Patterns of Palliative Care Consultation in Neurosurgical Patients.

Numerous neurosurgical (NSG) conditions entail high morbidity, mortality, and prolonged ICU stays. Palliative care (PC) serves to alleviate suffering, align treatment with patient preferences, and is linked to enhanced patient and family outcomes as well as reduced care costs. Notably, no studies have addressed demographic and clinical factors associated with PC receipt in NSG patients. Our aim is to identify characteristics and outcomes, particularly end of life outcomes, of hospitalized NSG patients associated with a PC consult compared with usual NSG care. A retrospective chart review was performed of patients admitted to the NSG service from January 1, 2017 to December 31, 2018 at the University of Iowa Hospitals & Clinics. Data regarding demographics, clinical outcomes, and GOC and ACP documentation were collected. The most common reasons for a PC consult were goals of care, end of life issues, and comfort care. Of 121 total decedent patients, 97 (80.2%) had PC referrals. Patients with a PC referral had longer hospital stays (10.3 days vs 4 days) and had the majority of care in the ICU (90.7% vs 83.3%). However, fewer PC patients died in the ICU (42.3% vs 75%) and more had PCA/NCA use (51.5% vs 8.3%), code status changes to DNR (90.7% vs 62.5%), GOC documented (78.4% vs 0%) and ACP documentation (35.1% vs 16.7%). In conclusion, in NSG patients, the integration of PC may contribute to improved end-of-life care.

Evaluating motor progression of juvenile-onset Huntington's Disease: An Enroll-HD analysis.

INTRODUCTION: Juvenile-onset Huntington's disease (JOHD) is characterized by a unique motor phenotype relative to patients with adult-onset Huntington's Disease (AOHD). This study characterized motor progression of JOHD to propose improved outcome measures for this group. METHODS: We used linear mixed effect regression models to compare progression of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score (TMS) and the chorea score between patients with JOHD and AOHD. We then evaluated all 31 subscales that make up the UHDRS over time within patients with JOHD to identify measures that may be used to track motor progression most reliably. RESULTS: The JOHD cohort had faster TMS progression compared to AOHD (p = 0.006) but no group difference in the rate of change of chorea. Patients with JOHD did not show significant change in any of the chorea subscales. The subscales that changed most reliably over time amongst patients with JOHD were dysarthria, upper extremity dystonia, tandem walking, gait, bilateral pronate/supinate, bilateral finger-tapping, and tongue protrusion. When these subscales were summed, they progressed at a faster rate (7.07%, 95% CI [5.96-8.18]) than the TMS (4.92%, 95% CI [3.95-5.89]). CONCLUSION: While the TMS changes at a significant rate in JOHD subjects, not all subscales that make up the TMS accurately represent the unique motor features of JOHD. A JOHD-specific scale performed better at tracking motor progression relative to the TMS. This scale may improve clinical care for patients with JOHD and allow for the development of more efficient clinical trials.

Factors Influencing Discharges to Hospice for Patients With Late-Stage Huntington's Disease.

Background: Hospice services for patients with Huntington's disease (HD) are likely beneficial in relieving significant burdens and minimizing costly hospitalizations at the end of life, though there has been little study or clinical guidance on hospice enrollment for patients with HD. Objectives: The primary objective of this study was to identify clinical, sociodemographic, and system-level factors associated with discharges to hospice compared to other dispositions for hospitalized patients with late-stage HD. Methods: These analyses used data from the Nationwide Inpatient Sample between the years 2007 and 2011. Weighted logistic regression with a forward selection approach was performed to identify factors associated with discharge to hospice compared to discharge to home, facility, other locations, and death in hospital. Results: These analyses included 6544 hospitalizations of patients with late-stage HD. There was a significant increasing trend in discharges to hospice over the study period (P < 0.001). After adjustment, multiple clinical, sociodemographic, and system-level variables were identified as being associated with discharges to hospice. Patients with aspiration pneumonia and non-aspiration pneumonias had lower odds of being discharged to hospice compared to dying in the hospital. When comparing to discharges to facilities and home, weight loss and palliative care consultation were associated with greater odds of discharge to hospice. Conclusions: Our findings serve as a foundation for future studies on these factors, and thus help clinician decision-making on when to start advance care planning or end-of-life care for patients with HD. These results also support studies developing hospice referral criteria specific to patients with HD.

Memantine Use and Cognitive Decline in Huntington's Disease: An Enroll-HD Study.

Background: Memantine is an N-methyl-d-aspartate (NMDA) receptor antagonist that is used to treat moderate to severe Alzheimer's Dementia (AD) and has been speculated to provide clinical benefits in Huntington's disease (HD). Objective: To assess the effectiveness of memantine on the trajectory of cognitive decline in individuals with manifest HD. Methods: Using participants from the Enroll-HD study, the primary analysis compared trajectories in cognition over a 5-year period using linear mixed effect models of prevalent and incident memantine users who were propensity-score-matched with non-users on measures of disease progression and demographics. Results: In the primary analysis there were no significant differences in the trajectories between memantine users and non-users on any primary outcomes of interest. Conclusions: Memantine use was not associated with any clinical benefit for individuals with manifest HD. Further studies are warranted to assess the impact of memantine on clinical outcomes in HD.

