Months Of Life In Patients Research Articles

#1002 End of life healthcare utilisation and costs of older patients receiving kidney replacement therapy—analysis of Dutch health insurance claims data

Abstract Background and Aims The increasing prevalence of chronic kidney disease (CKD), an aging population and advancements in treatment options collectively contribute to a rise in older patients with a functioning kidney transplant (KTX) or undergoing dialysis. These treatments are associated with extensive healthcare utilisation, placing substantial demands on both patients and the healthcare system. Healthcare utilisation typically increases near the end of life, and is associated with increased costs. However, little is known about the end-of-life healthcare utilisation of patients receiving kidney replacement therapy (KRT). Therefore, our study aims to assess healthcare utilisation and costs during the last year of life. Method We analysed Dutch health insurance claims data from patients aged >65 years on KRT who deceased between June 2016 and December 2021. We matched each patient with two controls, defined as individuals who died within the same calendar year without any insurance claims related to CKD or KRT. Matching was performed on sex, age and socio-economic status. The primary outcomes were healthcare utilisation and costs in the last twelve months of life for patients treated with different KRT modalities and compared to matched controls. Healthcare utilisation was detailed at hospital and intensive care unit (ICU) admissions, emergency department (ED) and outpatient department (OPD) visits, hospital daycare and institutionalised care. Healthcare costs encompassed costs related to primary care, hospital care (inpatient and outpatient), mental care, institutionalised care, prescription medication, transportation and other costs. Hospital care costs were categorised as KRT-related and -unrelated costs. Results In total 7279 decedents were included; 4614 haemodialysis patients (HD), 766 peritoneal dialysis (PD) patients and 1899 KTx recipients. KRT patients had a mean age of 77.6 ± 6.6 years, with 64% being male, and had significantly more comorbidities than the control group. In the year preceding death, KRT patients had significantly more hospital admissions, ICU admissions, ED visits, outpatient visits, hospital daycare and institutionalised care than controls (see Fig. 1). When comparing across KRT-modalities, KTx patients were more often admitted to the ICU than HD and PD patients (p = 0.001 and p = 0.024, respectively). For both HD, PD and KTx patients, the mean number of days admitted to the hospital and ICU, as well as ED visits and OPD visits significantly increased in last three months preceding death, compared to the initial nine months of the last year of life (p < 0.0001). Mean total healthcare costs in the last year of life were €59.489 for KTx patients, €108.294 for PD and €117.520 for HD patients, compared to €19.820 for the controls. The majority of costs for dialysis patients were attributed to KRT, accounting for 55.5% (€65.216) and 60.0% (€64.559) of the total expenditures for HD and PD patients, respectively. In contrast, KRT-related costs constituted 25.7% (€15.262) of the total expenses in KTx patients. Besides substantial KRT-related costs, KRT-patients also incurred higher costs for specialist care in the hospital, primary care, medication and transport, compared to controls. Conclusion Healthcare utilisation is substantial for older KRT patients and intensifies during the last year of life. This is accompanied with elevated costs. Further research is necessary to evaluate the impact of healthcare utilisation on the quality of life and whether advanced care planning could prevent overutilisation.

Doppler Ultrasound Flow Reversal in the Superior Sagittal Sinus to Detect Cerebral Venous Congestion in Vein of Galen Malformation.

Vein of Galen malformation is a rare congenital cerebrovascular malformation. In affected patients, increased cerebral venous pressure constitutes an important etiologic factor for the development of brain parenchymal damage. The aim of this study was to investigate the potential of serial cerebral venous Doppler measurements to detect and monitor increased cerebral venous pressure. This was a retrospective monocentric analysis of ultrasound examinations within the first 9 months of life in patients with vein of Galen malformation admitted at <28 days of life. Categorization of perfusion waveforms in the superficial cerebral sinus and veins into 6 patterns was based on antero- and retrograde flow components. We performed an analysis of flow profiles across time and correlation with disease severity, clinical interventions, and congestion damage on cerebral MR imaging. The study included 44 Doppler ultrasound examinations of the superior sagittal sinus and 36 examinations of the cortical veins from 7 patients. Doppler flow profiles before interventional therapy correlated with disease severity determined by the Bicêtre Neonatal Evaluation Score (Spearman ρ = -0.97, P = < .001). At this time, 4 of 7 patients (57.1%) showed a retrograde flow component in the superior sagittal sinus, whereas after embolization, none of the 6 treated patients presented with a retrograde flow component. Only patients with a high retrograde flow component (equal or more than one-third retrograde flow, n = 2) showed severe venous congestion damage on cerebral MR imaging. Flow profiles in the superficial cerebral sinus and veins appear to be a useful tool to noninvasively detect and monitor cerebral venous congestion in vein of Galen malformation.

