Prognostic evaluation in patients with advanced cancer in the last months of life:ESMO Clinical Practice Guideline

: • This ESMO Clinical Practice Guideline provides key recommendations for using prognostic estimates in advanced cancer. • The guideline covers recommendations for patients with cancer and an expected survival of months or less. • An algorithm for use of clinical predictions, prognostic factors and multivariable risk prediction models is presented. • The author group encompasses a multidisciplinary group of experts from different institutions in Europe, USA and Asia. • Recommendations are based on available scientific data and the authors’ collective expert opinion

Papel del ESAD en el tratamiento del dolor. Análisis pre-post intervención en un entorno rural

Objetivos: determinar la frecuencia de uso de analgésicos en pacientes terminales atendidos en domicilio, analizando factores que pudieran intervenir en la percepción del dolor, además de las actuaciones llevadas a cabo. Material y métodos: estudio analítico prospectivo e intervencional con pacientes derivados al Equipo de Soporte para Atención Domiciliaria (ESAD) de Barbastro. Variables estudiadas: edad, sexo, número de visitas, tiempo de seguimiento, presencia de dolor y de otros síntomas concomitantes, Escala Visual Analógica (EVA), diagnóstico, analgésicos previos y post intervención, dosis media previa de analgésicos y post-intervención. Estudio estadístico con SPSS 15.0. Resultados: n = 638, 53,9 % hombres (n = 344), edad media 79,64 ± 10,8 años, 56 % oncológicos (n = 357), seguimiento medio 56 ± 56,56 días, media de 2,68 ± 2,5 visitas por proceso. Dolor en primera visita 43,3 % (n = 276), EVA media 6,54 ± 1,87, dolor 47,1 % de hombres (n = 162) y 38,8 % de mujeres (n = 114) (p < 0,05), dolor en 56,6 % de oncológicos (n = 202) y en 26,3 % de crónico-dependientes (n = 74) (p < 0,001). No diferencias en EVA entre grupos. Entre analgésicos pautados en pacientes con dolor controlado y sin controlar previa intervención del ESAD encontramos diferencias estadísticamente significativas (p < 0,005) en morfina y tramadol, y con mayor significación (p < 0,001) en fentanilo transdérmico y transmucoso, paracetamol, metamizol y AINE, todos más frecuentes en dolor no controlado. Las dosis medias previas de todos estos fármacos no mostraron diferencias significativas entre los grupos, aunque eran mayores en el grupo de dolor no controlado. En estos, se pautan o modifican analgésicos, encontrándose diferencias estadísticamente significativas pre post-intervención (p < 0,001) en fentanilo transdérmico y transmucoso, tramadol, paracetamol, metamizol, AINE, pregabalina y con p < 0,05 en gabapentina. Se obtiene diferencias (p < 0,05) únicamente en las dosis posteriores a la actuación del ESAD en fentanilo transdérmico y codeína. Obtenemos correlaciones positivas entre dolor y anorexia, ansiedad, depresión e insomnio; en pacientes oncológicos entre dolor y ansiedad e insomnio, y en pacientes crónico-dependientes entre dolor, náuseas y depresión. No diferencias entre grupos en uso previo de benzodiacepinas, antidepresivos y otros tratamientos, aunque sí en clínica de depresión, ansiedad e insomnio. Tras intervención, diferencias significativas en uso de estos tratamientos y de sedación. Conclusiones: Tras la actuación del ESAD se puede apreciar el aumento progresivo de todas las medicaciones analgésicas; se debería realizar una valoración completa de la sintomatología del paciente y un tratamiento de síntomas multifactorial, además de interrogar al paciente de forma adecuada acerca de la presencia de síntomas asociados, dada la elevada correlación de los mismos

Characteristics of the case mix, organisation and delivery in cancer palliative care: a challenge for good-quality research

