Community-Based Palliative Care Consultations: Comparing Dementia to Nondementia Serious Illnesses.

Background: Little is known about the provision of palliative care to people with dementia (PWD). Objective: To examine demographic and clinical characteristics of PWD versus nondementia serious illnesses receiving community-based palliative care. Design: Retrospective study of people 65+ receiving an initial consultation from a community-based palliative care practice between September 2014 and February 2018 using registry data entered by clinicians into the Quality Data Collection Tool for Palliative Care. Setting: Large not-for-profit organization that provides community-based hospice and palliative care services. Measurements: Demographics, consult characteristics, advance care planning, and caregiver support. Results: Of 3883 older adults receiving a first palliative care consultation from this organization, 22% (855) had a dementia diagnosis. Compared to those with nondementia serious illnesses, PWD were older with more impaired function; 36% had a prognosis of less than six months. More PWD than those without dementia had a proxy decision maker and documented advance directive. A quarter of PWD were full code before consultation; nearly half changed to some limitation afterward. Symptom characteristics were missing for 67% of PWD due to collection through self-report. Caregivers of PWD were responsible for significantly more activities of daily living than caregivers of people with nondementia serious illnesses. Conclusions: This is the first comparison of a large cohort of people with and without dementia receiving a community-based palliative care consult in the United States. Alternative measures of symptom burden should be used in registries to capture data for PWD. Understanding the unique characteristics of PWD will guide future services for this growing population.

Paying for Palliative Care in Medicare: Evidence From the Four Seasons/Duke CMMI Demonstration.

CONTEXT: Palliative care improves patient and family outcomes and may reduce the cost of care, but this service is underutilized among Medicare beneficiaries. OBJECTIVES: To describe enrollment patterns and outcomes associated with the Center for Medicare and Medicaid Innovation expansion of a multisetting community palliative care program in North and South Carolina. METHODS: This observational study characterizes the Center for Medicare and Medicaid Innovation cohort's care and cost trajectories after enrollment. Program participants were age-eligible Medicare fee-for-service beneficiaries living in Western North Carolina and South Carolina who enrolled in a palliative care program from September 1, 2014, to August 31, 2017. End-of-life costs were compared between enrolled and nonenrolled decedents. Program administrative data and 100% Medicare claims data were used. RESULTS: A total of 5243 Medicare beneficiaries enrolled in the program from community (19%), facility (21%), small hospital (27%), or large hospital (33%) settings. Changes in Medicare expenditures in the 30 days after enrollment varied by setting. Adjusted odds of hospice use were 60% higher (OR = 1.60; CI = 1.47, 1.75) for enrolled decedents relative to nonenrolled decedents. Participants discharged to hospice vs. participants not had 17% (OR = 0.83 CI = 0.72, 0.94) lower costs. Among enrolled decedents those enrolled for at least 30 days vs. <30 days had 42% (OR = 0.58, CI = 0.49, 0.69) lower costs in the last 30 days of life. CONCLUSIONS: Expansion of community palliative care programs into multiple enrollment settings is feasible. It may improve hospice utilization among enrollees. Heterogeneous program participation by program setting pose challenges to a standardizing reimbursement policy.

A Team-Based Approach to Delivering Person-Centered Care at the End of Life.

The use of team-based models of care is widely regarded as a mechanism for enhancing the delivery of high-quality care, especially at the end of life. Active collaboration to promote effective coordination and delivery of person-centered care is an integral part of the team-based model that is the focus of this article.

Evaluating the Feasibility and Acceptability of a Telehealth Program in a Rural Palliative Care Population: TapCloud for Palliative Care.