Demographic, clinical, immunological, and molecular features of iranian national cohort of patients with defect in DCLRE1C gene

BackgroundDCLRE1C gene mutation leads to Artemis deficiency, a severe form of combined immunodeficiency (SCID). Impaired DNA repair and block in early adaptive immunity maturation results in T-B-NK+ immunodeficiency associated with radiosensitivity. Recurrent infections early in life are the main characteristic of Artemis patients.MethodAmong 5373 registered patients, 9 Iranian patients (33.3% female) with confirmed DCLRE1C mutation were identified since 1999–2022. The demographic, clinical, immunological and genetic features were collected through retrospective investigation of medical records and using next generation sequencing.ResultsSeven patients were born in a consanguineous family (77.8%). The median age of onset was 6.0 (5.0–17.0) months. Severe combined immunodeficiency (SCID) was clinically detected at a median (IQR) age of 7.0 (6.0–20.5) months, following a median diagnostic delay of 2.0 (1.0–3.5) months The most typical first presentation was pneumonia (44.4%) and otitis media (3.33%), followed by BCG lymphadenitis (22.2%) and gastroenteritis (11.1%). The most prevalent manifestations were respiratory tract infections (including otitis media) (66.6%) and chronic diarrhea (66.6%). In addition, juvenile idiopathic arthritis (P5) and celiac disease and idiopathic thrombocytopenic purpura (P9) as autoimmune disorders were reported in 2 patients. All patients had reduced B CD19+ and CD4+ cell counts. IgA deficiency occurred in 77.8% of individuals.ConclusionRecurrent infections particulary respiratory tract infection and chronic diarrhea during the first months of life in patients born to consanguineous parents should raise the suspicion for inborn errors of immunity, even in the presence of normal growth and development.

Cost savings associated with palliative care among patients with genitourinary malignancies.

474 Background: The cost of cancer treatment has increased significantly in recent decades, and highest costs incurred in the last 6-months of life. Patients’ health insurance status is a factor influencing to cost of care in different from individuals’ ability to access hospital care. 80% of Thai people use the Thailand’s Universal Coverage Scheme (UCS), about 15% use the Civil Servants Medical Benefit Scheme (CSMBS). Only CSMBS can reimburse all costs of in-patient care, but UCS had to co-pay at some cost. All health scheme is equality accessibility to palliative care. Early integrated palliative care services improve the GU malignancy patients care experience, decreases healthcare utilization, and improved quality of life. Study aim was to examine Hospital-based palliative care interventions in GU malignancy patients may reduce costs. Methods: A retrospective claims database in Ramathibodi Hospital was analyzed, that included cancer patients had a medical claim for death between Jan 1, 2016 - Dec 31, 2020. Our study compared cost in patients receiving palliative care (PC) and patients receiving usual care. Costs were determined by summing paid amounts on all hospital services used within the last 6, 3 and 1 months before death, including cancer-related inpatient service, emergency room visits, cancer-related outpatient services and other hospital services with cancer diagnosis. Results: Of the 1,772 cancer patients who died, 289 (16.3%) integrated treated with PC matched to 1,483 (83.7%) were usual care patients. 107 Genitourinary Malignancies patients including 44 TCC, 36 Prostate, 22 RCC and 2 Testicular cancer, that 22 (20.6%) integrated treated with PC. Median age was 72.4 years. Patients categorized as CSMBS 48% and UCS 44.4%. The PC group had $10,244.1 (+/- 8,705.6) in last 3 months hospital costs that significantly less than in usual care $(17,174.3 +/-14,262.5) (P= 0.032) that PC group had significant reductions in medications, laboratory, and intensive care unit costs compared with usual care patients. Direct costs of inpatient care in the last 3 months of life for patients were lower in patient who received earlier PC that patients who received PC consults &lt; 90 days was $9,728.8 (+/- 1,044.5) and patients received PC consults &lt; 30 days cost was $12,517.7 +/- 1,476. Patients in SSS and UCS had a significantly saving cost when they received PC consultation, P=0.032. However, there was no difference in CSMBS. Conclusions: Integrated palliative care in caring GU malignant patients associates with significant hospital cost savings. Insurance status not limited in access to palliative care consultation, but influences in cost of end-of-life care.

