexion Pharmaceuticals, and Addenbrooke's Charitable Trust.

Efficacy and safety of subcutaneous tocilizumab in rheumatoid arthritis over 1 year: a UK real-world, open-label study.

OBJECTIVE: The ACT-MOVE study assessed the real-world efficacy and safety of s.c. tocilizumab (TCZ-SC), provided as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) over 1 year, in patients with RA and an inadequate response to csDMARD therapy and/or first TNF inhibitor. METHODS: In this UK multicentre, open-label phase IIIb study, patients received TCZ-SC 162 mg once weekly for 52 weeks as monotherapy or with csDMARDs. Efficacy and safety were evaluated at baseline, weeks 2 and 4 and every 4 weeks thereafter up to week 52. RESULTS: Of 161 patients who received at least one dose of TCZ-SC, 21 (13.0%) received TCZ-SC alone and 140 (87.0%) TCZ-SC with a csDMARD(s). From baseline to week 52, there was a mean decrease in DAS28-ESR score among all patients (-3.68), and within monotherapy (-3.75) and combination therapy (-3.67) groups. The proportion of patients who achieved DAS28 clinical remission (DAS28-ESR <2.6) at week 52 was 75.4% (95% CI 66.8, 82.8). At the same time point, ≥80% of patients who remained on TCZ-SC achieved DAS28 clinical remission or had low disease activity (DAS28-ESR ≥2.6 and ≤3.2). Overall, 6.2% of patients had at least one serious adverse event (10.2/100 patient-years), and there was one death; 11.2% of patients discontinued owing to adverse events. CONCLUSION: TCZ-SC was effective and tolerated in a real-world setting over 1 year. The efficacy of TCZ-SC was similar whether given as monotherapy or with csDMARDs; its safety profile was consistent with that previously established. TRIAL REGISTRATION: ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT02046603.

Citrullination facilitates cross-reactivity of rheumatoid factor with non-IgG1 Fc epitopes in rheumatoid arthritis.

Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the two most prevalent autoantibodies in rheumatoid arthritis (RA), and are thought to have distinct autoantigen targets. Whilst RF targets the Fc region of antibodies, ACPAs target a far broader spectrum of citrullinated peptides. Here we demonstrate significant sequence and structural homology between proposed RF target epitopes in IgG1 Fc and the ACPA target fibrinogen. Two of the three homologous sequences were susceptible to citrullination, and this modification, which occurs extensively in RA, permitted significant cross-reactivity of RF+ patient sera with fibrinogen in both western blots and ELISAs. Crucially, this reactivity was specific to RF as it was absent in RF- patient and healthy control sera, and could be inhibited by pre-incubation with IgG1 Fc. These studies establish fibrinogen as a common target for both RF and ACPAs, and suggest a new mechanism in RF-mediated autoimmune diseases wherein RF may act as a precursor from which the ACPA response evolves.

The Brief Assessment of Family Functioning Scale (BAFFS): a three-item version of the General Functioning Scale of the Family Assessment Device.

The purpose of the present study is to compare results from the 12-item General Functioning Scale (GF-FAD) of the Family Assessment Device (FAD) to a three-item version, the Brief Assessment of Family Functioning Scale (BAFFS), designed to be used when brevity is especially important. We used principal components analysis of the GF-FAD, followed by multiple sample confirmatory factor analyses to test the robustness of the BAFFS in different samples. The BAFFS correlated highly with the GF-FAD, and demonstrated good concurrent validity with another measure of global marital functioning, the Dyadic Adjustment Scale-4 in a help-seeking sample. Like the 12-item version, the BAFFS moderately correlated with an objective, interview-based rating of family functioning, the McMaster Clinical Rating Scale. The BAFFS appears to serve as a good proxy for the GF-FAD when an ultra-brief family assessment measure is needed.

Practices of Depression Care in Home Health Care: Home Health Clinician Perspectives.