CONTEXT: The impact of telehealth and remote patient monitoring has not been well established in palliative care populations in rural communities. OBJECTIVES: The objectives of this study were to 1) describe a telehealth palliative care program using the TapCloud remote patient monitoring application and videoconferencing; 2) evaluate the feasibility, usability, and acceptability of a telehealth system in palliative care; and 3) use a quality data assessment collection tool in addition to TapCloud ratings of symptom burden and hospice transitions. METHODS: A mixed-methods approach was used to assess feasibility, usability, and acceptability. Quantitative assessments included patient symptom burden and improvement, hospice transitions, and advanced directives. Qualitative semistructured interviews on a subpopulation of telehealth patients, caregivers, and providers were performed to learn about their experiences using TapCloud. RESULTS: One-hundred one palliative care patients in rural Western North Carolina were enrolled in the program. The mean age of patients enrolled was 72 years, with a majority (60%) being female and a pulmonary diagnosis accounting for the largest percentage of patients (23%). Remote patient monitoring using TapCloud resulted in improved symptom management, and patients in the model had a hospice transition rate of 35%. Patients, caregivers, and providers reported overwhelmingly positive experiences with telehealth with three main advantages: 1) access to clinicians, 2) quick responses, and 3) improved efficiency and quality of care. CONCLUSION: This is one of the first articles to describe a telehealth palliative care program and to demonstrate acceptability, feasibility, and usability as well as describe symptom outcomes and hospice transitions.

Standardization and Scaling of a Community-Based Palliative Care Model.

BACKGROUND: Although limited, the descriptions of Community-Based Palliative Care (CBPC) demonstrates variability in team structures, eligibility, and standardization across care settings. OBJECTIVE: In 2014, Four Seasons Compassion for Life, a nonprofit hospice and palliative care (PC) organization in Western North Carolina (WNC), was awarded a Centers for Medicare and Medicaid Services Health Care Innovation (CMMI) Award to expand upon their existing innovative model to implement, evaluate, and demonstrate CBPC in the United States. The objective of this article is to describe the processes and challenges of scaling and standardizing the CBPC model. DESIGN: Four Season's CBPC model serves patients in both inpatient and outpatient settings using an interdisciplinary team to address symptom management, psychosocial/spiritual care, advance care planning, and patient/family education. Medicare beneficiaries who are ≥65 years of age with a life-limiting illness were eligible for the CMMI project. RESULTS: The CBPC model was scaled across numerous counties in WNC and Upstate South Carolina. Over the first two years of the project, scaling occurred into 21 counties with the addition of 2 large hospitals, 52 nursing facilities, and 2 new clinics. To improve efficiency and effectiveness, a PC screening referral guide and a risk stratification approach were developed and implemented. Care processes, including patient referral and initial visit, were mapped. CONCLUSION: This article describes an interdisciplinary CBPC model in all care settings to individuals with life-limiting illness and offers guidance for risk stratification assessments and mapping care processes that may help PC programs as they develop and work to improve efficiencies.

One Size Does Not Fit All: Disease Profiles of Serious Illness Patients Receiving Specialty Palliative Care.

INTRODUCTION: Understanding the symptom profiles of seriously ill patients who receive palliative care, especially noncancer diagnoses where the data are sparse and are critical to better targeting our resources to the needs of patients. METHODS: We performed a retrospective, multicohort study of patients evaluated during their first consultative palliative care visit in a community-based palliative care registry. We placed into one of seven major disease categories based on clinician-reported primary diagnosis for consultation. Our primary aim of this analysis was to determine the univariate association between several patient-specific characteristics (e.g., demographics, care of setting, initial screening score) and the primary diagnosis. RESULTS: We evaluated the first visit consultation records of 1615 patients. Most prevalent diagnosis was Neurologic (564; 35%), followed by Cardiovascular (266; 16%), Pulmonary (229; 14%), and Cancer (208; 13%). Patients in the study with the highest symptom burden were those diagnosed with cancer or pulmonary disease, with 45% and 37% of cancer and pulmonary patients, respectively, having two or more moderate-to-severe symptoms; 26% of cardiovascular disease patients reported two or more moderate-to-severe symptoms, whereas 11% reported three or more. Patients with a neurologic or infectious diagnosis had less symptom burden, but a large percentage of neurologic patients were unable to respond. DISCUSSION: This study is one of the first to describe symptom burden and functional scores by diagnostic categories and care settings across a community-based interdisciplinary specialty palliative care program. Results demonstrated statistically significant and clinically relevant differences among settings of care, functional status, and symptom profiles between patients with various serious illnesses.

