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OBJECTIVE: Virtual Reality (VR) has been demonstrated to be an effective option for integrating psychological interventions in different therapeutic settings. This randomized controlled interventional study aims to assess the effects of VR, compared to tablet controlled intervention, on anxiety, depression, pain, and short-term psychophysical symptoms in advanced cancer patients assisted at home. METHODS: Participants were provided with a VR headset or a tablet (TAB) for 4 days. On the first and last day, anxiety and depression were measured by Hospital Anxiety and Depression Scale and pain by Brief Pain Inventory. Before and after each VR and tablet session, symptoms were collected by the Edmonton Symptom Assessment Scale (ESAS). RESULTS: Fifty-three patients (27 VR vs. 26 TAB) completed the study. Anxiety significantly decreased in the VR group after the 4-day intervention. The analysis of ESAS showed a significant improvement in pain (p = 0.013), tiredness (p < 0.001), and anxiety (p = 0.013) for TAB group, and a significant reduction in tiredness (p < 0.001) in the VR group. CONCLUSIONS: Technological and user-friendly tools, such as VR and tablets, might be integrated with traditional psychological interventions to improve anxiety and cancer-related short-term symptoms. Further studies are needed to better consolidate the possible beneficial effects of VR.
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Ansiedad , Depresión , Neoplasias , Realidad Virtual , Humanos , Femenino , Masculino , Neoplasias/psicología , Neoplasias/terapia , Neoplasias/complicaciones , Ansiedad/terapia , Ansiedad/psicología , Persona de Mediana Edad , Anciano , Depresión/terapia , Depresión/psicología , Adulto , Fatiga/terapia , Servicios de Atención de Salud a Domicilio , Dolor en Cáncer/terapia , Dolor en Cáncer/psicologíaRESUMEN
OBJECTIVES: Timely, effective and personalized identification of the multidimensional needs in patients with advanced cancer are major goals of appropriate palliative care (PC) delivery. However, there is considerable variation in structures, processes, and patient demographics that might influence the intensity of end-of-life care. This study aims to characterize patterns in clinical and demographic characteristics at the inception point and their association with the intensity of care during the last month of life in advanced cancer patients assisted at home. METHODS: Cancer patients entered in home PC during 2020 in Italy were considered. The association between home PC services during the last month of life (primary outcome) and demographic data, performance status (Karnofsky Performance Score [KPS]), symptoms, and therapies at the entry was explored in this retrospective study. RESULTS: Among 1,721 consecutive patients (919 in Centre-North and 802 in Centre-South Italy), patients from Centre-South were younger (p < 0.001), had worse KPS (p < 0.001), and shorter survival (p = 0.010). Patient age was inversely associated with the number of total/physician/nurses services during the last month of life (p < 0.001, p = 0.001, and p = 0.008, respectively). Patients with severe symptoms (asthenia, pain, and anxiety) at inception needed more PC services at the end of life (p = 0.026, p = 0.008, and p = 0.038, respectively). The distribution of workload differed according to the geographical area, with higher number of PC services provided by physicians (p < 0.001) in Centre-North and by nurses (p = 0.002) in Centre-South. SIGNIFICANCE OF RESULTS: These findings highlight major disparity in access and nature of PC in a country with universal access to health services. Studies aimed at comparing PC models among different countries should pay attention to the local heterogeneity within each health-care system.
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Cuidados Paliativos al Final de la Vida , Neoplasias , Cuidado Terminal , Humanos , Estudios Retrospectivos , Cuidados Paliativos/métodos , Neoplasias/terapiaRESUMEN
OBJECTIVE: Deprescribing, i.e. the suspension of drugs whose existing or potential harms outweigh the benefits in the context of care for the individual patient, is an increasingly frequently encountered topic in various congresses today. This issue becomes predominant especially in patients with chronic pathologies with a life expectancy of less than a year, in whom the goal of the treatments passes from healing to caring. Currently there are few validated deprescribing tools, one of these is certainly the STOPPFrail, currently available in its second version. Therefore, we decided to provide for the translation into Italian, to make the description for the elderly patient with limited life expectation more applicable. METHODS: For the translation, we used the method expressed by the European organisation for research and treatment of cancer (Eortc), using forward-backward translation and a Pilot Testing to verify the clarity and comprehensibility of the translation itself. RESULTS: We interviewed 15 experts, of whom 13 responded and completed the evaluation, without bringing to light any unclear sections or sources of misunderstanding. CONCLUSIONS: STOPPFrail2 can be a valid deprescribing tool in the elderly with limited life expectancy; the Italian version can help the physicians in the therapeutic appropriateness in this time of life where it is necessary to focus on the quality of life and on the ethical aspect of the choices, as well as being of help in a "cost-opportunity" logic.
