Early Incorporation to Palliative Care (EPC) in Patients With Advanced Non-Small Cell Lung Cancer: The PACO Randomized Clinical Trial.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) experience a considerable disease burden, evident in symptomatic and psychological spheres. Advanced cancer represents a complex scenario for patients and the healthcare team. Early palliative care (EPC) has been proven as a clinically meaningful strategy in this context by several randomized trials but not in a resource-limited setting. This study aimed to evaluate the effect of EPC compared with standard oncological care (SOC) in patients with metastatic NSCLC in Mexico. MATERIALS AND METHODS: A prospective, randomized clinical trial was conducted at Instituto Nacional de Cancerologia in Mexico. All patients had histologically confirmed metastatic NSCLC without previous treatment. Patients were randomly assigned (1:1) to receive SOC or SOC + EPC. The EPC group was introduced to the palliative care team at baseline after randomization, which was integrated by psychologists, bachelor's in nutrition, specialized nurses, and physicians. Patients randomized to this arm had programmed visits to meet with the team at baseline and through the 2nd, 4th-, and 6th cycles thereafter. The primary endpoint was overall survival (OS); secondary outcomes included quality of life (QoL), anxiety and depression, and symptom intensity. They were assessed using the instruments EORTC QLQ-C30 questionnaire, Edmonton Symptom Assessment Scale (ESAS), and the Hospital Anxiety and Depression Scale (HADS) (clinicaltrials.gov [NCT01631565]). Questionnaires were completed at baseline, at 2nd, 4th, and 6th cycles of treatment. RESULTS: Between March 2012 and June 2015, 201 patients were assessed for eligibility and 146 were enrolled and allocated to receive EPC (73) or SOC (73). Median OS for patients in the EPC vs SOC arm was 18.1 months (95% CI, 7.9-28.4) and 10.5 months (95% CI, 4.7-16.2) (P = .029). Having a poor performance status (HR 1.7 [1.2-2.5]; P = .004) and allocation to the control group (HR 1.5 [1.03-2.3]; P = .034) were independently associated with a worse OS. Those patients with a global QoL > 70 at baseline had a better OS if they were In the EPC arm (38.7 months (95% CI, 9.9-67.6) vs SOC 21.4 months (95% CI, 12.4-30.3)). Mean QoL had a numerical improvement in patients allocated to EPC after 6 cycles of follow-up, nonetheless this difference was not statistically significant (55.1 ±â€…23.7 vs 56.9 ±â€…25.3; P = .753). There were no significant differences in anxiety and depression at all study points. CONCLUSIONS: EPC is associated with a significant improvement in OS, although, we observed that the greatest benefit of providing EPC was observed in those with a global QoL > 70 at baseline. This study did not identify significant changes in terms of QoL or symptom burden between the study groups after follow-up. Evidence robustly suggests that EPC should be considered part of the multidisciplinary treatment of metastatic NSCLC patients since diagnosis. According to our study, EPC can be implemented in low- or middle-income countries (LMIC).

Factors Associated With Distress Related to Perceived Dignity in Patients With Rheumatic Diseases.

BACKGROUND: The loss of perceived dignity is an existential source of human suffering, described in patients with cancer and chronic diseases and hospitalized patients but rarely explored among patients with rheumatic diseases (RMDs). We recently observed that distress related to perceived dignity (DPD) was present in 26.9% of Mexican patients with different RMDs. The study aimed to investigate the factors associated with DPD. METHODS: This cross-sectional study was performed between February and September 2022. Consecutive patients with RMDs completed patient-reported outcomes (to assess mental health, disease activity/severity, disability, fatigue, quality of life [QoL], satisfaction with medical care, and family function) and had a rheumatic evaluation to assess disease activity status and comorbidity. Sociodemographic variables and disease-related and treatment-related variables were retrieved with standardized formats. DPD was defined based on the Patient Dignity Inventory score. Multivariate regression analysis was used. RESULTS: Four hundred patients were included and were representative of outpatients with RMDs, while 7.5% each were inpatients and patients from the emergency care unit. There were 107 patients (26.8%) with DPD. Past mental health-related comorbidity (Odds Ratio [OR]: 4.680 [95% Confidence Interval [CI]: 1.906-11.491]), the number of immunosuppressive drugs/patient (OR: 1.683 [95% CI: 1.015-2.791]), the physical health dimension score of the World Health Organization Quality of Life-Brief questionnaire (WHOQOL-BREF) (OR: 0.937 [95% CI: 0.907-0.967]), and the emotional health dimension score of the WHOQOL-BREF (OR: 0.895 [95% CI: 0.863-0.928]) were associated with DPD. CONCLUSIONS: DPD was present in a substantial proportion of patients with RMDs and was associated with mental health-related comorbidity, disease activity/severity-related variables, and the patient QoL.