Tracking Patients in Community-Based Palliative Care through the Centers for Medicare & Medicaid Services Healthcare Innovation Project.

BACKGROUND: Although limited, the evidence base for Community-Based Palliative Care (CBPC) has shown that it improves patient health outcomes, increases satisfaction, and decreases cost. Minimal data exist comparing points of entry into palliative care and patient transition outcomes. OBJECTIVES: In 2014, Four Seasons Compassion for Life was awarded a Centers for Medicare & Medicaid Services Healthcare Innovation Award to expand an existing CBPC model into additional counties and to propose a new payment approach. The goal of this article is to evaluate the tracking of point of entry into palliative care and patient transition outcomes in the model. DESIGN: All participant transition outcomes are tracked from point of entry, including large and small hospitals, nursing facilities, and home/clinic. Evaluation of tracking data was conducted over the first two years of the project (September 1, 2014-September 1, 2016). RESULTS: A total of 2482 patients entered the project, 905 through smaller hospitals (<300 beds, 32%), 474 through larger hospital systems (>500 beds, 17%), 823 from nursing facilities (29%), and 640 in the home/clinic (22%). Hospice transition was highest with home/clinic referrals, followed by nursing facilities, smaller hospitals, and larger hospitals. Palliative care deaths and discharges are higher in larger hospitals. Re-enrollment back into palliative care after previous discharge occurred in 177 (17.8%) of discharged patients. CONCLUSION: CBPC leads to the highest percentage of hospice transitions coming from the home/clinic setting. Differences between small and large hospitals demonstrate a different patient population with higher transitions to hospice and lower palliative care deaths in smaller hospitals.

Top 10 Tips About the Physician Quality Reporting System for Palliative Care Professionals.

The U.S. healthcare system is shifting from a fee-for-service (FFS) system to a valued-based reimbursement system focused on improving the quality of healthcare. The Centers for Medicare and Medicaid Services (CMS) implemented the Physician Quality Reporting System (PQRS) as an important component of this transition. All clinicians, including physicians, nurse practitioners, or physician assistants who bill to Medicare Part B FFS, should submit quality data to the PQRS in 2015 or they will receive up to a 4% negative reimbursement penalty in 2017. As implementing and reporting PQRS measures can be a daunting task, especially for palliative care professionals, this article provides high priority tips identified by the authors for PQRS reporting in the palliative care field.

Loss of the N-terminal methyltransferase NRMT1 increases sensitivity to DNA damage and promotes mammary oncogenesis.

Though discovered over four decades ago, the function of N-terminal methylation has mostly remained a mystery. Our discovery of the first mammalian N-terminal methyltransferase, NRMT1, has led to the discovery of many new functions for N-terminal methylation, including regulation of DNA/protein interactions, accurate mitotic division, and nucleotide excision repair (NER). Here we test whether NRMT1 is also important for DNA double-strand break (DSB) repair, and given its previously known roles in cell cycle regulation and the DNA damage response, assay if NRMT1 is acting as a tumor suppressor. We find that NRMT1 knockdown significantly enhances the sensitivity of breast cancer cell lines to both etoposide treatment and γ-irradiation, as well as, increases proliferation rate, invasive potential, anchorage-independent growth, xenograft tumor size, and tamoxifen sensitivity. Interestingly, this positions NRMT1 as a tumor suppressor protein involved in multiple DNA repair pathways, and indicates, similar to BRCA1 and BRCA2, its loss may result in tumors with enhanced sensitivity to diverse DNA damaging chemotherapeutics.

NRMT1 knockout mice exhibit phenotypes associated with impaired DNA repair and premature aging.