Phase-Specific Costs of Care in Hematological Malignancies in Ontario, Canada

Background: Hematological malignancies contribute a significant economic burden to health care systems. Therefore, to improve health care system planning, this Canadian study analyzed real-world data to estimate phase-specific costs and health care resource utilization for patients with hematological malignancies. Methods: A cohort of adult patients diagnosed with hematological malignancies (diffuse large B-cell lymphoma [DLBCL], Hodgkin lymphoma [HL], follicular lymphoma [FL], chronic lymphocytic leukemia [CLL], multiple myeloma [MM], acute myeloid leukemia [AML], acute lymphocytic leukemia [ALL], and others) were identified between 2003-2014 from the Ontario Cancer Registry (OCR) and linked to treatment data from Cancer Care Ontario and other provincial administrative health care databases. Health system costs and resource utilization were determined for four defined phases of care in which index date was defined as the diagnosis date, including: pre-diagnosis (90 days prior to index date), initial treatment (index date to 6 months), follow-up (end of treatment phase to beginning of end-of-life or completion of cohort follow-up) and end-of-life (last 6 months of life for patients who died). Costs (Canadian dollars in 2014) and resource utilization were normalized to 30-days. Results: There were 35,556 individuals (45% females and 55% males) diagnosed with hematological malignancies. The median age of diagnosis was 64 (IQR: 53-74) years. The median follow-up was 1,874 (IQR: 1,232-2,814) days. At follow-up completion, 26,092 (73.4%) individuals were alive. The median survival time among those who died was 1,005 (568-1,682) days. The phase-specific costs were highest overall in AML and ALL for the initial treatment and end-of-life phases; the costs were $1,169 (±3,230) and $733 (±1,787) for pre-diagnosis, $12,424 (±8,181) and $10,565 (±9,823) for initial treatment, $4,051 (±6,152) and $3,033 (±5,991) for follow-up, as well as $11,815 (±13,973) and $13,484 (±12,039) for end-of-life for AML and ALL, respectively. The phase-specific costs of care for DLBCL and HL were $1,175 (±2,267) and $813 (±1,541) in the pre-diagnosis phase, $9,166 (±5,581) and $5,474 (±3,485) in the initial treatment phase, $1,462 (±2,757) and $895 (±1,619) in the follow-up phase, and $7,966 (±7,104) and $8,679 (±9,087) in the end-of-life phase. For MM, the costs were $1,537 (±3,011) in pre-diagnosis, $7,254 (±6,870) in initial treatment, $4,100 (±4,217) in follow-up, and $9,820 (±8,294) in end-of-life. In comparison, the costs of care for FL and CLL were less in the initial treatment phase but remained elevated in the end-of-life phase; the costs were $775 (±1,798) and $674 (±1,902) in pre-diagnosis, $3,884 (±3,997) and $1,610 (±3,345) in initial treatment, $1,253 (±1,744) and $1,010 (±1,827) in follow-up, and $7,310 (±6,852) and $6,189 (±6,413) in end-of-life phases. Across the phases, the key cost driver was inpatient care. In particular, the increased costs due to inpatient care for the initial treatment and end-of-life phases, respectively, were: $3,864 (±5,013) and $5,045 (±5,908) for DLBCL; $2,384 (±3,712) and $6,441 (±8,129) for HL; $2,131 (±3,502) and $5,146 (±5,612) for FL; $2,435 (±3,860) and $4,498 (±5,582) for CLL; $3,798 (±4,847) and $5,026 (±6,788) for MM; $9,330 (±6,985) and $7,941 (±9,063) for AML; and $8,133 (±8,178) and $10,144 (±10,780) for ALL. The second largest contributor to the cost of care, particularly in the initial treatment phase, was the cost of cancer treatment medication; $3,115 (±1,236) for DLBLC, $1,132 (±766) for HL, $2,851 (±1,755) for FL, $1,069 (±1,549) for CLL, $1,602 (±1,877) for MM, $843 (±1,429) for AML, and $494 (±756) for ALL. Of note, the cost of cancer treatment medication remains elevated for MM across the phases after diagnosis; $1,602 (±1,877) in initial treatment, $1,622 (±2,160) in follow-up, and $2,078 (±2,697) in end-of-life. Conclusions: In general, the mean total costs were highest in the initial treatment and end-of-life phases, and lowest in the pre-diagnosis and follow-up phases of care for all hematological malignancies, following a U-shaped pattern. Inpatient care was the cost driver across all phases. These findings can help allocate appropriate resources throughout the different phases of cancer care for hematological malignancies, with particular focus on improving access to palliative-care at end-of-life. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Phase-specific costs of care in diffuse large B-cell lymphoma in Ontario, Canada.

e18840 Background: This Canadian study analyzes real-world data to estimate phase-specific costs and health care resource utilization for patients with diffuse large B-cell lymphoma (DLBCL). Methods: A cohort of adult patients diagnosed with DLBCL were identified between 2003-2014 from the Ontario Cancer Registry (OCR) and linked to treatment data from Cancer Care Ontario and other provincial administrative health care databases. Health system costs and resource utilization were determined for four defined phases of care in which index date was defined as the OCR diagnosis date, including: pre-diagnosis (90 days prior to index date), initial treatment (index date to 6 months), follow-up (end of treatment phase to beginning of end-of-life or completion of cohort follow-up) and end-of-life (last 6 months of life for patients who died). Costs (Canadian dollars in 2014) and resource utilization were normalized to 30-days. Results: There were 5,392 individuals (53% males; median age 64 years (IQR 53-74)) diagnosed with DLBCL. The median follow-up was 1,903 days (IQR 1,194-2,882) from index date. At follow-up completion, 4,015 (74.5%) individuals were alive. Total mean 30-day cost was $1,175 (±2,267) in pre-diagnosis, $9,166 (±5,581) during initial treatment, $1,462 (±2,757) during follow-up, and $7,965 (±7,104) during end-of-life. The total 30-day cost for inpatient care was $3,864 (±5,013) during treatment (n = 3,362 hospitalized during treatment) and $5,045 (±5,908) for end-of-life (n = 1,367 hospitalized during end-of-life). For home care, the mean 30-day costs were $528 (±512) during initial treatment (n = 3,508, 65% of cohort) and $725 (±884) during end-of-life (n = 1,211, 23% of cohort). Mean 30-day cost of cancer medication was $80 (±455) in pre-diagnosis, $3,115 (±1,236) during initial treatment, $232 (±712) during follow-up, and $305 (±694) during end-of-life. A subset of 239 individuals had autologous stem cell transplantation (ASCT) for relapsed/refractory DLBCL. For the ASCT subgroup, the mean total 30-day cost was $11,653 (±4632) in pre-ASCT phase, $1,542 (±2961) in post-ASCT phase, and $14,094 (±12,845) in end-of-life phase for those that subsequently died (n = 118). A further subset of 52 individuals had relapsed and proceeded to third-line therapy. The total mean total 30-day cost was $8,288 (±8,943) in the first 6-month follow-up, $2,584 (±4,000) in the post 6-month follow-up, and $14,999 (±9,443) in end-of-life phase for those that died (n = 29). Conclusions: Total mean 30-day cost was highest in initial treatment phase and end-of-life phases following a U-shaped pattern. Inpatient care was the cost driver across all phases. Individuals who required ASCT had significantly increased costs. Home care was less frequently accessed during end-of-life phase compared to initial treatment phase (23% vs. 65%). These findings can help allocate appropriate resources throughout the different phases of cancer care.