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Deprescripciones , Medicina , Humanos , Anciano , Calidad de Vida , Lenguaje , ItaliaRESUMEN
Background: Treatment of cancer pain remains suboptimal worldwide. In Italy, a law requires that pain be regularly assessed and reported in both medical and nursing records. Aim: To provide a homogeneous form to get exhaustive clinical information in the clinical report according to Italian legislation. Methods: A board, including oncologists and pain therapists, designed a form to report the pain characteristics of cancer patients in Italy in clinical records. The form was voted on through a Delphi process among directors of 18 clinical oncology specialization schools in Italy to obtain agreement on its content. Results: A form useful for collecting and reporting comprehensive and homogeneous information on pain among oncologists in Italy was produced. Conclusion: The development of common strategies for pain management can be improved by using this tool.
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Oncología Médica , Neoplasias , Humanos , Dimensión del Dolor , Dolor/diagnóstico , Dolor/etiología , Manejo del Dolor , Neoplasias/complicaciones , Neoplasias/diagnóstico , Neoplasias/epidemiología , Italia/epidemiologíaRESUMEN
During the pandemic, telemedicine and telehealth interventions have been leading in maintaining the continuity of care independently of patients' physical location. However, the evidence available about the effectiveness of the telehealth approach for advanced cancer patients with chronic disease is limited. This interventional randomized pilot study aims to evaluate the acceptability of a daily telemonitoring of five vital parameters (heart rate, respiratory rate, blood oxygenation, blood pressure, and body temperature) using a medical device in advanced cancer patients with relevant cardiovascular and respiratory comorbidities assisted at home. The purpose of the current paper is to describe the design of the telemonitoring intervention in a home palliative and supportive care setting with the objective of optimizing the management of patients, improving both their quality of life and psychological status and the caregiver's perceived care burden. This study may improve scientific knowledge regarding the impact of telemonitoring. Moreover, this intervention could foster continuous healthcare delivery and closer communication among the physician, patient and family, enabling the physician to have an updated overview of the clinical trajectory of the disease. Finally, the study may help family caregivers to maintain their habits and professional position and to limit financial consequences.
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Malnutrition is one of the main factors determining cachexia syndrome, which negatively impacts the quality of life and survival. In cancer patients, artificial nutrition is considered as an appropriate therapy when the impossibility of an adequate oral intake worsened nutritional and clinical conditions. This study aims to verify, in a home palliative care setting for cancer patients, if home artificial nutrition (HAN) supplies a patient's energy requirement, improving nutritional and performance status. A nutritional service team performed counseling at a patient's home and assessed nutritional status (body mass index, weight loss in the past 6 months), resting energy expenditure (REE), and oral food intake; Karnofsky Performance Status (KPS); cachexia degree; and survival. From 1990 to 2021, 1063 patients started HAN. Among these patients, 101 suspended artificial nutrition for oral refeeding. Among the 962 patients continuing HAN until death, 226 patients (23.5%) survived 6 weeks or less. HAN allowed to achieve a positive energy balance in 736 patients who survived more than 6 weeks, improving body weight and KPS when evaluated after 1 month of HAN. Advanced cancer and cachexia degree at the entry of the study negatively affected the positive impact of HAN.
