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BACKGROUND AND AIMS: The criteria for the use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) more restrictive than those approved were established in Catalonia by the Health System (CatSalut) to improve their efficiency, with different LDL-C values from which to start treatment according to risk factors. The aim of the study is to analyse adherence to these criteria and results. METHODS: A retrospective study of patients treated with PCSK9i at Vall d'Hebron University Hospital between 2016 and 2021 was performed using data from the Registry of Patients and Treatments and medical records. The degree of agreement with the CatSalut criteria, LDL-C-responders (decrease ≥30%), cardiovascular events and discontinuations were analysed. RESULTS: A total of 193 patients treated with PCSK9i were followed for a median of 27 months (IQR 23). The median age was 61 (IQR 15); 62.7% were men. Seventy percent of the patients had non-familial hypercholesterolemia. Treatment was for secondary prevention of cardiovascular disease in 82.4% of cases. The median LDL-C decreased from 139 (IQR 52) to 59 (IQR 45) mg/dL. The percentage of LDL-C reduction was 61.0% (IQR 30). In 72.5% of patients, all CatSalut criteria for starting treatment were met. The rate of responders was 85.4%. During follow-up, 19 patients (9.8%) had a cardiovascular event, and 15 (7.7%) discontinued treatment, in two cases due to toxicity. CONCLUSION: PCSK9i were used according to CatSalut criteria in three out of four cases. In this high-risk population, incidence of cardiovascular events was similar to that in clinical trials.
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Cardiovascular diseases continue to be the main cause of death in Venezuela, and hypertension is the principal risk factor. The May Measurement Month (MMM) campaign is a global initiative aimed to raising awareness of hypertension, which has been conducted in Venezuela since 2017. May Measurement Month 2021 included 46 732 participants with a mean age of 56.4 years (SD 14.4), 57.9% of whom were female. The percentage with hypertension was 60.3% (57.9% of females and 63.7% of males), 82.3% (84.8% of females and 79.2% of males) were aware, and 80.2% were taking antihypertensive medication. Of those on antihypertensive medication, 44.2% (41.2% of females and 48.2% of males) were not controlled [blood pressure (BP) ≥ 140/≥90â mmHg], with 61.3% receiving one drug, 30.0% two drugs, and 8.7% three or more drugs. 87.5% of those on treatment reported taking it regularly. Conditions associated with higher BP levels include fewer years of education, having a previous diagnosis of hypertension, and women who were hypertensive during a previous pregnancy. Physical activity and pregnancy were conditions associated with lower BP levels. A previous positive COVID-19 test was reported in 11.1%, and one or more COVID-19 vaccinations reported in 22.7% of participants. Of those on antihypertensive medication, 78.8% reported their treatment was not affected by COVID-19. Results are consistent with previous MMM campaigns and indicate that the screening campaign is feasible and useful to identify hypertension even in exceptional conditions such as the COVID-19 pandemic.
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Detección Precoz del Cáncer , Neumonías Intersticiales Idiopáticas , Neoplasias Pulmonares , Guías de Práctica Clínica como Asunto , Humanos , Detección Precoz del Cáncer/métodos , Neumonías Intersticiales Idiopáticas/diagnóstico por imagen , Neumonías Intersticiales Idiopáticas/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Tomografía Computarizada por Rayos XRESUMEN
Understanding the differences in ventilatory responses during exercise between patients with fibromyalgia and those with other chronic pain disorders is crucial for developing effective therapeutic interventions, especially in exercise to identify the better physical therapy prescription. Both populations face unique challenges that impact their ability to engage in physical activity; yet, the underlying physiological responses can vary significantly. In this context, the methodology of this study entailed conducting a comparative analysis of the ventilatory response during exercise in patients with fibromyalgia and those with other chronic pain disorders. The experimental protocol included a total of 31 participants (n = 13 diagnosed with fibromyalgia and n = 18 diagnosed with other chronic pain conditions). All participants completed a stress test, where the ventilatory parameters were measured in three stages (i.e., resting, incremental exercise, and recovery). The results revealed significant differences (p<0.05) in ventilatory responses between both groups. Patients with fibromyalgia exhibited reduced time for the aerobic threshold and a higher respiratory frequency in the anaerobic threshold compared to those with other chronic pain disorders. Furthermore, fibromyalgia patients demonstrated higher values in the ventilatory coefficient during the test and in the recovery stage. In conclusion, these differences underscore the need for tailored exercise programs that specifically address the unique ventilatory challenges faced by fibromyalgia patients to improve their physical function and overall quality of life.