Antibiotic use in end-of-life care patients: A nationwide Veterans’ Health Administration cohort study

Background: Antibiotic use during end-of-life (EOL) care is an increasingly important target for antimicrobial stewardship given the high prevalence of antibiotic use in this setting with limited evidence on safety and effectiveness to guide antibiotic decision making. We estimated antibiotic use during the last 6 months of life for patients under hospice or palliative care, and we identified potential targets (ie time points) during the EOL period when antimicrobial stewardship interventions could be targeted for maximal benefit. Methods: We conducted a retrospective cohort study of nationwide Veterans’ Affairs (VA) patients, 18 years and older who died between January 1, 2014, and December 31, 2019, and who had been hospitalized within 6 months prior to death. Data from the VA’s integrated electronic medical record (EMR) were collected including demographics, comorbid conditions, and duration of inpatient antibiotics administered, along with outpatient antibiotics dispensed. A propensity-score matched-cohort analysis was conducted to compare antibiotic use between patients placed into palliative care or hospice matched to patients not receiving palliative care or hospice care. Repeated measures ANOVA and repeated measures linear regression methods were used to analyze difference in difference (D-I-D) of days of therapy (DOT) between the 2 cohorts. Results: There were 251,822 patients in the cohort, including 23,746 in hospice care, 89,768 in palliative care, and 138,308 without palliative or hospice care. The median days from last discharge to death was 9 days. The most common comorbidities were chronic obstructive pulmonary diseases (50%), malignancy (46%), and diabetes mellitus (43%). Overall, 18,296 (77%) of 23,746 hospice patients, and 71,812 (80%) of 89,768 palliative care patients received at least 1 antibiotic, whereas 95,167 (69%) of 138,308 who were not placed in hospice or did not receive palliative care received antibiotics. In the primary matched cohort analysis that compared patients placed into hospice or palliative care to propensity-score matched controls, entry into palliative care was associated with a 11% absolute increase in antibiotic prescribing, and entry into hospice was associated with a 4% absolute increase during the 7–14 days after entry versus the 7–14 days before entry (Fig. 1). The stratified cohorts had very similar balanced covariates as the overall cohort. Conclusions: In our large cohort study, we observed that patients receiving EOL care had high levels of antibiotic exposure across VA population, particularly on entry to hospice or during admissions when they received palliative care consultation. Future studies are needed to identify the optimal EOL strategies for collaboration between antimicrobial stewardship and palliative care.Funding: NoneDisclosures: None

Anti-tumor treatment and healthcare consumption near death in the era of novel treatment options for patients with melanoma brain metastases

BackgroundEffective systemic treatments have revolutionized the management of patients with metastatic melanoma, including those with brain metastases. The extent to which these treatments influence disease trajectories close to death is unknown. Therefore, this study aimed to gain insight into provided treatments and healthcare consumption during the last 3 months of life in patients with melanoma brain metastases.MethodsRetrospective, single-center study, including consecutive patients with melanoma brain metastases diagnosed between June-2015 and June-2018, referred to the medical oncologist, and died before November-2019. Patient and tumor characteristics, anti-tumor treatments, healthcare consumption, presence of neurological symptoms, and do-not-resuscitate status were extracted from medical charts.Results100 patients were included. A BRAF-mutation was present in 66 patients. Systemic anti-tumor therapy was given to 72% of patients during the last 3 months of life, 34% in the last month, and 6% in the last week. Patients with a BRAF-mutation more frequently received systemic treatment during the last 3 (85% vs. 47%) and last month (42% vs. 18%) of life than patients without a BRAF-mutation. Furthermore, patients receiving systemic treatment were more likely to visit the emergency room (ER, 75% vs. 36%) and be hospitalized (75% vs. 36%) than those who did not.ConclusionThe majority of patients with melanoma brain metastases received anti-tumor treatment during the last 3 months of life. ER visits and hospitalizations occurred more often in patients on anti-tumor treatment. Further research is warranted to examine the impact of anti-tumor treatments close to death on symptom burden and care satisfaction.

The Palliative Approach and Terminal Heart Failure Admissions – Are We Getting it Right?