Though defective genome maintenance and DNA repair have long been known to promote phenotypes of premature aging, the role protein methylation plays in these processes is only now emerging. We have recently identified the first N-terminal methyltransferase, NRMT1, which regulates protein-DNA interactions and is necessary for both accurate mitotic division and nucleotide excision repair. To demonstrate if complete loss of NRMT1 subsequently resulted in developmental or aging phenotypes, we constructed the first NRMT1 knockout (Nrmt1(-/-)) mouse. The majority of these mice die shortly after birth. However, the ones that survive, exhibit decreased body size, female-specific infertility, kyphosis, decreased mitochondrial function, and early-onset liver degeneration; phenotypes characteristic of other mouse models deficient in DNA repair. The livers from Nrmt1(-/-) mice produce less reactive oxygen species (ROS) than wild type controls, and Nrmt1(-/-) mouse embryonic fibroblasts show a decreased capacity for handling oxidative damage. This indicates that decreased mitochondrial function may benefit Nrmt1(-/-) mice and protect them from excess internal ROS and subsequent DNA damage. These studies position the NRMT1 knockout mouse as a useful new system for studying the effects of genomic instability and defective DNA damage repair on organismal and tissue-specific aging.

Machine oil inhibits the osseointegration of orthopaedic implants by impairing osteoblast attachment and spreading.

The most important factor contributing to short-term and long-term success of cementless total joint arthroplasties is osseointegration. Osseointegration leads to a direct structural and functional connection between living bone and the surface of an implant. Surface contaminants may remain on orthopaedic implants after sterilization procedures and impair osseointegration. For example, specific lots of hip replacement Sulzer Inter-OP(TM) acetabular shells that were associated with impaired osseointegration and early failure rates were found to be contaminated with both bacterial debris and machine oil residues. However, the effect of machine oil on implant integration is unknown. Therefore, the goal of this study was to determine if machine oil inhibits the osseointegration of orthopaedic implants. To test this hypothesis in vivo we used our murine model of osseointegration where titanium alloy implants are implanted into a unicortical pilot hole in the mid-diaphysis of the femur. We found that machine oil inhibited bone-to-implant contact and biomechanical pullout measures. Machine oil on titanium alloy discs inhibited early stages of MC3T3-E1 osteogenesis in vitro such as attachment and spreading. Inhibition of osteoblast attachment and spreading occurred in both areas with and without detectable oil. Osteoblast growth was in turn inhibited on discs with machine oil due to both a decrease in proliferation and an increase in cell death. Later stages of osteogenic differentiation and mineralization on titanium alloy discs were also inhibited. Thus, machine oil can inhibit osseointegration through cell autonomous effects on osteoblast cells. These results support routine testing by manufacturers of machine oil residues on orthopaedic implants.

NRMT2 is an N-terminal monomethylase that primes for its homologue NRMT1.

NRMT (N-terminal regulator of chromatin condensation 1 methyltransferase) was the first eukaryotic methyltransferase identified to specifically methylate the free α-amino group of proteins. Since the discovery of this N-terminal methyltransferase, many new substrates have been identified and the modification itself has been shown to regulate DNA-protein interactions. Sequence analysis predicts one close human homologue of NRMT, METTL11B (methyltransferase-like protein 11B, now renamed NRMT2). We show in the present paper for the first time that NRMT2 also has N-terminal methylation activity and recognizes the same N-terminal consensus sequences as NRMT (now NRMT1). Both enzymes have similar tissue expression and cellular localization patterns. However, enzyme assays and MS experiments indicate that they differ in their specific catalytic functions. Although NRMT1 is a distributive methyltransferase that can mono-, di- and tri-methylate its substrates, NRMT2 is primarily a monomethylase. Concurrent expression of NRMT1 and NRMT2 accelerates the production of trimethylation, and we propose that NRMT2 activates NRMT1 by priming its substrates for trimethylation.

Adherent lipopolysaccharide inhibits the osseointegration of orthopedic implants by impairing osteoblast differentiation.