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Desnutrición , Neoplasias , Humanos , Caquexia/etiología , Caquexia/terapia , Calidad de Vida , Neoplasias/complicaciones , Neoplasias/terapia , Desnutrición/etiología , Metabolismo Energético , Estado NutricionalRESUMEN
CONTEXT: The COVID-19 pandemic strongly challenged healthcare workers, disrupting their work routine and impacting on their professional life. A previous investigation explored levels of burnout and psychological morbidity among palliative care professionals (PCPs) during COVID-19 first wave. OBJECTIVE: To update data about burnout and psychological morbidity among PCPs after a year of COVID-19 pandemic. METHODS: The same questionnaires on burnout (Maslach Burnout Inventory, MBI) and psychological morbidity (General Health Questionnaire 12 items, GHQ-12) were administered a year after. Differences in MBI and GHQ-12 scores obtained in the two studies (COVID2020 and COVID2021), as well as distributions of PCPs showing burnout symptoms and psychological morbidity were analyzed and compared. We also explored the association between the three dimensions of burnout and socio-demographic and professional characteristics. RESULTS: The sample consisted of 145 PCPs (59% physicians and 41% nurses). Response rate (70.4%) was quite similar to the previous study (73.2%). No differences were observed in the frequency of burnout between COVID2021 and COVID2020; the PCPs in COVID2021 reported marginally higher level of EE (P = .049) and this result is confirmed in physicians (P = .010) while no difference was observed in nurses (P = .326). In addition, the percentage of cases showing psychological morbidity significantly decreased. CONCLUSION: Our findings show stable levels of burnout and decreasing levels of psychological morbidity among PCPs one year after the onset of the COVID-19 pandemic. However, more research is needed to detail the significance of emotional exhaustion dimension, a variable influenced by the survey.
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Agotamiento Profesional , COVID-19 , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , Agotamiento Psicológico , Humanos , Cuidados Paliativos/psicología , Pandemias , Encuestas y CuestionariosRESUMEN
BACKGROUND: The Surprise Question ('Would I be surprised if this patient died within 12 months?') identifies patients in the last year of life. It is unclear if 'surprised' means the same for each clinician, and whether their responses are internally consistent. AIM: To determine the consistency with which the Surprise Question is used. DESIGN: A cross-sectional online study of participants located in Belgium, Germany, Italy, The Netherlands, Switzerland and UK. Participants completed 20 hypothetical patient summaries ('vignettes'). Primary outcome measure: continuous estimate of probability of death within 12 months (0% [certain survival]-100% [certain death]). A threshold (probability estimate above which Surprise Question responses were consistently 'no') and an inconsistency range (range of probability estimates where respondents vacillated between responses) were calculated. Univariable and multivariable linear regression explored differences in consistency. Trial registration: NCT03697213. SETTING/PARTICIPANTS: Registered General Practitioners (GPs). Of the 307 GPs who started the study, 250 completed 15 or more vignettes. RESULTS: Participants had a consistency threshold of 49.8% (SD 22.7) and inconsistency range of 17% (SD 22.4). Italy had a significantly higher threshold than other countries (p = 0.002). There was also a difference in threshold levels depending on age of clinician, for every yearly increase, participants had a higher threshold. There was no difference in inconsistency between countries (p = 0.53). CONCLUSIONS: There is variation between clinicians regarding the use of the Surprise Question. Over half of GPs were not internally consistent in their responses to the Surprise Question. Future research with standardised terms and real patients is warranted.
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Enfermería de Cuidados Paliativos al Final de la Vida , Cuidados Paliativos , Estudios Transversales , Humanos , Atención Primaria de Salud , PronósticoRESUMEN
BACKGROUND: Home palliative care services have played an essential role during the first wave of the SARS-CoV-2 outbreak by providing symptom control, drug procurement, and psychological support for frail patients and their families unable to leave their homes. AIM: To understand how home palliative care professionals were affected by the outbreak, describing changes and challenges in their daily work as well as their reactions to the Covid-19 pandemic in Italy. DESIGN: Qualitative study conducted using telephone semi-structured interviews, with thematic analysis. SETTING/PARTICIPANTS: Thirty home care professionals working for an Italian non-profit organization which provides home palliative care for cancer patients and their families. RESULTS: Three main themes were identified. The first theme showed both patient-related and practice-related challenges participants faced in their daily work, requiring the implementation of different communication methods and patient and family education on risk prevention. The second theme showed the perception of increased responsibility and being the only landmark for family played a decisive role in participants' positive attitude. The third theme highlighted the participants' perception of the critical role of a home care setting in this emergency situation. CONCLUSIONS: The first wave of the Covid-19 pandemic brought many challenges and stressors for home palliative care professionals. On the other side, they reported a satisfaction with their critical role in carrying out their work with patients at risk.
