Diagnóstico: cáncer. ¿Queremos conocer la verdad?

ObjetivoConocer los deseos de información y otras actitudes ante el diagnóstico de cáncerDiseñoEstudio descriptivo transversaEmplazamientoCentros de Salud de Irún, Oñati y Asteasu en GipuzkoaParticipantesDe las citaciones a las 19 consultas durante marzo-mayo del 2002 se obtuvo una muestra aleatoria, prospectiva y sistemática, estratificada por cupos (n=725). Se administró una encuestamodificada de Fernández Díaz en la que se recogieron los datos personales y 8preguntas con respuestas cerradas: aspectos de comunicación (5 ítems) y actitudes relacionadas con la muerte (3 ítems)ResultadosEl 81,3% (IC del 95%, 78,4- 84,1) quiere conocer su diagnóstico. El 68,9% (IC del 95%, 65,5–72,2) elige al médico para comunicarlo. De éstos, el 36,6%, al especialista, y el 26,6%, al médicode familia. Si el afectado es un familiar, el 46,6% (IC del 95%, 42,9–50,2) se lo dirían siempre, sólo si él lo pregunta el 38,6% (ICdel 95%, 35–42,1) y nunca el 9,6% (IC del 95%, 7,4–11,7). El 49,3% (IC del 95%,45,6–52,9) preferiría morir en casa. Para el 44% (IC del 95%, 40,3–47,6) el dolor es el mayor temorConclusionesLa mayoría de la población quiere que se le informe de su diagnóstico, sin que el hábitat urbano o rural o la experiencia de haber tenido familiares con cáncer modifique la opinión. Si el afectadode cáncer es un familiar, son muy pocos los partidarios de no decírselo nunca. Eligen almédico para transmitir la información,prefieren morir en casa y el dolor es lamayor preocupaciónObjectivesTo find people's desire for information and their other attitudes when faced with a cancer diagnosisDesignTransversal, descriptive studySettingIrun, Oñati and Asteasu Health Centres, Gipuzkoa, SpainParticipantsFrom the appointments for 19 clinics in March-May 2002, a randomised, prospective and systematic sample, stratified by lists, was extracted (n=725). A modified Fernández Díaz questionnaire was administered. It had personal details and 8questions with closed replies on aspects of communication (5) and attitudes to death (3Results81.3% (95% CI, 78.4–84.1) wanted to know their diagnosis. 68.9% (95% CI, 65.5- 72.2) chose the doctor to tell them. Of these, 6.6% chose the specialist and 26.6%, thegeneral practitioner. If the person affected was a family member, 46.6% (95% CI, 42.9–50.2) would always tell the person; 38.6% (95% CI, 35–42.1), only if the person asked; and 9.6%, never (95% CI, 7.4–11.7). 49.3% (95% CI, 45.6–52.9) would prefer to die at home. The greatest fear for 44% (95% CI, 40.3–47.6) waspainConclusionsMost people want to be informed of their diagnosis. Neither an urban or rural environment nor having had family members with cancer affects their view. If the personaffected by cancer is a family member, very few people favour not telling him/her at all. Sufferers want the doctor to tell them the information, prefer to die at home and pain is what worries them mos

Evaluación cualitativa del programa comunitario Irunsasoi para la promoción de la actividad física: la perspectiva de los médicos

