Association of Disease Trajectory and Place of Care with End-of-Life Burdensome Transitions: A Retrospective Cohort Study.

OBJECTIVES: End-of-life (EOL) transitions to hospital can be burdensome for older adults and may contribute to poor outcomes. We investigated the association of disease trajectory and place of care with EOL burdensome transitions. DESIGN: Retrospective cohort study using administrative data. SETTING/PARTICIPANTS: Ontarians aged ≥65 years who died between 2015 and 2018 and received long-term care (LTC) or home care 6 months before death. METHODS: Disease trajectories were defined based on EOL functional decline: terminal illness, organ failure, frailty, sudden death, and other. Places of care included LTC, EOL home care, and non-EOL home care. Burdensome transitions were defined as early (≥3 hospitalizations for any reason or ≥2 hospitalizations due to pneumonia, urinary tract infection, sepsis, or dehydration in the last 90 days of life) or late (≥1 hospitalizations for any reason in the last 3 days of life). Multinomial logistic regression tested for effect modification between disease trajectory and places of care on burdensome transitions. RESULTS: Of 110,776 decedents, 40.7% had organ failure, 37.5% had frailty, and 12.8% had a terminal illness, with the remainder in sudden death or other categories. Most were in LTC (62.5%), and 37.5% received home care, with 6.8% receiving designated EOL home care and 30.7% non-EOL home care. There was a significant interaction (P < .001) between disease trajectory and care settings. Compared with terminal illness, organ failure was associated with increased odds of early transitions across all care settings [odds ratios (ORs) ranging 1.14-1.21]. Frailty was associated with increased odds of early transitions solely for non-EOL home care recipients (OR 1.17, 95% CI 1.06-1.28). Organ failure and frailty were associated with increased odds of late transitions across all settings, with organ failure having greater odds in LTC (organ failure OR 2.29, 95% CI 2.02-2.60, vs frailty OR 1.79, 95% CI 1.58-2.04). CONCLUSIONS AND IMPLICATIONS: Disparities exist in burdensome transitions, notably for noncancer decedents with organ failure in LTC. Enhancing palliative care may help reduce burdensome transitions and improve patient outcomes.

Key quality parameter comparison of mesenchymal stem cell product cryopreserved in different cryopreservation solutions for clinical applications.

Introduction: Cryopreservation is a critical process of cell products for achieving a commercial viability through wide scale adoption. By preserving cells in a lower temperature, cryopreservation enables a product to be off-the-shelf and ready for infusion. An optimized cryopreservation strategy can maintain the viability, phenotype, and potency of thawed mesenchymal stromal/stem cells (MSCs) while being regulatory compliant. We compared three clinical-ready formulations with one research cryopreservation solutions and evaluated key quality parameters of post thawed MSCs. Method and result: MSCs were cryopreserved at 3, 6, and 9 million cells/mL (M/mL) in four different cryopreservation solutions: NutriFreez (10% dimethyl sulfoxide [DMSO]), Plasmalyte A (PLA)/5% human albumin (HA)/10% DMSO (PHD10), CryoStor CS5 (5% DMSO), and CryoStor CS10 (10% DMSO). To establish post thaw viability, cells were evaluated with no dilution of DMSO (from 3 M/mL), 1:1 dilution (from 6 M/mL), or 1:2 dilution (from 9 M/mL) with PLA/5% HA, to achieve uniform concentration at 3 M/mL. Cell viability was measured at 0-, 2-, 4-, and 6-h post thaw with Trypan blue exclusion and Annexin V/PI staining. Dilution (1:2) of final cell products from 9M/mL resulted in an improvement of cell viability over 6 h but showed a trend of decreased recovery. MSCs cryopreserved in solutions with 10% DMSO displayed comparable viabilities and recoveries up to 6 h after thawing, whereas a decreasing trend was noted in cell viability and recovery with CS5. Cells from all groups exhibited surface marker characteristics of MSCs. We further evaluated cell proliferation after 6-day recovery in culture. While cells cryopreserved in NutriFreez and PHD10 presented similar cell growth post thaw, MSCs cryopreserved in CS5 and CS10 at 3 M/mL and 6M/mL showed 10-fold less proliferative capacity. No significant differences were observed between MSCs cryopreserved in NutriFreez and PHD10 in their potency to inhibit T cell proliferation and improve monocytic phagocytosis. Conclusion: MSCs can be cryopreserved up to 9 M/mL without losing notable viability and recovery, while exhibiting comparable post thaw potency with NutriFreez and PHD10. These results highlight the importance of key parameter testing for selecting the optimal cryopreservation solution for MSC-based therapy.

