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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 r = 0.567, p 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. .

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.

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 e...

Background: Opioids are used for pain management in cancer patients. Morphine is considered the best option. For some patients with pain of difficult control management and adverse effects, an opioid rotation should be considered. Oral methadone is an opioid to which patients can be rotated safely and effectively and inexpensive for Mexico and Latin America. Our study describes the 9-year experience of opioid rotation to methadone, the population profile, efficacy of methadone in cancer patients of the palliative care service. Methods: Retrospective study of cancer patients rotated to oral methadone for pain control. Tables of frequencies, median and interquartile ranges were made, as well as overall survival. Results: 311 patients were rotated to methadone, predominantly males (58.5%), median age of 54 years with oncological diagnoses in cervix (10.3%), germinal tumors (8.4%), breast (8.0%), prostate (7.4%) and rectal (5.5%). These patients experienced visceral (17.6%) or other types of pain (68.6%), and a combination of different types of pain, the most prevalent pain was neuropathic (88.7%) and 50% received morphine, 21% buprenorphine or fentanyl 19% previously, with a median dose of 60 mg (30-120). The main reason for rotation was difficult pain control (54%), obtaining an efficacy of 70.0%. Conclusion: In this cohort at advanced disease stage, 54% suffered from difficult pain control, thus rotation became necessary, reducing pain and manageable adverse events, without major changes of the initial and final dose. Should be promoted more widely in the management of pain of difficult control by cancer in first position prescription.

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.

ObjectiveAccurate 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.MethodsRetrospective 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.ResultsOverall survival was significantly associated with ECOG and KPS (pConclusionsPS 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.

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 Mexico. 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 Cancerologia 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.

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 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.

ObjectiveThis 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.MethodsAn 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.ResultsEighty-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 resultsThe 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.

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.

Background: Brain metastases (BM) occur in almost one third of patients with solid tumors. The aim of the study was to compare the prognosis of patients treated with whole brain radiotherapy (WBRT) among patients with supra- or infratentorial lesions.Material and Methods: At a single center, 263 patients with either breast (BC) or lung (LC) cancer, that 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 and infratentorial in 133 patients (51%); exclusively supratentorial in 105 patients (40%); and exclusively infratentorial in 10%. Globally, 238 patients (90%) had supratentorial lesions, and 158 (60%) had infratentorial lesions. Median overall survival was 13 months (95%CI 11.1-14.8 months), without significant difference between supra- or infratentorial location.Conclusion: In patients with LC or BC that develop BM, palliative WBRT is equally effective in those with supra- or infratentorial locations.

Background Abnormally elevated levels of gamma-aminobutyric acid (GABA) in the medial prefrontal cortex (mPFC) have been reported in antipsychotic-free patients with schizophrenia. Whether such GABA elevations are also present in other brain regions and persist after antipsychotic treatment has not been previously investigated. Methods Twenty-eight antipsychotic-naive patients with first-episode psychosis (FEP) and 18 healthy control subjects completed the study. Following baseline proton magnetic resonance spectroscopy scans targeting the mPFC and a second region, the dorsal caudate, patients with FEP were treated with oral risperidone for 4 weeks at an initial dose of 1 mg/day that was titrated as necessary based on clinical judgment. After the 4-week treatment period, both groups were brought back to undergo outcome magnetic resonance spectroscopy scans, which were identical to the scans conducted at baseline. Results At baseline, higher GABA levels were found both in the mPFC and in the dorsal caudate of patients with FEP compared with healthy control subjects. Following 4 weeks of antipsychotic treatment, GABA levels in patients with FEP decreased relative to baseline in the mPFC, but decreased only at the trend level relative to baseline in the dorsal caudate. For either brain region, GABA levels at 4 weeks or posttreatment did not differ between patients with FEP and healthy control subjects. Conclusions The results of the present study documented elevations of GABA levels both in the mPFC and, for the first time, in the dorsal caudate of antipsychotic-naive patients with FEP, which normalized in both regions following 4 weeks of antipsychotic treatment.