Palliative Care and End-of-Life Outcomes in Patients Considered for Liver Transplantation: A Single-Center Experience in the US Midwest.

Introduction: Previous research has shown limited palliative care (PC) utilization among patients evaluated for liver transplantation (LT) despite the cohort's significant symptom burden, high frequency of hospitalization and risk of rapid decompensation. Our aim was to evaluate patient characteristics and end-of-life (EOL) outcomes (i.e. ICU utilization, code status, advance care planning) associated with the use of PC services in patients who were evaluated for LT. Methods: We performed a single-center cross-sectional study comprised of 223 deceased patients evaluated for LT between 1/1/2017 and 12/31/2021. We evaluated demographic characteristics and EOL outcomes for differences between patients who received PC consultation and those who did not. EOL outcomes associated with PC use were assessed using logistic and linear regression analysis adjusted for patient demographics. Results: Patients who received PC consultation were younger (mean 57 vs. 61; P = 0.048), had higher Model for end-stage Liver Disease (MELD) scores (27.5 vs. 22; P = 0.001), higher rates of hepatic encephalopathy (96% vs. 84%, P = 0.005), and were more frequently declined for LT (77% vs. 57%; P = 0.008). Patients who received PC services were less likely to die in the ICU (OR = 0.07 [0.02-0.18]) and were more likely to have documented advance care planning (OR = 3.16 [1.47-6.97]), family meetings (OR = 6.58 [2.72-17.08]), and goals-of-care discussions (OR = 14.83 [4.39-69.29]). Conclusion: For patients being evaluated for LT, PC utilization differed based on demographics, disease complications and severity, and transplant status. Those who received PC services had higher quality EOL care planning and fewer ICU admissions.

Patterns of Evidence-Based Care for the Diagnosis, Staging, and First-line Treatment of Breast Cancer by Race-Ethnicity: A SEER-Medicare Study.

BACKGROUND: Racial and ethnic disparities in guideline-recommended breast cancer treatment are well documented, however studies including diagnostic and staging procedures necessary to determine treatment indications are lacking. The purpose of this study was to characterize patterns in delivery of evidence-based services for the diagnosis, clinical workup, and first-line treatment of breast cancer by race-ethnicity. METHODS: SEER-Medicare data were used to identify women diagnosed with invasive breast cancer between 2000 and 2017 at age 66 or older (n = 2,15,605). Evidence-based services included diagnostic procedures (diagnostic mammography and breast biopsy), clinical workup (stage and grade determination, lymph node biopsy, and HR and HER2 status determination), and treatment initiation (surgery, radiation, chemotherapy, hormone therapy, and HER2-targeted therapy). Poisson regression was used to estimate rate ratios (RR) and 95% confidence intervals (CI) for each service. RESULTS: Black and American Indian/Alaska Native (AIAN) women had significantly lower rates of evidence-based care across the continuum from diagnostics through first-line treatment compared to non-Hispanic White (NHW) women. AIAN women had the lowest rates of HER2-targeted therapy and hormone therapy initiation. While Black women also had lower initiation of HER2-targeted therapy than NHW, differences in hormone therapy were not observed. CONCLUSIONS: Our findings suggest patterns along the continuum of care from diagnostic procedures to treatment initiation may differ across race-ethnicity groups. IMPACT: Efforts to improve delivery of guideline-concordant treatment and mitigate racial-ethnic disparities in healthcare and survival should include procedures performed as part of the diagnosis, clinical workup, and staging processes.

The effects of antidepressants on depressive symptoms in manifest Huntington's disease.

OBJECTIVE: Currently there is little evidence to guide the treatment of depression in Huntington's disease (HD). The primary objective was to determine the effectiveness of antidepressant medications on lowering depressive symptom scores in patients with manifest HD. The secondary objective was to determine the effect of antidepressant use on measures of disease progression. METHODS: After retrospectively identifying motor-manifest HD participants with at least borderline depressive symptoms from the Enroll-HD database, 86 new users of antidepressant medication were exact matched with non-users on depression score, and matched on propensity scores developed using age, sex, CAG repeat length, anxiety scores, and disease progression measures. Linear mixed effect models were used to assess the change in depression scores, anxiety scores, and disease progression measures based on antidepressant use between two visits approximately one-year apart. RESULTS: There was no significant difference in the change in depression score between antidepressant users and non-users (p = 0.46). There were also no significant differences in the change in total motor score (p = 0.88), total functional capacity score (p = 0.16), number correct on the symbol digit modality test (p = 0.49), or anxiety score (p = 0.68). CONCLUSIONS: Initiation of antidepressant medication was not associated with a greater reduction in depressive symptoms or changes in other symptoms when compared to non-use. The findings of this study support further research on the effectiveness of antidepressants in Huntington's disease patients. Clinical trials or studies with a larger sample of new antidepressant users should be used to assess the causal effects of antidepressant medications on depressive symptoms.

