Expression of existential suffering in two patients with advanced cancer in an acute palliative care unit.

BACKGROUND: Recognizing and managing existential suffering remains challenging. We present two cases demonstrating how existential suffering manifests in patients and how to manage it to alleviate suffering. CASE DESCRIPTION: Case 1: A 69-year-old man with renal cell carcinoma receiving end-of-life care expressed fear of lying down "as he may not wake up." He also expressed concerns of not being a good Christian. Supportive psychotherapy and chaplain support were provided, with anxiolytic medications as needed. He was able to express his fear of dying and concern about his family, and Edmonton Symptom Assessment System scores improved. He died peacefully with family at bedside. Case 2: A 71-year-old woman presented with follicular lymphoma and colonic obstruction requiring nasogastric drain of fecaloid matter. Initially, she felt that focusing on comfort rather than cure symbolized giving up but eventually felt at peace. Physical symptoms were well-controlled but emotionally she became more distressed, repeatedly asking angrily, "Why is it taking so long to die?." She was supported by her family through Bible readings and prayers, but she was distressed about being a burden to them. An interdisciplinary approach involving expressive supportive counseling, spiritual care, and integrative medicine resulted in limited distress relief. Owing to increasing agitation, the patient and family agreed to titrate chlorpromazine to sedation. Her family was appreciative that she was restful until her death. CONCLUSION: Existential suffering manifests through multiple domains in each patient. A combination of pharmacologic and non-pharmacologic techniques may be needed to relieve end-of-life suffering.

Patterns of Opioid Prescription, Use, and Costs Among Patients With Advanced Cancer and Inpatient Palliative Care Between 2008 and 2014.

PURPOSE: An understanding of opioid prescription and cost patterns is important to optimize pain management for patients with advanced cancer. This study aimed to determine opioid prescription and cost patterns and to identify opioid prescription predictors in patients with advanced cancer who received inpatient palliative care (IPC). MATERIALS AND METHODS: We reviewed data from 807 consecutive patients with cancer who received IPC in each October from 2008 through 2014. Patient characteristics; opioid types; morphine equivalent daily dose (MEDD) in milligrams per day of scheduled opioids before, during, and after hospitalization; and in-admission opioid cost per patient were assessed. We determined symptom changes between baseline and follow-up palliative care visits and the in-admission opioid prescription predictors. RESULTS: A total of 714 (88%) of the 807 patients were evaluable. The median MEDD per patient decreased from 150 mg/d in 2008 to 83 mg/d in 2014 ( P < .001). The median opioid cost per patient decreased and then increased from $22.97 to $40.35 over the 7 years ( P = .03). The median MEDDs increased from IPC to discharge by 67% ( P < .001). The median Edmonton Symptom Assessment Scale pain improvement at follow-up was 1 ( P < .001). Younger patients with advanced cancer (odds ratio [OR[, 0.95; P < . 001) were prescribed higher preadmission MEDDs (OR, 1.01; P < .001) more often in the earlier study years (2014 v 2009: OR, 0.18 [ P = .004] v 0.30 [ P = .02]) and tended to use high MEDDs (> 75 mg/d) during hospitalization. CONCLUSION: The MEDD per person decreased from 2008 to 2014. The opioid cost per patient decreased from 2008 to 2011 and then increased from 2012 to 2014. Age, prescription year, and preadmission opioid doses were significantly associated with opioid doses prescribed to patients with advanced cancer who received IPC.

Frequency, Outcomes, and Associated Factors for Opioid-Induced Neurotoxicity in Patients with Advanced Cancer Receiving Opioids in Inpatient Palliative Care.

