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.

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.

Palliative care at any stage of amyotrophic lateral sclerosis: a prospective feasibility study.

Introduction: Many patients with amyotrophic lateral sclerosis (ALS) receive palliative care (PC) very late or not at all. The impact of PC on patients with ALS and caregivers has not been quantified. Study goals included (1) measuring the impact of early PC on quality of life and mood of patients/caregivers and (2) describing patient/caregiver satisfaction with PC. Methods: The study was a non-randomized, prospective feasibility study of patients with ALS being treated at The Ottawa Hospital ALS Clinic and their caregivers. Exclusion criteria were age < 18 years, inability to complete questionnaires, and prior receipt of PC. The ALS Specific Quality of Life-Revised (ALSSQOL-R) questionnaire (patients only) and Hospital Anxiety and Depression Scale (HADS) were completed at regular intervals for up to 2 years. Patients accepting a PC consultation completed a post-PC satisfaction survey. Primary outcome measures included ALSSQOL-R and HADS scores compared before and after PC consultation, and between groups receiving and not receiving a PC consultation. Secondary outcome measures included responses on the post-PC satisfaction survey (1 = strongly disagree, 5 = strongly agree). Results: 39 patients with ALS (age 66 ± 10 years, median time from diagnosis = 6 months) and 22 caregivers were enrolled. 32 patients had a PC consultation (30 were virtual). Patients and caregivers agreed with statements that the PC consult was helpful (mean ± SD = 4.54 ± 0.60, range = 3-5) and they would recommend PC to others with ALS (4.59 ± 0.59, range = 3-5). Participants disagreed with statements that the consult would have been better later in disease course (1.87 ± 0.80, range = 1-4) and that it took too much time/energy (1.44 ± 0.85, range = 1-4). Average ALSSQOL-R scores worsened significantly over time. HADS and ALSSQOL-R scores did not significantly differ between groups receiving and not receiving PC. Conclusion: Patients with ALS and their caregivers found virtual PC consultations beneficial irrespective of disease duration or severity. Offering routine PC to all patients with ALS is feasible and should be considered as part of standard care. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04257760, identifier NCT04257760.

Management of Motor Symptoms for Patients with Advanced Parkinson's Disease without Safe Oral Access: A Scoping Review.

Context: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Oral medications for control of motor symptoms are the mainstay of treatment. However, as the disease progresses, patients with PD may develop dysphagia that prohibits them from safely taking oral medications. Currently there are no clinical guidelines for managing distressing motor symptoms in patients with PD and severe dysphagia, which can therefore be quite challenging. Objectives: To provide an exhaustive summary of current literature on pharmacological interventions for patients with PD who do not have safe oral access in managing distressing motor symptoms. Indication, route, doses, frequency, outcome, and adverse effects will be discussed. Methods: A scoping review using Medline, Embase, CENTRAL, CINAHL, AgeLine, and PsycINFO databases (1946-2021) was conducted. Articles examining patients with PD and dysphagia who are eligible to receive palliative care or at end of life were included. Studies that included patients who were also on oral PD medications or received device-aided therapy were excluded from this review. Results: A total of 3821 articles were screened for title and abstract, 259 were selected for full-text review, and 20 articles were selected for data extraction. These included five case reports, one retrospective cohort study, one book chapter, and 13 narrative reviews. There are very few articles addressing the issue of treatment of patients with advanced PD who are unable to take oral medications. Although rotigotine patch and apormorphine injections are most frequently recommended, there are no clinical trials in this patient population to support those recommendations. Conclusion: This study highlights a need for further research examining the efficacy and dosing of nonoral medications in advanced PD with dysphagia.

Use and Discontinuation of Milrinone for Advanced Heart Failure in an Academic Palliative Care Unit: A Case Report and Discussion of Recommendations.

The use of intravenous inotropic medications in advanced heart failure (HF) has been shown to improve symptoms and decrease hospitalizations, prompting support for their use as a palliative measure for symptom management. Recommendations regarding inotrope management and method of discontinuation at the end of life are not specifically detailed in the literature and current guidelines. This case report describes the use of milrinone in a patient with advanced HF during the terminal phase of illness in a non-monitored palliative care unit setting, including dose reduction and discontinuation of milrinone. Increased patient anxiety during the weaning process was managed with midazolam. The provision of individualized milrinone therapy in non-monitored palliative care settings is feasible and well-tolerated using the presented detailed recommendations for its use and administration, monitoring, dose reduction and discontinuation and proactive symptom management at the end of life. Further research is needed for the optimal management of terminally ill patients with advanced HF.Supplemental data for this article is available online at here. show.

Probable Delirium and Associated Patient Characteristics in Long-Term Care and Complex Continuing Care: A Population-Based Observational Study.