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Although teixobactin is a promising antibiotic drug candidate against Gram-positive bacteria, it aggregates to form gels that may limit intravenous administration. We previously reported O-acyl isopeptide prodrugs of teixobactin analogues that address the problem of gel formation while retaining antibiotic activity. We termed these compounds isobactins. In the current Letter, we present nine new isobactin analogues that exhibit a reduced propensity to form gels in aqueous conditions while maintaining potent antibiotic activity against MRSA, VRE, and other Gram-positive bacteria. These isobactin analogues contain commercially available amino acid residues at position 10, replacing the synthetically challenging l-allo-enduracididine residue that is present in teixobactin. The isobactins undergo clean conversion to their corresponding teixobactin analogues at physiological pH and exhibit little to no hemolytic activity or cytotoxicity. Because isobactin analogues exhibit enhanced solubility, delayed gel formation, and are more synthetically accessible, it is anticipated that isobactin prodrug analogues may be superior drug candidates to teixobactin.
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A classical question in biology is how different processes are controlled in space and time, with research pointing to different mechanisms as timers. In this collection of Voices, we asked researchers to define their scientific questions related to time-keeping and the approaches they use to answer them.
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Fenómenos Cronobiológicos , Animales , Crecimiento y DesarrolloRESUMEN
Moral reasoning skills among medical students have regressed despite the implementation of ethics teachings in medical education curricula. This inability to retain moral reasoning capability is attributed to difficulty transitioning to the principled thinking stage of moral reasoning as well as worsening of ethical decision-making skills during clerkship education due to the "hidden curriculum." Prior studies have examined the efficacy of individual strategies for moral education, but there is insufficient analysis comparing multiple educational interventions and moral reasoning assessment tools. The role and impact of these instruments in medical curricula for the advancement of health equity is reviewed.
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Dynamic epigenomic reprogramming occurs during mammalian oocyte maturation and early development. However, the underlying transcription circuitry remains poorly characterized. By mapping cis-regulatory elements using H3K27ac, we identified putative enhancers in mouse oocytes and early embryos distinct from those in adult tissues, enabling global transitions of regulatory landscapes around fertilization and implantation. Gene deserts harbour prevalent putative enhancers in fully grown oocytes linked to oocyte-specific genes and repeat activation. Embryo-specific enhancers are primed before zygotic genome activation and are restricted by oocyte-inherited H3K27me3. Putative enhancers in oocytes often manifest H3K4me3, bidirectional transcription, Pol II binding and can drive transcription in STARR-seq and a reporter assay. Finally, motif analysis of these elements identified crucial regulators of oogenesis, TCF3 and TCF12, the deficiency of which impairs activation of key oocyte genes and folliculogenesis. These data reveal distinctive regulatory landscapes and their interacting transcription factors that underpin the development of mammalian oocytes and early embryos.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Elementos de Facilitación Genéticos , Regulación del Desarrollo de la Expresión Génica , Oocitos , Oogénesis , Animales , Oocitos/metabolismo , Femenino , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Oogénesis/genética , Ratones , Histonas/metabolismo , Histonas/genética , Embrión de Mamíferos/metabolismo , Ratones Endogámicos C57BL , Desarrollo Embrionario/genética , Folículo Ovárico/metabolismo , Ratones NoqueadosRESUMEN
During development, H3K9me3 heterochromatin is dynamically rearranged, silencing repeat elements and protein coding genes to restrict cell identity. Enhancer of Rudimentary Homolog (ERH) is an evolutionarily conserved protein originally characterized in fission yeast and recently shown to be required for H3K9me3 maintenance in human fibroblasts, but its function during development remains unknown. Here, we show that ERH is required for proper segregation of the inner cell mass and trophectoderm cell lineages during mouse development by repressing totipotent and alternative lineage programs. During human embryonic stem cell (hESC) differentiation into germ layer lineages, ERH is crucial for silencing naïve and pluripotency genes, transposable elements, and alternative lineage genes. Strikingly, ERH depletion in somatic cells reverts the H3K9me3 landscape to an hESC state and enables naïve and pluripotency gene and transposable element activation during iPSC reprogramming. Our findings reveal a role for ERH in initiation and maintenance of developmentally established gene repression.