OBJECTIVE: The study assessed gaps between published best practices and real-world practices of treating depression in home health care (HHC) and barriers to closing gaps. METHODS: The qualitative study used semistructured interviews with nurses and administrators (N=20) from five HHC agencies in five states. Audio-recorded interviews were transcribed and analyzed by a multidisciplinary team using grounded theory method to identify themes. RESULTS: Routine HHC nursing overlapped with all functional areas of depression care. However, gaps were noted between best and real-world practices. Gaps were associated with perceived scope of practice by HHC nurses, knowledge gaps and low self-efficacy in depression treatment, stigma attached to depression, poor quality of antidepressant management in primary care, and poor communication between HHC and primary care clinicians. CONCLUSIONS: Strategies to close gaps between typical and best practices include enhancing HHC clinicians' knowledge and self-efficacy with depression treatment and improving the quality of antidepressant management and communication with primary care.

Clinical effectiveness of integrating depression care management into medicare home health: the Depression CAREPATH Randomized trial.

IMPORTANCE: Among older home health care patients, depression is highly prevalent, is often inadequately treated, and contributes to hospitalization and other poor outcomes. Feasible and effective interventions are needed to reduce this burden of depression. OBJECTIVE: To determine whether, among older Medicare Home Health recipients who screen positive for depression, patients of nurses receiving randomization to an intervention have greater improvement in depressive symptoms during 1 year than patients receiving enhanced usual care. DESIGN, SETTING, AND PARTICIPANTS: This cluster randomized effectiveness trial conducted at 6 home health care agencies nationwide assigned nurse teams to an intervention (12 teams) or to enhanced usual care (9 teams). Between January 13, 2009, and December 6, 2012, Medicare Home Health patients 65 years and older who screened positive for depression on routine nursing assessments were recruited, underwent assessment, and were followed up at 3, 6, and 12 months by research staff blinded to intervention status. Patients were interviewed at home and by telephone. Of 502 eligible patients, 306 enrolled in the study. INTERVENTIONS: The Depression Care for Patients at Home (Depression CAREPATH) trial requires nurses to manage depression at routine home visits by weekly symptom assessment, medication management, care coordination, education, and goal setting. Nurses' training totaled 7 hours (4 onsite and 3 via the web). Researchers telephoned intervention team supervisors every other week. MAIN OUTCOMES AND MEASURES: Depression severity, assessed by the 24-item Hamilton Scale for Depression (HAM-D). RESULTS: The 306 participants were predominantly female (69.6%), were racially/ethnically diverse (18.0% black and 16.0% Hispanic), and had a mean (SD) age of 76.5 (8.0) years. In the full sample, the intervention had no effect (P = .13 for intervention × time interaction). Adjusted HAM-D scores (Depression CAREPATH vs control) did not differ at 3 months (10.5 vs 11.4, P = .26) or at 6 months (9.3 vs 10.5, P = .12) but reached significance at 12 months (8.7 vs 10.6, P = .05). In the subsample with mild depression (HAM-D score, <10), the intervention had no effect (P = .90), and HAM-D scores did not differ at any follow-up points. Among 208 participants with a HAM-D score of 10 or higher, the Depression CAREPATH demonstrated effectiveness (P = .02), with lower HAM-D scores at 3 months (14.1 vs 16.1, P = .04), at 6 months (12.0 vs 14.7, P = .02), and at 12 months (11.8 vs 15.7, P = .005). CONCLUSION AND RELEVANCE: Home health care nurses can effectively integrate depression care management into routine practice. However, the clinical benefit seems to be limited to patients with moderate to severe depression. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01979302.

ATA practice guidelines for video-based online mental health services.