Corrigendum: Measuring the Use of End-of-Life Symptom Relief Medications in Long-Term Care Homes-a Qualitative Study.

[This corrects the article DOI: 10.5770/cgj.27.712.].

Enablers and Barriers for End-of-Life Symptom Management Medications in Long-Term Care Homes: A Qualitative Study.

OBJECTIVES: Long-term care (LTC) homes provide personal and medical care 24/7 to individuals unable to live at home due to illness or disability and are often the final place of care and death for their residents. Therefore, LTC homes are tasked with providing quality end-of-life care, often requiring injectable symptom management medications to relieve distressing symptoms (eg, pain). In this study, we aimed to understand the enablers and barriers to prescribing and administering end-of-life symptom management medications in LTC homes. DESIGN: Qualitative study. SETTING AND PARTICIPANTS: From February 2021 to December 2022, we conducted virtual semi-structured interviews with health care providers (physicians and nurses) who worked in Ontario LTC homes and family caregivers of residents who died in LTC. METHODS: We analyzed interview transcripts using thematic analysis. RESULTS: We identified 4 themes related to factors that may impact the prescribing and administering of medications for end-of-life symptom management: (1) identifying the end-of-life period and symptoms, (2) communication among health care providers and between health care providers and family caregivers, (3) health care provider competency with end-of-life medications, and (4) resources for LTC staff to support medication prescribing and administrating. CONCLUSIONS AND IMPLICATIONS: In LTC, there are distinct challenges in the prescribing and administrating of end-of-life symptom management medications. Our findings can be used to inform interventions aimed at improving end-of-life care for LTC residents. However, these interventions require buy-in and investment from the provincial government and the LTC sector.

Stem cells, cell therapies, and bioengineering in lung biology and diseases 2023.

Repair and regeneration of a diseased lung using stem cells or bioengineered tissues is an exciting therapeutic approach for a variety of lung diseases and critical illnesses. Over the past decade, increasing evidence from preclinical models suggests that mesenchymal stromal cells, which are not normally resident in the lung, can be used to modulate immune responses after injury, but there have been challenges in translating these promising findings to the clinic. In parallel, there has been a surge in bioengineering studies investigating the use of artificial and acellular lung matrices as scaffolds for three-dimensional lung or airway regeneration, with some recent attempts of transplantation in large animal models. The combination of these studies with those involving stem cells, induced pluripotent stem cell derivatives, and/or cell therapies is a promising and rapidly developing research area. These studies have been further paralleled by significant increases in our understanding of the molecular and cellular events by which endogenous lung stem and/or progenitor cells arise during lung development and participate in normal and pathological remodeling after lung injury. For the 2023 Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases Conference, scientific symposia were chosen to reflect the most cutting-edge advances in these fields. Sessions focused on the integration of "omics" technologies with function, the influence of immune cells on regeneration, and the role of the extracellular matrix in regeneration. The necessity for basic science studies to enhance fundamental understanding of lung regeneration and to design innovative translational studies was reinforced throughout the conference.

Qualitative Analysis of Initial Palliative Care Consultations in Amyotrophic Lateral Sclerosis.