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COVID-19 , Servicios de Atención de Salud a Domicilio , Brotes de Enfermedades , Humanos , Italia , Cuidados Paliativos , Pandemias , Percepción , Investigación Cualitativa , SARS-CoV-2RESUMEN
BACKGROUND: Current understanding of genetic factors associated with pain severity, and improvement of pain with opioids in advanced cancer patients (AC) is inadequate for delivery of personalized pain therapy (PPT). Therefore, the aim of this study was to determine the genetic factors associated with pain severity, daily opioid dose, and pain response in AC patients receiving supportive care. METHODS: In this prospective study, AC patients were eligible if they had cancer pain ≥4/10 on Edmonton Symptom Assessment Scale (ESAS) - Pain Item and needed opioid rotation for pain control by specialist at the outpatient supportive care center. Association of genetic factors with pain phenotype was assessed using logistic regression models and SKATO (Gene-block) analysis. RESULTS: About 174/178 (98%) patient samples were analyzed. After adjustment for demographic and clinical variables, pain severity was negatively associated with intron variant alleles in OPRM1 rs9322446, P = 0.02; rs2270459, P = 0.038; rs62052210, P = 0.038. Opioid daily dose was positively associated NFKBIA rs2233419, P = 0.008; rs2233417, P = 0.007; rs3138054, P = 0.008; rs1050851, P = 0.015; ORPM1 rs9479759, P = 0.046; rs2003185, P = 0.047; rs636433, P = 0.044; COMT (rs9306234, P = 0.014; rs165728, P = 0.014; rs2020917, P = 0.036; rs165728, P = 0.034); ARRB2 (rs1045280, P = 0.045); and pain response to opioids was negatively associated OPRM1 rs1319339, P = 0.024; rs34427887, P = 0.048; and COMT rs4646316, P = 0.03; rs35478083, P = 0.028, respectively. SKATO analysis showed association between pain severity and CXCL8 (P = 0.0056), and STAT6 (P = 0.0297) genes respectively, and pain response with IL-6 (P = 0.00499). CONCLUSIONS: This study identified that SNPs of OPRM1, COMT, NFKBIA, CXCL8, IL-6, STAT6, and ARRB2 genes were associated with pain severity, opioid daily dose, and pain response in AC receiving supportive care. Additional studies are needed to validate our findings for PPT.
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Dolor en Cáncer , Neoplasias , Analgésicos Opioides/uso terapéutico , Dolor en Cáncer/tratamiento farmacológico , Dolor en Cáncer/genética , Humanos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Dolor/tratamiento farmacológico , Dolor/genética , Polimorfismo de Nucleótido Simple/genética , Estudios ProspectivosRESUMEN
Objective: Recognizing delirium phenomenology (DP) aids the early diagnosis of this syndrome and improves quality of life in patients with advanced cancer. The aim of this study was to identify the neurobehavioral and cognitive patterns of delirium-related symptoms in persons with advanced cancer. Methods: We conducted an observational comparative prospective study on delirium in patients with advanced cancer in different palliative care settings, assessing the presentation/evolution of DP with the Memorial delirium assessment scale (MDAS). Results: Two hundred twenty-seven patients were enrolled on hospital/hospice admission. Of these, 57 were admitted with delirium, 170 without delirium, and 31 developed delirium during hospitalization. Of the 88 patients admitted with delirium or who developed it during hospitalization, only 32 underwent two consecutive MDAS evaluations (at diagnosis and after one week). Delirium resolved in 22 patients (first average MDAS score 10.08 vs. second 3.6 [p < 0.001]). Disorientation, short-term memory, and memory span were altered in all patients with unresolved delirium. The same features were altered in 18 (80%), 17 (80%), and 16 (70%) of the patients with resolved delirium, respectively, and in 58 (35%), 114 (67%), and 38 (23%) of no-delirium patients, respectively. Conclusion: Cognitive-related symptoms appear to be the most prevalent and earliest signs of DP in patients with advanced cancer.
