Practical Application of a Battery of Brief Tools to Evaluate Geriatric Medical Inpatients for the Three Ds.

OBJECTIVE: The investigators aimed to identify the clinical characteristics of patients with or without delirium and preexisting depression, dementia, both, or neither by using validated tools easily administered in clinical practice. METHODS: In this cross-sectional prospective observational study conducted in Medellín, Colombia, 200 geriatric inpatients were evaluated with the Delirium Diagnostic Tool-Provisional (DDT-Pro), Informant Questionnaire on Cognitive Decline in the Elderly, Hachinski Ischemic Scale, Cornell Scale for Depression in Dementia, and Charlson Comorbidity Index-short form. Delirium motor subtype, mortality, and length of hospital stay were assessed. RESULTS: The study included 134 patients without delirium (67%), 14 with delirium only (7%), 16 with delirium and dementia (8%), 13 with delirium and depression (7%), and 23 with delirium, dementia, and depression (the three Ds) (12%). Prevalence rates of dementia (59%) and depression (55%) among 66 patients with delirium were higher than prevalence rates among patients without delirium (13% and 28%, respectively), suggesting that both conditions are risk factors. Main medical diagnoses, mortality, and dementia type did not differ among groups. Motor subtypes were similar among delirium groups. Patients in the delirium groups, except those in the delirium and depression group, were older than patients without delirium. Medical burden was highest among the patients with delirium and dementia and those with all three conditions. Delirium and dementia were more severe when comorbid with each other. Depression was most severe among patients with delirium and depression. Patients with all three conditions had a longer length of hospital stay than those without delirium. CONCLUSIONS: Using brief tools to detect dementia and depression in conjunction with the DDT-Pro to assess delirium diagnosis and severity is feasible and enables a more in-depth evaluation of elderly hospitalized patients. Because previous longitudinal research suggests that these comorbid conditions influence prognosis following a delirium episode, better identification of the three Ds offers proactive interventional opportunities. Depression is an underrecognized risk factor for delirium.

Validation of the Delirium Diagnostic Tool-Provisional (DDT-Pro) With Medical Inpatients and Comparison With the Confusion Assessment Method Algorithm.

OBJECTIVE: Delirium remains underdetected as a result of its broad constellation of symptoms and the inadequate neuropsychiatric expertise of most medical-surgical clinicians. Brief, accurate tools are needed to enhance detection. METHODS: The authors extended validation of the Delirium Diagnostic Tool-Provisional (DDT-Pro), originally validated in a study of inpatients with traumatic brain injury for diagnosis of delirium by nonexpert clinicians, for 200 general medical inpatients in Colombia. The three structured, quantitatively rated items in DDT-Pro represent the three core delirium domains. RESULTS: High interrater reliability between physician and nurse (0.873) administrators, internal consistency (>0.81), and content validity were found. Compared with independent reference standard diagnosis with DSM-5 or the Delirium Rating Scale-Revised-98, the area under the receiver operating characteristic (ROC) curve (global diagnostic accuracy) range was 93.8%-96.3%. ROC analysis revealed the same cutoff score (≤6) as that for the original study, with somewhat lower sensitivities of 88.0%-90.0% and specificities of 85.3%-81.2% (independent expert physician or nurse ratings). Even when rated by a trained expert physician, the original version of the Confusion Assessment Method algorithm (CAM-A) performed moderately, with lower sensitivities (61.8%-70.0%) than the DDT-Pro (88.0%-100%) and somewhat higher specificities (84.8%-95.3% versus 67.4%-86.7%), with values depending on dementia status, reference standard, and rater type. Accuracies for the DDT-Pro and CAM-A were comparable (DDT-Pro: 83.0%-87.5% versus CAM-A: 87.5%-88.5%), although lower in the dementia subgroup, especially for CAM-A. However, these tools were significantly discordant, especially in negative cases, which suggests that they do not detect diagnosis of patients in the same way. CONCLUSIONS: The DDT-Pro had high validity and reliability in provisional delirium diagnosis by physicians and nonexpert clinicians, although further validation is warranted before widespread use can be recommended.

Further insights of selenium-containing analogues of WC-9 against Trypanosoma cruzi.

As a continuation of our project aimed at searching for new chemotherapeutic agents against American trypanosomiasis (Chagas disease), new selenocyanate derivatives were designed, synthesized and biologically evaluated against the clinically more relevant dividing form of Trypanosoma cruzi, the etiologic agent of this illness. In addition, in order to establish the role of each part of the selenocyanate moiety, different derivatives, in which the selenium atom or the cyano group were absent, were conceived, synthesized and biologically evaluated. In addition, in order to study the optimal position of the terminal phenoxy group, new regioisomers of WC-9 were synthesized and evaluated against T. cruzi. Finally, the resolution of a racemic mixture of a very potent conformationally rigid analogue of WC-9 was accomplished and further tested as growth inhibitors of T. cruzi proliferation. The results provide further insight into the role of the selenocyanate group in its antiparasitic activity.