BACKGROUND: Palliative care (PC) benefits patients with amyotrophic lateral sclerosis (ALS), however the needs of patients and caregivers and the optimal timing of PC discussions remains unclear. This study reports the analysis of PC consult notes from a larger feasibility trial. The specific aims of this analysis were to i) identify the PC needs of patients with ALS via qualitative analysis and ii) identify characteristics of patients and caregivers that could predict specific PC needs. METHODS: This study was nested within a nonrandomized, prospective study of patients with ALS (and their caregivers) being treated at a multidisciplinary ALS clinic. Exclusion criteria of the main study were age <18 years, inability to complete questionnaires, and prior receipt of PC. All patients were offered a PC consultation (PCC); those who accepted were included in this nested study. Consultation notes were reviewed and thematic and content analyses were conducted. The occurrence of themes across patient and caregiver contextual variables were examined. RESULTS: Thirty-two PCCs were completed between October 2020 and April 2022. Six major themes were identified: PC roles (with subthemes encompassing the spectrum of specialist PC practice including symptom management and advance care planning), engagement with PC, patients' concerns for their caregivers, caregiver-specific concerns, finances, and COVID-19. An average of 12 topics were discussed per PCC (range = 3-22). Discussion of advance care planning, care coordination, and symptom management was common, and these topics were not discussed more frequently in PCCs with patients with lower functional status, more bulbar symptoms, or lower quality of life. Time from diagnosis did not impact topics of discussion. Patients reporting more symptoms of depression more frequently required psychological support, particularly regarding loss of independence, employment, and leisure activities. DISCUSSION: Patients with ALS and their caregivers have a wide range of PC needs. These needs vary irrespective of time from diagnosis, functional status, or quality of life, therefore PCC is recommended for all patients with ALS. PCC should be individualized based on patient and caregiver preferences. TRIAL REGISTRATION INFORMATION: The study was registered with ClinicalTrials.gov (NCT04257760; https://clinicaltrials.gov/ct2/show/NCT04257760) on February 6, 2020. The first enrollment occurred on October 20, 2020.

Continuous palliative sedation until death: a qualitative study of palliative care clinicians' experiences.

BACKGROUND: The practice of continuous palliative sedation until death is the subject of much medical and ethical debate, which is reflected in the inconsistency that persists in the literature regarding the definition and indications of palliative sedation. AIM: This study aims to gain a better understanding of palliative care clinicians' experiences with continuous palliative sedation. DESIGN: We conducted a qualitative study based on focus group discussions. SETTING/PARTICIPANTS: We conducted six focus groups with a total of 28 palliative care clinicians (i.e., 15 nurses, 12 physicians, and 1 end-of-life doula) from diverse care settings across Canada, where assisted dying has recently been legalized. RESULTS: An interpretative phenomenological analysis was used to consolidate the data into six key themes: responding to suffering; grappling with uncertainty; adapting care to ensure ongoing quality; grounding clinical practice in ethics; combining medical expertise, relational tact, and reflexivity; and offering an alternative to assisted death. CONCLUSIONS: Interaction with the patient's family, uncertainty about the patient's prognosis, the concurrent practice of assisted dying, and the treatment of existential suffering influence the quality of sedation and indicate a lack of clear palliative care guidelines. Nevertheless, clinicians exhibit a reflective and adaptive capacity that can facilitate good practice.

Advancing the Care Experience for patients receiving Palliative care as they Transition from hospital to Home (ACEPATH): Codesigning an intervention to improve patient and family caregiver experiences.

BACKGROUND: Returning home from the hospital for palliative-focused care is a common transition, but the process can be emotionally distressing and logistically challenging for patients and caregivers. While interventions exist to aid in the transition, none have been developed in partnership with patients and caregivers. OBJECTIVE: To undergo the initial stages of codesign to create an intervention (Advancing the Care Experience for patients receiving Palliative care as they Transition from hospital to Home [ACEPATH]) to improve the experience of hospital-to-home transitions for adult patients receiving palliative care and their caregiver(s). METHODS: The codesign process consisted of (1) the development of codesign workshop (CDW) materials to communicate key findings from prior research to CDW participants; (2) CDWs with patients, caregivers and healthcare providers (HCPs); and (3) low-fidelity prototype testing to review CDW outputs and develop low-fidelity prototypes of interventions. HCPs provided feedback on the viability of low-fidelity prototypes. RESULTS: Three patients, seven caregivers and five HCPs participated in eight CDWs from July 2022 to March 2023. CDWs resulted in four intervention prototypes: a checklist, quick reference sheets, a patient/caregiver workbook and a transition navigator role. Outputs from CDWs included descriptions of interventions and measures of success. In April 2023, the four prototypes were presented in four low-fidelity prototype sessions to 20 HCPs. Participants in the low-fidelity prototype sessions provided feedback on what the interventions could look like, what problems the interventions were trying to solve and concerns about the interventions. CONCLUSION: Insights gained from this codesign work will inform high-fidelity prototype testing and the eventual implementation and evaluation of an ACEPATH intervention that aims to improve hospital-to-home transitions for patients receiving a palliative approach to care. PATIENT OR PUBLIC CONTRIBUTION: Patients and caregivers with lived experience attended CDWs aimed at designing an intervention to improve the transition from hospital to home. Their direct involvement aligns the intervention with patients' and caregivers' needs when transitioning from hospital to home. Furthermore, four patient/caregiver advisors were engaged throughout the project (from grant writing through to manuscript writing) to ensure all stages were patient- and caregiver-centred.