Objectives: The sedentarism is an important conditioner of morbidity and mortality. The communitarian programs of promotion of physical activity that include a pursuit protocol can help and complement to the medical advice in the consultation. The objectives that we marked ourselves with this study have been to know the opinion the doctors on the prescription of physical activity and the implantation of the Irunsasoi program, collaboration between the doctors of Primary Attention and the technicians of physical activity of the council of Irún City to help the sedentary people. Methodology Design: Technique of focal groups. The discussions were recorded and later transcribed, previous authorization, for their analysis. Location: Primary attention. Irún Centro health Center. Subjects: The study population was the 15 doctors of AP. Two groups of 5 doctors, homogenous were made in age and sex, the recruitment was made, the invitation at random to participate was verbal by the investigator without no refusal took place. Measures: The discussion lines were grouped in: attitude before the advice and participation in the program, difficulties of collaboration and proposals of improvement. Results: Positive evaluation of the program to have enabled personnel, sufficient time and guarantees of pursuit. The collaboration difficulties are based on the forgetfulness not to have it built-in to our mechanics of work and to wort in other activities by lack of time. Conclusions: He is positive to work jointly with the technicians of physical activity. Aspects to improve: the formation in prescription of physical activity, the implication of nurses, the circuit of communication and the support in computerized historyObjetivos: El sedentarismo es un importante condicionante de morbilidad y mortalidad. Los programas comunitarios de promoción de actividad física que incluyan un protocolo de seguimiento pueden ayudar y complementar al consejo médico en la consulta. Los objetivos que nos marcamos con este estudio han sido conocer la opinión de los médicos sobre la prescripción de actividad física y sobre la implantación del programa Irunsasoi, de colaboración entre los médicos de Atención Primaria y los técnicos de actividad física del Ayuntamiento de Irún para ayudar a las personas sedentarias. Metodología: Diseño: Técnica de grupos focales. Las discusiones fueron grabadas y posteriormente transcritas, previa autorización, para su análisis. Emplazamiento: Atención primaria. Centro de salud Irún Centro. Sujetos: La población de estudio fueron los 15 médicos de AP. Se realizaron dos grupos de 5 médicos, homogéneos en edad y sexo, el reclutamiento se realizó al azar, la invitación a participar fue verbal por el investigador sin que se produjera ninguna negativa. Medidas: Los ejes de discusión se agruparon en: actitud ante el consejo y participación en el programa, dificultades de colaboración y propuestas de mejora. Resultados: Valoración positiva del programa por disponer de personal capacitado, tiempo suficiente y garantías de seguimiento. Las dificultades de colaboración se basan en el olvido por no tenerlo incorporado a nuestra mecánica de trabajo y priorización de otras actividades por falta de tiempo. Conclusiones: Es positivo trabajar conjuntamente con los técnicos de actividad física. Aspectos a mejorar: la formación en prescripción de actividad física, la implicación de enfermería, el circuito de comunicación y el soporte en la historia informatizad

Evaluación de la calidad de comunicación entre niveles asistenciales mediante el documento interconsulta

ObjetivosEvaluar la calidad y mejora de cumplimentación de los documentos de interconsulta en el equipo de atención primaria (EAP).DiseñoCiclo completo de calidad.EmplazamientoAtención primaria (AP).Componentes de la evaluaciónDimensión estudiada: calidad científico-técnica. Sujetos: todos los documentos de interconsulta (DI-1) dirigidos por los médicos de AP del centro de salud de Irún Centro a atención especializada durante 15 días, 223 DI-1 para la evaluación en abril de 1998 y 287 para la reevaluación en octubre 1998. Tipo de evaluación: retrospectiva. Fuente de datos: documentos interconsulta e historias clínicas. Criterios: explícitos y normativos. Medidas correctoras: educativas (discusión de resultados en reunión del EAP).ResultadosEn la reevaluación se observó una mejoría estadísticamente significativa: datos de filiación (91,5-96,8%), legibilidad (86-92,7%), antecedentes y/o medicación habitual (35,9-50%) y sintomatología (77,8-87,2%). Por niveles de calidad se ha pasado en los buenos del 20,6 al 42,5% y en los malos del 40,8 al 33,4%. Obtuvimos respuesta en un 22,2% de nuestras derivaciones. La falta de respuesta se produce en un 34% por no haber informe del especialista, un 47,8% se atribuyen al paciente o al circuito y el 18% de los pacientes está pendiente de pruebas.ConclusionesLa información proporcionada en los DI-1 ha mejorado significativamente después del ciclo de calidad. Conocer nuestra práctica habitual de trabajo sirve como estimulo de mejora. Los criterios que peor cumplimos son: referencia a antecedentes personales y/o medicación habitual, exploración física y medidas terapéuticas empleadas. Gran perdida de información en la respuesta a nuestras derivaciones.ObjectivesTo evaluate the quality and improvement of compliance in the inter-consultation documents of the primary care team (PCT).DesignEntire care cycle.SettingPrimary care (PC).MeasurementsDimension studied: scientific-technical quality. Subjects: all the inter-consultation documents (ID-1) sent by PC doctors from Irun Health Centre to specialist clinics over a 15-day period. 223 ID-1 for evaluation in April 1998, and 287 for re-evaluation in October 1998. Type of evaluation: retrospective. Source of data: inter-consultation documents and clinical records. Criteria: explicit and standard. Corrective measures: educational (discussion of results in meeting of the PCT).ResultsA statistically significant improvement was found at the re-evaluation: basic personal details (91.5%-96.8%), legibility (86%-92.7%), medical history and/or customary medication (35.9%-50%) and symptoms (77.8%-87.2%). Good quality levels rose from 20.6% to 42.5%; and bad quality levels fell from 40.8% to 33.4%. 22.2% of our referrals received a reply. 34% of the lack of replies was because of no report from the specialist, 47.8% were attributed to the patient or circuit, and 18% of the patients were awaiting test results.ConclusionsThe information supplied in the ID-1 improved significantly after the quality cycle. Knowing our habitual working practice can serve to stimulate improvement. The criteria we complied with least were: reference to personal antecedents and/or habitual medication, physical examination, and therapeutic measures employed. There was a huge loss of information in the replies to our referrals