Table of Contents PREAMBLE SCOPE INTRODUCTION Internet-Based Telemental Health Models of Care Today CLINICAL GUIDELINES A. Professional and Patient Identity and Location 1. Provider and Patient Identity Verification 2. Provider and Patient Location Documentation 3. Contact Information Verification for Professional and Patient 4. Verification of Expectations Regarding Contact Between Sessions B. Patient Appropriateness for Videoconferencing-Based Telemental Health 1. Appropriateness of Videoconferencing in Settings Where Professional Staff Are Not Immediately Available C. Informed Consent D. Physical Environment E. Communication and Collaboration with the Patient's Treatment Team F. Emergency Management 1. Education and Training 2. Jurisdictional Mental Health Involuntary Hospitalization Laws 3. Patient Safety When Providing Services in a Setting with Immediately Available Professionals 4. Patient Safety When Providing Services in a Setting Without Immediately Available Professional Staff 5. Patient Support Person and Uncooperative Patients 6. Transportation 7. Local Emergency Personnel G. Medical Issues H. Referral Resources I .Community and Cultural Competency TECHNICAL GUIDELINES A. Videoconferencing Applications B. Device Characteristics C. Connectivity D. Privacy ADMINISTRATIVE GUIDELINES A. Qualification and Training of Professionals B. Documentation and Record Keeping C. Payment and Billing REFERENCES.

Anxiety symptoms in older home health care recipients: prevalence and associates.

This study examined the prevalence and associates of anxiety symptoms in older home health care recipients (N = 249) who completed structured interviews assessing sociodemographic, cognitive, medical and disability, and psychosocial variables--including anxiety (assessed by the Clinical Anxiety Scale). Mild or moderate anxiety was reported by 3.6% of the sample. No anxiety symptoms whatsoever were reported by 63.9%, while the remaining endorsed at least one symptom. Binary logistic regression analysis revealed that the odds of having any anxiety were elevated among participants who had had a recent fall, OR = 2.81, 95% CI [1.46, 5.43]; and those with major depression, OR = 4.78, 95% CI [1.46, 15.68]. These findings point to the importance of conducting studies to clarify whether the mild severity of anxiety found in this sample is best accounted for by protective factors inherent to the home health care setting or assessment factors that diminish the reporting of anxiety symptoms.

A descriptive study of older bipolar disorder residents living in New York City's adult congregate facilities.

OBJECTIVES: Much of the research on geriatric bipolar disorder is from outpatient populations or epidemiological surveys with small samples. In contrast, in this study a descriptive analysis was conducted of geriatric and younger adult residents with bipolar disorder or mania in non-clinical adult congregate facilities (ACFs) in the greater New York City region. METHODS: A total of 2602 ACF residents were evaluated in 19 facilities, across multiple demographic and health domains. Within this sample, 200 residents had chart diagnoses of bipolar disorder or mania. Among these, 50 geriatric residents (age ≥ 60) were compared to 50 younger adult residents (age < 50) on a number of demographic and health measures. RESULTS: Based on chart diagnoses, the overall prevalence of bipolar disorder was 7.8%. Compared to other studies of outpatient, epidemiological, and census samples, both older and younger residents with bipolar disorder had higher rates of cognitive impairment, impairment in executive functioning, vision impairment, and proportion of residents who had never been married. The younger group also had higher rates of obesity and the elderly group had a greater proportion of residents without high-school education. Both age groups had rates of lithium or valproate use comparable to those found in outpatient studies. Comparing the two age groups, the elderly sample had lower overall cognitive and executive functioning, and was using a larger number of medication classes than the younger group. The elderly group also had a larger proportion of residents who were separated/divorced or widowed compared to the younger group, which had higher rates of never-married residents. CONCLUSIONS: Overall, both age groups had relatively high rates of bipolar disorder, with significant cognitive impairment, medical burden, obesity, mental health service use, and lower education levels, as compared to outpatient, epidemiological, and census samples. Of note was the significant cognitive impairment across age groups.

Depression Care for Patients at Home (Depression CAREPATH): home care depression care management protocol, part 2.

High levels of depressive symptoms are common and contribute to poorer clinical outcomes even in geriatric patients who are already taking antidepressant medication. The Depression CARE for PATients at Home (Depression CAREPATH) intervention was designed to meet the needs of medical and surgical patients who suffer from depression. The intervention's clinical protocols are designed to guide clinicians in managing depression as part of routine home care.