Chronic heart failure has a high mortality and early provision of palliative care supports complex decision-making and improves quality of life. To explore whether and when a palliative approach was adopted during the last 12 months of life in patients who experienced an in-hospital death from heart failure. Retrospective medical record review of all deaths from chronic heart failure (January 2010 to December 2019). Admissions with chronic heart failure resulting in death were analysed from an Australian tertiary referral centre. The cohort (n=517) were elderly (median age 83.8 years IQR=77.6-88.7) and male (55.1%). Common comorbidities were ischaemic heart disease (n=293 56.7%) and atrial fibrillation (n=289 55.9%). Life sustaining interventions occurred in 97 (18.8%) patients. In 31 (6.0%) patients referral to specialist palliative care occurred prior to, and in 263 (50.9%) during, the terminal admission. Opioids were prescribed to 440 (85.1%) patients. Comfort care was the documented goal in 158 patients (30.6%). A palliative approach was significantly associated with prior admission in the preceding 12 months (OR=1.5 95% CI=1.0-2.1 p<0.043), receiving outpatient care (OR=2.6 95% CI=1.6-4.1 p<0.01), and admissions in the latter half of the decade (OR=1.5 95% CI=1.0-2.0 p<0.038). Despite greater adoption of a palliative approach in the terminal admission over the last decade, a significant proportion of patients receive palliative care late, just prior to death.

Healthcare Use during the Last Six Months of Life in Patients with Advanced Breast Cancer.

Simple SummaryIn the last decades, new treatment options for advanced (breast) cancer have resulted in increased use of health care resources near the end of life. We assessed health care use near the end of life of patients with advanced breast cancer (ABC). In this study, we have shown that ICU admission, and CPR occurred rarely during the last six months of life of ABC patients. However, hospital admissions occurred often, especially in patients who received new chemotherapy within 30 days of end of life. Those patients were also more likely to die in the hospital. However, death was most often due to disease progression. To improve quality of life near the end of life of advanced breast cancer patients, it is vital to develop tools to help clinicians identify those patients who will benefit from chemotherapy at the end of life.New treatment options in cancer have resulted in increased use of health care resources near the end of life. We assessed health care use near the end of life of patients with advanced breast cancer (ABC). From the Southeast Netherlands Breast cancer (SONABRE) registry, we selected all deceased patients diagnosed with ABC in Maastricht University Medical Center between January 2007 and October 2017. Frequency of health care use in the last six months of life was described and predictors for health care use were assessed. Of 203 patients, 76% were admitted during the last six months, 6% to the intensive care unit (ICU) and 2% underwent cardiopulmonary resuscitation (CPR). Death in hospital occurred in 25%. Nine percent of patients received a new line of chemotherapy ≤30 days before death, which was associated with age <65 years and <1 year survival since diagnosis of metastases. In these patients, the hospital admission rate was 95%, of which 79% died in the hospital, mostly due to progressive disease (80%). In conclusion, the frequency of ICU-admission, CPR or a new line of chemotherapy ≤30 days before death was low. Most patients receiving a new line of chemotherapy ≤30 days before death, died in the hospital.

Chemotherapy use at the end of life in Brazil.

e24003 Background: Chemotherapy in the last days of life is not associated with a survival benefit, and recent data suggest it may cause harm by decreasing quality of life and increasing costs. Both ESMO and ASCO have published position statements encouraging discussions about the appropriate cessation of chemotherapy. End-of-life chemotherapy rates vary worldwide but in summary, up to a fifth of cancer patients are treated with chemotherapy in the last month of life with no clear benefits. The aim of this study is to describe the rate of chemotherapy use in the last month of life in patients who are candidates for palliative care in Brazil. Methods: It is a prospective non-concurrent cohort carried out from a database developed through probabilistic and deterministic linkage of data from information systems of the Brazilian Public Health System. The study population is composed of all patients who started cancer treatment between 2009 and 2014 and who was hospitalized at least 1 time after starting treatment. To address the indication for palliative care, patients whose death occurred within one year after the first hospitalization were selected. Results: A total of 299,202 patients started cancer treatment in that period and 62,249 died 1year after hospitalization. Among the deceased patients, the median age was 62 years, 50.9% of them were in stage IV and 34.1% in stage III and 46% lived in the southeastern region of the country. The most common cancers were lung (n = 17805; 28.6%) colorectal (n = 12273; 19.7%) and gastric (n = 10248; 16.5%). The average number of hospitalizations was 2.7 and 89% of these patients required emergency hospitalization. About half (45,4%; n=28,250) of the patients underwent chemotherapy at the last 30 days of life. The rates of use of chemotherapy in the last month was 44% for lung cancer, 74,4% for colon, 50.2% for gastric and 51.8% breast cancers. Conclusions: Despite international recommendations on the use of chemotherapy at the end of life, this seems to be a common practice unfortunately. Measures to implement early palliative care should be a priority for the care of cancer patients in Brazil.