OBJECTIVES: To estimate the prevalence of probable delirium in long-term care (LTC) and complex continuing care (CCC) settings and to describe the resident characteristics associated with probable delirium. DESIGN: Population-based cross-sectional study using routinely collected administrative health data. SETTING AND PARTICIPANTS: All LTC and CCC residents in Ontario, Canada, assessed with the Resident Assessment Instrument-Minimum Dataset (RAI-MDS) assessment between July 1, 2016, and December 31, 2016 (LTC n=86,454, CCC n=10,217). METHODS: Probable delirium was identified via the delirium Clinical Assessment Protocol on the RAI-MDS assessment, which is triggered when individuals display at least 1 of 6 delirium symptoms that are of recent onset and different from their usual functioning. RAI-MDS assessments were linked to demographic and health services utilization databases to ascertain resident demographics and health status. Multivariable logistic regression was used to identify characteristics associated with probable delirium, with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) reported. RESULTS: Delirium was probable in 3.6% of LTC residents and 16.5% of CCC patients. LTC patients displayed fewer delirium symptoms than CCC patients. The most common delirium symptom in LTC was periods of lethargy (44.6% of delirium cases); in CCC, it was mental function varying over the course of the day (63.5% of delirium cases). The odds of probable delirium varied across individual demographics and health characteristics, with increased health instability having the strongest association with the outcome in both care settings (LTC: OR 30.4, 95% CI 26.2-35.3; CCC: OR 21.0, 95% CI 16.7-26.5 for high vs low instability). CONCLUSIONS AND IMPLICATIONS: There were differences in the presentation and burden of delirium symptoms between LTC and CCC, potentially reflecting differences in delirium severity or symptom identification. Several risk factors for probable delirium in LTC and CCC were identified that may be amenable to interventions to prevent this highly distressing condition.

The Palliative Care Information Needs of Patients with Amyotrophic Lateral Sclerosis and their Informal Caregivers: A Scoping Review.

CONTEXT: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease, associated with impaired quality of life for patients and caregivers. As treatment is largely supportive, early involvement of palliative care (PC) is recommended as standard of care. Despite this, literature surrounding PC information needs is limited. OBJECTIVES: To explore the PC information needs of patients with ALS and their caregivers and identify gaps in the literature. METHODS: A scoping review using MEDLINE, EMBASE, CINAHL and PsycINFO databases (2000-2019) was conducted. Articles examining PC information needs as stated by ALS patients and/or current/bereaved caregivers were included. Studies examining other diagnoses and those focused on healthcare workers were excluded. Thematic synthesis was used to summarize and identify prevalent domains and themes in the literature. RESULTS: 581 articles underwent primary screening, with thirty-two ultimately included (26 original articles, six reviews). Fourteen examined information needs of both patients and caregivers, 13 caregivers only, 5 patients only. The most common PC information needs were as follows: for patients, disease course/prognosis (n = 10), general disease information (n = 9), decision-making (n = 7) and symptoms (n = 6); for caregivers, services and resources (n = 15), disease course/prognosis (n = 14), general disease information (n = 13) and skills (n = 10). There was substantial variability in information needs, both between patients and caregivers and among members of the same group. CONCLUSION: ALS patients and caregivers have unique and varying PC information needs. Future research should better characterize these needs to improve patient and caregiver quality of life. The delivery of information must be tailored to individual patient or caregiver preferences.

Delirium screening tools validated in the context of palliative care: A systematic review.

BACKGROUND: Delirium is a distressing neuropsychiatric disorder affecting patients in palliative care. Although many delirium screening tools exist, their utility, and validation within palliative care settings has not undergone systematic review. AIM: To systematically review studies that validate delirium screening tools conducted in palliative care settings. DESIGN: Systematic review with narrative synthesis (PROSPERO ID: CRD42019125481). A risk of bias assessment via Quality Assessment Tool for Diagnostic Accuracy Studies-2 was performed. DATA SOURCES: Five electronic databases were systematically searched (January 1, 1982-May 3, 2020). Quantitative studies validating a screening tool in adult palliative care patient populations were included. Studies involving alcohol withdrawal, critical or perioperative care were excluded. RESULTS: Dual-reviewer screening of 3749 unique titles and abstracts identified 95 studies for full-text review and of these, 17 studies of 14 screening tools were included (n = 3496 patients). Data analyses revealed substantial heterogeneity in patient demographics and variability in screening and diagnostic practices that limited generalizability between study populations and care settings. A risk of bias assessment revealed methodological and reporting deficits, with only 3/17 studies at low risk of bias. CONCLUSIONS: The processes of selecting a delirium screening tool and determining optimal screening practices in palliative care are complex. One tool is unlikely to fit the needs of the entire palliative care population across all palliative care settings. Further research should be directed at evaluating and/or adapting screening tools and practices to fit the needs of specific palliative care settings and populations.

