Age-related differences in care receipt and symptom experience of elderly cancer patients dying at home: Lessons from the DEATH project

Background:   Data on the differences between older and younger elderly cancer patients dying at home is sparse. To clarify age-related differences in symptom experience and care receipt of elderly cancer patients at end-of-life, we conducted a subanalysis study of the Dying Elderly at Home (DEATH) project, a multicenter study of 240 elderly aged 65 and older dying at home.
Methods:   We assessed the frequency of symptom experience and end-of-life care receipt in home elderly patients during the last 2 days of their lives and evaluated the differences between younger elderly (aged 65–74) and older elderly (aged 75+) cancer decedents. The general practitioners were asked to fill out a questionnaire immediately after the death of study patients. A total of 66 younger and 51 older elderly cancer decedents were included in the analysis.
Results:   Coma and dementia were common among younger and older elderly patients. Older decedents were less likely to experience anxiety, but, after adjustment for baseline characteristics, this age-related difference did not clearly appear. Older decedents were also less likely to receive opioids than younger decedents. There were no significant differences in volume of i.v. hydration between the two groups.
Conclusions:   Our results suggested that there were no differences in symptom experience and care receipt among older and younger decedents, except in opioid use, at end-of-life. These findings imply a similar need of end-of-life care for younger and older elderly cancer patients who opt for home death.     

Onset heart rate of microvolt-level T-wave alternans provides clinical and prognostic value in nonischemic dilated cardiomyopathy.

OBJECTIVES: This study was designed to determine the prognostic value of onset heart rate (OHR) in T-wave alternans (TWA) in patients with nonischemic dilated cardiomyopathy (DCM). BACKGROUND: One of the current major issues in DCM is to prevent sudden cardiac death (SCD). However, the value of the OHR of TWA as a prognostic indicator in DCM remains to be elucidated. METHODS: We prospectively investigated 104 patients with DCM undergoing TWA testing. The end point of this study was defined as SCD, documented sustained ventricular tachycardia/ventricular fibrillation. Relations between clinical parameters and subsequent outcome were evaluated. RESULTS: Forty-six patients presenting with TWA were assigned to one of the following two subgroups according to OHR for TWA of < or = 100 beats/min: group A (n = 24) with OHR < or = 100 beats/min and group B (n = 22) with 100 < OHR < or = 110 beats/min. T-wave alternans was negative in 37 patients (group C) and indeterminate in 21 patients. The follow-up result comprised 83 patients with determined TWA. During a follow-up duration of 21 +/- 14 months, there was a total of 12 arrhythmic events, nine of which included three SCDs in group A, two in group B and one in group C. The forward stepwise multivariate Cox hazard analysis revealed that TWA with an OHR < or = 100 beats/min and left ventricular ejection fraction were independent predictors of these arrhythmic events (p = 0.0001 and p = 0.0152, respectively). CONCLUSIONS: The OHR of TWA is of additional prognostic value in DCM.     

Evolocumab Effects on Lipoproteins,Measured by High-Performance Liquid Chromatography

Aims: Profiling of lipoproteins can predict risk of cardiovascular disease; gel permeation high-performance liquid chromatography (HPLC) improves prediction accuracy by providing detailed data for specific lipoprotein subclasses. This study applied HPLC to examine the effects of evolocumab, which effectively treats hyperlipidemia and mixed dyslipidemia, on lipoprotein subclasses, specifically the number and size of lipoprotein particles.Methods: This post-hoc analysis used patient blood samples from YUKAWA-2, a phase 3 trial evaluating the efficacy of evolocumab in Japanese adult patients with hyperlipidemia or mixed dyslipidemia and at high risk for cardiovascular disease. We used HPLC to assess observed values and percent change from baseline in cholesterol and triglyceride (TG) concentrations, number of particles in lipoprotein subclasses to week 12, and mean observed values and mean percent change from baseline in variables to weeks 10 and 12. HPLC was also compared with conventional methods in assessing low-density lipoprotein (LDL) cholesterol (LDL-C) values.Results: Data for all 404 patients were analyzed. Evolocumab significantly decreased cholesterol and TG concentrations, and total particle count, in very low-density lipoprotein (VLDL) and LDL subclasses. Particle size increased slightly in LDL, high-density lipoprotein (HDL), and VLDL, but data varied widely. At very low L-DLC, HPLC measurements were higher than those from conventional methods.Conclusion: This research used HPLC to assess the effects of evolocumab in 20 lipid subclasses. By lowering lipid content and improving the lipid profile, evolocumab may reduce atherogenicity. This reduction is better quantified by HPLC than by conventional methods in the very low LDL-C range.     

