How do treatment aims in the last phase of life relate to hospitalizations and hospital mortality? A mortality follow-back study of Dutch patients with five types of cancer

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The Intensity of Hospital Care Utilization by Dutch Patients With Lung or Colorectal Cancer in their Final Months of Life

Understanding the overuse and underuse of health-care services in the end-of-life (EoL) phase for patients with lung cancer (LC) and colorectal cancer (CRC) is important, but knowledge is limited. To help identify inappropriate care, we present the health-care utilization profiles for hospital care at the EoL of patients with LC (N = 25 553) and CRC (N = 14 911) in the Netherlands between 2013 and 2015. An administrative database containing all in-hospital health-care activities was analyzed to investigate the association between the number of days patients spent in the emergency department (ED) or intensive care unit (ICU) and their exposure to chemotherapy or radiotherapy. Fewer patients received hospital care as death neared, but their intensity of care increased. In the last month of life, the average numbers of hospital bed days, ICU days, and ER contacts were 9.0, 5.5, and 1.2 for patients with CRC, and 8.9, 6.2 and 1.2 for patients with LC in 2015. On the other hand, the occurrence of palliative consultations ranged from 1% to 4%. Patients receiving chemotherapy 6 months before death spent fewer days in ICU than those who did not receive this treatment (odds ratios: CRC = 0.6 [95% confidence interval: 0.4-0.8] and LC = 0.7 [0.5-0.9]), while those receiving chemotherapy 1 month before death had more ED visits (odds ratios: CRC = 17.2 [11.8-25.0] and LC = 15.8 [12.0-20.9]). Our results showed that patients who were still receiving hospital care when death was near had a high intensity of care, yet palliative consultations were low. Receiving chemotherapy or radiotherapy in the final month of life was significantly associated with more ED and ICU contacts in patients with LC

CSF or serum neurofilament light added to α-Synuclein panel discriminates Parkinson's from controls

Background: Neurofilament light chain is a marker of axonal damage and is of interest as a biofluid biomarker for PD. The objective of this study was to investigate whether CSF or serum neurofilament contributes to a combination of CSF biomarkers in defining the optimal biomarker panel for discriminating PD patients from healthy controls. In addition, we aimed to assess whether CSF and/or serum neurofilament levels are associated with clinical measures of disease severity. Methods: We measured neurofilament light chain levels in CSF and/or serum of 139 PD patients and 52 age-matched healthy controls. We used stepwise logistic regression analyses to test whether neurofilament contributes to a biomarker CSF panel including total, oligomeric, and phosphorylated α-synuclein and Alzheimer's disease biomarkers. Measures of disease severity included disease duration, UPDRS-III, Hoehn & Yahr stage, and MMSE. Results: After correcting for age, CSF neurofilament levels were 42% higher in PD patients compared with controls (P < 0.01), whereas serum neurofilament levels were 37% higher (P = 0.08). Combining CSF neurofilament, phosphorylated-/total α-synuclein, and oligomeric-/total α-synuclein yielded the best-fitting model for discriminating PD patients from controls (area under the curve 0.92). The discriminatory potential of serum neurofilament in the CSF biomarker panel was similar (area under the curve 0.90). Higher serum neurofilament was associated with a lower MMSE score. There were no other associations between CSF and/or serum neurofilament levels and clinical disease severity. Conclusions: CSF neurofilament contributes to a panel of CSF α-synuclein species in differentiating PD patients from healthy controls. Serum neurofilament may have added value to a biofluid biomarker panel for differentiating PD patients from controls

Contactin-1 Is Reduced in Cerebrospinal Fluid of Parkinson's Disease Patients and Is Present within Lewy Bodies