Utilization of medical interventions in hospitalized Mexican adults with cancer at the end of life in a referral hospital: The importance of early palliative care.

OBJECTIVES: To investigate the impact of early vs. late palliative care (PC) on the frequency of admissions to acute hospital settings and the utilization of end-of-life (EoL) interventions in cancer decedents. METHODS: In this single-center, cross-sectional study, we examined the frequency of intensive care unit (ICU) and emergency department (ED) admissions among adult cancer decedents between 2018 and 2022 in a referral hospital in México. Additionally, we assessed EoL medical interventions, categorizing patients into 3 groups: those who received early PC (EPC), late PC (LPC), and those who did not receive PC (NPC). RESULTS: We analyzed data from 1762 patients, averaging 56 ± 16.3 years old, with a predominant representation of women (56.8%). PC was administered to 45.2% of patients, but EPC was limited to only 12.3%. The median time from the initiation of PC to death was 5 days (interquartile range: 2.0-31.5). Hematological malignancies were the most prevalent, affecting 21.5% of patients. EPC recipients demonstrated notable reductions in ICU and ED admissions, as well as diminished utilization of chemotherapy, radiotherapy (RT), antibiotics, blood transfusions, and surgery when compared to both LPC and NPC groups. EPC also exhibited fewer medical interventions in the last 14 days of life, except for RT. SIGNIFICANCE OF RESULTS: The findings of this study indicate that a significant proportion of EoL cancer patients receive PC; however, few receive EPC, emphasizing the need to improve accessibility to these services. Moreover, the results underscore the importance of thoughtful deliberation regarding the application of EoL medical interventions in cancer patients.

Real-World Experience in Hispanic Patients With Breast Cancer and Brain Metastases Using Different Prognostic Tools.

PURPOSE: Only a small percentage of Hispanic patients have been included in studies that developed prognostic models for breast cancer and brain metastases. Therefore, there is a clear need for tools tailored to this demographic. This study assesses the efficacy of common prognostic tools in a Hispanic population. METHODS AND MATERIALS: We retrospectively analyzed a data set of Hispanic patients with breast cancer and newly diagnosed brain metastases from 2009 to 2023 at a single referral center. For each prognostic tool, Kaplan-Meier curves were built. The performances of the models were compared using the area under the curve (AUC), C-statistic, and Akaike information criteria (AIC). RESULTS: Of 492 patients, the median time from breast cancer to brain metastasis diagnosis was 22.7 months (IQR, 12.1-53.3). The median overall survival was 11.6 months (95% CI, 9.9-13.4). All models were validated as prognostic tools (P < .001). The model with the better performance was the breast graded prognostic assessment (GPA; AIC, 402; AUC, 0.65), followed by the modified GPA (AIC, 406; AUC, 0.64), the disease-specific GPA (AIC, 407; AUC, 0.62), recursive partitioning analysis (AIC, 421; AUC, 0.62), and GPA (AIC, 422; AUC, 0.60). CONCLUSIONS: The breast GPA demonstrated superior accuracy in prognosticating outcomes for Hispanic patients with breast cancer and brain metastases. This underscores the critical importance of incorporating racial and ethnic diversity in creating and validating medical prognostic tools.

Mirtazapine as Appetite Stimulant in Patients With Non-Small Cell Lung Cancer and Anorexia: A Randomized Clinical Trial.

