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.

Accelerated transcranial magnetic stimulation for psychological distress in advanced cancer: A phase 2a feasibility and preliminary efficacy clinical trial.

BACKGROUND: Psychological and existential suffering affects many people with advanced illness, and current therapeutic options have limited effectiveness. Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective therapy for refractory depression, but no previous study has used rTMS to treat psychological or existential distress in the palliative setting. AIM: To determine whether a 5-day course of "accelerated" rTMS is feasible and can improve psychological and/or existential distress in a palliative care setting. DESIGN: Open-label, single arm, feasibility, and preliminary efficacy study of intermittent theta-burst stimulation to the left dorsolateral prefrontal cortex, 600 pulses/session, 8 sessions/day (once per hour) for 5 days. The outcomes were the rates of recruitment, completion of intervention, and follow-up (Feasibility); and the proportion of participants achieving 50% improvement on the Hamilton Depression Rating Scale (HDRS) or Hospital Anxiety and Depression Scale (HADS) 2 weeks post-treatment (Preliminary Efficacy). SETTING/PARTICIPANTS: Adults admitted to our academic Palliative Care Unit with advanced illness, life expectancy >1 month and psychological distress. RESULTS: Due to COVID-19 pandemic-related interruptions, a total of nine participants were enrolled between August 2021 and April 2023. Two withdrew before starting rTMS, one stopped due to clinical deterioration unrelated to rTMS, and six completed the rTMS treatment. Five of six participants had a >50% improvement in HDRS, HADS-Anxiety, or both between baseline and the 2 week follow up; the sixth died prior to the 2-week follow-up. In this small sample, mean depression scores decreased from baseline to 2 weeks post-treatment (HDRS 18 vs 7, p = 0.03). Side effects of rTMS included transient mild scalp discomfort. CONCLUSIONS: Accelerated rTMS improved symptoms of depression, anxiety, or both in this small feasibility and preliminary efficacy study. A larger, sham-controlled study is warranted to determine whether rTMS could be an effective, acceptable, and scalable treatment in the palliative setting. TRIAL REGISTRATION: NCT04257227.

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.

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.

Dying with Parkinson's Disease: Healthcare Utilization and Costs in the Last Year of Life.

BACKGROUND: The end-of-life period is associated with disproportionately higher health care utilization and cost at the population level but there is little data in Parkinson's disease (PD). OBJECTIVE: The goals of this study were to 1) compare health care use and associated cost in the last year of life between decedents with and without PD, and 2) identify factors associated with palliative care consultation and death in hospital. METHODS: Using linked administrative datasets held at ICES, we conducted a retrospective, population-based cohort study of all Ontario, Canada decedents from 2015 to 2017. We examined demographic data, rate of utilization across healthcare sectors, and cost of health care services in the last year of life. RESULTS: We identified 291,276 decedents of whom 12,440 (4.3%) had a diagnosis of PD. Compared to decedents without PD, decedents with PD were more likely to be admitted to long-term care (52% vs. 23%, p < 0.001) and received more home care (69.0 vs. 41.8 days, p < 0.001). Receipt of palliative homecare or physician palliative home consultation were associated with lower odds of dying in hospital (OR: 0.24, 95% CI: 0.19- 0.30, and OR: 0.38, 95% CI: 0.33- 0.43, respectively). Mean cost of care in the last year of life was greater for decedents with PD ($68,391 vs. $59,244, p < 0.001). CONCLUSION: Compared to individuals without PD, individuals with PD have higher rates of long-term care, home care and higher health care costs in the last year of life. Palliative care is associated with a lower rate of hospital death.

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.

Breath Regulation and yogic Exercise An online Therapy for calm and Happiness (BREATH) for frontline hospital and long-term care home staff managing the COVID-19 pandemic: A structured summary of a study protocol for a feasibility study for a randomised controlled trial.