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Contemporary research on the genomics of Attention Deficit Hyperactivity Disorder (ADHD) often underrepresents admixed populations of diverse genomic ancestries, such as Latin Americans. This study explores the relationship between admixture and genetic associations for ADHD in Colombian and Mexican cohorts. Some 546 participants in two groups, ADHD and Control, were genotyped with Infinium PsychArray®. Global ancestry levels were estimated using overall admixture proportions and principal component analysis, while local ancestry was determined using a method to estimate ancestral components along the genome. Genome-wide association analysis (GWAS) was conducted to identify significant associations. Differences between Colombia and Mexico were evaluated using appropriate statistical tests. 354 Single-nucleotide polymorphisms (SNPs) and Single-nucleotide variants (SNVs) related to some genes and intergenic regions exhibited suggestive significance (p-value < 5*10e-5) in the GWAS. None of the variants revealed genome-wide significance (p-value < 5*10e-8). The study identified a significant relationship between risk SNPs and the European component of admixture, notably observed in the LOC105379109 gene. Despite differences in risk association loci, such as FOXP2, our findings suggest a possible homogeneity in genetic variation's impact on ADHD between Colombian and Mexican populations. Current reference datasets for ADHD predominantly consist of samples with high European ancestry, underscoring the need for further research to enhance the representation of reference populations and improve the identification of ADHD risk traits in Latin Americans.
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Trastorno por Déficit de Atención con Hiperactividad , Predisposición Genética a la Enfermedad , Adolescente , Niño , Femenino , Humanos , Masculino , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Estudios de Cohortes , Colombia/epidemiología , Estudio de Asociación del Genoma Completo , Genotipo , México/epidemiología , Polimorfismo de Nucleótido SimpleRESUMEN
Sex inequities in liver transplantation (LT) have been documented in several, mostly US-based, studies. Our aim was to describe sex-related differences in access to LT in a system with short waiting times. All adult patients registered in the RETH-Spanish Liver Transplant Registry (2000-2022) for LT were included. Baseline demographics, presence of hepatocellular carcinoma, cause and severity of liver disease, time on the waiting list (WL), access to transplantation, and reasons for removal from the WL were assessed. 14,385 patients were analysed (77% men, 56.2 ± 8.7 years). Model for end-stage liver disease (MELD) score was reported for 5,475 patients (mean value: 16.6 ± 5.7). Women were less likely to receive a transplant than men (OR 0.78, 95% CI 0.63, 0.97) with a trend to a higher risk of exclusion for deterioration (HR 1.17, 95% CI 0.99, 1.38), despite similar disease severity. Women waited longer on the WL (198.6 ± 338.9 vs. 173.3 ± 285.5 days, p < 0.001). Recently, women's risk of dropout has reduced, concomitantly with shorter WL times. Even in countries with short waiting times, women are disadvantaged in LT. Policies directed at optimizing the whole LT network should be encouraged to guarantee a fair and equal access of all patients to this life saving resource.
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Accesibilidad a los Servicios de Salud , Trasplante de Hígado , Sistema de Registros , Listas de Espera , Humanos , Femenino , Trasplante de Hígado/estadística & datos numéricos , Persona de Mediana Edad , Masculino , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Anciano , España , Enfermedad Hepática en Estado Terminal/cirugía , Disparidades en Atención de Salud/estadística & datos numéricos , Factores Sexuales , Adulto , Estados Unidos , Índice de Severidad de la Enfermedad , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugíaRESUMEN
Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial pneumonia with distinct clinicopathologic features. It has been associated with exposure to hematopoietic stem cell transplantation (HSCT) and classical alkylating agents. Here, we highlight PPFE as a late complication of childhood cancer therapy by describing the cases of four survivors of childhood cancer with a diagnosis of treatment-related PPFE. All patients received high-dose alkylating agents. PPFE should be considered in the differential diagnosis of restrictive lung disease in patients with history of exposure to alkylating agents or HSCT. Development of PPFE-specific, noninvasive diagnostic tools and disease-modifying therapies will clinically benefit these patients.
