The prevalence of cancer-related pain is 64% among patients with metastatic, advanced, or terminal cancer, 59% among patients undergoing anticancer treatment, and 33% among patients who completed curative treatment. According to the World Health Organization cancer pain relief guidelines, opioid analgesics are the mainstay analgesic therapy in addition to conventional first-step analgesics, such as non-steroidal anti-inflammatory drugs and acetaminophen. The indications for strong opioids have recently been expanded to include mild-to-moderate pain in addition to moderate-to-severe pain. The U.S. Centers for Disease Control and Prevention guidelines emphasize that realistic expectations should be weighed against potential serious harm from opioids, rather than relying on the unrealized long-term benefits of these drugs. Therefore, treatment strategies for both cancer-related chronic or acute pain have been unfortunately deviated from opioid analgesics. The barriers hindering adequate cancer-related pain management with opioid analgesics are related to the inadequate knowledge of opioid analgesics (e.g., effective dose, adverse effects, and likelihood of addiction or tolerance). To achieve adequate opioid availability, these barriers should be overcome in a clinically suitable manner. Genetic assessments could play an important role in overcoming challenges in opioid management. To balance the improvement in opioid availability and the prevention of opioid misuse and addiction, the following two considerations concerning opioids and genetic polymorphisms warrant attention: (A) pain severity, opioid sensitivity, and opioid tolerance; and (B) vulnerability to opioid dependence and addiction.
Palliative care may be an opportunity to discuss cancer family history and familial cancer risks with patients' relatives. It may also represent the last opportunity to collect, from dying patients, clinical data and biospecimens that will inform cancer risk assessment and prevention in their surviving relatives. This study aims to explore the perspectives of cancer patients' relatives about cancer heritability, addressing cancer family history, and performing genetic testing in palliative care settings. Thirteen first-degree relatives of cancer patients who died in palliative care participated in the study. Two focus groups were conducted and transcribed verbatim. Two independent coders conducted a thematic content analysis. The themes included: (1) Knowledge of cancer heritability; (2) Experiences and expectations regarding cancer family history discussions, and (3) Views on genetic testing in palliative care patients and DNA biobanking. Participants seemed aware that cancer family history is a potential risk factor for developing the disease. They considered the palliative care period an inappropriate moment to discuss cancer heritability. They also did not consider palliative care providers as appropriate resources to consult for such matters as they are not specialized in this field. Participants welcomed DNA biobanking and genetic testing conducted at the palliative care patients' request. Cancer occurrence within families raises concerns among relatives about cancer heritability, but the palliative care period is not considered the most appropriate moment to address this issue. However, discussions about the risk to cancer patients' relatives might need to be considered on a case-by-case basis.
Cancer family history is not systematically assessed during the cancer care trajectory. Palliative care may emerge as the last opportunity for health professionals to collect, from dying cancer patients, family history and biological samples that could inform relatives’ cancer risk assessment and management. At-risk relatives can then be offered genetic counseling and testing and preventive strategies if needed. Discussions on cancer heritability between patients, family members, and providers may become more frequent in palliative care due to increasing public awareness about advances in genomics and risks associated with a cancer family history.
[Début de l'article]
People with an inherited condition who receive palliative care may be missing out on the opportunity to store a DNA sample for future use by their families and offspring. A DNA sample from a family member affected with an inherited condition can help at-risk relatives to access accurate risk assessment and, where relevant, enhanced surveillance and risk-reducing measures. As genetic and genomic testing becomes increasingly important in all aspects of healthcare, health professionals specialising in palliative care will be asked to communicate about family history risk and testing. This article highlights the importance of discussing genetics and genomics issues for people receiving palliative care, their families and the health professionals caring for them.