Measuring the Use of End-of-Life Symptom Relief Medications in Long-Term Care Homes-a Qualitative Study.

Background: At the end of life, individuals may experience physical symptoms such as pain, and guidelines recommend medications to manage these symptoms. Yet, little is known about the symptom management long-term care (LTC) residents receive at the end of life. Our research team developed a metric-whether residents receive one or more prescriptions for an end-of-life symptom management medication in their last two weeks-to explore end-of-life care for LTC residents. This qualitative study aimed to inform the refinement of the end-of-life prescribing metric, including the acceptability and applicability to assess the quality of a resident's symptom management at end-of-life. Methods: We conducted 14 semi-structured interviews with Ontario health-care providers (physicians and nurses) who work in LTC homes and family caregivers of residents who died in LTC. Interviews were conducted virtually between February 2021 and December 2022, and were analyzed using thematic analysis. Results: We identified three major themes relating to perceptions of the metric: 1) appropriateness, 2) health-care provider applicability, and 3) caregiver applicability. Participants noted that the metric may be appropriate to assess end-of-life care, but noted important nuances. Regarding applicability, health-care providers found value in the metric and that it could inform their practice. Conversely, caregivers found limited value in the metric. Conclusion: The proposed metric captures a very specific aspect of end-of-life care-whether end-of-life medications were prescribed or not. Participants deemed that the metric may reflect whether LTC homes have processes to manage a resident's end-of-life symptoms with medication. However, participants thought the metric could not provide a complete picture of end-of-life care and its quality.

Changes in End-of-Life Symptom Management Prescribing among Long-Term Care Residents during COVID-19.

OBJECTIVE: To examine changes in the prescribing of end-of-life symptom management medications in long-term care (LTC) homes during the COVID-19 pandemic. DESIGN: Retrospective cohort study using routinely collected health administrative data in Ontario, Canada. SETTING AND PARTICIPANTS: We included all individuals who died in LTC homes between January 1, 2017, and March 31, 2021. We separated the study into 2 periods: before COVID-19 (January 1, 2017, to March 17, 2020) and during COVID-19 (March 18, 2020, to March 31, 2021). METHODS: For each LTC home, we measured the percentage of residents who died before and during COVID-19 who had a subcutaneous symptom management medication prescription in their last 14 days of life. We grouped LTC homes into quintiles based on their mean prescribing rates before COVID-19, and examined changes in prescribing during COVID-19 and COVID-19 outcomes across quintiles. RESULTS: We captured 75,438 LTC residents who died in Ontario's 626 LTC homes during the entire study period, with 19,522 (25.9%) dying during COVID-19. The mean prescribing rate during COVID-19 ranged from 46.9% to 79.4% between the lowest and highest prescribing quintiles. During COVID-19, the mean prescribing rate in the lowest prescribing quintile increased by 9.6% compared to before COVID-19. Compared to LTC homes in the highest prescribing quintile, homes in the lowest prescribing quintile experienced the highest proportion of COVID-19 outbreaks (73.4% vs 50.0%), the largest mean outbreak intensity (0.27 vs 0.09 cases/bed), the highest mean total days with a COVID-19 outbreak (72.7 vs 24.2 days), and the greatest proportion of decedents who were transferred and died outside of LTC (22.1% vs 8.6%). CONCLUSIONS AND IMPLICATIONS: LTC homes in Ontario had wide variations in the prescribing rates of end-of-life symptom management medications before and during COVID-19. Homes in the lower prescribing quintiles had more COVID-19 cases per bed and days spent in an outbreak.

Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stromal Cell Therapy in Preclinical Models of Sepsis: A Systematic Review and Meta-analysis.

BACKGROUND: In preclinical studies, mesenchymal stromal cells (MSCs), including umbilical cord-derived MSCs (UC-MSCs), demonstrate the ability to modulate numerous pathophysiological processes related to sepsis; however, a systematic synthesis of the literature is needed to assess the efficacy of UC-MSCs for treating sepsis. OBJECTIVE: To examine the effects of UC-MSCs on overall mortality (primary outcome) as well as on organ dysfunction, coagulopathy, endothelial permeability, pathogen clearance, and systemic inflammation (secondary outcomes) at prespecified time intervals in preclinical models of sepsis. METHODS: A systematic search was conducted on Embase, Ovid MEDLINE, and Web of Science up to June 20, 2023. Preclinical controlled studies using in vivo sepsis models with systemic UC-MSC administration were included. Meta-analyses were conducted and expressed as odds ratios (OR) and ratios of the weighted means with 95% CI for categorical and continuous data, respectively. Risk of bias was assessed with the SYRCLE tool. RESULTS: Twenty-six studies (34 experiments, n = 1258 animals) were included in this review. Overall mortality was significantly reduced with UC-MSC treatment as compared to controls (OR: 0.26, 95% CI: 0.18-0.36). At various prespecified time intervals, UC-MSCs reduced surrogate measures of organ dysfunction related to the kidney, liver, and lung; reduced coagulopathy and endothelial permeability; and enhanced pathogen clearance from multiple sites. UC-MSCs also modulated systemic inflammatory mediators. No studies were rated as low risk across all SYCLE domains. CONCLUSIONS: These results demonstrate the efficacy of UC-MSC treatment in preclinical sepsis models and highlight their potential as a therapeutic intervention for septic shock.

Mapping an undergraduate medical education curriculum against national and international palliative care reference learning objectives.

BACKGROUND: The teaching of palliative care competencies is an essential component of undergraduate medical education. There is significant variance in the palliative care content delivered in undergraduate medical curricula, revealing the utility of reference standards to guide curricular development and assessment. To evaluate our university's undergraduate palliative care teaching, we undertook a curriculum mapping exercise, comparing official learning objectives to the national Educating Future Physicians in Palliative and End-of-Life Care (EFPPEC) and the international Palliative Education Assessment Tool (PEAT) reference objectives. METHODS: Multiple assessors independently compared our university's UGME learning objectives with EFPPEC and PEAT reference objectives to determine the degree-of-coverage. Visual curriculum maps were created to depict in which part of the curriculum each objective is delivered and by which medical specialty. RESULTS: Of 122 EFPPEC objectives, 55 (45.1%) were covered fully, 42 (34.4%) were covered partially, and 25 (20.5%) were not covered by university objectives. Of 89 PEAT objectives, 40 (44.9%) were covered fully, 35 (39.3%) were covered partially, and 14 (15.7%) were not covered by university objectives. CONCLUSIONS: The majority of EFPPEC and PEAT reference objectives are fully or partially covered in our university's undergraduate medical curriculum. Our approach could serve as a guide for others who endeavour to review their universities' specialty-specific medical education against reference objectives. Future curriculum development should target the elimination of identified gaps and evaluate the attainment of palliative care competencies by medical learners.

A phase 1 study of triple-targeted therapy with BRAF, MEK, and AKT inhibitors for patients with BRAF-mutated cancers.