Introduction. Delirium is a neurocognitive disorder, frequently present in advanced cancer patients. It morbidity, mortality, health expenditure, and causes distress to patients, family members, and health care professionals. Despite its impact, the disorder is still underdiagnosed, and consequently, mistreated. Objective. To describe the prevalence, clinical features, impact on the survival and percentage of missed diagnosis of delirium, in palliative care inpatients treated in a tertiary center. Method. We conducted a prospective study, including all the inpatients referred to the Palliative Care Service of the Instituto Nacional de Cancerología in Mexico, from August, 2014 to March, 2015. As a first step, we collected clinical and sociodemographic data, and determined the presence/absence of delirium, using the Confusion Assessment Method. Then, we reviewed the clinical file to determine if a previous delirium diagnosis was stablished by the primary referring team. Finally, thirty days after the initial assessment, we contacted the patients in order to know their survival status (alive/death). We performed a survival analysis to compare mortality among patients with delirium/non-delirium, and reported the percentage of delirium missed diagnosis. Results. We included 174 patients, 40.2% were diagnosed with delirium. Mean survival time in patients with delirium was 11 days, while in non-delirium patient’s mean survival time was 21 days; Log Rank 23.50, p < .001. We found a 73% of missed delirium diagnosis by the primary referring team. Discussion and conclusion. Prevalence of delirium in this population is similar to that observed in other palliative care populations. Also, delirium is the principal determinant of short-term mortality, and it is frequently underdiagnosed. Preventive strategies and early identification could help to reduce its burden.

ObjectiveMajor 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.MethodWe report a case of a patient with advanced cervical cancer who presented with uncontrollable pain, MDD, and a suicide attempt.ResultA 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 resultsThis 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.

Background Suicidal behavior may be divided into completed suicide, suicide attempts, and suicidal ideation. It has been suggested that these behaviors represent a continuum and result from 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. Methods 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) and 419 non-suicide controls. 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. Methylation profile from individuals in the target sample was assessed with the Illumina Infinium Human Methylation EPIC BeadChip. Results We identified 153 differentially methylated sites between individuals with low and high-PRS. From these, 91 sites were hypermethylated and 62 hypomethylated in the high PRS group relative to low PRS group. Among genes mapped to differentially methylated sites, we found genes involved in neurodevelopment and ATP binding. Discussion To our knowledge, this is the first study integrating polygenic risk scores and DNA methylation in suicidality. 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.

espanolAntecedentes: la concurrencia de trastornos por uso de sustancias (TUS) es alta en personas con enfermedades psiquiatricas; Mas importante aun, las personas con ambos trastornos (diagnostico dual) tienen sintomas mas graves. Se han propuesto trastornos psiquiatricos para compartir una susceptibilidad genetica con los TUS. Para explorar esta susceptibilidad genetica compartida, analizamos si alguna de las puntuaciones de riesgo poligenico (PRS) para los trastornos psiquiatricos podria estar asociada al diagnostico dual en pacientes con esquizofrenia (SCZ) o trastorno bipolar (BD). Metodos: Se incluyeron 192 individuos de ascendencia mexicana: 72 con SCZ, 53 con BD y 67 controles no relacionados sin trastornos psiquiatricos. Derivamos calculos de PRS para trastornos del espectro autista, trastorno de deficit de atencion / hiperactivo, BD, depresion mayor y SCZ utilizando estadisticas resumidas de asociacion de genoma previamente publicadas. Resultados: Encontramos que el diagnostico dual tenia una susceptibilidad genetica compartida con el trastorno depresivo mayor (MDD) y SCZ; Ademas, en individuos con BD, PRS podria predecir el diagnostico dual para MDD. Conclusiones: Nuestros resultados refuerzan la nocion de que las personas con diagnostico dual tienen una mayor susceptibilidad genetica a desarrollar ambos trastornos. Sin embargo, se requieren analisis de muestras de mayor tamano para aclarar aun mas como predecir riesgos a traves de PRS dentro de diferentes poblaciones. EnglishBackground: 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. (REV INVEST CLIN. 2019;71:321-9)