Neurocognitive subtypes of schizophrenia.

OBJECTIVE: To empirically identify schizophrenia neurocognitive subtypes and establish their association with clinical characteristics. METHODS: Sustained attention, executive function, facial emotion recognition, verbal learning, and working memory tests were applied to 253 subjects with schizophrenia. We identified neurocognitive subtypes by a latent class analysis of the tests results. After, we made a search for the association of these subtypes with clinic characteristics. RESULTS: We identified four neurocognitive subtypes: 1) “Global cognitive deficit”, 2) “Memory and executive function deficit”, 3) “Memory and facial emotion recognition deficit,” and 4) “Without cognitive deficit.” In comparison with the subtype “without cognitive deficit,” we found that the “memory and executive function deficit subtype” and the “global cognitive deficit subtype” had a higher frequency of male, unemployed, severe impairment, and adherence to treatment participants. However, in the “global cognitive deficit subtype” the differences were higher and there was also a lower frequency of past major depressive episodes (OR 0.39; 95%CI: 0.16 to 0.97). The “memory and facial recognition deficit subtype” had a higher probability of severe impairment (OR 5.52; 95%CI: 1.89 to 16.14) and unemployed (OR 2.43; 95%CI: 1.06 to 5.55) participants, but also a lower probability of past depressive episodes (OR 0.21; 95%CI: 0.07 to 0.66). CONCLUSION: Our results suggest the existence of four neurocognitive subtypes in schizophrenia with a spectrum of dysfunction and severity. We found higher dysfunction in those with worse cognitive dysfunction, and higher affective psychopathology and less treatment adherence in those with less cognitive dysfunction.

Validation of the delirium diagnostic tool-provisional (DDT-Pro) in geriatric medical inpatients with diagnostic permutations of the 3Ds with and without delirium.

OBJECTIVE: Validations of brief delirium tools have not included analysis of psychiatric disorders comorbidities or control groups. We validated the Delirium Diagnostic Tool-Provisional (DDT-Pro) in 422 geriatric inpatients with high incidence of depression and/or dementia. METHODS: Cross-sectional study using two delirium reference standards, DSM-5-TR and Delirium Rating Scale-Revised-98 (DRS-R98). We assessed concurrent and construct DDT-Pro validity too. RESULTS: There were 117 (27.7%) delirium cases using DDT-Pro, 104 (24.6%) per DSM-5-TR and 93 (22.0%) per DRS-R98; 133 patients (31.5%) had depression and 105 (24.9%) dementia, some comorbid with delirium. DDT-Pro accuracy (AUC under ROC curve) ranges were 88.3-95.9% vs DSM-5-TR and 92.7-95.0% vs DRS-R98 for whole sample and four diagnostic groups, without statistical differences. DDT-Pro ≤6 had the most balanced sensitivity-specificity for delirium diagnosis against both DSM-5-TR and DRS-R98 with similar specificity but higher sensitivity for DRS-R98 than DSM-5-TR delirium, with the highest values in patients with depression and dementia (≥92% sensitivity, ≥81% specificity). Positive and negative likelihood ratios support diagnostic strength. Concurrent validity was high reflected by significant correlations (p < 0.001) of DDT-Pro total and item scores with DRS-R98 and Delirium Frontal Index scores, highest in groups with comorbid depression and/or dementia. The DDT-Pro represented a single construct for delirium demonstrated by one factor with high item loadings and high internal consistency reliability of its items. CONCLUSIONS: The DDT-Pro demonstrated strong performance metrics in general hospital elderly inpatients with preexisting depression and/or dementia, which is unique among brief delirium tools. Its optimized cutoff score was the same as in other populations.

Verbal working memory in individuals with schizophrenia and their first degree relatives: relationship with negative and disorganized symptoms.