Hospitalization Outcomes of Delirium in Patients Admitted to Acute Care Hospitals in Their Last Year of Life: A Population-Based Retrospective Cohort Study.

CONTEXT: Delirium is a highly distressing neurocognitive disorder for patients at the end of life. OBJECTIVES: To compare hospitalization outcomes between patients with and without delirium admitted to acute care hospitals in the last year of life. METHODS: Using linked administrative data from ICES (previously known as the Institute for Clinical Evaluative Sciences), this population-based retrospective cohort study included adults who died in Ontario between January 1, 2014 and December 31, 2016 and were admitted to an acute care hospital in their last year of life. Delirium was identified via diagnosis codes on the hospitalization discharge record. Outcomes included lengths of stay, discharge location, and in-hospital mortality. We used multivariable generalized estimating equations to compare outcomes between patients with and without delirium. RESULTS: Of 208,715 decedents, 9.3% experienced delirium in at least one hospitalization in the last year of life. The mean hospitalization lengths of stay was 13.8 days in patients with delirium (SD = 21.1) or 1.80 times longer (95% CI = 1.75-1.84) compared with those without delirium. Among patients discharged alive, patients with delirium were 1.32 times (95% CI = 1.27-1.38) more likely to be discharged to another institution rather than discharged home. There was no difference in in-hospital mortality between patients with and without delirium (relative risk = 1.01; 95% CI = 0.98-1.05). CONCLUSION: In the last year of life, hospitalized patients with recorded delirium experience poorer outcomes, including longer lengths of stay and increased risk of postdischarge institution use, compared with those without delirium. These outcomes illustrate added burden for patients, their families, and the health care system, thus highlighting the need for delirium prevention and early detection in addition to informed transitional care decisions.

The occurrence and timing of delirium in acute care hospitalizations in the last year of life: A population-based retrospective cohort study.

BACKGROUND: Delirium is a distressing neurocognitive disorder that is common among terminally ill individuals, although few studies have described its occurrence in the acute care setting among this population. AIM: To describe the prevalence of delirium in patients admitted to acute care hospitals in Ontario, Canada, in their last year of life and identify factors associated with delirium. DESIGN: Population-based retrospective cohort study using linked health administrative data. Delirium was identified through diagnosis codes on hospitalization records. SETTING/PARTICIPANTS: Ontario decedents (1 January 2014 to 31 December 2016) admitted to an acute care hospital in their last year of life, excluding individuals age of <18 years or >105 years at admission, those not eligible for the provincial health insurance plan between their hospitalization and death dates, and non-Ontario residents. RESULTS: Delirium was recorded as a diagnosis in 8.2% of hospitalizations. The frequency of delirium-related hospitalizations increased as death approached. Delirium prevalence was higher in patients with dementia (prevalence ratio: 1.43; 95% confidence interval: 1.36-1.50), frailty (prevalence ratio: 1.67; 95% confidence interval: 1.56-1.80), or organ failure-related cause of death (prevalence ratio: 1.23; 95% confidence interval: 1.16-1.31) and an opioid prescription (prevalence ratio: 1.17; 95% confidence interval: 1.12-1.21). Prevalence also varied by age, sex, chronic conditions, antipsychotic use, receipt of long-term care or home care, and hospitalization characteristics. CONCLUSION: This study described the occurrence and timing of delirium in acute care hospitals in the last year of life and identified factors associated with delirium. These findings can be used to support delirium prevention and early detection in the hospital setting.

The incidence and prevalence of delirium across palliative care settings: A systematic review.

BACKGROUND: Delirium is a common and distressing neurocognitive condition that frequently affects patients in palliative care settings and is often underdiagnosed. AIM: Expanding on a 2013 review, this systematic review examines the incidence and prevalence of delirium across all palliative care settings. DESIGN: This systematic review and meta-analyses were prospectively registered with PROSPERO and included a risk of bias assessment. DATA SOURCES: Five electronic databases were examined for primary research studies published between 1980 and 2018. Studies on adult, non-intensive care and non-postoperative populations, either receiving or eligible to receive palliative care, underwent dual reviewer screening and data extraction. Studies using standardized delirium diagnostic criteria or valid assessment tools were included. RESULTS: Following initial screening of 2596 records, and full-text screening of 153 papers, 42 studies were included. Patient populations diagnosed with predominantly cancer (n = 34) and mixed diagnoses (n = 8) were represented. Delirium point prevalence estimates were 4%-12% in the community, 9%-57% across hospital palliative care consultative services, and 6%-74% in inpatient palliative care units. The prevalence of delirium prior to death across all palliative care settings (n = 8) was 42%-88%. Pooled point prevalence on admission to inpatient palliative care units was 35% (confidence interval = 0.29-0.40, n = 14). Only one study had an overall low risk of bias. Varying delirium screening and diagnostic practices were used. CONCLUSION: Delirium is prevalent across all palliative care settings, with one-third of patients delirious at the time of admission to inpatient palliative care. Study heterogeneity limits meta-analyses and highlights the future need for rigorous studies.