Influence of PD‐L1 cross‐linking on cell death in PD‐L1‐expressing cell lines and bovine lymphocytes

Programmed death‐ligand 1 (PD‐L1) blockade is accepted as a novel strategy for the reactivation of exhausted T cells that express programmed death‐1 (PD‐1). However, the mechanism of PD‐L1‐mediated inhibitory signalling after PD‐L1 cross‐linking by anti‐PD‐L1 monoclonal antibody (mAb) or PD‐1–immunogloblin fusion protein (PD‐1‐Ig) is still unknown, although it may induce cell death of PD‐L1⁺ cells required for regular immune reactions. In this study, PD‐1‐Ig or anti‐PD‐L1 mAb treatment was tested in cell lines that expressed PD‐L1 and bovine lymphocytes to investigate whether the treatment induces immune reactivation or PD‐L1‐mediated cell death. PD‐L1 cross‐linking by PD‐1‐Ig or anti‐PD‐L1 mAb primarily increased the number of dead cells in PD‐L1^high cells, but not in PD‐L1^low cells; these cells were prepared from Cos‐7 cells in which bovine PD‐L1 expression was induced by transfection. The PD‐L1‐mediated cell death also occurred in Cos‐7 and HeLa cells transfected with vectors only encoding the extracellular region of PD‐L1. In bovine lymphocytes, the anti‐PD‐L1 mAb treatment up‐regulated interferon‐γ (IFN‐γ) production, whereas PD‐1‐Ig treatment decreased this cytokine production and cell proliferation. The IFN‐γ production in B‐cell‐depleted peripheral blood mononuclear cells was not reduced by PD‐1‐Ig treatment and the percentages of dead cells in PD‐L1⁺ B cells were increased by PD‐1‐Ig treatment, indicating that PD‐1‐Ig‐induced immunosuppression in bovine lymphocytes could be caused by PD‐L1‐mediated B‐cell death. This study provides novel information for the understanding of signalling through PD‐L1.     

Butyric acid induces apoptosis in both human monocytes and lymphocytes equivalently

Short-chain fatty acids (SCFAs) are metabolites from anaerobic periodontopathic bacteria that induce apoptosis in immune cells such as lymphocytes, monocytes and macrophages. However, it remains unclear if SCFAs from pathogens induce apoptosis in monocytes/macrophages similarly with lymphocytes. This study investigated whether SCFAs-induced apoptosis is equal among the immunoregulatory cells. Cell apoptosis of the employed human cells was evaluated after treatment with culture supernatants from various periodontopathic bacteria or sodium butyrate. Apoptosis and viability were determined by detection of DNA fragmentation and using an MTS assay kit, respectively. Porphyromonas gingivalis and Fusobacterium nucleatum culture filtrates strongly induced apoptosis whereas Prevotella nigrescens and Prevotella intermedia culture filtrates failed to induce apoptosis in the THP-1 and U937 human monocyte and macrophage cell lines. Healthy gingival fibroblasts and oral epithelial cells were resistant to all the culture filtrates. Gas-liquid chromatography detected butyric acid in P. gingivalis (21.0-34.0 mM) and F. nucleatum (36.0 mM) in culture filtrates, whereas, only trace levels were seen in P. nigrescens and P. intermedia. These results suggest that butyric acid produced by periodontopathic bacteria severely damages immunoregulatory cells in a consistent manner and, likewise, could be involved in mediating periodontal chronic inflammation.     

Clinical study on anti-fungal drug activity against clinically isolated strains of oral Candida species

ObjectivesThe present study was undertaken to evaluate the anti-fungal activity of amphotericin B (AMPH-B), flucytosine (5-FC), fluconazole (FLCZ), miconazole (MCZ), itraconazole (ITCZ), and micafungin (MCFG) against clinically isolated Candida strains from oral candidiasis (OC) patients and to collect information useful for the treatment of OC.Subjects and methodsThe study includes 116 strains of Candida isolated from patients. The Candida species were identified by polymerase chain reaction. The minimum inhibitory concentration (MIC) of each drug against each Candida species was determined.ResultsOf the 106 participants (30 males and 76 females), 57 had OC, including 42 cases of pseudomembranous OC, 11 cases of erythematous OC, 2 cases of hypertrophic OC, and 2 cases of mixed pseudomembranous/erythematous OC. The Candida species isolated were Candida albicans (93 strains), C. glabrata (19 strains), and C. tropicalis (4 strains). AMPH-B and 5-FC had low MIC values against all species of Candida and a low incidence of resistance development. In some species of Candida, FLCZ and ITCZ showed high MICs, but MCZ had a low MIC value. AMPH-B, MCZ, and ITCZ prescribed to OC patients were effective against OC with respect to alleviation of OC symptoms.ConclusionMIC values of anti-fungal drugs against Candida strains isolated from OC patients were obtained and the 3 anti-fungal drugs given to OC patients were found to be effective against OC in spite of differences in their MIC values and in the number of resistant strains (or strains with a high MIC value).     