BACKGROUND: Aberrant PI3K/AKT signaling in BRAF-mutant cancers contributes to resistance to BRAF inhibitors. The authors examined dual MAPK and PI3K pathway inhibition in patients who had BRAF-mutated solid tumors (ClinicalTrials.gov identifier NCT01902173). METHODS: Patients with BRAF V600E/V600K-mutant solid tumors received oral dabrafenib at 150 mg twice daily with dose escalation of oral uprosertib starting at 50 mg daily, or, in the triplet cohorts, with dose escalation of both oral trametinib starting at 1.5 mg daily and oral uprosertib starting at 25 mg daily. Dose-limiting toxicities (DLTs) were assessed within the first 56 days of treatment. Radiographic responses were assessed at 8-week intervals. RESULTS: Twenty-seven patients (22 evaluable) were enrolled in parallel doublet and triplet cohorts. No DLTs were observed in the doublet cohorts (N = 7). One patient had a DLT at the maximum administered dose of triplet therapy (dabrafenib 150 mg twice daily and trametinib 2 mg daily plus uprosertib 75 mg daily). Three patients in the doublet cohorts had partial responses (including one who had BRAF inhibitor-resistant melanoma). Two patients in the triplet cohorts had a partial response, and one patient had an unconfirmed partial response. Pharmacokinetic data suggested reduced dabrafenib and dabrafenib metabolite exposure in patients who were also exposed to both trametinib and uprosertib, but not in whose who were exposed to uprosertib without trametinib. CONCLUSIONS: Concomitant inhibition of both the MAPK and PI3K-AKT pathways for the treatment of BRAF-mutated cancers was well tolerated, leading to objective responses, but higher level drug-drug interactions affected exposure to dabrafenib and its metabolites.

Palliative End-of-Life Medication Prescribing Rates in Long-Term Care: A Retrospective Cohort Study.

BACKGROUND: Medications are often needed to manage distressing end-of-life symptoms (eg, pain, agitation). OBJECTIVES: In this study, we describe the variation in prescribing rates of symptom relief medications at the end of life among long-term care (LTC) decedents. We evaluate the extent these medications are prescribed in LTC homes and whether prescribing rates of end-of-life symptom management can be used as an indicator of quality end-of-life care. DESIGN: Retrospective cohort study using administrative health data. SETTING AND PARTICIPANTS: LTC decedents in all 626 publicly funded LTC homes in Ontario, Canada, between January 1, 2017, and March 17, 2020. METHODS: For each LTC home, we measured the percent of decedents who received 1+ prescription(s) for a subcutaneous end-of-life symptom management medication ("end-of-life medication") in their last 14 days of life. We then ranked LTC homes into quintiles based on prescribing rates. RESULTS: We identified 55,916 LTC residents who died in LTC. On average, two-thirds of decedents (64.7%) in LTC homes were prescribed at least 1 subcutaneous end-of-life medication in the last 2 weeks of life. Opioids were the most common prescribed medication (overall average prescribing rate of 62.7%). LTC homes in the lowest prescribing quintile had a mean of 37.3% of decedents prescribed an end-of-life medication, and the highest quintile mean was 82.5%. In addition, across these quintiles, the lowest prescribing quintile had a high average (30.3%) of LTC residents transferred out of LTC in the 14 days compared with the highest prescribing quintile (12.7%). CONCLUSIONS AND IMPLICATIONS: Across Ontario's LTC homes, there are large differences in prescribing rates for subcutaneous end-of-life symptom relief medications. Although future work may elucidate why the variability exists, this study provides evidence that administrative data can provide valuable insight into the systemic delivery of end-of-life care.

Long-term bereavement outcomes in family members of those who died in acute care hospitals before and during the first wave of COVID-19: A cohort study.