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Delirio , Neoplasias , Delirio/diagnóstico , Delirio/etiología , Humanos , Neoplasias/complicaciones , Cuidados Paliativos , Estudios Prospectivos , Calidad de VidaRESUMEN
Exactly one year ago, between February and March 2020, the COVID-19 infection went from an epidemic confined to China to a worldwide pandemic that was particularly lethal in Italy. This study examined the media accounts during that period by analysing the representation of death-related constructs in Corriere della Sera, the most widely read newspaper in Italy. A textual and thematic analysis of articles published between period A (epidemic: 23 January-22 February 2020) and period B (pandemic: 23 February-31 March 2020) was conducted using Nvivo-11. A total of 141 articles comprising 48,524 words were collected. The most utilised words and meanings linked to COVID-19 were computed. In the rank distribution, 'China' and 'virus' were the terms most frequently used in both periods. The terms 'death' and 'dead' were completely absent in period A and appeared in the 535th position in period B. The term 'dead' was used primarily to indicate the number of deceased. From a Terror Management Theory perspective, it is possible that the minimal reference to death-related issues was a reflection of death denial and a manifestation of efforts to deny death to manage terror. These findings highlight the ambiguities and ambivalence surrounding any issue pertaining to death; on the one side, undue alarmism may provoke exaggerated reactions, such as moral panic, while on the other denial-based messages that minimise references to mortality may reduce safe behaviour during a pandemic.
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CONTEXT: Providing palliative care (PC) at home for patients with advanced cancer has become essential during the COVID-19 emergency. Nevertheless, the home PC professionals (PCPs) faced a challenging situation because of increased number of discharged patients, reduced availability of health-care facilities, and physical/relational barriers between them and patients. OBJECTIVES: This study aimed to investigate the impact of COVID-19 pandemic on burnout and psychological morbidity among home PCPs in Italy. METHODS: One hundred and ninety-eight PC physicians and nurses working in home assistance in Italy were invited to participate. The results obtained by the investigation conducted during the COVID-19 emergency (COVID2020) were compared with data collected in 2016 in the same setting (BURNOUT2016). The questionnaires (socio-demographics, Maslach Burnout Inventory and General Health Questionnaire-12) were the same for both the surveys. The PCPs participating in COVID2020 survey (n = 145) were mostly the same (70%) who participated in the BURNOUT2016 study (n = 179). RESULTS: One hundred and forty-five PCPs participated in the study (response rate 73.2%). During the COVID-19 emergency, home PCPs presented a lower burnout frequency (P < .001) and higher level of personal accomplishment than in 2016 (P = .047). Conversely, the risk for psychological morbidity was significantly higher during the pandemic (P < .001). CONCLUSIONS: In the age of COVID-19, the awareness of being at the forefront of containing the pandemic along with the sense of responsibility toward their high-risk patients may arouse PCPs' psychological distress, but, on the other hand, this condition may improve their sense of professional satisfaction and personal accomplishment.
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Actitud del Personal de Salud , Agotamiento Profesional/epidemiología , COVID-19/epidemiología , Servicios de Atención de Salud a Domicilio/organización & administración , Neoplasias/terapia , Cuidados Paliativos/organización & administración , Adulto , COVID-19/prevención & control , COVID-19/transmisión , Miedo/psicología , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Distrés Psicológico , Encuestas y CuestionariosRESUMEN
Following publication of the original article [1], an error in reference 18 was reported.