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Enfermedades Pulmonares Intersticiales , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Antineoplásicos Alquilantes/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedades Pulmonares Intersticiales/patología , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/inducido químicamente , Enfermedades Pulmonares Intersticiales/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Neoplasias/patología , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/patologíaRESUMEN
The centromere is a fundamental higher-order structure in chromosomes ensuring their faithful segregation upon cell division. Centromeric transcripts have been described in several species and suggested to participate in centromere function. However, low sequence conservation of centromeric repeats appears inconsistent with a role in recruiting highly conserved centromeric proteins. Here, we hypothesized that centromeric transcripts may function through a secondary structure rather than sequence conservation. Using mouse embryonic stem cells (ESCs), we show that an imbalance in the levels of forward or reverse minor satellite (MinSat) transcripts leads to severe chromosome segregation defects. We further show that MinSat RNA adopts a stem-loop secondary structure, which is conserved in human α-satellite transcripts. We identify an RNA binding region in CENPC and demonstrate that MinSat transcripts function through the structured region of the RNA. Importantly, mutants that disrupt MinSat secondary structure do not cause segregation defects. We propose that the conserved role of centromeric transcripts relies on their secondary RNA structure.
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Segregación Cromosómica , Satélite de ARN , Animales , Humanos , Ratones , División Celular , Células Madre Embrionarias de Ratones , Satélite de ARN/química , Satélite de ARN/metabolismo , Centrómero/metabolismoRESUMEN
Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17-44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors.
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Cuidados Críticos , Obtención de Tejidos y Órganos , Humanos , Estudios Prospectivos , Masculino , Femenino , Obtención de Tejidos y Órganos/métodos , Persona de Mediana Edad , Anciano , España , Adulto , Lesiones Encefálicas , Muerte Encefálica , Unidades de Cuidados IntensivosRESUMEN
Impostor phenomenon (IP) is described as a pattern typified by doubting one's accomplishments and a persistent fear of being exposed as a fraud. These feelings of self-doubt are pervasive along the medical education continuum, beginning with medical students where IP has been associated with emotional stress, physical exhaustion, depression, and anxiety. We, therefore, conducted an interactive workshop with first-year medical students to educate them about the manifesting patterns and risk factors of IP and strategies to mitigate these feelings. The 60-min workshop began with participants voluntarily completing the Young Imposter Scale (YIS) followed by an interactive presentation that reviewed the literature related to IP and its prevalence in medicine. Participants were then assigned to small groups where they discussed three cases of IP in academia and the medical profession. Medical school faculty acted as facilitators and utilized pre-designed prompt questions to stimulate discussion. Students re-convened for a large group report out, where each group shared main discussion points. The session ended with facilitators discussing IP mitigation strategies that can be implemented at the individual, peer, and institutional levels. Participants were also invited to complete a post-workshop evaluation. Fifty first-year medical students participated in the session. A total of 49 (96 %) completed the YIS and post-workshop evaluation. Nineteen (40 %) participants obtained scores on the YIS to indicate a positive finding of IP. The percentage of female medical students meeting the threshold for IP was significantly higher (84 %, n = 41 vs 16 %, n = 7) than male medical students. The workshop was effective at identifying IP and associated risk factors and providing mitigation strategies, with 95.8 % of participants agreeing or strongly agreeing. In qualitative feedback, participants reported that the workshop was "very interactive", "provided strategies to manage impostor syndrome" and "helped me become more vulnerable with my peers." This workshop provided a novel interactive and effective method to increase medical students' awareness about IP which can be employed as a strategy to enhance student's wellness.
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Remnants of transposable elements (TEs) are widely expressed throughout mammalian embryo development. Originally infesting our genomes as selfish elements and acting as a source of genome instability, several of these elements have been co-opted as part of a complex system of genome regulation. Many TEs have lost transposition ability and their transcriptional potential has been tampered as a result of interactions with the host throughout evolutionary time. It has been proposed that TEs have been ultimately repurposed to function as gene regulatory hubs scattered throughout our genomes. In the early embryo in particular, TEs find a perfect environment of naïve chromatin to escape transcriptional repression by the host. As a consequence, it is thought that hosts found ways to co-opt TE sequences to regulate large-scale changes in chromatin and transcription state of their genomes. In this review, we discuss several examples of TEs expressed during embryo development, their potential for co-option in genome regulation and the evolutionary pressures on TEs and on our genomes.