OBJECTIVE: To determine whether there are differences in verbal working memory amongst subjects with schizophrenia, their first degree relatives and controls, and to evaluate the influence of symptoms on these differences, as an initial step to assess whether this cognitive function is an endophenotype. METHODS: We examined 197 cases with schizophrenia, 197 first degree relatives and 200 controls through psychiatric interviews and the Letters and Numbers Sequencing test (LNS). Performance was compared among the three groups adjusting for age, sex and education level. Adjustment for "negative symptoms" and "disorganization" was performed afterwards. RESULTS: Subjects with schizophrenia showed lower performance in the LNS than their first degree relatives and the healthy controls; the effect sizes were 0.75 and 1.18 respectively. There was a small difference between relatives and controls (effect size =0.38). These differences were significant after adjustment for negative and disorganized symptoms, but the effect sizes became smaller: 0.26 for relatives vs. subjects with schizophrenia, 0.56 for controls vs. subjects with schizophrenia and 0.33 for relatives vs. controls. Among individuals with schizophrenia, performance in the LNS was not associated with disorder duration, disease onset age, antipsychotics, history of depressive episodes or substance use disorders. CONCLUSION: Results suggest verbal working memory may be considered as an endophenotype in schizophrenia.

Variables associated with concordance or discordance for delirium diagnosis between referring and consulting physicians at a Tertiary Hospital in Colombia: Prospective observational study.

Delirium is an acute state of impaired consciousness and a medical urgency. Its broad range of alterations in mental status make diagnosis challenging. Awareness and accurate provisional diagnosis by nonpsychiatric clinicians are important for prompt management. Because delirium symptoms overlap and mimic other neuropsychiatric conditions, a referral to a consultant psychiatrist is often needed. The aim of this study was to determine the discriminating variables that are associated with concordance or discordance for a DSM-5 delirium diagnosis made by the consultation/liaison (C/L) psychiatrist as compared to the referral diagnosis/reasons given by the referring physicians for inpatients from a Tertiary Hospital in a Latin-American country. Prospective study of a cohort of 399 consecutive patients admitted to any ward of a university hospital in Medellin-Colombia and referred by a specialist physician to the C/L Psychiatry service. Analyses for diagnostic concordance used a nested sample of 140 cases diagnosed with delirium by the psychiatrist. Two multivariate logistic models were run, for delirium diagnosis concordance and discordance between the referring physician and C/L psychiatrist. The referral diagnosis was concordant with that of Psychiatry in 90/140 patients in 64.3%, with 35.7% discordance. Increasing age (OR = 1.024) and internal medicine ward (OR = 3.0) were significantly related (Wald statistic P < .05) to concordance in the multivariate analysis whose model accuracy was 68.6%. Trauma/orthopedics ward (OR = 5.7) and SARS-CoV-2 infection (OR = 3.8) were important contributors to the model fit though not significant. Accuracy of the discordance model was 70.7%, where central nervous system (CNS) disorder (OR = 6.1) and referrals from ICU (OR = 4.9), surgery (OR = 4.6), neurology/neurosurgery (OR = 5.1) and another consultant (OR = 4.7) were significantly related (Wald statistic P < .05), while metabolic/endocrine disorder (OR = 2.7) was important for model fit, but not significant. Concordance for delirium diagnosis was higher from services where education, guidelines and working relationships with C/L Psychiatry could have contributed beneficially whereas, surprisingly, CNS disorders and neurology/neurosurgery services had higher discordance, as well as the ICU. Routine use of brief sensitive delirium assessment tools such as the DDT-Pro could enhance provisional delirium diagnosis.

Discriminant Performance of Dysexecutive and Frontal Release Signs for Delirium in Patients With High Dementia Prevalence: Implications for Neural Network Impairment.

BACKGROUND: Prevalence of signs of abnormal executive function (EF) and primitive reflexes (PR) with delirium in older hospitalized patients with or without comorbid dementia has not been reported. OBJECTIVE: To describe prevalence of signs of EF deficits and PR in older inpatients and their discriminant value for delirium while accounting for dementia. METHODS: Participants were evaluated for delirium using the Diagnostic and Statistical Manual of Mental Disorders 5th edition and the Delirium Rating Scale Revised-98, dementia using Informant Questionnaire on Cognitive Decline in the Elderly, and signs of PR (n = 5) and EF deficits (n = 3) using bedside neuropsychiatric examination. Three indices (PR, EF, and Combined) and 4 diagnostic groups were created for correlational and discriminant analyses. RESULTS: Correlations of indices were higher with the Delirium Rating Scale Revised-98 than with the Informant Questionnaire on Cognitive Decline in the Elderly and even higher in those with dementia, especially the Combined index (Delirium Frontal Index). Among individual signs, glabellar and Simple Luria Hand Sequence were most common in delirium and the best for delirium discrimination irrespective of dementia status. The Combined index had about 80% sensitivity and specificity at the ≥2 cutoff in the whole cohort (positive and negative predictive values and likelihood ratios: PPV 50.0%, NPV 93.8%, +LR 3.82, -LR 0.25). The Combined index also had the best performance on discriminating delirium in dementia patients at the ≥3 cutoff, with about 80% for both sensitivity and specificity. CONCLUSIONS: PR and EF deficit signs are consistent with reduced neural network integration during delirium, even worse in those with dementia whose baseline structural injury impairs network connectivity with frontal regions. We recommend simple bedside assessment of PR and EF signs to help assess for delirium as an indicator of cerebral cortical neural network impairment in older persons.