Heterozygous loss-of-function mutation in Odd-skipped related 1 (Osr1) is associated with vesicoureteric reflux, duplex systems, and hydronephrosis.

Odd-skipped related 1 (Osr1) is a transcriptional repressor that plays critical roles in maintaining the mesenchymal stem cell population within the developing kidney. Here, we report that newborn pups with a heterozygous null mutation in Osr1 exhibit a 21% incidence of vesicoureteric reflux and have hydronephrosis and urinary tract duplications. Newborn pups have a short intravesical ureter, resulting in a less competent ureterovesical junction which arises from a delay in urinary tract development. We describe a new domain of Osr1 expression in the ureteral mesenchyme and within the developing bladder in the mouse. OSR1 was sequenced in 186 children with primary vesicoureteric reflux, and 17 have single nucleotide polymorphisms. Fifteen children have a common synonymous variant, rs12329305, one child has a rare nonsynonymous variant, rs3440471, and one child has a rare 5'-UTR variant, rs45535040 The impact of these SNPs is not clear; therefore, the role of OSR1 in human disease remains to be elucidated. Osr1 is a candidate gene implicated in the pathogenesis of vesicoureteric reflux and congenital abnormalities of the kidney and urinary tract in mice.

Vesicoureteric reflux and reflux nephropathy: from mouse models to childhood disease.

Vesicoureteric reflux (VUR) is a common congenital urinary tract defect that predisposes children to recurrent kidney infections. Kidney infections can result in renal scarring or reflux nephropathy defined by the presence of chronic tubulo-interstitial inflammation and fibrosis that is a frequent cause of end-stage renal failure. The discovery of mouse models with VUR and with reflux nephropathy has provided new opportunities to understand the pathogenesis of these conditions and may provide insight on the genes and the associated phenotypes that need to be examined in human studies.

Interplay between vesicoureteric reflux and kidney infection in the development of reflux nephropathy in mice.

Vesicoureteric reflux (VUR) is a common congenital defect of the urinary tract that is usually discovered after a child develops a urinary tract infection. It is associated with reflux nephropathy, a renal lesion characterized by the presence of chronic tubulointersitial inflammation and fibrosis. Most patients are diagnosed with reflux nephropathy after one or more febrile urinary tract infections, suggesting a potential role for infection in its development. We have recently shown that the C3H mouse has a 100% incidence of VUR. Here, we evaluate the roles of VUR and uropathogenic Escherichia coli infection in the development of reflux nephropathy in the C3H mouse. We find that VUR in combination with sustained kidney infection is crucial to the development of reflux nephropathy, whereas sterile reflux alone fails to induce reflux nephropathy. A single bout of kidney infection without reflux fails to induce reflux nephropathy. The host immune response to infection was examined in two refluxing C3H substrains, HeN and HeJ. HeJ mice, which have a defect in innate immunity and bacterial clearance, demonstrate more significant renal inflammation and reflux nephropathy compared with HeN mice. These studies demonstrate the crucial synergy between VUR, sustained kidney infection and the host immune response in the development of reflux nephropathy in a mouse model of VUR.

Assessing urinary tract defects in mice: methods to detect the presence of vesicoureteric reflux and urinary tract obstruction.

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) encompass a spectrum of kidney and urinary tract disorders. Here, we describe two assays that can be used to determine if a mouse has vesicoureteric reflux (VUR) or urinary tract obstruction, two urinary tract defects observed in CAKUT. To test for VUR, dye is injected into the mouse bladder and then monitored to determine if it passes retrogradely from the bladder towards the kidneys, indicating the presence of VUR. To test for urinary tract obstruction, the renal pelvis is microinjected with dye and its passage along the urinary tract is monitored to determine if there is evidence of impaired flow along the tract. These methods will facilitate the analysis of CAKUT phenotypes in the mouse.

Vesico-ureteric reflux: using mouse models to understand a common congenital urinary tract defect.

Vesico-ureteric reflux (VUR) is a common congenital urinary tract defect in which urine flows retrogradely from the bladder to the kidneys because of an abnormally formed uretero-vesical junction. It is associated with recurrent urinary tract infections, renal hypo/dysplasia, reflux nephropathy, hypertension, and end-stage renal disease. In humans, VUR is genetically and phenotypically heterogeneous, encompassing diverse renal and urinary tract phenotypes. To understand the significance of these phenotypes, we and others have used the mouse as a model organism and this has led to the identification of new candidate genes. Through careful phenotypic analysis of these models, a new understanding of the genetics and biology of VUR is now underway.