OBJECTIVES: Objective 1: To determine if it is feasible to conduct an RCT of online Sudarshan Kriya Yoga (SKY) for frontline hospital and long-term care home staff under the constraints imposed by the COVID-19 pandemic and need for remote trial monitoring. Objective 2: To assess whether online versions of SKY and/or Health Enhancement Program (HEP) result in improvement in self-rated measures of insomnia, anxiety, depression, and resilience. TRIAL DESIGN: This is an open-label feasibility randomized controlled trial (RCT), comparing an online breath based yogic intervention SKY versus an online control mind-body intervention HEP in frontline hospital and long-term care home staff managing the COVID-19 pandemic. PARTICIPANTS: Participants will include frontline hospital and long-term care home staff that are involved in the management of COVID-19 patients in London, Ontario, Canada. Participants will be willing and able to attend via online video conferencing software to participate in the study interventions. Participants must have an adequate understanding of English and be able to sit without physical discomfort for 60 minutes. INTERVENTION AND COMPARATOR: Sudarshan Kriya Yoga (SKY): The online version of SKY will be delivered by at least one certified Canadian SKY teacher, with at least one back up teacher at all times, under the supervision of Ms. Ronnie Newman, Director of Research and Health Promotion, Art of Living Foundation, USA. The online version of SKY for healthcare workers has a total duration of 3 hours. Phase I will consist of 5 self-paced online modules of 4-10 minutes each to learn the breath control techniques. Participants will be sent an online survey in REDCap requesting that they self-confirm completion of the Phase I modules. In Phase II, 2 interactive online sessions of 1 hour each will be held on consecutive days with a certified SKY teacher, during which participants will learn the fast, medium and slow breaths. For ease of scheduling, multiple time windows will be offered for Phase II. There will be at least one back up teacher at all times. Both Phase I and II will be completed in the first week. Health Enhancement Program (HEP): The active control arm, HEP, will consist of time-matched online self-paced modules for Phase I. Phase II will consist of mindfulness-based meditation sessions delivered by mental health staff. HEP will be an active treatment program that incorporates mind-body interventions. HEP will consist of time-matched online self-paced modules with psychoeducation on healthy active living as well as interactive modules comprising of guided de-stressing exercises including music therapy, mindfulness and progressive muscle relaxation. Weekly follow up sessions will be offered to all recruited participants for 30 minutes each for the subsequent 4 weeks in both study arms. MAIN OUTCOMES: The following feasibility outcomes will be measured at the end of the study: (1) rate of participant recruitment, (2) rate of retention, (3) completeness of data entry, (4) cost of interventions, and (5) unexpected costs. Such measures will be collected on a daily basis through-out the study and tabulated 5 weeks later at the end of the study. RANDOMISATION: Participants will be randomized after they have electronically signed the consent form and the research staff have confirmed eligibility. We will use REDCap to perform randomization in a 1:1 ratio as well as allocation concealment. REDCap is widely used by health researchers worldwide to significantly reduce data entry and study management errors to improve data fidelity. BLINDING (MASKING): All study participants will be blinded to the study hypotheses so as to prevent any expectation bias. Group allocation will be masked during analysis. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This study will randomize a total of 60 participants in a 1:1 ratio to either SKY or HEP interventions. TRIAL STATUS: Protocol version number 2.0 (June 5, 2020). Recruitment is currently ongoing (starting June 25, 2020). We anticipate to complete recruitment by June 30, 2021 and complete the study by September 30, 2021. TRIAL REGISTRATION: ClinicalTrials.gov protocol ID NCT04368676 (posted April 30, 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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.

Thermoneutral temperature reduces liver volume but increases fat content in a mammalian hibernator.

Hibernators survive challenging winters by entering torpor, which lowers body temperature (Tb) to ∼5 °C for 12-14 days, followed by spontaneous arousals where Tb increases to ∼37 °C for 10-12 h before entering another torpor bout. This Tb cycle is accompanied by significant fluctuations in metabolic rate. Little is known about the role of the liver in lipid metabolism during hibernation. In this study we measured the effect of ambient temperature on liver volume and lipid content in 13-lined ground squirrels (Ictidomys tridecemlineatus). We housed animals at thermoneutral (25 °C) or cold (5 °C) ambient temperatures, with the same photoperiod (12 h light:12 h dark) for an entire year. We determined volume and water-fat ratio of the liver using magnetic resonance imaging (MRI). Ambient temperature significantly affected both liver volume and fat content. From October to August squirrels housed at 25 °C had 25% smaller livers compared to the squirrels housed at 5 °C, but their average lipid content (13.3%) was 37% higher. Because the squirrels housed at 25 °C appeared to continue feeding throughout the winter but did not enter extended torpor, more carbohydrates may have been diverted to lipid stores. By contrast, animals housed at 5 °C did not appear to feed, and carbohydrates would likely be preferentially stored in the liver as glycogen to supply glucose for brain metabolism. These results suggest that the fat burden caused by hibernators preparing for winter can lead to symptoms of metabolic syndrome, but that these symptoms are reversible in the spring.

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.

Community- and Healthcare-Associated Methicillin-Resistant Staphylococcus aureus Strains: An Investigation Into Household Transmission, Risk Factors, and Environmental Contamination.

