Abstract
Background
The role of haloperidol as treatment for ICU delirium and related symptoms remains controversial despite two recent large controlled trials evaluating its efficacy and safety. We ...sought to determine whether haloperidol when compared to placebo in critically ill adults with delirium reduces days with delirium and coma and improves delirium-related sequelae.
Methods
This multi-center double-blind, placebo-controlled randomized trial at eight mixed medical-surgical Dutch ICUs included critically ill adults with delirium (Intensive Care Delirium Screening Checklist ≥ 4 or a positive Confusion Assessment Method for the ICU) admitted between February 2018 and January 2020. Patients were randomized to intravenous haloperidol 2.5 mg or placebo every 8 h, titrated up to 5 mg every 8 h if delirium persisted until ICU discharge or up to 14 days. The primary outcome was ICU delirium- and coma-free days (DCFDs) within 14 days after randomization. Predefined secondary outcomes included the protocolized use of sedatives for agitation and related behaviors, patient-initiated extubation and invasive device removal, adverse drug associated events, mechanical ventilation, ICU length of stay, 28-day mortality, and long-term outcomes up to 1-year after randomization.
Results
The trial was terminated prematurely for primary endpoint futility on DSMB advice after enrolment of 132 (65 haloperidol; 67 placebo) patients mean age 64 (15) years, APACHE IV score 73.1 (33.9), male 68%. Haloperidol did not increase DCFDs (adjusted RR 0.98 95% CI 0.73–1.31,
p
= 0.87). Patients treated with haloperidol (vs. placebo) were less likely to receive benzodiazepines (adjusted OR 0.41 95% CI 0.18–0.89,
p
= 0.02). Effect measures of other secondary outcomes related to agitation (use of open label haloperidol OR 0.43 (95% CI 0.12–1.56) and other antipsychotics OR 0.63 (95% CI 0.29–1.32), self-extubation or invasive device removal OR 0.70 (95% CI 0.22–2.18)) appeared consistently more favorable with haloperidol, but the confidence interval also included harm. Adverse drug events were not different. Long-term secondary outcomes (e.g., ICU recall and quality of life) warrant further study.
Conclusions
Haloperidol does not reduce delirium in critically ill delirious adults. However, it may reduce rescue medication requirements and agitation-related events in delirious ICU patients warranting further evaluation.
Trial registration
: ClinicalTrials.gov (#NCT03628391), October 9, 2017.
The neuregulin 1 (NRG1) receptor ErbB4 is involved in the development of cortical inhibitory GABAergic circuits and NRG1-ErbB4 signaling has been implicated in schizophrenia (SCZ). A magnetic ...resonance spectroscopy ((1)H-MRS) study has demonstrated that a single-nucleotide polymorphism in ERBB4, rs7598440, influences human cortical GABA concentrations. Other work has highlighted the significant impact of this genetic variant on expression of ERBB4 in the hippocampus and dorsolateral prefrontal cortex in human post mortem tissue. Our aim was to examine the association of rs7598440 with cerebrospinal fluid (CSF) GABA levels in healthy volunteers (n=155). We detected a significant dose-dependent association of the rs7598440 genotype with CSF GABA levels (G-allele standardized β=-0.23; 95% CIs: -0.39 to -0.07; P=0.0066). GABA concentrations were highest in A homozygous, intermediate in heterozygous, and lowest in G homozygous subjects. When excluding subjects on psychotropic medication (three subjects using antidepressants), the results did not change (G-allele standardized β=-0.23; 95% CIs: -0.40 to -0.07; P=0.0051). The explained variance in CSF GABA by rs7598440 in our model is 5.2% (P=0.004). The directionality of our findings agrees with the aforementioned (1)H-MRS and gene expression studies. Our observation therefore strengthens the evidence that the A-allele of rs7598440 in ERBB4 is associated with increased GABA concentrations in the human central nervous system (CNS). To our knowledge, our finding constitutes the first confirmation that CSF can be used to study genotype-phenotype correlations of GABA levels in the CNS. Such quantitative genetic analyses may be extrapolated to other CSF constituents relevant to SCZ in future studies.
Background: Aims of this study were to investigate the prevalence and incidence of catheter-related infection, identify risk factors, and determine the relation of catheter-related infection with ...mortality in critically ill COVID-19 patients. Methods: This was a retrospective cohort study of central venous catheters (CVCs) in critically ill COVID-19 patients. Eligible CVC insertions required an indwelling time of at least 48 hours and were identified using a full-admission electronic health record database. Risk factors were identified using logistic regression. Differences in survival rates at day 28 of follow-up were assessed using a log-rank test and proportional hazard model. Results: In 538 patients, a total of 914 CVCs were included. Prevalence and incidence of suspected catheter-related infection were 7.9% and 9.4 infections per 1,000 catheter indwelling days, respectively. Prone ventilation for more than 5 days was associated with increased risk of suspected catheter-related infection; odds ratio, 5.05 (95% confidence interval 2.12-11.0). Risk of death was significantly higher in patients with suspected catheter-related infection (hazard ratio, 1.78; 95% confidence interval, 1.25-2.53). Conclusions: This study shows that in critically ill patients with COVID-19, prevalence and incidence of suspected catheter-related infection are high, prone ventilation is a risk factor, and mortality is higher in case of catheter-related infection.
To assess, validate and compare the predictive performance of models for in-hospital mortality of COVID-19 patients admitted to the intensive care unit (ICU) over two different waves of infections. ...Our models were built with high-granular Electronic Health Records (EHR) data versus less-granular registry data.