Physician aid-in-dying (PAD) is now legalized in more than half a dozen states across the United States yet remains controversial among health care providers and the general public. Previous studies have described physicians' and nurses' experiences with and attitudes about PAD; however, there is no data about PAD in the context of genetic counseling. This study explores genetic counselors' experiences, understanding, training, and perspectives about PAD. Fifteen participants were recruited to complete semistructured telephone interviews. Five participants had received patient inquiries about PAD. Most participants (n = 10) did not feel prepared to discuss PAD with patients and felt that they did not have adequate knowledge to answer patient questions about the practice. Participants described how the unique training, skills, and experiences of genetic counselors could be beneficial for discussing PAD with patients, in comparison to other providers. All participants supported training for genetic counselors about PAD, with many suggesting integration with education about palliative care and end-of-life planning. This is the first study to investigate PAD in the context of genetic counseling. Genetic counselors have had patients ask questions about PAD, want education and access to resources about PAD, and believe they can provide important support and guidance to patients considering PAD in some genetic counseling contexts.
Gastrointestinal cancer is one of the most common causes of mortality globally. The present study examined the influence of cytokine genetic polymorphisms [interleukin (IL)-1B C-31T, IL-1RN VNTR, IL-6 C-634G, IL-8 T-251A, IL-10 T-819C and IL-10 A-1082G] on clinical outcomes in patients with gastrointestinal cancer in palliative care. A total of 59 patients with gastrointestinal cancer who were admitted to Iga City General Hospital were analyzed. Genotyping was conducted using a polymerase chain reaction with confronting two-pair primers. Patients with at least one IL-1RN 2 allele demonstrated a significantly better survival (P=0.0275) while those with IL-6-634 G/G demonstrated a worse survival (P=0.0024). Multivariate analyses using the Cox proportional hazard model revealed that those with at least one IL-1RN 2 allele, IL-6-634 G/G or IL-10-1082 A/G had a significantly elevated adjusted hazard ratio of 9.20 (P=0.014), 41.01 (P=0.001) or 6.49 (P=0.046), respectively, compared with those with each homozygous wild-type polymorphism. In addition, the evaluation of weight loss by genotype revealed the potential influence of IL-10 T-819C genotype (P=0.072). IL-1RN, IL-6 and IL-10 polymorphisms were associated with the survival of patients with gastrointestinal cancer, suggesting the clinical feasibility of genetic testing in patients with gastrointestinal cancer in palliative care.
PURPOSE: Different amounts of opioid are required for the relief of cancer pain in different individuals, raising the possibility that genetic factors play a role. We tested the hypothesis that genetic variations in the TAOK3 (TAO kinase 3, encoding serine/threonine-protein kinase) explain some of the inter-individual variations related to the morphine equivalent daily dose (MEDD) in cancer patients.
EXPERIMENTAL DESIGN: We selected 2 single-nucleotide polymorphisms (SNPs) in the TAOK3, earlier reported to associate with higher MEDD in post-operative pain based on Genome-wide association study (GWAS). We investigated their association with MEDD in Canadian cancer patients (n=110) admitted to a tertiary palliative care unit (TPCU). SNPs analyzed were rs1277441 (C/T, C = minor allele) and rs795484 (A/G, A = minor allele).
RESULTS: Minor allele frequencies in our population were 0.29 (rs1277441) and 0.28 (rs795484). These SNPs were in perfect linkage disequilibrium (r2 = 0.97). SNPs in TAOK3 showed a significant association with mean MEDD =800 mg. For rs795484, MEDD values =800 mg occurred in patients who were GG (7%), GA (18%), and AA (57%) (P = 0.004; Fisher's exact test); similar results were obtained for rs1277441. Homozygous variants for either SNP had received higher numbers of different opioids (P = 0.021).
CONCLUSION: In this cohort of advanced cancer pain patients TAOK3 SNPs were associated with opioid doses. This result supports the original findings from a GWAS in postoperative patients. The proportions of variant homozygotes (8.2% of patients) and their requirement for higher doses of opioids would appear potentially clinically important and should be validated in further studies.
BACKGROUND: Hereditary cancer assessment and communication about family history risks can be critical for surviving relatives. Palliative care (PC) is often the last set of providers before death.