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Elementos Transponibles de ADN , Regulación de la Expresión Génica , Animales , Elementos Transponibles de ADN/genética , Evolución Biológica , Cromatina/genética , Embrión de Mamíferos , Evolución Molecular , Mamíferos/genéticaRESUMEN
The COVID-19 pandemic has created unprecedented challenges for health care systems globally. This study aimed to explore the presence of mental illness in a Spanish cohort of COVID-19-infected population and to evaluate the association between the presence of specific mental health conditions and the risk of death and hospitalization. This is a retrospective cohort study including all individuals with confirmed infection by SARS-CoV-2 from the PRECOVID (Prediction in COVID-19) Study (Aragon, Spain). Mental health illness was defined as the presence of schizophrenia and other psychotic disorders, anxiety, cognitive disorders, depression and mood disorders, substance abuse, and personality and eating disorders. Multivariable logistic regression models were used to examine the likelihood of 30-day all-cause mortality and COVID-19 related hospitalization based on baseline demographic and clinical variables, including the presence of specific mental conditions, by gender. We included 144,957 individuals with confirmed COVID-19 from the PRECOVID Study (Aragon, Spain). The most frequent diagnosis in this cohort was anxiety. However, some differences were observed by sex: substance abuse, personality disorders and schizophrenia were more frequently diagnosed in men, while eating disorders, depression and mood, anxiety and cognitive disorders were more common among women. The presence of mental illness, specifically schizophrenia spectrum and cognitive disorders in men, and depression and mood disorders, substance abuse, anxiety and cognitive and personality disorders in women, increased the risk of mortality or hospitalization after COVID-19, in addition to other well-known risk factors such as age, morbidity and treatment burden. Identifying vulnerable patient profiles at risk of serious outcomes after COVID-19 based on their mental health status will be crucial to improve their access to the healthcare system and the establishment of public health prevention measures for future outbreaks.
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COVID-19 , Trastornos Relacionados con Sustancias , Masculino , Humanos , Femenino , COVID-19/epidemiología , Salud Mental , Estudios Retrospectivos , SARS-CoV-2 , España/epidemiología , Pandemias , Hospitalización , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
BACKGROUND: Imaging with late gadolinium enhancement (LGE) magnetic resonance (MR) and 18F-fluorodeoxyglucose (18F-FDG) PET allows complementary assessment of myocardial injury and disease activity and has shown promise for improved characterization of active cardiac sarcoidosis (CS) based on the combined positive imaging outcome, MR(+)PET(+). OBJECTIVES: This study aims to evaluate qualitative and quantitative assessments of hybrid MR/PET imaging in CS and to evaluate its association with cardiac-related outcomes. METHODS: A total of 148 patients with suspected CS underwent hybrid MR/PET imaging. Patients were classified based on the presence/absence of LGE (MR+/MR-), presence/absence of 18F-FDG (PET+/PET-), and pattern of 18F-FDG uptake (focal/diffuse) into the following categories: MR(+)PET(+)FOCAL, MR(+)PET(+)DIFFUSE, MR(+)PET(-), MR(-)PET(+)FOCAL, MR(-)PET(+)DIFFUSE, MR(-)PET(-). Further analysis classified MR positivity based on %LGE exceeding 5.7% as MR(+/-)5.7%. Quantitative values of standard uptake value, target-to-background ratio, target-to-normal-myocardium ratio (TNMRmax), and T2 were measured. The primary clinical endpoint was met by the occurrence of cardiac arrest, ventricular tachycardia, or secondary prevention implantable cardioverter-defibrillator (ICD) before the end of the study. The secondary endpoint was met by any of the primary endpoint criteria plus heart failure or heart block. MR/PET imaging results were compared between those meeting or not meeting the clinical endpoints. RESULTS: Patients designated MR(+)5.7%PET(+)FOCAL had increased odds of meeting the primary clinical endpoint compared to those with all other imaging classifications (unadjusted OR: 9.2 [95% CI: 3.0-28.7]; P = 0.0001), which was higher than the odds based on MR or PET alone. TNMRmax achieved an area under the receiver-operating characteristic curve of 0.90 for separating MR(+)PET(+)FOCAL from non-MR(+)PET(+)FOCAL, and 0.77 for separating those reaching the clinical endpoint from those not reaching the clinical endpoint. CONCLUSIONS: Hybrid MR/PET image-based classification of CS was statistically associated with clinical outcomes in CS. TNMRmax had modest sensitivity and specificity for quantifying the imaging-based classification MR(+)PET(+)FOCAL and was associated with outcomes. Use of combined MR and PET image-based classification may have use in prognostication and treatment management in CS.