BACKGROUND: Severe grief is highly distressing and prevalent up to 1 year post-death among people bereaved during the first wave of COVID-19, but no study has assessed changes in grief severity beyond this timeframe. AIM: Understand the trajectory of grief during the pandemic by reassessing grief symptoms in our original cohort 12-18 months post-death. DESIGN: Prospective matched cohort study. SETTINGS/PARTICIPANTS: Family members of decedents who died in an acute care hospital between November 1, 2019 and August 31, 2020 in Ottawa, Canada. Family members of patients who died of COVID (COVID +ve) were matched 2:1 with those who died of non-COVID illness (COVID -ve) during pandemic wave 1 or immediately prior to its onset (pre-COVID). Grief was assessed using the Inventory of Complicated Grief (ICG). RESULTS: Follow-up assessment was completed by 92% (111/121) of family members in the initial cohort. Mean ICG score on the 12-18-month assessment was 19.9 (SD = 11.8), and severe grief (ICG > 25) was present in 28.8% of participants. One-third (33.3%) had either a persistently high (>25) or worsening ICG score (⩾4-point increase between assessments). Using a modified Poisson regression analysis, persistently high or worsening ICG scores were associated with endotracheal intubation in the deceased, but not cause of death (COVID +ve, COVID -ve, pre-COVID) or physical presence of the family member in the final 48 h of life. CONCLUSIONS: Severe grief is a substantial source of psychological morbidity in the wake of the COVID-19 pandemic, persisting more than a year post-death. Our findings highlight an acute need for effective and scalable means of addressing severe grief.

Real-world clinical, psychosocial and economic burden of atopic dermatitis: Results from a multicountry study.

BACKGROUND: Atopic dermatitis (AD), a relapsing, inflammatory skin disease, is associated with pruritus that can negatively affect patients' quality of life. Understanding the burden of AD is critical for informing and tailoring treatment and disease management to improve patient outcomes. This study characterized global treatment patterns and the clinical, psychosocial and economic burden of moderate-to-severe AD. METHODS: MEASURE-AD was a cross-sectional 28-country study in patients with physician-confirmed moderate-to-severe AD who were either receiving or eligible for systemic therapy for AD. Patients ≥12 years were enrolled between December 2019 and December 2020 while attending routine office or clinic visit. Primary outcomes included Worst Pruritus Numeric Rating Scale (WP-NRS; range: 0-10) and Dermatology Life Quality Index (DLQI; range: 0-30) and Children's DLQI (CDLQI; range: 0-30). Secondary outcomes included physician- and patient-reported clinical, psychosocial and economic burden. RESULTS: Of the 1591 patients enrolled, 1558 (1434 adults and 124 adolescents) fulfilled all patient selection criteria and were included in this analysis. Almost all patients (98.4%) in the total population were using AD medications and more than half (56%) were receiving systemic medication (15% systemic monotherapy). The most used systemic therapies were dupilumab (56.3%), systemic glucocorticoids (18.1%) and methotrexate (16.2%). Mean WP-NRS was 5.3 in the total population, and most patients (≥55%) reported moderate-to-severe pruritus (WP-NRS ≥4). Mean DLQI was 10.8 and mean CDLQI was 9.6. Secondary endpoints demonstrated substantial clinical, psychosocial, and economic burden of disease. Subgroup analysis demonstrated that patients receiving systemic therapy had lower disease burden than those not taking systemic medications. CONCLUSIONS: While systemic therapy lowers overall disease burden, patients with moderate-to-severe AD continue to have substantial multidimensional disease burden and uncontrolled disease. Overall, there is a need for effective disease management, including effective treatments that improve patients' psychosocial outcomes and reduce the economic burden of AD.

Potentially Inappropriate Prescribing in Long-Term Care and its Relationship With Probable Delirium.

OBJECTIVES: This study examined potentially inappropriate prescribing (PIP) of medication and its association with probable delirium among long-term care (LTC) residents in Ontario, Canada. DESIGN: Population-based cross-sectional study using provincial health administrative data, including LTC assessment data via the Resident Assessment Instrument-Minimum Dataset version 2.0 (RAI-MDS 2.0). SETTING AND PARTICIPANTS: LTC residents in Ontario between January 1, 2016, and December 31, 2019. METHODS: We used residents' first RAI-MDS 2.0 assessment in the study period as the index assessment. Probable delirium was identified via the delirium Clinical Assessment Protocol. Medication use in the 2 weeks preceding assessment was captured using medication claims data. PIP was measured using the STOPP/START criteria and 2015 Beers criteria, with residents classified as having 0, 1, 2, or 3+ instances of PIP. Relationships between PIP and probable delirium was assessed via bivariate and multivariable logistic regression models. RESULTS: The study population included 171,190 LTC residents (mean age 84.5 years, 66.8% female, 62.9% with dementia). More than half (51.8%) of residents had 1+ instances of PIP and 21% had 3+ instances of PIP according to the STOPP/START criteria; PIP prevalence was slightly lower when assessed using Beers criteria (36.5% with 1+, 11.1% with 3+). Overall, 3.7% of residents had probable delirium. The prevalence of probable delirium increased as the number of instances of PIP increased, with residents with 3+ instances of STOPP/START PIP being 1.66 times more likely (95% CI 1.56-1.77) to have probable delirium compared to those with no instances of PIP. Similar findings were observed when PIP was measured using the Beers criteria. Central nervous system (CNS)-related PIP criteria showed a stronger association with probable delirium than non-CNS-related PIP criteria. CONCLUSIONS AND IMPLICATIONS: This population-based study highlighted that PIP was highly prevalent in long-term care residents and was associated with an increased prevalence of probable delirium.