Effect of switching from salmeterol/fluticasone to formoterol/ budesonide combinations in patients with uncontrolled asthma

BackgroundCombination therapy with an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) in a single inhaler is the mainstay of asthma management and salmeterol/fluticasone combination (SFC) and fixed-dose formoterol/budesonide combination (FBC) are currently available in Japan; however, there is nothing to choose between the two. The purpose of this study was to clarify the effect of switching from SFC to FBC in patients with asthma not adequately controlled under the former treatment regimen.MethodsThis was a prospective, multicenter, open-label, uncontrolled longitudinal study in 87 adult patients with an Asthma Control Questionnaire, 5-item version (ACQ5) score of greater than 0.75 under treatment with SFC 50/250 μg one inhalation twice daily (bid). SFC was switched to FBC 4.5/160 μg two inhalations bid. Study outcomes included ACQ5 score, peak expiratory flow (PEF), FEV₁, and fractional exhaled nitric oxide (FeNO) at the end of treatment period.ResultsEighty-three patients completed the study. ACQ5 scores improved and exceeded the clinically meaningful difference after 12 weeks of treatment and well-controlled asthma (ACQ5 score ≤ 0.75) was attained in 37 (44.6%) patients. Minimum and maximum PEF and FEV₁ values improved significantly, but not FeNO values, after switching from SFC to FBC.ConclusionsSwitching ICS/LABA combination therapy is a useful option in the management of asthma that is not optimally controlled.     

Comparison of the psychosocial quality of life in hemodialysis patients between the elderly and non‐elderly using a visual analogue scale: The importance of appetite and depressive mood

Aim: The number of hemodialysis (HD) patients is increasing along with their mean age in Japan. The assessment of their psychosocial status and quality of life (QOL) is therefore becoming more and more important along with laboratory data or comorbidities. Methods: We examined the psychosocial status of 211 HD patients (72 elderly and 139 non‐elderly) and compared the difference between elderly and non‐elderly patients using a visual analogue scale (VAS). We then examined how QOL affected mortality rate in 3‐year prospective follow up. We assessed 10 items of QOL: health condition, appetite, sleep, mood, memory, family relationships, friendship, economical status, life satisfaction in daily life, and happiness with qualified self‐evaluating questionnaires along with laboratory data and comorbidities. Furthermore, we investigated the correlation between the scores of mood and geriatric depression scale (GDS)‐15. Results: There was no difference in VAS scores between elderly and non‐elderly patients. Lower VAS scores for appetite and mood correlated with higher mortality in HD patients, especially in the non‐elderly. VAS scores for mood correlated with GDS‐15 in HD patients. Conclusions: More attention should be paid to appetite and the diagnosis and therapy of depressive mood to improve the prognosis of HD patients, especially for the non‐elderly. Geriatr Gerontol Int 2012; 12: 65–71.     

Effects of telmisartan on cognition and regional cerebral blood flow in hypertensive patients with Alzheimer's disease

Aim: Recent studies have shown that some antihypertensive medications are associated with a significant reduction in the incidence of Alzheimer's disease (AD). However, it remains uncertain whether antihypertensive drugs may have a preventive effect on cognitive decline in patients with AD. We investigated the effects of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator‐activated receptor γ‐stimulating activity, on cognition and regional cerebral blood flow (rCBF) in elderly hypertensive patients with AD. Methods: A total of 20 patients with probable AD and essential hypertension were randomly assigned to the telmisartan group (n = 10, 40–80 mg daily) or the amlodipine group (n = 10, 5–10 mg daily) for 6 months. Results: The groups had a similar significant reduction in systolic and diastolic blood pressure after treatment. The telmisartan group did not show any changes in cognitive function test scores, while the amlodipine group showed significantly higher scores on the AD Assessment Scale‐Cognitive Subscale (Japanese version). Analysis of covariance to analyze treatment effect revealed that the telmisartan group showed increased rCBF in the right supramarginal gyrus, superior parietal lobule, cuneus, and lingual gyrus compared with the amlodipine group, while the amlodipine group showed increased rCBF only in the right cingulate gyrus compared with the telmisartan group at 6 months. Conclusion: These findings suggest that telmisartan may have additional benefits and be useful for the treatment of elderly hypertensive patients with AD. Geriatr Gerontol Int 2012; 12: 207–214.