Modeling anti-IL-6 therapy using breast cancer patient-derived xenografts

The pleiotropic cytokine IL-6 accelerates the progression of breast cancer in a variety of preclinical models through the activation of the STAT3 (signal transducer and activator of transcription 3) signaling pathway. However, the proportion of breast cancers sensitive to anti-IL-6 therapies is not known. This study evaluates the efficacy of anti-IL-6 therapies using breast cancer patient derived xenografts (PDXs). During the generation of our collection of PDXs, we showed that the successful engraftment of tumor tissue in immunodeficient mice correlates with bad prognosis. Four PDXs out of six were resistant to anti-IL-6 therapies and the expression of IL-6, its receptor or the levels of phospho-STAT3 (the active form of the signal transducer) did not correlate with sensitivity. Using cell cultures established from the PDXs as well as samples from in vivo treatments, we showed that only tumors in which the activation of STAT3 depends on IL-6 respond to the blocking antibodies. Our results indicate that only a fraction of breast tumors are responsive to anti-IL-6 therapies. In order to identify responsive tumors, a functional assay to determine the dependence of STAT3 activation on IL-6 should be performed

Estimation of Admission D-dimer Cut-off Value to Predict Venous Thrombotic Events in Hospitalized COVID-19 Patients: Analysis of the SEMI-COVID-19 Registry

Background: Venous thrombotic events (VTE) are frequent in COVID-19, and elevated plasma D-dimer (pDd) and dyspnea are common in both entities. Objective: To determine the admission pDd cut-off value associated with in-hospital VTE in patients with COVID-19. Methods: Multicenter, retrospective study analyzing the at-admission pDd cut-off value to predict VTE and anticoagulation intensity along hospitalization due to COVID-19. Results: Among 9386 patients, 2.2% had VTE: 1.6% pulmonary embolism (PE), 0.4% deep vein thrombosis (DVT), and 0.2% both. Those with VTE had a higher prevalence of tachypnea (42.9% vs. 31.1%; p = 0.0005), basal O2 saturation <93% (45.4% vs. 33.1%; p = 0.0003), higher at admission pDd (median [IQR]: 1.4 [0.6–5.5] vs. 0.6 [0.4–1.2] µg/ml; p < 0.0001) and platelet count (median [IQR]: 208 [158–289] vs. 189 [148–245] platelets × 109/L; p = 0.0013). A pDd cut-off of 1.1 µg/ml showed specificity 72%, sensitivity 49%, positive predictive value (PPV) 4%, and negative predictive value (NPV) 99% for in-hospital VTE. A cut-off value of 4.7 µg/ml showed specificity of 95%, sensitivity of 27%, PPV of 9%, and NPV of 98%. Overall mortality was proportional to pDd value, with the lowest incidence for each pDd category depending on anticoagulation intensity: 26.3% for those with pDd >1.0 µg/ml treated with prophylactic dose (p < 0.0001), 28.8% for pDd for patients with pDd >2.0 µg/ml treated with intermediate dose (p = 0.0001), and 31.3% for those with pDd >3.0 µg/ml and full anticoagulation (p = 0.0183). Conclusions: In hospitalized patients with COVID-19, a pDd value greater than 3.0 µg/ml can be considered to screen VTE and to consider full-dose anticoagulation. © 2021, Society of General Internal Medicine