Feasibility and impact of telemonitor-based depression care management for geriatric homecare patients.

OBJECTIVE: The objective of this study was to test the feasibility, acceptability, and preliminary clinical outcomes of a method to leverage existing home healthcare telemonitoring technology to deliver depression care management (DCM) to both Spanish- and English-speaking elderly homebound recipients of homecare services. MATERIALS AND METHODS: Three stand-alone, nonprofit community homecare agencies located in New York, Vermont, and Miami participated in this study. Evidence-based DCM was adapted to the telemonitor platform by programming questions and educational information on depression symptoms, antidepressant adherence, and side effects. Recruited patients participated for a minimum of 3 weeks. Telehealth nurses were trained on DCM and received biweekly supervision. On-site trained research assistants conducted in-home research interviews on depression diagnosis and severity and patient satisfaction with the protocol. RESULTS: An ethnically diverse sample of 48 English- and Spanish-only-speaking patients participated, along with seven telehealth nurses. Both patients and telehealth nurses reported high levels of protocol acceptance. Among 19 patients meeting diagnostic criteria for major depression, the mean depression severity was in the "markedly severe" range at baseline and in the "mild" range at follow-up. CONCLUSIONS: Results of this pilot support the feasibility of using homecare's existing telemonitoring technology to deliver DCM to their elderly homebound patients. This was true for both English- and Spanish-speaking patients. Preliminary clinical outcomes suggest improvement in depression severity, although these findings require testing in a randomized clinical trial. Implications for the science and service of telehealth-based depression care for elderly patients are discussed.

The PHQ-2 on OASIS-C: a new resource for identifying geriatric depression among home health patients.

Since Medicare first implemented the home care Outcome and Assessment Information Set (OASIS) in 1999, we have learned a great deal about depression among the homebound elderly. First, we know that major depression is a highly prevalent illness in home care. With depression rates at almost 15%, home care-along with nursing homes-has among the highest rates of any healthcare setting.

Depression and increased short-term hospitalization risk among geriatric patients receiving home health care services.

OBJECTIVE: This study evaluated the association between depression and hospitalization among geriatric home care patients. METHODS: A sample of 477 patients newly admitted to home care over two years was assessed for depression. Bivariate and logistic regression analyses examined the likelihood of hospitalization during a 60-day home care episode. RESULTS: The hospitalization rate was similar for the 77 depressed patients and 400 nondepressed patients (about 7%). However, mean time to hospitalization was 8.4 versus 19.5 days after start of care, respectively. Hospitalization risk was significantly higher for depressed patients during the first few weeks. A main effect for depression and a depression-by-time interaction was found when analyses controlled for medical comorbidity, cognitive status, age, gender, race, activities of daily living and instrumental activities of daily living, and referral to home care after hospitalization. CONCLUSIONS: Depression appears to increase short-term risk of hospitalization for geriatric home care patients immediately after starting home care.

Training nursing staff to recognize depression in home healthcare.

OBJECTIVES: To describe the implementation and acceptability of the TRaining In the Assessment of Depression (TRIAD) intervention, which has been tested in a randomized trial. The primary aim of TRIAD is to improve the ability of homecare nurses to detect depression in medically ill, older adult homecare patients. DESIGN: Description of the important components of TRIAD, its implementation, and evaluation results from nurse surveys. SETTING: Three certified home healthcare agencies in Westchester County, New York. PARTICIPANTS: Thirty-six homecare nurses. INTERVENTION: Participants randomly assigned to TRIAD (n=17) were provided with the opportunity to observe and practice patient interviewing. The approach focused on clinically meaningful identification of the two "gateway" symptoms of depression and is consistent with the newly revised Medicare mandatory Outcome and Assessment Information Set (OASIS-C). Control group participants (n=19) received no training beyond that which agencies may have provided routinely. MEASUREMENTS: Baseline and 1-year nurse confidence in depression detection, and postintervention acceptability ratings of the TRIAD intervention. RESULTS: Participants randomized to the TRIAD intervention reported a statistically significant increase in confidence in assessing for depression mood (P<.001), whereas the usual care group's confidence remained unchanged (P=.34) 1 year later. CONCLUSION: An educational program designed to improve depression detection by giving nurses the skills and confidence to integrate depression assessment into the context of routine care can be successfully implemented with homecare agency support. The authors discuss the intervention in terms of OASIS-C and the "real world" realities of intervention implementation.