Long-term cognitive impairment after probable delirium in long-term care residents: A population-based retrospective cohort study.

BACKGROUND: The impact of delirium on cognition has not been well-studied in long-term care (LTC) residents. This study examined changes in cognition 1 year after a probable delirium episode among LTC residents, compared to LTC residents without probable delirium. We also evaluated whether the relationship between probable delirium and cognitive change differed according to a diagnosis of dementia. METHODS: We conducted a population-based retrospective cohort study using linked health administrative data. The study population included adults aged 65+ residing in LTC in Ontario, Canada and assessed via the Resident Assessment Instrument-Minimum Dataset between January 1, 2016 and December 31, 2018. Probable delirium was ascertained via the delirium Clinical Assessment Protocol on the index assessment. Cognition was measured quarterly using the Cognitive Performance Scale (range 0-6, higher values indicate greater impairment). Cognitive decline up to 1 year after index was evaluated using multivariable proportional odds regression models. RESULTS: Of 92,005 LTC residents, 2816 (3.1%) had probable delirium at index. Residents with probable delirium had an increased odds of cognitive decline compared to those without probable delirium, with adjusted odds ratios of 1.64 (95% confidence interval [CI] 1.35-1.99), 1.56 (95% CI 1.34-1.85), 1.57 (95% CI 1.32-1.86) and 1.50 (95% CI 1.25-1.80) after 1-3, 4-6, 7-9, and 10-12 months of follow-up. Residents with probable delirium and a comorbid dementia diagnosis had the highest adjusted odds of cognitive decline (adjusted odds ratio 5.57, 95% CI 4.79-6.48) compared to those without probable delirium or dementia. Residents with probable delirium were also more likely to die within 1 year than those without probable delirium (52.5% vs. 23.4%). CONCLUSIONS: Probable delirium is associated with increased mortality and worsened cognition in LTC residents that is sustained months after the probable delirium episode. Efforts to prevent delirium in this population may help limit these adverse effects.

Implementation of the Richmond Agitation-Sedation Scale (palliative version) on an inpatient palliative care unit.

BACKGROUND: The Richmond Agitation-Sedation Scale - Palliative version (RASS-PAL) tool is a brief observational tool to quantify a patient's level of agitation or sedation. The objective of this study was to implement the RASS-PAL tool on an inpatient palliative care unit and evaluate the implementation process. METHODS: Quality improvement implementation project using a short online RASS-PAL self-learning module and point-of-care tool. Participants were staff working on a 31-bed inpatient palliative care unit who completed the RASS-PAL self-learning module and online evaluation survey. RESULTS: The self-learning module was completed by 49/50 (98%) of regular palliative care unit staff (nurses, physicians, allied health, and other palliative care unit staff). The completion rate of the self-learning module by both regular and casual palliative care unit staff was 63/77 (82%). The follow-up online evaluation survey was completed by 23/50 (46%) of respondents who regularly worked on the palliative care unit. Respondents agreed (14/26; 54%) or strongly agreed (10/26; 38%) that the self-learning module was implemented successfully, with 100% agreement that it was effective for their educational needs. CONCLUSION: Using an online self-learning module is an effective method to engage and educate interprofessional staff on the RASS-PAL tool as part of an implementation strategy.