Synaptic degeneration is an early phenomenon in Parkinson’s disease (PD) pathogenesis. We aimed to investigate whether levels of synaptic proteins contactin-1 and contactin-2 in cerebrospinal fluid (CSF) of PD patients are reduced compared to dementia with Lewy bodies (DLB) patients and controls and to evaluate their relationship with α-synuclein aggregation. Contactin-1 and-2 were measured in CSF from PD patients (n = 58), DLB patients (n = 72) and age-matched controls (n = 90). Contactin concentration differences between diagnostic groups were assessed by general linear models adjusted for age and sex. Contactin immunoreactivity was characterized in postmortem substantia nigra, hippocampus and entorhinal cortex tissue of PD patients (n = 4) and controls (n = 4), and its relation to α-syn aggregation was evaluated using confocal laser scanning microscopy. Contactin-1 levels were lower in PD patients (42 (36–49) pg/mL) compared to controls (52 (44–58) pg/mL, p = 0.003) and DLB patients (56 (46–67) pg/mL, p = 0.001). Contactin-2 levels were similar across all diagnostic groups. Within the PD patient group, contactin-1 correlated with t-α-syn, tTau and pTau (r = 0.30–0.50, p < 0.05), whereas contactin-2 only correlated with t-α-syn (r = 0.34, p = 0.03). Contactin-1 and-2 were observed within nigral and cortical Lewy bodies and clustered within bulgy Lewy neurites in PD brains. A decrease in CSF contactin-1 may reflect synaptic degeneration underlying Lewy body pathology in PD

Mild brain lesions do not affect brain volumes in moderate-late preterm infants

Purpose: It is unknown whether frequently occurring mild brain lesions affect brain volumes in moderate (MP2; 32+0-33+6 weeks' gestation) and late (LP3; 34+0-35+6 weeks’ gestation) preterm infants. Therefore, we aimed to investigate the effect of mild brain lesions on brain volumes in moderate-late preterm (MLPT4) infants and to compare brain volumes between MP and LP infants. Methods: From August 2017 to November 2019, eligible MLPT infants born at Isala Women and Children's Hospital were enrolled in a prospective cohort study (Brain Imaging in Moderate-late Preterm infants ‘BIMP-study’). MRI was performed around term equivalent age (TEA5). MRI scans were assessed for (mild) brain lesions. T2-weighted images were used for automatic segmentation of eight brain structures. Linear regression analysis was performed to compare absolute and relative brain volumes between infants with and without mild brain lesions and between MP and LP infants. Results: 36 MP and 68 LP infants were included. In infants with mild brain lesions, intracranial volume (B = 27.4 cm3, p = 0.02), cerebrospinal fluid (B = 8.78 cm3, p = 0.01) and cerebellar volumes (B = 1.70 cm3, p = 0.03) were significantly larger compared to infants without mild brain lesions. After correction for weight and postmenstrual age at MRI, these volumes were no longer significantly different. LP infants had larger brain volumes than MP infants, but differences were not significant. Relative brain volumes showed no significant differences in both analyses. Conclusion: Neither having mild brain lesions, nor being born moderate prematurely affected brain volumes at TEA in MLPT infants

CSF Biomarkers Reflecting Protein Pathology and Axonal Degeneration Are Associated with Memory, Attentional, and Executive Functioning in Early-Stage Parkinson's Disease

In early-stage Parkinson's disease (PD), cognitive impairment is common, and a variety of cognitive domains including memory, attention, and executive functioning may be affected. Cerebrospinal fluid (CSF) biomarkers are potential markers of cognitive functioning. We aimed to explore whether CSF α-synuclein species, neurofilament light chain, amyloid-β42, and tau are associated with cognitive performance in early-stage PD patients. CSF levels of total-α-synuclein and phosphorylated-α-synuclein, neurofilament light chain, amyloid-β42, and total-tau and phosphorylated-tau were measured in 26 PD patients (disease duration ≤5 years and Hoehn and Yahr stage 1-2.5). Multivariable linear regression models, adjusted for age, gender, and educational level, were used to assess the relationship between CSF biomarker levels and memory, attention, executive and visuospatial function, and language performance scores. In 26 early-stage PD patients, attention and memory were the most commonly affected domains. A higher CSF phosphorylated-α-synuclein/total-α-synuclein ratio was associated with better executive functioning (sβ = 0.40). Higher CSF neurofilament light was associated with worse memory (sβ = -0.59), attentional (sβ = -0.32), and executive functioning (sβ = -0.35). Reduced CSF amyloid-β42 levels were associated with poorer attentional functioning (sβ = 0.35). Higher CSF phosphorylated-tau was associated with worse language functioning (sβ = -0.33). Thus, CSF biomarker levels, in particular neurofilament light, were related to the most commonly affected cognitive domains in early-stage PD. This indicates that CSF biomarker levels may identify early-stage PD patients who are at an increased risk of developing cognitive impairment