Utility of Restricted Mean Survival Time Analysis for Heart Failure Clinical Trial Evaluation and Interpretation

ObjectivesThis study sought to demonstrate the statistical and utilitarian properties of restricted mean survival time (RMST) and restricted mean time lost (RMTL) for assessing treatments for heart failure (HF) with reduced ejection fraction. BackgroundAlthough the hazard ratio (HR) is the most commonly used measure to quantify treatment effects in HF clinical trials, HRs may be difficult to interpret and require the proportional hazards assumption to be valid. RMST and RMTL are intuitive summaries of groupwise survival that measure treatment effects without model assumptions. MethodsPatient time-to-event data were reconstructed from published landmark HF clinical trial Kaplan-Meier curves. We estimated RMST differences (ΔRMSTs) and RMTL ratios between treatment groups for primary and secondary outcomes, and compared test statistics and effect sizes with proportional hazards models. We fit Weibull estimations to extrapolate trial data to 5 years of treatment. ResultsUsing RMSTs and RMTLs yielded similar statistical conclusions as HR analysis for a compendium of 16 HF clinical trials including 48,581 patients. RMTL ratios approximated HRs for each trial, but ΔRMSTs provided absolute effect sizes unavailable with HRs. For instance, spironolactone added 2.2 months of life over 34 months of treatment, and dapagliflozin added 0.3 months of life over 24 months of treatment. When normalized to 5-years follow-up with Weibull estimation, spironolactone and dapagliflozin added 6.0 months and 1.8 months of life for patients, respectively. ConclusionsStatistically, RMST and RMTL perform similarly to proportional hazards modeling but may help patients by providing clinically relevant intuitive estimates of treatment effects without prohibitive assumptions.

Association of Hospice Care Services With the Utilization of Life-Sustaining Treatments During End-of-Life Care Among Patients With Cancer: A Nationwide 11-Year Cohort Study

ContextThe impact of hospice care services on the utilization of life-sustaining treatments during end-of-life care in terminally ill patients has not been extensively studied. ObjectivesTo determine the impact of hospice care services on the utilization of life-sustaining treatments during the last three months of life among patients with cancer. MethodsThis nationwide population-based cohort study identified adults with cancer diagnosis from the Taiwan Registry for Catastrophic Illness, 2006–2016. Life-sustaining treatments included cardiopulmonary resuscitation, intubation, mechanical ventilation support, nasogastric tube feeding, and total parenteral nutrition. Hospice care services consisted of hospice inpatient care, hospice-shared care, and hospice home care. The association of hospice care services with the utilization of life-sustaining treatments was determined using multiple logistic regression. ResultsOf 516,409 patients with cancer, 310,722 (60.2%) patients used life-sustaining treatments during the last three months of life. After adjusting for covariates, patients with hospice care services were less likely to receive life-sustaining treatments during the last three months of life than those without the services (adjusted odds ratio [AOR]: 0.70; 95% CI: 0.69–0.71). While type of life-sustaining treatments were considered, hospice care services were associated with a lower likelihood of receiving cardiopulmonary resuscitation (AOR: 0.125; 95% CI: 0.118–0.131), endotracheal intubation (AOR: 0.204; 95% CI: 0.199–0.210), mechanical ventilation support (AOR: 0.265; 95% CI: 0.260–0.270), nasogastric tube feeding (AOR: 0.736; 95% CI: 0.727–0.744), and total parenteral nutrition (AOR: 0.86; 95% CI: 0.84–0.88). ConclusionHospice care services were associated with a lower likelihood of receiving life-sustaining treatments during the last three months of life in patients with cancer.

Chemotherapy and Tyrosine Kinase Inhibitors in the last month of life in patients with metastatic lung cancer: A patient file study in the Netherlands.

ObjectiveChemotherapy in the last month of life for patients with metastatic lung cancer is often considered as aggressive end‐of‐life care. Targeted therapy with Tyrosine Kinase Inhibitors (TKIs) is a relatively new treatment of which not much is known yet about use in the last month of life. We examined what percentage of patients received chemotherapy or TKIs in the last month of life in the Netherlands.MethodsPatient files were drawn from 10 hospitals across the Netherlands. Patients had to meet the following eligibility criteria: metastatic lung cancer; died between June 1, 2013 and July 31, 2015.ResultsFrom the included 1,322 patients, 39% received no treatment for metastatic lung cancer, 52% received chemotherapy and 9% received TKIs. A total of 232 patients (18%) received treatment in the last month of life (11% chemotherapy, 7% TKIs). From the patients who received chemotherapy, 145 (21%) received this in the last month of life and 79 (11%) started this treatment in the last month of life. TKIs were given and started more often in the last month of life: from the patients who received TKIs, 87 (72%) received this treatment in the last month of life and 15 (12%) started this treatment in the last month of life.ConclusionA substantial percentage of patient received and even started chemotherapy or TKIs in the last month of life. For chemotherapy, this might be seen as aggressive care. TKIs are said to have less side effects, do not lead to many hospital visits and due to the rapid response, are considered good palliation. However, it is not known, yet possible that, when patients still receiving treatment until shortly before death, this might influence preparing for death in a negative way.