Sleep disturbances by disease type and stage in Huntington's disease.

INTRODUCTION: Sleep disturbances are a common symptom in patients with Huntington's disease (HD). However, it is unclear when in the disease course of HD sleep disturbances become more frequent compared to the general population. This study investigated the frequency and odds of developing sleep disturbances between adults with HD or at-risk for HD and non-HD controls. METHODS: Participants from the Enroll-HD study were split by both disease type and disease severity using CAG length, diagnostic confidence level, and total functional capacity score. Multivariate logistic regression was used to calculate odds ratios adjusted for age, sex, tobacco and alcohol use, depression and psychosis scores, and cognition to compare HD groups to non-HD controls. Cox proportional hazards models and Kaplan Meier curves were used to determine differences in probabilities of developing sleep disturbances and how sleep disturbances are related to age at motor onset. RESULTS: There were significant differences between HD participants and non-HD controls in both the disease type and disease stage analyses (p < 0.001). The odds of a sleep disturbance increased with worsening disease stage and was highest in those with juvenile HD. The development of a sleep disorder in manifest HD participants was observed to be around the time of disease onset. CONCLUSIONS: Sleep disturbances are more frequent in HD patients than those without HD. There are also differences based on disease type and stage. This is supplemented by the finding that the onset of sleep disturbances occurs near the time of motor onset of HD.

Quantifying the Onset of Unintended Weight Loss in Huntington's Disease: A Retrospective Analysis of Enroll-HD.

BACKGROUND: Unintended weight loss and decreased body mass indexes (BMIs) are common symptoms of individuals with manifest HD. It is unknown at what point during disease progression weight loss starts to accelerate relative to a healthy individual's weight and when recommended interventions should be initiated to have the strongest impact on patient care. OBJECTIVE: The objective of this study was to identify a point in time relative to age at motor onset when the decline in weight in HD starts to accelerate relative to a non-HD population. The relationship between initiation of weight loss interventions and changes in weight loss was also explored. METHODS: Participants from the fifth version of the Enroll-HD study were identified for this research. Linear mixed-effects piecewise regression models were used to estimate the point in time relative to the reported age of motor onset in which BMI started to decline in participants with HD compared to healthy non-HD controls. A post-hoc descriptive analysis was performed to look at when nutritional supplements and swallow therapy were initiated in participants with HD relative to motor onset. RESULTS: BMI decline in the HD group began to accelerate compared to controls approximately 5.7 years after the reported age of motor onset (95% CI: 4.7-6.9). The average initiation times of swallow therapy and nutritional supplements were 7.7 years (SD = 5.5 years) and 6.7 years (SD = 6.5 years) after motor onset, respectively. CONCLUSION: Our findings suggest a potential point for intervention of nutrition programs or therapies used to prevent future weight loss.

COVID-19 Case Fatality and Alzheimer's Disease.

Previous studies have identified dementia as a risk factor for death from coronavirus disease 2019 (COVID-19). However, it is unclear whether Alzheimer's disease (AD) is an independent risk factor for COVID-19 case fatality rate. In a retrospective cohort study, we identified 387,841 COVID-19 patients through TriNetX. After adjusting for demographics and comorbidities, we found that AD patients had higher odds of dying from COVID-19 compared to patients without AD (Odds Ratio: 1.20, 95%confidence interval: 1.09-1.32, p < 0.001). Interestingly, we did not observe increased mortality from COVID-19 among patients with vascular dementia. These data are relevant to the evolving COVID-19 pandemic.

Moderate Intensity Exercise in Pre-manifest Huntington's Disease: Results of a 6 months Trial.

BACKGROUND: While it has been shown that aerobic exercise interventions are well tolerated in participants with the Huntington disease (HD) gene mutation, no study to date has tested whether an aerobic exercise intervention benefits brain structure and function in pre-manifest HD. OBJECTIVE: In this study we utilized magnetic resonance (MR) imaging techniques to assess the efficacy of moderate-to-vigorous exercise treatment relative to active stretching and toning control. METHODS: Forty pre-manifest participants with confirmed HD gene expansion were recruited into a two-arm intervention study that included a moderate-to-vigorous intensity home-based walking exercise intervention (N=34) and an active stretching and toning control intervention (N=6). Participants were assessed at baseline and after 26 weeks in one of the two study arms. RESULTS: 25 of the 34 (74%) participants assigned to the moderate-to-vigorous intensity group completed the intervention while 4 of the 6 (67%) participants in the stretching and toning intervention completed the study. The primary analyses compared the two arms of the study and found no statistical differences between the groups. Both groups were found to have improved their cardiorespiratory fitness as assessed by maximal oxygen uptake (VO2max). A secondary analysis combined the two arms of the study and there was a significant relationship (p<0.05) between change in VO2max and change in brain structure. CONCLUSIONS: Though this study did not show efficacy for the exercise intervention, secondary results suggest that aerobic exercise interventions increasing cardiorespiratory fitness may be a potential way to slow progression in pre-manifest HD.