ICO-ICS Praxis para el tratamiento médico y con irradiación del adenocarcinoma del páncreas

Tractament mèdic; Tractament amb irradiació; Adenocarcinoma; Pàncrees; CàncerTratamiento médico; Tratamiento con irradiación; Adenocarcinoma; Páncreas; CáncerMedical treatment; Irradiation treatment; Adenocarcinoma; Pancreas; CancerEl càncer de pàncrees se situa com la tercera causa més freqüent de càncer en la forma d'adenocarcinoma ductal pancreàtic. És un dels càncers més agressius i amb un percentatge més baix de curació. Els objectius d'aquesta guia són: -Desenvolupar, difondre, implementar i avaluar resultats de la ICO-ICSPraxi de càncer de pàncrees. -Disminuir la variabilitat terapèutica entre els pacients tractats als diferents centres d'aquesta institució. -Implementar els resultats de la terapèutica en els pacients amb adenocarcinoma de pàncrees tractats d'acord amb les recomanacions d'aquesta guia

Week 48 resistance analyses of the once-daily, single-tablet regimen darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in adults living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) >= 400 copies/mL at failure/later time points. Post hoc analyses were deep sequencing in AMBER, and HIV-1 proviral DNA from baseline samples (VL = 3 thymidine analog-associated mutations (24% not fully susceptible to tenofovir) detected at screening. All achieved VL <50 copies/mL at week 48 or prior discontinuation. D/C/F/TAF has a high genetic barrier to resistance; no darunavir, primary PI, or tenofovir RAMs were observed through 48 weeks in AMBER and EMERALD. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. In EMERALD, baseline archived RAMs to darunavir, emtricitabine, and tenofovir in participants with prior VF did not preclude virologic response

Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location

RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer.

BACKGROUND: BRCA1 and BRCA2 (BRCA1/2)-deficient tumors display impaired homologous recombination repair (HRR) and enhanced sensitivity to DNA damaging agents or to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). Their efficacy in germline BRCA1/2 (gBRCA1/2)-mutated metastatic breast cancers has been recently confirmed in clinical trials. Numerous mechanisms of PARPi resistance have been described, whose clinical relevance in gBRCA-mutated breast cancer is unknown. This highlights the need to identify functional biomarkers to better predict PARPi sensitivity. PATIENTS AND METHODS: We investigated the in vivo mechanisms of PARPi resistance in gBRCA1 patient-derived tumor xenografts (PDXs) exhibiting differential response to PARPi. Analysis included exome sequencing and immunostaining of DNA damage response proteins to functionally evaluate HRR. Findings were validated in a retrospective sample set from gBRCA1/2-cancer patients treated with PARPi. RESULTS: RAD51 nuclear foci, a surrogate marker of HRR functionality, were the only common feature in PDX and patient samples with primary or acquired PARPi resistance. Consistently, low RAD51 was associated with objective response to PARPi. Evaluation of the RAD51 biomarker in untreated tumors was feasible due to endogenous DNA damage. In PARPi-resistant gBRCA1 PDXs, genetic analysis found no in-frame secondary mutations, but BRCA1 hypomorphic proteins in 60% of the models, TP53BP1-loss in 20% and RAD51-amplification in one sample, none mutually exclusive. Conversely, one of three PARPi-resistant gBRCA2 tumors displayed BRCA2 restoration by exome sequencing. In PDXs, PARPi resistance could be reverted upon combination of a PARPi with an ataxia-telangiectasia mutated (ATM) inhibitor. CONCLUSION: Detection of RAD51 foci in gBRCA tumors correlates with PARPi resistance regardless of the underlying mechanism restoring HRR function. This is a promising biomarker to be used in the clinic to better select patients for PARPi therapy. Our study also supports the clinical development of PARPi combinations such as those with ATM inhibitors

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population