METHODS: We replicated a prior study of the prevalence of hereditary cancer risk among patients with cancer receiving PC consultations, assessed the history in the electronic medical record (EMR), and explored patients' attitudes toward discussions about family history. This study was conducted at an academic urban hospital between June 2016 and March 2017.
RESULTS: The average age of the 75 adult patients with cancer was 60 years, 49 (55%) male and 49 (65%) white. A total of 19 (25%) patients had no clear documentation of family history in the EMR, sometimes because no family history was included in the admission template or an automatically imported template lacked content. In all, 24 (32%) patients had high-risk pedigrees that merited referral to genetic services. And, 48 (64%) patients thought that PC was an appropriate venue to discuss the implications of family history. The mean comfort level in addressing these questions was high.
CONCLUSIONS: At an academic center, 25% of patients had no family history documented in the EMR. And, 32% of pedigrees warranted referral to genetic services, which was rarely documented. There is substantial room for quality improvement for oncologists and PC specialists-often the last set of providers-to address family cancer risk before death and to increase use and ease of documenting family history in the EMR. Addressing cancer family history could enhance prevention, especially among high-risk families.
OBJECTIVES: Complicated grief (CG) following bereavement significantly increases the risk for mood and anxiety disorders. The severity of grief reactions may be interactively influenced by temperamental and psychological factors such as behavioural inhibition (BI) and separation anxiety (SA) as well as biological factors. Given its central role in attachment and stress processing, a genetic variant in the oxytocin receptor (OXTR) gene was thus investigated in order to elucidate the direction of association as well as its interaction with BI and SA in the moderation of CG severity.
METHODS: Ninety-three patients with mood and anxiety disorders were evaluated for CG by means of the Inventory of Complicated Grief (ICG), for BI using the Retrospective Self-Report of Inhibition (RSRI), and for symptoms of SA during adulthood using the Adult Separation Anxiety Scale (ASA-27). All patients were genotyped for OXTR rs2254298.
RESULTS: OXTR genotype interacted with BI and, on a trend-level, with adult SA, to increase CG. Specifically, higher levels on the RSRI and ASA-27 scales, respectively, were related to higher ICG scores in GG genotype carriers.
CONCLUSIONS: The present study for the first time suggests a gene-environment interaction effect of an OXTR gene variant with behavioural inhibition and possibly also symptoms of adult separation anxiety in the moderation of vulnerability for complicated grief.
PURPOSE: In the palliative oncology setting, genetic assessment may not impact on the patient's management but can be of vital importance to their surviving relatives. Despite care of the family being central to the ethos of palliative care, little is known about how hereditary aspects of cancer are addressed in this setting. This review aims to examine current practices, identify practice barriers and determine the genetic information and support needs of patients, family members and health providers.
METHODS: Key databases were systematically searched to identify both quantitative and qualitative studies that addressed these aims. Data was extracted and coded using thematic analysis.
RESULTS: Eight studies were included for review. Suboptimal genetic practices were identified, with lack of knowledge and poor confidence amongst providers reported as barriers in both qualitative and quantitative studies. Providers expressed concern about the emotional impact of initiating these discussions late in the disease trajectory; however, qualitative interviews amongst palliative patients suggested there may be emotional benefits.
CONCLUSIONS: All lines of evidence suggest that genetics is currently missing from the palliative agenda, signifying lost opportunities for mutation detection, genetic counselling and appropriate risk management for surviving relatives. There is an urgent need for interventions to improve provider knowledge and awareness of genetic referral pathways and for research into the genetic information and support needs of palliative care patients.