Context: Opioid-induced neurotoxicity (OIN) is an underdiagnosed yet distressing symptom in palliative care patients receiving opioids. However, there have been only a limited number of studies on OIN. Objectives: Our aim was to determine the frequency of and risk factors for OIN in patients receiving opioids during inpatient palliative care. Methods: We randomly selected 390 of 3014 eligible patients who had undergone palliative care consultations from January 2014 to December 2014. Delirium, drowsiness, hallucinations, myoclonus, seizures, and hyperalgesia were defined as OIN and were recorded. The other 10 common symptoms in cancer patients were assessed using the Edmonton Symptom Assessment Scale (ESAS). Patient demographics, morphine equivalent daily dose (MEDD), comorbidities, OIN management, and overall survival (OS) duration were also assessed. The associations between the incidence of OIN and MEDD, the other 10 symptoms, and OS were analyzed. Results: Fifty-seven (15%) patients had OIN. The most common symptom was delirium (n = 27). On multivariate analysis, a high MEDD (p = 0.020), high ESAS pain score (p = 0.043), drowsiness (p = 0.007), and a poor appetite (p = 0.014) were significantly associated with OIN. OIN was not significantly associated with a shorter OS duration (p = 0.80). Conclusions: OIN was seen in 15% of patients receiving opioids as part of inpatient palliative care. Although OIN was not associated with OS, routine monitoring is especially needed in cancer patients.

Human peroxiredoxin 5 gene organization, initial characterization of its promoter and identification of alternative forms of mRNA.

Peroxiredoxin 5 (PRDX5) is a mammalian thioredoxin peroxidase ubiquitously expressed in tissues. Its role as antioxidant enzyme has been previously supported in different pathological situations. In this study, we determined the complete human PRDX5 genomic organization and isolated the 5'-flanking region of the gene. Human PRDX5 gene is composed of six exons and five introns similarly to other chordate PRDX5 genes. Several single nucleotide polymorphisms were identified. Six out of them have amino acid substitutions in protein-coding region. Analysis of the 5'-flanking region of human PRDX5 revealed the presence of a TATA-less promoter containing a canonical CpG island and several putative response elements for transcription factors. To analyze the regulatory mechanisms controlling human PRDX5 expression, we characterized the 5'-flanking region by cloning various segments of this region in front of a luciferase reporter sequence. Transfection in HepG2 cells indicate that the 5'-flanking region contains regulatory elements for constitutive expression of human PRDX5. Multiple transcription start sites were also identified by 5'-RACE-PCR in human liver. Moreover, although no corresponding proteins were reported, we present new alternative splicing variants encoded specifically by human PRDX5 gene. The characterization of human PRDX5 gene revealed the complexity of its regulation and a high variability of sequences that might be associated with pathological situations.

Mitochondrial and cytosolic expression of human peroxiredoxin 5 in Saccharomyces cerevisiae protect yeast cells from oxidative stress induced by paraquat.

Human peroxiredoxin 5 is a recently discovered mitochondrial, peroxisomal and cytosolic thioredoxin peroxidase able to reduce hydrogen peroxide and alkyl hydroperoxides. To gain insight into peroxiredoxin 5 antioxidant role in cell protection, we investigated the resistance of yeast cells expressing human peroxiredoxin 5 in mitochondria or in the cytosol against oxidative stress induced by paraquat. The herbicide paraquat is a redox active drug known to generate superoxide anions in mitochondria and the cytosol of yeast and mammalian cells leading to the formation of several reactive oxygen species. Here, we report that mitochondrial and cytosolic human peroxiredoxin 5 protect yeast cells from cytotoxicity and lipid peroxidation induced by paraquat.

Alkyl hydroperoxide reductase 1 protects Saccharomyces cerevisiae against metal ion toxicity and glutathione depletion.

Alkyl hydroperoxide reductase 1 (Ahp1p) is a thioredoxin peroxidase of the peroxiredoxin family expressed by Saccharomyces cerevisiae. Recently, disruption of the AHP1 gene has shown that the gene is not essential for yeast growth on glucose medium but revealed a high sensitivity of null mutants to organic peroxides, suggesting that Ahp1p is an important enzyme implicated in oxidative stress protection in S. cerevisiae. To gain insight into antioxidant enzymatic mechanisms involved in cell protection against metal toxicity and glutathione depletion, we investigated the resistance of S. cerevisiae, in which the AHP1 gene was disrupted, against several metals and diethyl maleate, a glutathione depleting agent. We report that Ahp1p protects yeast against toxicity induced by copper, cobalt, chromium, arsenite, arsenate, mercury, zinc and diethyl maleate, suggesting that Ahp1p plays an important role in S. cerevisiae in the protection against metals possibly by reducing peroxides generated in cells by these compounds.