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Background: Delirium in advanced cancer inpatient ranges between 13% and 85%. Reasons for this variability on the reported data could be related to the setting where they are admitted. Methods: This is an observational, comparative, prospective study on delirium diagnosis and delirium course of advanced cancer inpatients in two different palliative care settings. Hospice (C1) versus palliative care supportive team (C2). Differences between delirium precipitants, delirium treatment, and delirium survival were observed. Results: From 582 consecutive admissions, 494 from C1 and 88 from C2, finally 227 patients met inclusion criteria, were entered in the study. Total population delirium rate at admission, if we add both centers, was 57 patients (25%), 46 (26%) from C1 and 11 (22%) from C2; no statistically significant differences between delirium rate at admission between the two centers were found (χ2). When delirium course between delirious patients admitted in C1 and C2 was analyzed, a significantly higher rate of delirium reversibility was found in C2 [11/14 (78%)] versus [9/65 (14%)] in C1 (χ2p ≤ 0.001). Conclusion: The frequency of delirium at admission and during the hospitalization in advanced cancer patients does not seem to be related to the setting, what seems to be related is the delirium course.
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Delirio , Neoplasias , Delirio/epidemiología , Hospitalización , Humanos , Neoplasias/complicaciones , Cuidados Paliativos , Estudios ProspectivosRESUMEN
BACKGROUND: The Surprise Question (SQ) "would I be surprised if this patient were to die in the next 12 months?" has been suggested to help clinicians, and especially General Practitioners (GPs), identify people who might benefit from palliative care. The prognostic accuracy of this approach is unclear and little is known about how GPs use this tool in practice. Are GPs consistent, individually and as a group? Are there international differences in the use of the tool? Does including the alternative Surprise Question ("Would I be surprised if the patient were still alive after 12 months?") alter the response? What is the impact on the treatment plan in response to the SQ? This study aims to address these questions. METHODS: An online study will be completed by 600 (100 per country) registered GPs. They will be asked to review 20 hypothetical patient vignettes. For each vignette they will be asked to provide a response to the following four questions: (1) the SQ [Yes/No]; (2) the alternative SQ [Yes/No]; (3) the percentage probability of dying [0% no chance - 100% certain death]; and (4) the proposed treatment plan [multiple choice]. A "surprise threshold" for each participant will be calculated by comparing the responses to the SQ with the probability estimates of death. We will use linear regression to explore any differences in thresholds between countries and other clinician-related factors, such as years of experience. We will describe the actions taken by the clinicians and explore the differences between groups. We will also investigate the relationship between the alternative SQ and the other responses. Participants will receive a certificate of completion and the option to receive feedback on their performance. DISCUSSION: This study explores the extent to which the SQ is consistently used at an individual, group, and national level. The findings of this study will help to understand the clinical value of using the SQ in routine practice. TRIAL REGISTRATION: Clinicaltrials.gov NCT03697213 (05/10/2018). Prospectively registered.
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Actitud del Personal de Salud , Actitud Frente a la Muerte , Médicos Generales/psicología , Pronóstico , Bélgica , Médicos Generales/estadística & datos numéricos , Alemania , Humanos , Internet , Italia , Países Bajos , Cuidados Paliativos/métodos , Encuestas y Cuestionarios , Suiza , Reino UnidoRESUMEN
Imatinib represents the standard therapy for gastrointestinal stromal tumor (GIST) patients with metastatic/unresectable disease. Despite the excellent results achieved with its introduction, the majority of patients quite invariably experience disease progression. The aim of this study was to understand the contribution of germline DNA polymorphisms in discriminating between imatinib clinical response [evaluated as progression free survival (PFS)] and toxicity. In particular, a discovery cohort (34 GIST with a KIT exon 11 primary mutation, and no toxicity) was analyzed through DMET array that interrogates 1936 variants in 231 genes of the ADME process. We further confirmed the genotype of selected variants in an extended cohort of 49 patients (the original cohort and 15 new cases, all with exon 11 primary mutation), identifying 6 SNPs- ABCB4 rs1202283, ABCC2 rs2273697, ABCG1 rs1541290, CYP11B1 rs7003319, CYP7B1 rs6987861, and NQO1 rs10517-significantly associated with response to imatinib. Three SNPs, ABCB4 rs1202283, ABCC2 rs2273697, and NQO1 rs10517, which had a significant association after adjusted multivariate analysis, were included in a genetic prediction model. We confirmed that these SNPs could stratify the cohort of 49 patients according to the risk of developing progression under imatinib treatment. In conclusion, we identified a genetic signature of response to imatinib therapy in GIST patients able to stratify patients at low and high risk to progress, according to their genotype.