Even at the end of life, testing cancer patients for inherited susceptibility may provide life-saving information to their relatives. Prior research suggests palliative care inpatients have suboptimal understanding of genetic importance, and testing may be underutilized in this clinical setting. These conclusions are based on limited research. This study aimed to estimate genetic testing prevalence among high-risk palliative care patients in a National Cancer Institute-designated comprehensive cancer center. We also aimed to understand these patients' understanding of, and attitudes toward, hereditary cancer testing and DNA banking. Palliative care in-patients with cancer completed structured interviews, and their medical records were reviewed. Among patients at high risk for hereditary cancer, we assessed history of genetic testing/DNA banking; and related knowledge and attitudes. Among 24 high-risk patients, 14 (58.3%) said they/their relatives had genetic testing or they had been referred for a genetics consultation. Of the remaining 10 patients, seven (70%) said they would "probably" or "definitely" get tested. Patients who had not had testing were least concerned about the impact of future testing on their family relationships; two (20%) said they were "extremely concerned" about privacy related to genetic testing. Of patients without prior testing, five (50%) said they had heard or read "a fair amount" about genetic testing. No high-risk patients had banked DNA. Overall, 23 (95.8%) said they had heard or read "almost nothing" or "relatively little" about DNA banking. Written materials and clinician discussion were most preferred ways to learn about genetic testing and DNA banking. Overall, this study demonstrates underutilization of genetics services at the end of life continues to be problematic, despite high patient interest.
Oncology guidelines clearly outline evidence-based recommendations for patients with newly diagnosed cancer to help oncologists determine which patients are appropriate for a genetic assessment. Ideally, patients with newly diagnosed cancer, who have personal or family histories suggestive of hereditary cancer predisposition, are referred for genetics work up in the nonurgent setting. However, in some cases, a genetics work up is delayed until the end of life. This is a time of heightened stress and additional obstacles, including discordance between family members regarding the obtainment of genetic information, paying for testing, selecting a surrogate to receive and disperse information in the case of a patient's death, and the use of DNA banking for future evaluation. To meaningfully participate and support patients, family members, and our colleagues facing requests at the end of life for genetic testing, we provide a practical approach and highlight resources to effectively engage in this rising challenge.
OBJECTIVE: Experience of stressful life events is associated with risk of depression. Yet many exposed individuals do not become depressed. A controversial hypothesis is that genetic factors influence vulnerability to depression following stress. This hypothesis is often tested with a "diathesis-stress" model, in which genes confer excess vulnerability. The authors tested an alternative formulation of this model: genes may buffer against depressogenic effects of life stress.
METHOD: The hypothesized genetic buffer was measured using a polygenic score derived from a published genome-wide association study of subjective well-being. The authors tested whether married older adults who had higher polygenic scores were less vulnerable to depressive symptoms following the death of their spouse compared with age-matched peers who had also lost their spouse and who had lower polygenic scores. Data were analyzed from 8,588 non-Hispanic white adults in the Health and Retirement Study (HRS), a population-representative longitudinal study of older adults in the United States.
RESULTS: HRS adults with higher well-being polygenic scores experienced fewer depressive symptoms during follow-up. Those who survived the death of their spouses (N=1,647) experienced a sharp increase in depressive symptoms following the death and returned toward baseline over the following 2 years. Having a higher well-being polygenic score buffered against increased depressive symptoms following a spouse's death.
CONCLUSIONS: The effects were small, and the clinical relevance is uncertain, although polygenic score analyses may provide clues to behavioral pathways that can serve as therapeutic targets. Future studies of gene-environment interplay in depression may benefit from focus on genetics discovered for putative protective factors.
Objective: Cancer patients often suffer from chronic inflammation, anorexia and the resultant decrease of nutrient intake, followed by weight loss and muscle wasting called “sarcopenia”. Such conditions are known as “cachexia”. In this study, we examined the associations between genetic polymorphisms of AKT1 rs1130233, ICAM1 rs281432, SELP rs6128 and TNSRSF1A rs4149570, which are reportedly associated with cachexia in Caucasians, together with LIF rs929271, in Japanese gastrointestinal cancer patients with palliative care.
Methods: The study subjects were 59 patients (37 males and 22 females) with gastrointestinal cancers who visited the outpatient clinic at Iga General Hospital from December 2011 till August 2015. Genotypings for AKT1 rs1130233, ICAM1 rs281432, SELP rs6128, TNSRSF1A rs4149570 and LIF rs929271 were conducted with polymerase chain reaction with confronting two-pair primers (PCR-CTPP) or the Taqman SNP Genotyping assay. Associations of these SNPs with patients’ prognosis as well as weight loss defined as weight loss more than 5 percent during 6 months after the initiation of chemotherapy were evaluated.