Abstract P1-08-20: Healthcare use in the last six months of life in advanced breast cancer: An analysis from the Southeast Netherlands Advanced Breast Cancer (SONABRE) registry

Abstract In advanced breast cancer (ABC), a growing number of treatment options have become available the past 10 years, increasing overall survival. Healthcare use near the end of life has increased, although specific data for ABC are limited. This study describes healthcare use during the last 6 months of life in patients diagnosed with ABC in Maastricht University Medical Center (MUMC+). Methods: From our Southeast Netherlands Advanced Breast Cancer (SONABRE) Registry, we selected all patients from MUMC+ who were diagnosed with ABC and who also had passed away between January 1st, 2007 and October 1st, 2017. Patient, disease and treatment characteristics and data regarding health care use in the last period of life defined as ongoing chemotherapy ≤14 days before death, start of a new line of chemotherapy ≤30 days before death, and radiotherapy, hospital admission, surgery, intensive care unit (ICU) admission, mechanical ventilation, cardiopulmonary resuscitation (CPR) ≤ 6 months before death, and cause and place of death were collected by trained registration clerks. Healthcare use was described and univariate analyses were carried out for ongoing chemotherapy ≤14 days or start chemotherapy line ≤30 days before death, admission and death in the hospital using chi square and Fisher's exact test. The SONABRE Registry was approved by the Medical Research Ethics Committee of Maastricht University Medical Center. Results: Of 203 included patients, chemotherapy was continued ≤ 14 days before death in 21%, and a new line of chemotherapy ≤ 30 days before death was started in 9% of patients. In the last 6 months of life, radiotherapy was applied in 21% of patients. Hospital admission occurred in 76% of patients, because of tumor-related symptoms in 60%, and because of toxicity in 12% of these. Surgery (4%), ICU admission (6%), mechanical ventilation (5%), and CPR (2%) occurred infrequently. Of all patients, 25% died in the hospital; 74% due to progressive disease, 12% due to complications of therapy for ABC and 14% non-breast cancer related. Ongoing chemotherapy ≤14 days before death was associated with age&amp;lt;65 years (p&amp;lt;0.001) and negative hormone receptor (HR) status (p=0.04); start of a new line of chemotherapy ≤30 days before death was associated with age&amp;lt;65 years (p&amp;lt;0.001). Hospital admission was associated with age&amp;lt; 65 years (p=0.008), de novo ABC (p=0.01), negative HR status (p=0.04) and chemotherapy as last line of therapy (p=0.001). Death in the hospital was associated with ongoing chemotherapy ≤14 days (p&amp;lt;0.001) and start of a new line of chemotherapy ≤30 days before death (p&amp;lt;0.001). Conclusion: During the last 6 months of life, admission due to tumor-related symptoms occurred frequently, whereas ICU admission, mechanical ventilation and CPR occurred rarely. Death in the hospital occurred in a quarter of patients, and more frequently in those receiving chemotherapy shortly before death, which in turn was associated with younger age. Insight in real-life healthcare use may improve shared decision making and advanced care planning for patients with ABC. Citation Format: de Boer M, Schmitz RS, Ibragimova KI, van Kleef M, Geurts SM, Tjan-Heijnen VC. Healthcare use in the last six months of life in advanced breast cancer: An analysis from the Southeast Netherlands Advanced Breast Cancer (SONABRE) registry [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-20.

Abstract WP326: Factors in Acute Ischemic Stroke Predicting Pre-Hospital Notification by Emergency Medical Services

Introduction: Acute ischemic stroke (AIS) treatment is time sensitive and every 15 minutes saved in treatment results in 1 additional month of disability-free life in patients treated with thrombolysis. Pre-notification by Emergency Medical Services (EMS) has shown to reduce door to CT scan time, door to needle time for thrombolysis and increase the number of patients treated with thrombolysis. Determining which factors contribute to recognition and emergent treatment of stroke in the emergency department (ED) which are not recognized in the field can help improve models of pre-hospital notification. Objective: To determine which factors predict pre-hospital notification by EMS in patients with AIS treated with emergent therapy. Methods: We retrospectively reviewed our institutional database for all patients arriving through the ED by EMS who underwent acute stroke treatment from 2007-2018. All patient's arriving by EMS were dichotomized by the presence or absence of pre-hospital notification. We assessed the impact of demographic, clinical [NIHSS, FAST scores ((Face, Arm, Speech, Time) dichotomized into 0-1 or 2-3)], and diagnostic (vascular territory) factors on the likelihood of pre-hospital notification by EMS. A multivariate logarithmic regression analysis with assessment for confounding factors was applied. Results: A total of 183 patients were identified. The presence of 2 or 3 FAST criteria increased the odds of pre-hospital notification by EMS by 3.07 (p = 0.022, 95% CI 1.17-8.05) when adjusted for age. The vascular territory involved did not independently predict the likelihood of pre-hospital notification. We did not identify any significant confounders in the multivariate analysis. Conclusions: Patients with AIS receiving emergent treatment are over three times more likely to benefit from pre-hospital notification by EMS when presenting with 2 or 3 FAST criteria. Pre-hospital notification of AIS has established itself as a means to expedited clinical and radiographic evaluation and faster and more frequent treatment on hospital arrival. Improving EMS triage of AIS patients presenting with symptoms not well represented in the FAST criteria represents a stroke systems of care performance and quality improvement opportunity.

Differences in Medicare Utilization and Expenditures in the Last Six Months of Life among Patients with and without Alzheimer's Disease and Related Disorders.