OBJECTIVE To measure transmission frequencies and risk factors for household acquisition of community-associated and healthcare-associated (HA-) methicillin-resistant Staphylococcus aureus (MRSA). DESIGN Prospective cohort study from October 4, 2008, through December 3, 2012. SETTING Seven acute care hospitals in or near Toronto, Canada. PARTICIPANTS Total of 99 MRSA-colonized or MRSA-infected case patients and 183 household contacts. METHODS Baseline interviews were conducted, and surveillance cultures were collected monthly for 3 months from household members, pets, and 8 prespecified high-use environmental locations. Isolates underwent pulsed-field gel electrophoresis and staphylococcal cassette chromosome mec typing. RESULTS Overall, of 183 household contacts 89 (49%) were MRSA colonized, with 56 (31%) detected at baseline. MRSA transmission from index case to contacts negative at baseline occurred in 27 (40%) of 68 followed-up households. Strains were identical within households. The transmission risk for HA-MRSA was 39% compared with 40% (P=.95) for community-associated MRSA. HA-MRSA index cases were more likely to be older and not practice infection control measures (P=.002-.03). Household acquisition risk factors included requiring assistance and sharing bath towels (P=.001-.03). Environmental contamination was identified in 78 (79%) of 99 households and was more common in HA-MRSA households. CONCLUSION Household transmission of community-associated and HA-MRSA strains was common and the difference in transmission risk was not statistically significant. Infect Control Hosp Epidemiol 2016;1-7.

Characterization of methicillin-resistant Staphylococcus aureus isolates from patients with persistent or recurrent bacteremia.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with considerable morbidity and mortality, especially with persistent (PB) or recurrent bacteremia (RB). OBJECTIVE: To determine the frequency of PB and RB in patients with MRSA BSI, and to characterize the isolates from these patients. METHODS: Surveillance for MRSA BSI was performed for one year in 13 Canadian hospitals. PB was defined as a positive blood culture that persisted for ≥7 days; RB was defined as the recurrence of a positive blood culture ≥14 days following a negative culture. Isolates were typed using pulsed-field gel electrophoresis (PFGE). Vancomycin susceptibility was determined using Etest. RESULTS: A total of 183 patients with MRSA BSI were identified; 14 (7.7%) had PB and five (2.7%) had RB. Ten (5.5%) patients were known to have infective endocarditis, and five of these patients had PB or RB. Initial and subsequent MRSA isolates from patients with PB and RB had the same PFGE type. There were no significant differences in the distribution of PFGE types in patients with PB or RB (37% CMRSA-2/USA100; 37% CMRSA-10/USA300) compared with that in other patients (56% CMRSA-2/USA100; 32% CMRSA-10/USA300). All isolates were susceptible to vancomycin, but patients with PB or RB were more likely to have initial isolates with vancomycin minimum inhibitory concentration = 2.0 µg/mL (26% versus 10%; P=0.06). CONCLUSIONS: Persistent or recurrent MRSA bacteremia occurred in 10.4% of patients with MRSA BSIs. Initial isolates from patients with persistent or recurrent MRSA BSIs were more likely to exhibit reduced susceptibility to vancomcyin, but were not associated with any genotype.

HISTORIQUE: Les infections sanguines (IS) par le Staphylococcus aureus résistant à la méthicilline (SARM) s'associent à une morbidité et une mortalité considérables, particulièrement en présence d'une bactériémie persistante (BP) ou récurrente (BR). OBJECTIF: Déterminer la fréquence de BP et de BR chez les patients atteints d'une IS par le SARM et en caractériser les isolats. MÉTHODOLOGIE: Les chercheurs ont surveillé les IS par le SARM dans 13 hôpitaux canadiens pendant un an. La BP se définissait par une hémoculture positive qui persistait au moins sept jours, tandis que la BR désignait la récurrence d'une hémoculture positive au moins 14 jours après une hémoculture négative. Les chercheurs ont typé les isolats au moyen de l'électrophorèse sur gel en champ pulsé (ECP). Ils ont déterminé la susceptibilité à la vancomycine par Etest. RÉSULTATS: Les chercheurs ont retracé un total de 183 patients ayant une IS par le SARM. De ce nombre, 14 (7,7 %) avaient une BP et cinq (2,7 %), une BR. Dix patients (5,5 %) étaient atteints d'une endocardite infectieuse diagnostiquée, dont cinq avaient une BP ou une BR. Les isolats initiaux et subséquents de SARM chez les patients ayant une BP ou une BR présentaient le même type d'ECP. Il n'y avait pas de différence significative dans la distribution des types d'ECP chez les patients ayant une BP ou une BR (37 % de souche CSARM-2/USA100; 37% de souche CSARM-10/USA300) par rapport à celle des autres patients (56 % de souche CSARM-2/USA100; 32 % de souche CSARM-10/USA300). Tous les isolats étaient susceptibles à la vancomycine, mais les patients atteints d'une BP ou d'une BR étaient plus susceptibles de présenter des isolats initiaux de vancomycine dont la CMI = 2,0 µg/mL (26 % par rapport à 10 %; P=0,06). CONCLUSIONS: Les chercheurs ont observé une BP ou une BR par le SARM chez 10,4 % des patients atteints d'une IS par le SARM. Les isolats initiaux des patients atteints d'une IS persistante ou récurrente par le SARM risquaient davantage d'être moins susceptibles à la vancomycine, mais ne s'associaient à aucun génotype.