Results: A significant increase in the risk of 5% weight loss was observed in those with A/G genotype AKT1 rs1130233 polymorphism (AKT1 A/G vs. G/G, adjusted odds ratio [aOR]=7.11; 95%CI: 1.41-35.7), or in those with at least one A allele of AKT1 rs1130233 (AKT1 A/G+A/A vs. G/G, aOR=4.57; 95% CI: 1.14-18.3) when adjusted for age, sex and UICC clinical stage 4. There was no statistically significant correlation of the polymorphisms examined with patients’ survival.
Conclusion: The present study revealed that AKT1 rs1130233 A allele may play a key role in the development of cancer cachexia. Given the involvement of AKT1 in the development of cancer as well as in apoptosis, it would be worth studying the roles of this molecule in human cancers further from clinical, epidemiological and biological viewpoints in the near future.
Addressing the concerns of end-of-life patients or their relatives about their family history of cancer could benefit patients and family members. Little is known about how palliative care providers respond to these concerns. The purpose of this pilot study was to assess palliative care providers' knowledge about familial and hereditary cancers and explore their exposure to patients' and relatives' concerns about their family history of cancer, and their self-perceived ability to deal with such concerns. A cross-sectional survey was conducted in the Quebec City (Canada) catchment area among palliative care professionals. Fifty-eight palliative care professionals working in hospice, home care and hospital-based palliative care units completed the questionnaire. All physicians and 63% of nurses occasionally addressed concerns of patients and relatives about their family history of cancer, but they reported a low confidence level in responding to such concerns. They also showed knowledge gaps in defining features of a significant family history of cancer, and most (78%) would welcome specific training on the matter. Our findings highlight the relevance of offering education and training opportunities about familial cancers and associated risks to palliative care providers. The needs and concerns of end-of-life patients and their families need to be explored to ensure palliative care providers can adequately assist patients and their relatives about their family history of cancer. Ethical implications should be considered.
Lors d'une grossesse gémellaire avec décès de l'un des foetus en anténatal, l'enfant rescapé est marqué par l'empreinte du jumeau mort in utero. Son existence postnatale va être influencée à la fois par son vécu prénatal, par les liens étroits qui se sont établis entre les deux foetus, mais également par les stratégies d'adaptation que ses parents vont devoir développer pour s'ajuster à cette situation atypique où la vie et la mort sont profondément liées. (R.A.).
Origine : BDSP. Notice produite par APHPDOC B9R0xkl8. Diffusion soumise à autorisation
Dans ce travail de master (second prix Cnaf - Mémoire de Master 2), l'auteur s'intéresse à la manières dont le décès d'un adolescent affecte la famille nucléaire, tant au niveau de ses membres que dans les relations familiales - en optant pour une analyse en termes de trajectoires et de bifurcations. Une hypothèse sous-tendant l'analyse est ici que perdre un enfant c'est aussi perdre une personne qui participait à la définition de soi, de son identité. Les entretiens ont été, dans la mesure du possible, réalisés auprès de plusieurs membres d'une famille, ce qui permet de croiser la manières dont ils ont vécu l'évènement et dont ils ont perçu la réaction des autres. Cette recherche explore également les conséquences du deuil sur les relations sociales à l'extérieur de la famille.
Les situations cliniques dans lesquelles le caractère potentiellement héréditaire d'une maladie est évoqué sont variées. Elles ont des aspects médicaux, psychiques et relationnels différents. Les auteurs proposent quelques repères pratiques.
Les arbres généalogiques ouvrent la porte à une meilleure compréhension de la part jouée par les morts et les naissances au sein des familles. Dans cet article, l'auteure raconte les recherches qu'elle a menées sur sa famille et parle de sa soeur décédée à la naissance.