Importance: Currently there is no standard therapy to improve cancer-related anorexia, hampering survival. Mirtazapine has been suggested as a feasible option in this context. Objectives: To assess the effect of mirtazapine on appetite and energy consumption in patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and Participants: This randomized, double-blind, placebo-controlled clinical trial including adults was performed in a tertiary cancer care center from August 2018 to May 2022 with a follow-up of 8 weeks. Overall, 134 patients were screened; 114 were assessed for eligibility and 28 were excluded. Interventions: Patients were randomized in a 1:1 ratio to receive mirtazapine, 15 mg, or placebo for 2 weeks followed by a dose escalation to 30 mg until week 8 or placebo. Both groups received nutritional assessment and dietary advice. Main outcomes and measures: Appetite was assessed by the Anorexia Cachexia Scale and energy intake. Dietary parameters were evaluated at baseline, 4 weeks, and 8 weeks, with a 24-hour dietary recall, and energy quantification based on the Mexican system of nutritional equivalents. Results: A total of 86 patients met the inclusion criteria and were randomized to the placebo (n = 43) or the mirtazapine group (n = 43). The mean (SD) age was 63.5 (11.2) years, 41 were women (57.7%) and had adenocarcinoma, Eastern Cooperative Oncology Group performance status scale score of 1, stage IV NSCLC, and were receiving first-line treatment. Baseline characteristics were similar between groups. There was no difference in appetite scores in patients who received mirtazapine or placebo after 4 and 8 weeks. After 4 weeks, mirtazapine significantly increased energy intake (379.3 kcal; 95% CI, 1382.6-576.1; P < .001) including proteins (22.5 g; 95% CI, 11.5-33.4; P = .001), carbohydrates (43.4 g; 95% CI, 13.1-73.8; P = .006), and fats (13.2 g; 95% CI, 6.0-20.4; P = .006). Fats intake was significantly higher in patients in the mirtazapine group (14.5 g vs 0.7 g; P = .02) after 8 weeks. The mirtazapine group significantly decreased the proportion of patients with sarcopenia (82.8% vs 57.1%, P = .03) at 8 weeks. Patients on mirtazapine tolerated the treatment well, but reported a higher perception of nightmares at 2 weeks based on a 10 cm VAS score (0 [25th-75th percentile, 0-1] vs 0 [25th-75th percentile, 0-0] in the control group; P = .009) but this finding was nonsignificant after 4 and 8 weeks. Conclusion and Relevance: In this randomized clinical trial of patients with advanced NSCLC, there was no difference in appetite scores in all patients who received mirtazapine or placebo, but the mirtazapine group had a significant increase in energy intake through the 4- and 8-week follow-up, mainly in fat intake, which is a better and crucial source of energy. The addition of mirtazapine in the treatment of patients with advanced NSCLC and anorexia may help these patients achieve their energy requirements and improve health-related quality of life, specifically emotional and cognitive functioning. Trial Registration: ClinicalTrials.gov Identifier: NCT04748523.

Perceived dignity is an unrecognized source of emotional distress in patients with rheumatic diseases: Results from the validation of the Mexican version of the Patient Dignity Inventory.

INTRODUCTION: Dignity has rarely been explored in patients with rheumatic diseases (RMDs), which contrasts with patients´ observations that dignity is a relevant area for research focus. The study's primary objective was to adapt and validate the Mexican version of the Patient Dignity Inventory (PDI-Mx) in patients with RMDs, and to estimate the proportion of patients with distress related to perceived dignity (DPD) assessed with the PDI-Mx. METHODS: This cross-sectional study was developed in 2 phases. Phase 1 consisted of pilot testing and questionnaire feasibility (n = 50 patients), PDI-Mx content validity (experts' agreement), construct validity (exploratory factor analysis), discriminant validity (Heterotrait-Monotrait correlations' rate [HTMT]), criterion validity (Spearman correlations) and PDI-Mx reliability with internal consistency (Cronbach's alpha) and test-retest (intra-class correlation coefficients [ICC]) in 220 additional outpatients (among whom 30 underwent test-retest). Phase 2 consisted of quantifying DPD (PDI-Mx cut-off ≥54.4) in 290 outpatients with RMDs. RESULTS: Overall, patients were representative of typical outpatients with RMDs from a National tertiary care level center. The 25-item PDI-Mx was found feasible, valid (experts' agreement ≥82%; a 4-factor structure accounted for 68.7% of the total variance; HTMT = 0.608; the strength of the correlations was moderate to high between the PDI-Mx, the Depression, Anxiety, and Stress scale dimensions scores, and the Health Assessment Questionnaire Disability Index score) and reliable (Cronbach's ɑ = 0.962, ICC = 0.939 [95%CI = 0.913-0.961]). DPD was present in 78 patients (26.9%). CONCLUSIONS: The PDI-Mx questionnaire showed good psychometric properties for assessing DPD in our population. Perceived dignity in patients with RMDs might be an unrecognized source of emotional distress.