The effect of major and minor depression on Medicare home healthcare services use.

OBJECTIVES: To examine the associations between major and minor depression and categories of Medicare home healthcare use. DESIGN: Observational prospective study (1997-1999). SETTING: Visiting nurse agency in suburban New York State. PARTCIPANTS: Five hundred thirty-nine new Medicare admissions aged 65 and older (mean age 78.4), 65.1% female, and 15.0% nonwhite. Approximately 13.5% were diagnosed with major depression and another 10.8% with minor depression. MEASUREMENTS: Consensus "best estimate"Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnoses for major and minor depression assessed using Structured Clinical Interviews for DSM-IV (SCID) plus medical charts. RESULTS: Major and minor depression appear to have little association with probability and amount of use of the types of Medicare home health care (skilled nurse, home health aide, therapist (physical, occupational, and speech), and medical social services). Overall, patients with minor depression appear to have utilization similar to that of patients with major depression. CONCLUSION: It seems likely that any potential incremental depression effect on utilization is being offset by the transitional medical state of the patients that entered Medicare home healthcare directly from a hospital, nursing home, or rehabilitation facility, and the overall severity of disability and chronic illness present in long-term home healthcare patients. Further research is required to determine whether similar findings occur in other home healthcare agencies and whether these are present under the current Medicare Prospective Payment System reimbursement mechanism.

Depression and risk for adverse falls in older home health care patients.

Because falls are highly prevalent, harmful events for older adults, identification of patients at risk is a high priority for home health care agencies. Using routine administrative data, we demonstrated that patients with depressive symptoms on the Outcome and Assessment Information Set are at risk for falls. A prospective case-control study that matched 54 patients who experienced an adverse fall with 854 controls showed that patients who fell had twice the odds of being depressed (odds ratio = 1.90, 95% confidence interval = 1.01 to 3.59). Bowel incontinence, high medical comorbidity, stair use, injury and poisoning, memory deficit, and antipsychotic medication use were also predictors, but no association was found for antidepressant medications. These data suggest the potential benefit of including depression screening for multifactorial fall prevention interventions.

Frequency of manic symptoms and bipolar disorder in psychiatrically hospitalized adolescents using the K-SADS Mania Rating Scale.

OBJECTIVE: The aim of this study was to assess the frequency of manic symptoms and bipolar spectrum disorders in an adolescent inpatient psychiatric sample using the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) Mania Rating Scale (MRS), parent and adolescent measures. METHOD: A total of 391 consecutive admissions to a psychiatric inpatient unit were assessed using the K-SADS MRS, the Childhood Inventory of Psychiatric Syndromes (CHIPS), and other clinically relevant measures. RESULTS: The frequency of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) manic symptoms in this population was generally high. However, only 19.6% received a consensus diagnosis of juvenile bipolar disorder. The K-SADS MRS discriminated bipolar from non-bipolar patients when parents rated symptoms but not when rated by adolescents. CONCLUSIONS: This study of non-selected adolescents over a one-year period demonstrates that bipolar spectrum disorders in an inpatient population are common, and that the use of the KSADS MRS is effective in identifying this syndrome.

Does depression predict falls among home health patients? Using a clinical-research partnership to improve the quality of geriatric care.

This study found that patients with depressed mood or anhedonia identified on the OASIS were nearly three times more likely to fall. The authors describe the ways these findings are being used in a fall prevention program. The clinical-research partnership used in the study was found to help agencies develop clinically driven research, analyze clinical and administrative data for quality improvement, and provide a foundation for research consultation/collaboration in applied settings.