Objectives: Palliative care (PC) services and patients differ across countries. Data on PC delivery paired with medical and self-reported data are seldom reported. Aims were to describe (1) PC organisation and services in participating centres and (2) characteristics of patients in PC programmes. Methods: This was an international prospective multicentre study with a single web-based survey on PC organisation, services and academics and patients' self-reported symptoms collected at baseline and monthly thereafter, with concurrent registrations of medical data by healthcare providers. Participants were patients ≥18 enrolled in a PC programme. Results: 30 centres in 12 countries participated; 24 hospitals, 4 hospices, 1 nursing home, 1 home-care service. 22 centres (73%) had PC in-house teams and inpatient and outpatient services. 20 centres (67%) had integral chemotherapy/radiotherapy services, and most (28/30) had access to general medical or oncology inpatient units. Physicians or nurses were present 24 hours/7 days in 50% and 60% of centres, respectively. 50 centres (50%) had professorships, and 12 centres (40%) had full-time/part-time research staff. Data were available on 1698 patients: 50% females; median age 66 (range 21–97); median Karnofsky score 70 (10–100); 1409 patients (83%) had metastatic/disseminated disease; tiredness and pain in the past 24 hours were most prominent. During follow-up, 1060 patients (62%) died; 450 (44%) <3 months from inclusion and 701 (68%) within 6 months. ANOVA and χ2 tests showed that hospice/nursing home patients were significantly older, had poorer performance status and had shorter survival compared with hospital-patients (p<.0.001). Conclusions: There is a wide variation in PC services and patients across Europe. Detailed characterisation is the first step in improving PC services and research. Trial registration number: ClinicalTrials.gov Identifier: NCT01362816

A prospective study examining cachexia predictors in patients with incurable cancer

© 2019 The Author(s). Background: Early intervention against cachexia necessitates a predictive model. The aims of this study were to identify predictors of cachexia development and to create and evaluate accuracy of a predictive model based on these predictors. Methods: A secondary analysis of a prospective, observational, multicentre study was conducted. Patients, who attended a palliative care programme, had incurable cancer and did not have cachexia at baseline, were amenable to the analysis. Cachexia was defined as weight loss (WL) > 5% (6 months) or WL > 2% and body mass index< 20 kg/m2. Clinical and demographic markers were evaluated as possible predictors with Cox analysis. A classification and regression tree analysis was used to create a model based on optimal combinations and cut-offs of significant predictors for cachexia development, and accuracy was evaluated with a calibration plot, Harrell's c-statistic and receiver operating characteristic curve analysis. Results: Six-hundred-twenty-eight patients were included in the analysis. Median age was 65 years (IQR 17), 359(57%) were female and median Karnofsky performance status was 70(IQR 10). Median follow-up was 109 days (IQR 108), and 159 (25%) patients developed cachexia. Initial WL, cancer type, appetite and chronic obstructive pulmonary disease were significant predictors (p ≤ 0.04). A five-level model was created with each level carrying an increasing risk of cachexia development. For Risk-level 1-patients (WL < 3%, breast or hematologic cancer and no or little appetite loss), median time to cachexia development was not reached, while Risk-level 5-patients (WL 3-5%) had a median time to cachexia development of 51 days. Accuracy of cachexia predictions at 3 months was 76%. Conclusion: Important predictors of cachexia have been identified and used to construct a predictive model of cancer cachexia. Trial registration: ClinicalTrials.gov Identifier: NCT01362816

An international consensus definition of thewish to hasten death and Its related factors

Abstract Background The desire for hastened death or wish to hasten death (WTHD) that is experienced by some patients with advanced illness is a complex phenomenon for which no widely accepted definition exists. This lack of a common conceptualization hinders understanding and cooperation between clinicians and researchers. The aim of this study was to develop an internationally agreed definition of the WTHD. Methods Following an exhaustive literature review, a modified nominal group process and an international, modified Delphi process were carried out. The nominal group served to produce a preliminary definition that was then subjected to a Delphi process in which 24 experts from 19 institutions from Europe, Canada and the USA participated. Delphi responses and comments were analysed using a pre-established strategy. Findings All 24 experts completed the three rounds of the Delphi process, and all the proposed statements achieved at least 79% agreement. Key concepts in the final definition include the WTHD as a reaction to suffering, the fact that such a wish is not always expressed spontaneously, and the need to distinguish the WTHD from the acceptance of impending death or from a wish to die naturally, although preferably soon. The proposed definition also makes reference to possible factors related to the WTHD. Conclusions This international consensus definition of the WTHD should make it easier for clinicians and researchers to share their knowledge. This would foster an improved understanding of the phenomenon and help in developing strategies for early therapeutic intervention

Tabletas bucales oravescentes de fentanilo en el dolor episódico: revisión de datos clínicos