Validation of the Mexican version of the Schedule of Attitudes Toward Hastened Death in patients undergoing palliative care in Mexico.

OBJECTIVES: The Schedule of Attitudes Toward Hastened Death (SAHD) has emerged as a valid and reliable tool to assess the wish to hasten death (WTHD) among patients diagnosed with advanced cancer; however, the instrument has never been culturally adapted and validated for patients in Mexico. This study sought to validate and abbreviate the SAHD tool for use among patients attending the Palliative Care Service of the Instituto Nacional de Cancerología in Mexico. METHODS: The SAHD was culturally adapted from a previously published validation in patients from Spain. Eligible patients included Spanish literate subjects treated as outpatients in the Palliative Care Service, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3. Patients were asked to answer the Mexican version of SAHD (SAHD-Mx) instrument and the Brief Edinburgh Depression Scale (BEDS). RESULTS: A total of 225 patients were included in the study. Median positive response in the SAHD-Mx was 2 (range 0-18). Positive correlation was identified between the SAHD-Mx scale and ECOG performance status (r = 0.188, p = 0.005), as well as BEDS (r = 0.567, p < 0.001). SAHD-Mx displayed strong internal consistency (alpha = 0.85) and adequate reliability from test-retest phone interviews (r = 0.567, p < 0.001). Using the confirmatory factor analysis model, a factor was identified and the number of items was reduced to 6, including items 4, 5, 9, 10, 13, and 18. SIGNIFICANCE OF RESULTS: The SAHD-Mx emerges as an adequate tool, with appropriate psychometric characteristics, for assessing WTHD among patients diagnosed with cancer undergoing palliative care in Mexico. .

Performance status and survival in cancer patients undergoing palliative care: retrospective study.

OBJECTIVE: Accurate forecasting the life expectancy of patients with cancer is adamantly needed for adequate decision-making in the Palliative Care Services (PCS) context. Nonetheless, physician forecast is often inaccurate, hindering end of life (EOL) decisions. In this study, we determined the prognostic value of two oncology performance status (PS) scales at first referral to PCS. METHODS: Retrospective analysis of 6310 patients consecutively admitted to PCS at the Instituto Nacional de Cancerología (2012-2018). Demographic and PS (as per Karnofsky (KPS) and Eastern Cooperative Oncology Group (ECOG) scales) information was retrieved and the overall survival of patients calculated according to PS. Concordance of each scale was assessed in the overall population and according to age. RESULTS: Overall survival was significantly associated with ECOG and KPS (p<0.05). A total of 2278 (36.1%) and 2296 (36.4%) patients were referred to PCS in their last month of life and most had a poor PS (ECOG 3-4, 59.1%; KPS <50, 54.4%). Both PS scales had high concordance in the overall population (K=0.6189 (KPS); K=0.6058 (ECOG)), but a higher value was observed among the subgroup of patients aged ≥65 (K=0.6339 (KPS); 0.6252 (ECOG)). Concordance was lowest among younger (≤39) patients. CONCLUSIONS: PS as assessed by the most widely known tools is strongly associated with overall survival of patients with cancer attending PCS. No large differences were observed among the scales, though results slightly favour the use of KPS. Early referral to PCS and accurate survival prediction can aid in relevant decision-making for patients approaching EOL.

Suicide in cancer patients undergoing palliative care: A report of two cases / Suicidio en pacientes con cáncer que recibe cuidados paliativos: reporte de dos casos

Abstract Introduction Suicide represents a major public health problem worldwide, and cancer patients might have vulnerability factors which increase suicide risk. There are multiple factors associated with this tragic outcome, including those stemming from the disease itself, mental illness and social, personal and spiritual factors. Although previous reports have identified a suicide rate which ranges from .03-7% among cancer patients undergoing palliative care, this has not been studied in Mexico. Objective This study sought to report the cases of suicide in patients with cancer undergoing palliative care at a large cancer reference center. Method A retrospective review of records was performed between 2018-2019 for patients treated at the Palliative Care Service of the Instituto Nacional de Cancerología in Mexico City. Records for patients who committed suicide were reviewed to describe factors associated with this outcome. Results Among all deaths identified during the record review, two were due to suicide (.09%). The patients were one female and one male, 60 and 42 years of age, diagnosed with breast cancer and gastroesophageal junction cancer, respectively, associated with tobacco and alcohol consumption, as well as several economic, social, and familial stress factors. One of the patients was identified as likely having major depressive disorder. Discussion and conclusion Deaths might be underreported in our population. A systematic evaluation is required in order to establish and detect suicidal behavior risk factors, and a follow-up plan for all these patients.