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Antineoplásicos/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/genética , Células Germinativas/fisiología , Mesilato de Imatinib/uso terapéutico , Polimorfismo de Nucleótido Simple/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Exones/genética , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Mutación/genéticaRESUMEN
BACKGROUND: Pheochromocytomas (PCCs) show the highest degree of heritability in human neoplasms. However, despite the wide number of alterations until now reported in PCCs, it is likely that other susceptibility genes remain still unknown, especially for those PCCs not clearly syndromic. METHODS: Whole exome sequencing of tumor DNA was performed on a set of twelve PCCs clinically defined as sporadic. RESULTS: About 50% of PCCs examined had somatic mutations on the known susceptibility VHL, NF1, and RET genes. In addition to these driver events, mutations on SYNE1, ABCC10, and RAD54B genes were also detected. Moreover, extremely rare germline variants were present in half of the sporadic PCC samples analyzed, in particular variants of MAX and SAMD9L were detected in the germline of cases wild-type for mutations in the known susceptibility genes. CONCLUSIONS: Additional somatic passenger mutations can be associated with known susceptibility VHL, NF1, and RET genes in PCCs, and a wide number of germline variants with still unknown clinical significance can be detected in these patients. Therefore, many efforts should be aimed to better define the pathogenetic role of all these germline variants for discovering novel potential therapeutic targets for this disease still orphan of effective treatments.
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BACKGROUND: In Europe in recent decades, university teaching of palliative medicine (PM) has evolved. In some countries it has been introduced as a compulsory subject in all medical schools, but in a majority of countries it remains an isolated subject at few universities. OBJECTIVE: To explore how PM has been introduced into the curricula and how it is currently being taught at different European universities. METHOD: Case study method using face-to-face semistructured interviews with experienced PM professors, comparing how they have developed PM undergraduate programs at their universities. RESULTS: An intentional sample of eight university professors from Spain, France, UK, Italy, Hungary, Sweden, Germany, and Poland was chosen. The introduction of PM in the universities depends on the existence of a favorable social and political context in relation to palliative care and the initiative of pioneers, trusted by students, to push this education forward. A PM curriculum frequently starts as an optional subject and becomes mandatory in a short period. In the reported universities, PM uses a wide variety of teaching methods, such as lectures, workshops, role-plays, and discussions. PM assessment included tests, discussions, reflections, portfolios, and research works. According to respondents' opinions, lack of recognition, funding, and accredited teachers, along with competition from other curricula, are the main barriers for palliative medicine teaching development at universities. CONCLUSION: Diverse paths and tools have been identified for PM teaching in Europe. The described cases may shed light on other medical schools to develop PM curricula.
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Educación de Pregrado en Medicina/métodos , Medicina Paliativa/educación , Curriculum , Europa (Continente) , Humanos , Entrevistas como Asunto , UniversidadesRESUMEN
Despite the genomic characterization of pancreatic cancer (PC), marked advances in the development of prognosis classification and novel therapeutic strategies have yet to come. The present study aimed to better understand the genomic alterations associated with the invasive phenotype of PC, in order to improve patient selection for treatment options. A total of 30 PC samples were analysed by either whole transcriptome (9 samples) or exome sequencing (21 samples) on an Illumina platform (75X2 or 100X2 bp), and the results were matched with normal DNA to identify somatic events. Single nucleotide variants and insertions and deletions were annotated using public databases, and the pathogenicity of the identified variants was defined according to prior knowledge and mutation-prediction tools. A total of 43 recurrently altered genes were identified, which were involved in numerous pathways, including chromatin remodelling and DNA damage repair. In addition, an analysis limited to a subgroup of early stage patients (50% of samples) demonstrated that poor prognosis was significantly associated with a higher number of known PC mutations (P=0.047). Samples from patients with a better overall survival (>25 months) harboured an average of 24 events, whereas samples from patients with an overall survival of <25 months presented an average of 40 mutations. These findings indicated that a complex genetic profile in the early stage of disease may be associated with increased aggressiveness, thus suggesting an urgent requirement for an innovative approach to classify this disease.