Osseointegration is the process by which an orthopedic implant makes direct bone-to-implant contact and is crucial for the long-term function of the implant. Surface contaminants, such as bacterial debris and manufacturing residues, may remain on orthopedic implants after sterilization and impair osseointegration. For example, specific lots of implants that were associated with impaired osseointegration and high failure rates were discovered to have contaminants including bacterial debris. Therefore, the goals of this study were to determine if bacterial debris exists on sterile orthopedic implants and if adherent bacterial debris inhibits the osseointegration of orthopedic implants. We found that debris containing lipopolysaccharide (LPS) from Gram-negative bacteria exists on both sterile craniofacial implants and wrist implants. Levels of bacterial debris vary not only between different lots of implants but within an individual lot. Using our murine model of osseointegration, we found that ultrapure LPS adherent to the implants inhibited bone-to-implant contact and biomechanical pullout measures. Analysis of osseointegration in knock-out mice demonstrated that adherent LPS inhibited osseointegration by signaling through its primary receptor, Toll-like receptor 4, and not by signaling through Toll-like receptor 2. Ultrapure LPS adherent to titanium alloy discs had no detectable effect on early stages of MC3T3-E1 osteogenesis in vitro such as attachment, spreading or growth. However, later stages of osteogenic differentiation and mineralization were inhibited by adherent LPS. Thus, LPS may inhibit osseointegration in part through cell autonomous effects on osteoblasts. These results highlight bacterial debris as a type of surface contaminant that can impair the osseointegration of orthopedic implants.

Surface contaminants inhibit osseointegration in a novel murine model.

Surface contaminants, such as bacterial debris and manufacturing residues, may remain on orthopedic implants after sterilization procedures and affect osseointegration. The goals of this study were to develop a murine model of osseointegration in order to determine whether removing surface contaminants enhances osseointegration. To develop the murine model, titanium alloy implants were implanted into a unicortical pilot hole in the mid-diaphysis of the femur and osseointegration was measured over a five week time course. Histology, backscatter scanning electron microscopy and X-ray energy dispersive spectroscopy showed areas of bone in intimate physical contact with the implant, confirming osseointegration. Histomorphometric quantification of bone-to-implant contact and peri-implant bone and biomechanical pullout quantification of ultimate force, stiffness and work to failure increased significantly over time, also demonstrating successful osseointegration. We also found that a rigorous cleaning procedure significantly enhances bone-to-implant contact and biomechanical pullout measures by two-fold compared with implants that were autoclaved, as recommended by the manufacturer. The most likely interpretation of these results is that surface contaminants inhibit osseointegration. The results of this study justify the need for the development of better detection and removal techniques for contaminants on orthopedic implants and other medical devices.

The effects of farnesol on Staphylococcus aureus biofilms and osteoblasts. An in vitro study.

BACKGROUND: Bacterial biofilms play a major role in chronic orthopaedic infections. Recently, farnesol (an antifungal agent) has been shown to express antimicrobial activities against Staphylococcus aureus and Streptococcus mutans. However, the effects of farnesol on the formation of bacterial biofilms on orthopaedic biomaterials and its effects on osteoblasts have not been investigated, to our knowledge, and are therefore the focus of this study. METHODS: Biofilms of Staphylococcus aureus (Seattle 1945(GFPuvr)) were grown on titanium alloy discs. The effects of soluble farnesol on biofilm formation with or without gentamicin were examined with fluorescence microscopy and in quantitative cultures. The effect of farnesol coated on titanium alloy discs was also investigated, as was the effect of the agent on MC3T3-E1 pre-osteoblastic cells cultured on titanium alloy discs. RESULTS: Soluble farnesol at a 30-mM concentration reduced the number of viable bacteria 10(4)-fold and completely inhibited biofilm formation. Low concentrations of soluble farnesol (0.03 to 3 mM) did not inhibit biofilm formation and did not potentiate the effect of a submaximal concentration of gentamicin. Dried farnesol on titanium alloy discs reduced the number of viable bacteria fiftyfold. The effect of farnesol on bacterial biofilm formation lasted for at least three days. Soluble farnesol added after the biofilm had already formed also reduced the final number of viable bacteria, by fifty-six-fold. Soluble farnesol (3-mM and 30-mM concentrations) inhibited spreading of the MC3T3-E1 cells. CONCLUSIONS: In vitro, a high concentration of farnesol (30 mM) shows antimicrobial properties against bacterial biofilms; however, it also has a negative effect on pre-osteoblasts. Farnesol can also express antimicrobial activity when predried on titanium discs and when added to preformed biofilms.