Resumen Introducción El suicidio representa un problema de salud pública en todo el mundo. Los pacientes con cáncer pueden tener factores de vulnerabilidad para presentar conducta suicida. Hay múltiples factores asociados con este fenómeno, incluidos los derivados de la enfermedad en sí, enfermedades mentales y factores sociales, personales y espirituales. Aunque hay reportes previos que describen una tasa de suicidio que va del .03 al 7% entre los pacientes con cáncer que reciben cuidados paliativos, esto no se ha estudiado en México. Objetivo Reportar los casos de suicidio en pacientes oncológicos que reciben cuidados paliativos en un centro oncológico de referencia. Método Se trata de un estudio retrospectivo, donde se revisaron los expedientes de los pacientes atendidos en el Servicio de Cuidados Paliativos del Instituto Nacional de Cancerología entre 2018-2019. Se revisaron los expedientes de los pacientes que se suicidaron para describir los factores de riesgo que presentaban. Resultados Entre todas las muertes identificadas durante la revisión de expedientes, dos se debieron a suicidio (.09%). Los pacientes fueron una mujer y un hombre, de 60 y 42 años, diagnosticados de cáncer de mama y de una unión gastroesofágica, respectivamente. Los factores asociados fueron el consumo de tabaco y alcohol, así como varios factores de estrés económico, social y familiar. Se identificó, asimismo, que uno de los pacientes padecía trastorno depresivo mayor. Discusión y conclusión Es posible que los suicidios estén infrarreportados en nuestra población. Se requiere una evaluación sistemática para establecer y detectar factores de riesgo de conducta suicida, y un plan de seguimiento para todos estos pacientes.

Role of whole brain radiotherapy in the management of infratentorial metastases from lung and breast cancer.

BACKGROUND: Brain metastases (BM) occur in almost one third of patients with systemic malignancies. Only a small number of studies focus on infratentorial location and whole brain radiotherapy (WBRT) as the main non-surgical management. The aim of the study was to compare the prognosis of patients treated with WBRT among patients with supra- or infratentorial lesions. MATERIALS AND METHODS: At a single center, 263 patients with either breast (BC) or lung (LC) cancer, that had developed BM and received treatment with WBRT, were analyzed during an 8-year period. RESULTS: A total of 152 patients with BC and 111 with LC were analyzed, median age at the time of BM was 50.7 years, systemic activity other than BM was detected in 91%. Newly diagnosed BM were supratentorial in 40%, infratentorial in 10% and 51% in both locations. Median overall survival was 13 months (95% CI: 11.1-14.8 months), without significant difference between supra- or infratentorial location. WBRT alone was administered in 79% of patients, whereas WBRT with chemtoreapy was provided for 21%. CONCLUSION: In patients with BM from LC or BC that were not candidates for surgical resection, palliative WBRT appears to be equally effective in those with supra- or infratentorial locations.

Genome-wide association study of psychiatric and substance use comorbidity in Mexican individuals.

The combination of substance use and psychiatric disorders is one of the most common comorbidities. The objective of this study was to perform a genome-wide association study of this comorbidity (Com), substance use alone (Subs), and psychiatric symptomatology alone (Psych) in the Mexican population. The study included 3914 individuals of Mexican descent. Genotyping was carried out using the PsychArray microarray and genome-wide correlations were calculated. Genome-wide associations were analyzed using multiple logistic models, polygenic risk scores (PRSs) were evaluated using multinomial models, and vertical pleiotropy was evaluated by generalized summary-data-based Mendelian randomization. Brain DNA methylation quantitative loci (brain meQTL) were also evaluated in the prefrontal cortex. Genome-wide correlation and vertical pleiotropy were found between all traits. No genome-wide association signals were found, but 64 single-nucleotide polymorphism (SNPs) reached nominal associations (p < 5.00e-05). The SNPs associated with each trait were independent, and the individuals with high PRSs had a higher prevalence of tobacco and alcohol use. In the multinomial models all of the PRSs (Subs-PRS, Com-PRS, and Psych-PRS) were associated with all of the traits. Brain meQTL of the Subs-associated SNPs had an effect on the genes enriched in insulin signaling pathway, and that of the Psych-associated SNPs had an effect on the Fc gamma receptor phagocytosis pathway.