Objectives: to review the clinical literature on the oravescentes presentation of fentanyl buccal tablets with the aim of providing a critical view of published clinical data in breakthrough pain Methods: non systematic review of the literature published in Medline supplemented by manual search of related work and grey literature. Keywords: "Breakthrough pain" OR "Cancer pain" AND "Fentanyl buccal tablets" OR "Rapid onset opioids." Limits: Language: English or Spanish and studies in adults over 18 years. Inclusion criteria: clinical work with content related to the presentation of oral fentanyl "oravescente". Exclusion criteria referring to work pharmacokinetics or pharmacodynamics of the drug or its dosage, the work of general epidemiological nature and those that were not obtained in full text even though the query to several databases and national libraries. Results: from the 29 papers found, 12 studies were included following the inclusion and exclusion criteria. 4 were randomized double blind clinical trials, 1 was a multicenter open, 1 systematic review, 4 non-systematic reviews and 2 expert opinion papers. The four trials confirm that the analgesic effect is present 5 minutes after administration of the drug. There were significant differences with placebo since the 10 minutes till the 90 minutes. These differences kept stable for 2 hours. The Sum of Pain Intensity Differences (SPID) is favourable to the drug compared to placebo at 60 minutes after administration (p < 0.0001). It is noted that side effects mentioned were mild nausea (32%), vomiting (24%), asthenia (18%), constipation (15%) and headache (15%). No reference to neurocognitive changes at times of peak plasma concentration or behaviors of addiction or abuse were detected. The non systematic reviews offer the expert insight on the treatment of breakthrough pain with an independent position. They criticized the inclusion criteria of randomized trials for introducing significant bias in the sample selection and the lack of oral fentanyl compared with standard treatments available. Conclusions: fentanyl tablets "oravescentes" have proven more effective than placebo in the episodic pain caused by cancer or other diseases. The analgesic effects appear within 10 minutes of administration although the peak plasma concentration is reached at the time. Side effects are generally mild and not always motivated by the treatment. It is needed long-term studies to confirm the encouraging data currently available.Objetivos: revisar la literatura clínica sobre la presentación del fentanilo en tabletas bucales oravescentes con el objetivo de ofrecer una revisión crítica de los datos clínicos publicados, en dolor episódico. Material y método: revisión no sistemática de la literatura publicada en Medline complementada con una búsqueda manual de trabajos relacionados y literatura gris. Palabras clave: "Breakthrough pain" OR "Cancer pain" AND "Fentanyl bucal tablets" OR "Rapid onset opioids". Límites: idioma: inglés o español y estudios realizados en adultos mayores de 18 años. Criterios de inclusión: trabajos con contenido clínico relacionado con la presentación de fentanilo bucal "oravescente". Criterios de exclusión Trabajos que hacían referencia a farmacocinética o farmacodinámica del fármaco o su galénica, los trabajos de carácter epidemiológico general y aquellos que no se consiguieron en texto completo a pesar de la consulta a diversas bases de datos y bibliotecas nacionales. Resultados: de los 29 trabajos encontrados se incluyeron 12 trabajos, siguiendo los criterios de inclusión y exclusión. De ellos 4 fueron ensayos clínicos doble ciego randomizados, uno fue un estudio multicéntrico abierto, 1 revisión sistemática, 4 revisiones no sistemática y 2 comentarios de expertos. Los cuatro ensayos clínicos confirman que la actividad analgésica está presente a los 5 minutos de la administración del fármaco y presenta diferencias significativas con placebo a partir de los 10 minutos y se incrementa hasta los 90 minutos. Estas diferencias se mantienen a las 2 horas. La suma de las diferencias de intensidad del dolor (SPID) es favorable al fármaco, en comparación al placebo a los 60 minutos de la administración de manera significativa (p < 0,0001). Por lo que respecta a los efectos secundarios, se señala que los efectos secundarios referidos fueron leves: náuseas (32%), vómitos (24%), astenia (18%), estreñimiento (15%) y cefalea (15%). No se hace referencia a cambios neurocognitivos en los momentos de concentración plasmática pico o a conductas de adicción o abuso. Las revisiones no sistemáticas ofrecen la visión de expertos sobre el tratamiento del dolor episódico con carácter independiente y se critica los criterios de inclusión de los ensayos randomizados por introducir un sesgo importante así como la falta de comparación del fentanilo bucal con los tratamientos estándares disponibles. Conclusiones: las tabletas de fentanilo "oravescentes" han demostrado mayor eficacia que placebo en el dolor episódico producido por cáncer u otras enfermedades. Los efectos analgésicos aparecen antes de los 10 minutos de la administración aunque la concentración plasmática máxima se alcanza a la hora. Los efectos adversos son, en general, leves y no siempre motivados por el tratamiento. Son necesarios estudios a largo plazo que confirmen los esperanzadores datos disponibles actualmente