Relationship between cognitive status at admission and incident delirium in older medical inpatients.

To evaluate the relationship between cognitive status and incident delirium, 291 geriatric patients on internal medicine wards were evaluated on admission with the Mini-Mental State Examination (MMSE) and Confusion Assessment Method-Spanish. Those with incident delirium were assessed using the Delirium Rating Scale-Revised-98 (DRS-R98). Delirium incidence was 11.7%, and 82 patients (28.2%) had cognitive deficits on MMSE. As cognitive impairment worsened, the risk for delirium increased linearly, and for each unit of MMSE worsening the DRS-R98 severity score worsened 0.4 points (F=5.39, df=1, p=0.027). Optimal MMSE cutoff score from receiver-operating characteristic curve analysis was 24.5. Even mild cognitive deficits increase delirium risk and severity.

Delirium diagnostic tool-provisional (DDT-Pro) scores in delirium, subsyndromal delirium and no delirium.

OBJECTIVE: To evaluate whether the Delirium Diagnostic Tool-Provisional (DDT-Pro), a 0-9 point scale with three items each representing symptoms from delirium's three core domains, differentiates subsyndromal delirium (SSD) from delirium and no delirium. METHODS: We applied cluster analyses of DDT-Pro scores from 200 consecutive inpatients using three reference standards for delirium diagnosis to determine DDT-Pro cutoff values for delirium, SSD and no delirium groups. Clinical validators and DDT-Pro item scores were compared among groups. RESULTS: DDT-Pro SSD range was 6-7 (n = 54), with no delirium having higher scores (n = 98) and delirium lower (n = 48). Dementia prevalence in the SSD group (40.7%) was intermediate between no delirium (20.4%) and delirium (66.7%). SSD and delirium groups were more affected than no delirium regarding medical comorbidities, hospital stay (no delirium <1 week, SSD and delirium >1 week) and mortality (SSD = 7.4%, delirium = 18.8%, no delirium = 1%). Values for motor subtypes, frontal lobe signs, and DRS-R98 in the SSD group were intermediate between no delirium and delirium, as well as for the DDT-Pro items (all p < 0.05). CONCLUSIONS: All DDT-Pro items, which represent the three delirium core domains, are important for SSD diagnosis. Patients scoring in the SSD 6-7 range have significant clinical and prognostic features and deserve clinical attention.

Subtipos neurocognitivos de esquizofrenia / Neurocognitive Subtypes of Schizophrenia

Objetivo. Identificar empíricamente subtipos neurocognitivos de esquizofrenia y establecer la asociación de estos con características clínicas. Métodos. Se aplicaron pruebas de atención sostenida, función ejecutiva, reconocimiento facial de emociones, memoria verbal y de trabajo a 253 sujetos con esquizofrenia. A partir de los resultados de estas pruebas se identificaron los subtipos mediante análisis de clases latentes. Posteriormente, se evaluó la asociación de cada subtipo con características clínicas. Resultados. Se identificaron cuatro subtipos: 1) déficit cognitivo global, 2) déficit de memoria y función ejecutiva, 3) déficit de memoria y reconocimiento de emociones y 4) sin déficit cognitivo. Al comparar con el subtipo sin déficit cognitivo, se observó que tanto el de déficit de memoria y función ejecutiva como el de déficit cognitivo global tenían mayor frecuencia individuos de sexo masculino, desempleados, con deterioro grave y adherentes al tratamiento. Sin embargo, en el subtipo con déficit cognitivo global la diferencia fue más alta y presentaron una frecuencia más baja de antecedentes de episodios depresivos (OR 0,39; IC95%: 0,16 a 0,97). El subtipo de déficit de memoria y reconocimiento emocional tenía más sujetos con deterioro grave (OR 5,52; IC95%: 1,89 a 16,14) y desempleo (OR 2,43; IC95%: 1,06 a 5,55), pero menos con antecedentes de episodios depresivos (OR 0,21; IC95%: 0,07 a 0,66). Conclusión. Los resultados muestran cuatro subtipos neurocognitivos de esquizofrenia con un posible espectro de severidad, asociándose en un extremo con mayor disfunción, y en el otro con mayor psicopatología afectiva y menor adherencia al tratamiento