Validation of the Patient Dignity Inventory in Mexican Cancer Patients.

Introduction: The Patient Dignity Inventory (PDI) is a reliable screening instrument for a variety of problems (physical, existential, and social) that affect the dignity of patients during their end of life. The PDI has been translated into several different languages and has been validated in different settings. As such, it is important to validate the instrument in patients with cancer in Mexico to assess dignity in this population. The aim of this study was to translate and validate the Spanish version of the PDI in Mexican patients with cancer. Methods: This is a cross-sectional study that included patients with cancer, both those enrolled and not enrolled in palliative care, at the Instituto Nacional de Cancerología in Mexico City from September 2018 to August 2019. A translation and back translation were performed to obtain the Mexican version of the PDI (PDI-Mx) instrument. Patients completed the PDI-Mx, the Hospital Anxiety and Depression Scale (HADS), and functional scales (Eastern Cooperative Oncology Group [ECOG] and Karnofsky). Psychometric properties were evaluated by determining internal consistency, exploratory and confirmatory factor analysis (CFA), and concurrent validity with the HADS. Results: We included 290 participants with cancer (145 in palliative care and 145 not enrolled in palliative care). The Cronbach's alpha of the PDI-Mx was 0.95. There was a significant correlation with the HADS (rs = 0.757, p < 0.0001). The factor analysis showed four factors that explain 64.7% of the model. The CFA presented adequate indicators, which show the adjustment of the structure that indicates a balanced and parsimonious model. Conclusions: The Mexican version of the PDI shows adequate psychometric properties in patients with cancer. We suggest the use of PDI-Mx in clinical care and research. The study was approved by the Institutional Review Board and Ethics Committee with numbers (016/063/CPI) and (CEI/1115/16) respectively.

Comparing the hospital anxiety and depression scale to the Brief Edinburgh Depression Scale for identifying cases of major depressive disorder in advanced cancer palliative patients.

OBJECTIVE: This study sought to compare the Hospital Anxiety and Depression Subscale (HADS-D) and Brief Edinburgh Depression Scale (BEDS) as case-finding tools of major depressive disorder in patients with advanced cancer in a palliative care service. METHODS: An observational study was performed which included patients with advanced cancer who attended the palliative care service at the National Institute of Cancer in Mexico. Patients were asked to fill out the Hospital Anxiety and Depression Scale (HADS) and BEDS and were then assessed by a psychiatrist to evaluate major depressive disorder (MDD) as per the DSM-5 criteria. The case-finding capability of each scale was determined using receiver operating characteristic curves, assessing the area under the curve (AUC) in comparison to the clinical diagnosis. RESULTS: Eighty-nine patients were included; median age was 57 years, and 71% were female. Among these, 19 patients were diagnosed with MDD during the interview. When comparing the self-reported scales, BEDS had a better performance compared with HADS-D (AUC 0.8541 vs. 0.7665). Limitations include a heterogeneous population and a limited sample size. SIGNIFICANCE OF RESULTS: The BEDS outperformed the HADS-D tool in discriminating patients with and without depression. A BEDS cutoff value of ≥5 is suggested as a case-finding score for depression in this population.

High polygenic burden is associated with blood DNA methylation changes in individuals with suicidal behavior.