ObjectiveDepression in palliative advanced cancer patients is common, but often goes unrecognized. One of the first steps toward improving detection is the development of tools that are valid in the specific language and setting in which they are to be used. The Brief Edinburgh Depression Scale (BEDS) is a sensitive case-finding tool for depression in advanced cancer patients that was developed in the United Kingdom. There are no validated instruments to identify depression in Mexican palliative patients. Our aim was to validate the Spanish-language version of the BEDS in Mexican population with advanced cancer.MethodWe conducted a cross-sectional study with outpatients from the palliative care unit at the Instituto Nacional de Cancerología in Mexico City. The Mexican BEDS was validated against a semistructured psychiatric clinical interview according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, classification criteria for major depressive disorder. The interviewer was blind to the BEDS score at the time of the assessment.ResultSeventy subjects completed the scale and interview. Women represented 71.4% of the sample and median age of subjects was 56.5 years (range, 20–85 years). The prevalence of major depressive disorder according to the psychiatric interview was 20%. The most valid cutoff for defining a case of depression was a score ≥5 of 18 on the Mexican BEDS, which gave a sensitivity of 85.7% and specificity of 62.5%. The scale's Cronbach's alpha was 0.71.Significance of resultsMajor depressive disorder is frequent in Mexican palliative patients. The Spanish-language Mexican version of the BEDS is the first valid case-finding tool in advanced cancer patients in this setting.

Delirium is associated with circadian rhythm disruption. In this study we have explored whether circadian variation of melatonin is an indicator for delirium. Melatonin levels were determined from the first day of hospitalization and up to three days after the onset of delirium. Patients who did not developed delirium exhibited a daily melatonin rhythm, while in patients that developed delirium, the melatonin rhythm was lost and mean melatonin levels were found decreased as early as three days before the diagnosis of delirium, indicating that on arrival to the hospital circadian melatonin disruption can be used as an indicator of delirium.

Diffusion tensor imaging (DTI) studies in patients with schizophrenia have shown abnormalities in the microstructure of white matter tracts. Specifically, reduced fractional anisotropy (FA) has been described across multiple white matter tracts, in studies that have mainly included patients treated with antipsychotic medications.To compare FA in antipsychotic-naïve patients experiencing a first episode of psychosis (FEP) to FA in healthy controls to demonstrate that the variance of FA can be grouped, in a coincidental manner, in four predetermined factors in accordance with a theoretical partition of the white matter tracts, using a principal components analysis (PCA).Thirty-five antipsychotic-naïve FEP patients and 35 age- and gender-matched healthy controls underwent DTI at 3T. Analysis was performed using a tract-based spatial statistics (TBSS) method and exploratory PCA.DTI analysis showed extensive FA reduction in white matter tracts in FEP patients compared with the control group. The PCA grouped the white matter tracts into four factors explaining 66% of the total variance. Comparison of the FA values within each factor highlighted the differences between FEP patients and controls.Our study confirms extensive white matter tracts anomalies in patients with schizophrenia, more specifically, in drug-naïve FEP patients. The results also indicate that a small number of white matter tracts share common FA anomalies that relate to deficit symptoms in FEP patients. Our study adds to a growing body of literature emphasizing the need for treatments targeting white matter function and structure in FEP patients.

Background: Dysregulations of the major inhibitory and excitatory amino neurotransmitter systems of γ-aminobutyric acid and glutamate, respectively, have been described in patients with schizophrenia. However, it is unclear whether these abnormalities are present in subjects at ultra-high risk for psychosis. Methods: Twenty-three antipsychotic naive subjects at ultra-high risk and 24 healthy control subjects, matched for age, sex, handedness, cigarette smoking, and parental education, underwent proton magnetic resonance spectroscopy scans in the dorsal caudate bilaterally and the medial prefrontal cortex at 3T. Levels of γ-aminobutyric acid and of the combined resonance of glutamate and glutamine (Glx) were obtained using the standard J-editing technique and expressed as peak area ratios relative to the synchronously acquired unsuppressed voxel water signal. Results: Higher levels of γ-aminobutyric acid ( P