Previous research has not focused on differences at the end of life among Medicare beneficiaries with, and without, a diagnosis of Alzheimer's disease and related disorders (ADRDs). The purpose of this study was to examine differences in utilization of inpatient services and Medicare expenditures (overall and by category) in the last six months of life for patients with, versus those without, a diagnosis of ADRD. The study used 2013 Medicare Research Identifiable Files (5% sample) to study utilization and expenditures for a full six months before death (n = 7895 for ADRD; n = 30,639 for non-ADRD). A generalized linear model with a gamma distribution was used to examine the association of ADRD with end-of-life service utilization and expenditures. ADRD patients were overall less expensive than their non-ADRD peers through reduced use of high-cost services, and urban patients were more likely than rural patients to use hospice and other services among both the ADRD and non-ADRD groups. After controlling for age, gender, race, dual eligibility, residence, region, chronic conditions, and type of service utilization, ADRD beneficiaries cost Medicare 11% less than non-ADRD beneficiaries (p < 0.01). Future research should examine the informal caregiving costs of caring, which is a significant part of care for an ADRD patient, as the residential setting of the beneficiary highly influences costs.

Rural-Urban Differences in Costs of End-of-Life Care for the Last 6 Months of Life Among Patients with Breast, Lung, or Colorectal Cancer.

The purpose of this study was to examine rural-urban differences in utilization and expenditures in the last 6 months of life for patients with breast, lung, or colorectal cancer. The study used a 5% sample of the 2013 Medicare Research Identifiable Files to study utilization and expenditures for beneficiaries with breast, lung, or colorectal cancer during the last 6 months before death (n = 6,214). End of life expenditures were calculated as the sum of total Medicare expenditures for inpatient, outpatient, physician, home health, hospice, and skilled nursing facility costs during the last 6 months of life. For each type of cancer, total Medicare expenditures in the last 6 months of life were lower for rural decedents compared to their urban counterparts. During the last 6 months of life, median Medicare expenditures were lower for rural decedents for breast cancer ($21,839 vs $25,698), lung cancer ($22,814 vs $27,635), and colorectal cancer ($24,156 vs $28,035; all differences significant at P < .05). In adjusted models, care for rural decedents was less costly than urban decedents for breast, lung, and colorectal cancer, respectively. Our findings indicate that Medicare expenditures are lower for rural beneficiaries with each type of cancer than urban beneficiaries, even after adjusting for age, gender, race, dual eligibility, region, chronic conditions, and type of service utilization. The findings from this study can be useful for policymakers in developing programs and resource allocation decisions that impact rural beneficiaries.

Time Is Motor Neuron: Therapeutic Window and Its Correlation with Pathogenetic Mechanisms in Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of lower motor neurons (MNs) in the spinal cord and brain stem, which results in relentless muscle weakness and wasting, leading to premature death due to respiratory complications. The identification of the specific mutations in the survival motor neuron 1 (SMN1) gene that causes SMA has led to the development of experimental therapeutic strategies to increase SMN protein expression, including antisense oligonucleotides, small molecules, and gene therapy, which have so far shown promising results. The timing of therapeutic intervention is crucial since most of the degeneration in MNs occurs in the first months of life in patients with SMA type 1, which is the most severe and common form of SMA. Nevertheless, a precise temporal window for therapeutic intervention has not yet been identified. Evidence from in vivo studies in mice and large animals suggested that early therapeutic intervention for SMA correlated with better motor performance, longer survival, and, occasionally, rescue of the pathological phenotype. Indeed, the need to compensate for the loss of SMN protein function seemed to diminish during adulthood (even though repair ability after nerve injury remained impaired), suggesting the possibility of tapering the therapy administration late in the disease course. Moreover, recent clinical trials on children afflicted with SMA type 1 have shown a more rapid achievement of motor milestones and diminished disease severity when therapy was administered at an early age and earlier in the disease course. Finally, these results highlight the importance of newborn screening for SMA to facilitate early diagnosis and present the patient with available treatments while they are still in the presymptomatic stage.

A retrospective survey of the last 3�months of life in patients carrying glioblastoma: Clinical treatments and profiles

Glioblastoma is one of the most common types of primary brain tumor. In situations of local recurrence, physicians can suggest either specific palliative anticancer treatments (SPAT; surgery, chemotherapy, radiotherapy) or best supportive care (BSC). The objective of the present study was to identify clinical factors that may have influenced the continuation or cessation of SPAT during the final 3 months of life in patients with glioblastoma. In the present retrospective single-center study, all records of patients treated for glioblastoma, who succumbed to the disease between June 2006 and February 2014, were assessed. All selected patients were divided into two groups, according to treatments received during the last 3 months of life: The SPAT and BSC groups. A total of 148 patients were included: 81 patients in the SPAT group (group A) and 67 patients in the BSC group (group B). A performance status equal to 0 was observed for 17.3% of patients in group A vs. 6% in group B. Following progression, chemotherapy was administered in 39.5% of cases in group A vs. 20.9% of cases in group B (P=0.0149). The mean number of lines of chemotherapy administered in group A was equal to 1.44±0.77 as compared with 1.06±0.67 in group B (P=0.0017). SPAT are utilized frequently among patients approaching mortality due to a glioblastoma. Certain factors, including the utilization of novel chemotherapy after the first progression or number of lines of chemotherapy previously administered, may have influenced physicians' decisions whether to continue with the SPAT or not.