Suicidal behavior is result of the interaction of several contributors, including genetic and environmental factors. The integration of approaches considering the polygenic component of suicidal behavior, such as polygenic risk scores (PRS) and DNA methylation is promising for improving our understanding of the complex interplay between genetic and environmental factors in this behavior. The aim of this study was the evaluation of DNA methylation differences between individuals with high and low genetic burden for suicidality. The present study was divided into two phases. In the first phase, genotyping with the Psycharray chip was performed in a discovery sample of 568 Mexican individuals, of which 149 had suicidal behavior (64 individuals with suicidal ideation, 50 with suicide attempt and 35 with completed suicide). Then, a PRS analysis based on summary statistics from the Psychiatric Genomic Consortium was performed in the discovery sample. In a second phase, we evaluated DNA methylation differences between individuals with high and low genetic burden for suicidality in a sub-sample of the discovery sample (target sample) of 94 subjects. We identified 153 differentially methylated sites between individuals with low and high-PRS. Among genes mapped to differentially methylated sites, we found genes involved in neurodevelopment (CHD7, RFX4, KCNA1, PLCB1, PITX1, NUMBL) and ATP binding (KIF7, NUBP2, KIF6, ATP8B1, ATP11A, CLCN7, MYLK, MAP2K5). Our results suggest that genetic variants might increase the predisposition to epigenetic variations in genes involved in neurodevelopment. This study highlights the possible implication of polygenic burden in the alteration of epigenetic changes in suicidal behavior.

Ketamine as augmentation for the treatment of major depression and suicidal risk in advanced cancer: Case report.

OBJECTIVE: Major depressive disorder (MDD) is common in patients diagnosed with advanced cancer (AC), with a prevalence of 16.5%. It is associated with great disability and worsened quality of life, increased number and intensity of physical symptoms, and lower survival. It is the main factor for the presence of suicidal ideation. Antidepressants show modest efficacy, and response requires several weeks. Ketamine has demonstrated a fast and robust antidepressant effect in subanesthetic doses. This effect may prove useful in patients with AC, MDD, and suicidal risk. METHOD: We report a case of a patient with advanced cervical cancer who presented with uncontrollable pain, MDD, and a suicide attempt. RESULT: A 39-year-old woman diagnosed with cervical cancer stage IVB presented to the Emergency Department after a suicide attempt by hanging. Upon evaluation by the palliative care psychiatrist, she reported intense pain, unresponsive to analgesics, and had a history of persistent suicidal ideation. Antidepressant treatment was started (sertraline 50mg/d) after a single dose of ketamine hydrochloride IV (0.5 mg/kg) was administered. Treatment response was measured using the Brief Edinburgh Depression Scale before and after the intervention. The depressive symptoms decreased by 17% on day 1, 39% on day 3, and 72% on day 17. SIGNIFICANCE OF RESULTS: This case report shows ketamine's efficacy as an augmentation agent alongside conventional antidepressant treatment in patients with AC. Moreover, it shows rapid response in suicidal ideation that has not been achieved with treatment as usual. More clinical trials are needed to support the potential benefit and safety of ketamine in patients with AC, MDD, and persisting suicidal ideation.

EXPLORATORY ANALYSIS OF POLYGENIC RISK SCORES FOR PSYCHIATRIC DISORDERS: APPLIED TO DUAL DIAGNOSIS.

BACKGROUND: Concurrence of substance use disorders (SUDs) is high in individuals with psychiatric illnesses; more importantly, individuals with both disorders (dual diagnosis) have more severe symptoms. Psychiatric disorders have been proposed to share a genetic susceptibility with SUDs. To explore this shared genetic susceptibility, we analyzed whether any of the polygenic risk scores (PRSs) for psychiatric disorders could be associated to dual diagnosis in patients with schizophrenia (SCZ) or bipolar disorder (BD). METHODS: We included 192 individuals of Mexican ancestry: 72 with SCZ, 53 with BD, and 67 unrelated controls without psychiatric disorders. We derived calculations of PRS for autism spectrum disorders, attention-deficit/hyperactive disorder, BD, major depression, and SCZ using summary genome-wide association statistics previously published. RESULTS: We found that dual diagnosis had a shared genetic susceptibility with major depressive disorder (MDD) and SCZ; furthermore, in individuals with BD, dual diagnosis could be predicted by PRS for MDD. CONCLUSIONS: Our results reinforce the notion that individuals with dual diagnosis have a higher genetic susceptibility to develop both disorders. However, analyses of larger sample sizes are required to further clarify how to predict risks through PRS within different populations.