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Cardiomiopatías , Miocarditis , Sarcoidosis , Humanos , Fluorodesoxiglucosa F18 , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/terapia , Cardiomiopatías/complicaciones , Medios de Contraste , Radiofármacos , Valor Predictivo de las Pruebas , Gadolinio , Tomografía de Emisión de Positrones/métodos , Imagen por Resonancia Magnética/métodos , Miocarditis/complicaciones , Espectroscopía de Resonancia Magnética , Sarcoidosis/diagnóstico por imagen , Sarcoidosis/terapia , Sarcoidosis/complicacionesRESUMEN
OBJECTIVES: To study the impact of comorbidities, multimorbidity, and multimorbidity clusters on adherence to recommended follow-up guidelines among long-term breast cancer survivors. STUDY DESIGN: Retrospective cohort study based on 2078 women diagnosed with breast cancer from 2000 to 2006 and followed up from 2012 to 2016. MAIN OUTCOME MEASURES: Adherence to breast cancer follow-up recommendations (annual medical visit and imaging) was determined. Comorbidities were classified as acute/chronic. Multimorbidity was defined as the presence of two or more chronic comorbidities aside from breast cancer. Five multimorbidity clusters were considered. Multivariate logistic regression models were fitted to determine the relationship between adherence to recommendations and the presence of comorbidities and multimorbidity, considering both sociodemographic and clinical characteristics. RESULTS: Overall adherence to recommendations was 79.5 %. Adherence was lower among long-term breast cancer survivors with no comorbidities (75.8 %). Among multimorbidity clusters, adherence was highest in the anxiety and fractures cluster (84.3 %) and was lowest in the musculoskeletal and cardiovascular cluster (76.4 %). In adjusted multivariate models, multimorbidity was associated with higher levels of adherence (OR = 1.52 95 %CI 1.16-1.99), and adherence was highest in the metabolic and degenerative cluster (OR = 2.2 95 %CI 1.4-3.5). CONCLUSION: Adherence to follow-up recommendations was higher among long-term breast cancer survivors with multimorbidity than among those without. Adherence also differed by multimorbidity cluster. These results suggest suboptimal adherence to the current follow-up recommendations in certain groups, suggesting the need to adapt clinical practice guidelines to reflect patients' comorbidities and different characteristics.
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Neoplasias de la Mama , Supervivientes de Cáncer , Humanos , Femenino , Multimorbilidad , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Estudios de Seguimiento , Estudios Retrospectivos , ComorbilidadRESUMEN
BACKGROUND: In 2015, the Spanish National Transplant Organization developed a prioritization system (Program for Access to Transplantation for Highly Sensitized Patients [PATHI]) to increase transplant options for patients with calculated panel-reactive antibodies (cPRAs) ≥98%, based on virtual crossmatch. We describe the experience with the implementation of PATHI and assess its efficacy. METHODS: PATHI registry was used to collect characteristics of donors and patients between June 15, 2015, and March 1, 2018. One-year graft and patient survival and acute rejection were also measured. A Cox model was used to identify factors related to patient death and graft loss and logistical regression for those associated with rejection. RESULTS: One thousand eighty-nine patients were included, and 272 (25%) were transplanted. Transplant rate by cPRA was 54.9%, 40.5%, and 12.8% in patients with cPRA98%, cPRA99%, and cPRA100%, respectively. One-year patient survival was 92.5%. Recipient age ≥60, time under dialysis >7 y, and delayed graft function were mortality risk factors. One-year graft survival was 88.7%. The factor related to graft loss was delayed graft function. The rejection rate was 22%. Factors related to rejection were sex, older recipients, and posttransplant donor-specific antibodies. CONCLUSIONS: A prioritization approach increases transplant options for highly sensitized patients with appropriate short-term postransplant outcomes. Along with other programs, PATHI may inspire other countries to adopt strategies to meet transplant needs of these patients.