Objective. To empirically identify schizophrenia neurocognitive subtypes and establish their association with clinical characteristics. Methods. Sustained attention, executive function, facial emotion recognition, verbal learning, and working memory tests were applied to 253 subjects with schizophrenia. We identified neurocognitive subtypes by a latent class analysis of the tests results. After, we made a search for the association of these subtypes with clinic characteristics. Results. We identified four neurocognitive subtypes: 1) 'Global cognitive deficit', 2) 'Memory and executive function deficit', 3) 'Memory and facial emotion recognition deficit,' and 4) 'Without cognitive deficit.' In comparison with the subtype 'without cognitive deficit,' we found that the 'memory and executive function deficit subtype' and the 'global cognitive deficit subtype' had a higher frequency of male, unemployed, severe impairment, and adherence to treatment participants. However, in the 'global cognitive deficit subtype' the differences were higher and there was also a lower frequency of past major depressive episodes (OR 0.39; 95%CI: 0.16 to 0.97). The 'memory and facial recognition deficit subtype' had a higher probability of severe impairment (OR 5.52; 95%CI: 1.89 to 16.14) and unemployed (OR 2.43; 95%CI: 1.06 to 5.55) participants, but also a lower probability of past depressive episodes (OR 0.21; 95%CI: 0.07 to 0.66). Conclusion. Our results suggest the existence of four neurocognitive subtypes in schizophrenia with a spectrum of dysfunction and severity. We found higher dysfunction in those with worse cognitive dysfunction, and higher affective psychopathology and less treatment adherence in those with less cognitive dysfunction

Memoria de trabajo verbal en individuos con esquizofrenia y sus familiares de primer grado: Relación con los sintomas negativos y desorganizados / Verbal working memory in individuals with schizophrenia and their first degree relatives: relationship with negative and disorganized symptoms

Objetivo: Determinar si hay diferencias en la memoria de trabajo verbal entre sujetos con esquizofrenia, familiares de primer grado y controles, y evaluar la influencia que pueden tener en estas diferencias los síntomas del trastorno, como un paso para establecer si esta función cognitiva es un endofenotipo. Métodos: A 197 sujetos con esquizofrenia, 197 familiares de primer grado y 200 controles comunitarios, se les hizo evaluación psiquiátrica y se les aplicó la prueba sucesión de letras y números (SLN). Se comparó el desempeño de los tres grupos ajustando por edad, sexo y escolaridad, y luego se ajustó también por síntomas negativos y desorganizados. Resultados: Los sujetos con esquizofrenia mostraron un menor desempeño en la SLN con respecto a sus familiares de primer grado no-afectados y los controles, con tamaños de efecto de 0,75 y 1,18 respectivamente. Hubo una diferencia pequeña pero significativa entre familiares y controles (tamaño de efecto =0,38). Estas diferencias siguieron siendo significativas después de ajustar por síntomas negativos y desorganizados, pero los tamaños de efecto disminuyeron a: 0,26 para familiares vs sujetos con esquizofrenia, 0,56para controles vs sujetos con esquizofrenia y 0,33 para familiares vs controles. Entre los sujetos con esquizofrenia, el desempeño en la SLN no se asoció significativamente con duración del trastorno, edad de inicio, uso de antipsicóticos, ni historia de episodios depresivos o trastornos por uso de sustancias. Conclusión: Los resultados sugieren que la memoria de trabajo verbal puede ser considerada un endofenotipo de la esquizofrenia (AU)

Objective: To determine whether there are differences in verbal working memory amongst subjects with schizophrenia, their first degree relatives and controls, and to evaluate the influence of symptoms on these differences, as an initial step to assess whether this cognitive function is an endophenotype. Methods: We examined 197 cases with schizophrenia, 197 first degree relatives and 200 controls through psychiatric interviews and the Letters and Numbers Sequencing test (LNS). Performance was compared among the three groups adjusting for age, sex and education level. Adjustment for “negative symptoms” and “disorganization” was performed afterwards. Results: Subjects with schizophrenia showed lower performance in the LNS than their first degree relatives and the healthy controls; the effect sizes were 0.75 and 1.18 respectively. There was a small difference between relatives and controls (effect size =0.38). These differences were significant after adjustment for negative and disorganized symptoms, but the effect sizes became smaller: 0.26 for relatives vs. subjects with schizophrenia, 0.56 for controls vs. subjects with schizophrenia and 0.33 for relatives vs. controls. Among individuals with schizophrenia, performance in the LNS was not associated with disorder duration, disease onset age, antipsychotics, history of depressive episodes or substance use disorders. Conclusion: Results suggest verbal working memory may be considered as an endophenotype in schizophrenia (AU)