Exploratory analysis of polygenic risk scores for psychiatric disorders: Applied to dual diagnosis

Background Concurrence of substance use disorders (SUDs) is high in individuals with psychiatric illnesses; more importantly, individuals with both disorders (dual diagnosis) have more severe symptoms. Psychiatric disorders have been proposed to share a genetic susceptibility with SUDs. To explore this shared genetic susceptibility, we analyzed whether any of the polygenic risk scores (PRSs) for psychiatric disorders could be associated to dual diagnosis in patients with schizophrenia (SCZ) or bipolar disorder (BD). Methods We included 192 individuals of Mexican ancestry: 72 with SCZ, 53 with BD, and 67 unrelated controls without psychiatric disorders. We derived calculations of PRS for autism spectrum disorders, attention-deficit/hyperactive disorder, BD, major depression, and SCZ using summary genome-wide association statistics previously published. Results We found that dual diagnosis had a shared genetic susceptibility with major depressive disorder (MDD) and SCZ; furthermore, in individuals with BD, dual diagnosis could be predicted by PRS for MDD. Conclusions Our results reinforce the notion that individuals with dual diagnosis have a higher genetic susceptibility to develop both disorders. However, analyses of larger sample sizes are required to further clarify how to predict risks through PRS within different populations.

The desire to hasten death in advanced cancer patients at a Mexican palliative care service / Deseos de adelantar la muerte en pacientes con cáncer avanzado en un servicio de cuidados paliativos en México

Abstract Introduction The desire to hasten death (DHD) might be present in patients with advanced cancer. Multiple distressing physical and psychosocial symptoms may be related to it. There is limited literature about the characteristics of these patients in México. Objective To describe the prevalence and factors associated with DHD in advanced cancer patients evaluated by a palliative care psychiatrist. Method We conducted a cross-sectional study, including all patients referred to psychiatric assessment at the Servicio de Cuidados Paliativos of the Instituto Nacional de Cancerología in Mexico City, from January to December 2016. DHD was defined as the presence of death ideas, suicidal ideation, and/or request for euthanasia or medically assisted suicide. Patients with delirium, dementia, psychosis, or uncontrolled physical symptoms were excluded. Results Sixty-four patients were included in the study. Most of them were women (59%); the mean age was 49 years old (SD = 16). Of them, 64% met criteria for a major depressive disorder, 64% for generalized anxiety disorder and/or panic disorder, and 11% for substance use disorders. 44% expressed DHD. In a multivariate regression analysis predicting DHD, only one factor emerged: clinical depression (OR = 13.5, p = .002, 95% CI [02.562, 71.726]). Discussion and conclusion The desire to hasten death is a frequent issue for the patients evaluated at the psychiatric palliative care clinic. Depression and other distressing psychiatric pathologies were associated with DHD. Interdisciplinary interventions are needed to treat DHD. More research is warranted in order to understand the factors associated with the expression of DHD.

Resumen Introducción El deseo de acelerar la muerte (DHD, por sus siglas en inglés) es frecuente en pacientes con cáncer avanzado. Múltiples estresores físicos y psicosociales se asocian a la presencia de este fenómeno. En México es limitada la información sobre estos pacientes. Objetivo Describir la prevalencia y los factores asociados con la presencia del DHD en pacientes con cáncer avanzado evaluados por el psiquiatra de cuidados paliativos. Método Realizamos un estudio transversal, incluimos a todos los pacientes referidos a evaluación psiquiátrica en el Servicio de Cuidados Paliativos del Instituto Nacional de Cancerología en la Ciudad de México, de enero a diciembre de 2016. El DHD se definió como la presencia de ideas de muerte, ideación suicida y/o solicitud de eutanasia o suicidio médicamente asistido. Se excluyeron los pacientes con delirium, demencia, psicosis o algún síntoma físico descontrolado. Resultados Sesenta y cuatro pacientes fueron incluidos en el estudio; 59% fueron mujeres; la edad media era de 49 años (DE = 16). El 64% cumplieron criterios para un trastorno depresivo mayor, el 64% para el trastorno de ansiedad generalizada y/o trastorno de pánico y el 11% para los trastornos por uso de sustancias; 44% expresaron DHD. En un análisis de regresión multivariable, el factor depresión mayor (OR = 13.5; p = .002, IC 95% [02.562, 71.726]) fue el único significativo. Discusión y conclusión El DHD es frecuente en los pacientes valorados por psiquiatría de cuidados paliativos. La depresión mayor se asoció con DHD. Se necesitan intervenciones interdisciplinarias para tratar el DHD. Se requiere más investigación para comprender los factores asociados con la expresión de DHD.