Observational study of all COVID-19 patients admitted to 19 Dutch ICUs participating in both the national quality registry National Intensive Care Evaluation (NICE) and the EHR-based Dutch Data Warehouse (hereafter EHR). Multiple models were developed on data from the first 24 h of ICU admissions from February to June 2020 (first COVID-19 wave) and validated on prospective patients admitted to the same ICUs between July and December 2020 (second COVID-19 wave). We assessed model discrimination, calibration, and the degree of relatedness between development and validation population. Coefficients were used to identify relevant risk factors.
A total of 1533 patients from the EHR and 1563 from the registry were included. With high granular EHR data, the average AUROC was 0.69 (standard deviation of 0.05) for the internal validation, and the AUROC was 0.75 for the temporal validation. The registry model achieved an average AUROC of 0.76 (standard deviation of 0.05) in the internal validation and 0.77 in the temporal validation. In the EHR data, age, and respiratory-system related variables were the most important risk factors identified. In the NICE registry data, age and chronic respiratory insufficiency were the most important risk factors.
In our study, prognostic models built on less-granular but readily-available registry data had similar performance to models built on high-granular EHR data and showed similar transportability to a prospective COVID-19 population. Future research is needed to verify whether this finding can be confirmed for upcoming waves.
van Rens et al examine the changes in patterns of age-related visual impairment in people aged 50 and older who visited an eye clinic, and people who accepted an offer of rehabilitation. Findings of ...the study show that there was a change in the etiology of visual impairment from the first period to the second period.
En nombre de la Asociación Colombiana de Facultades de Terapia Ocupacional, ACOLFACTO, se envía un saludo de felicitación al Consejo Directivo Nacional del Colegio Colombiano de Terapia Ocupacional y ...a las y los colegas del país que celebran cincuenta años de agremiación.
Despite the recent progress in the field of causal inference, to date there is no agreed upon methodology to glean treatment effect estimation from observational data. The consequence on clinical ...practice is that, when lacking results from a randomized trial, medical personnel is left without guidance on what seems to be effective in a real-world scenario. This article proposes a pragmatic methodology to obtain preliminary but robust estimation of treatment effect from observational studies, to provide front-line clinicians with a degree of confidence in their treatment strategy. Our study design is applied to an open problem, the estimation of treatment effect of the proning maneuver on COVID-19 Intensive Care patients.
Establecer la ocurrencia del síndrome del cuidador entre los cuidadores de personas con enfermedad mental vinculadas al programa de hospital de día de una institución de tercer nivel de la ciudad de ...Cali (Colombia).
Se realizó un estudio descriptivo y observacional de corte transversal, para evaluar la ocurrencia del síndrome de sobrecarga en 70 cuidadores de personas con enfermedad mental, a través de entrevistas y la aplicación formal de la escala de Zarit y el cuestionario WHO-DAS 2.0.
Se estableció que el 68,6% de la población participante presenta algún grado de sobrecarga; el perfil del cuidador es el de una mujer, mayor de 55 años, madre de familia, perteneciente al régimen subsidiado de salud y con bajo ingreso económico que, en promedio, lleva 8 años ejerciendo el rol de cuidador por lo menos 12h diarias. El largo tiempo de dedicación a las actividades propias del rol y el nivel de demanda, producto del grado de discapacidad de la persona a la que se cuida, aparecen como factores asociados a la aparición de un mayor grado de sobrecarga para el cuidador, por lo que constituyen un factor que considerar en la implementación de procesos de intervención e investigación que vinculen al cuidador como agente clave en el mejoramiento de la calidad de vida de las personas con enfermedad mental.
To establish the occurrence of caregiver syndrome in caregivers of people with mental illness participating in the Day Hospital Program of a tertiary institution in the city of Cali.
A descriptive, cross-sectional observational study was carried out to evaluate the occurrence of overload syndrome in 70 caregivers of people with mental illness, through interviews and the formal application of the Zarit scale and the WHO-DAS 2.0 questionnaire.
It was established that 68.6% of the participating population presented some level of overload. The caregiver profile corresponds to women, over the age of 55, who belonged to the subsidized health system; earning a low income, and with an average of 8 years in caregiver role for at least 12 hours per day. The long time dedicated to the role's activities and the level of demand resulting from the degree of disability of the person receiving care, appear as associated factors for the presence of higher levels of overload for the caregiver, for which they are a factor to consider when implementing interventions and research processes in which the caregiver is involved as a key agent for improving the quality of life of people with mental illness.
Hay una ascendente prevalencia del trastorno por déficit de atención e hiperactividad (TDAH) en las instituciones educativas. Las dificultades en el desarrollo académico se manifiestan en la lentitud ...del procesamiento de información, dificultades en la planificación y la memoria de trabajo, dificultades en mantener la concentración y en seleccionar los datos o estímulos relevantes para la ejecución y la finalización de tareas. Si no se establecen medidas educativas y adecuada intervención especializada, estas características pueden afectar a los aprendizajes significativos. Se propuso identificar las habilidades motoras y de procedimiento que interfieren en las actividades académicas de un grupo de estudiantes de básica primaria con signos y síntomas de TDAH.
Investigación descriptiva, en la que participaron estudiantes de 2.° a 4.° grado de básica primaria, en quienes se detectaron signos y síntomas de TDAH a partir de los cuestionarios para profesores y de conducta en la escuela. Se determinaron las habilidades motoras y de procedimiento, y se evidenció cuáles interferían en la ejecución de actividades académicas.
La población que presentó comportamientos de inatención e hiperactividad manifestó dificultades de comportamiento, bajo funcionamiento académico y, a su vez, mayor dificultad en las habilidades de postura y de organización de espacio y objetos, lo que interfirió en las actividades de la vida académica diaria.
La valoración de las habilidades motoras y de procedimiento permitió determinar las dificultades específicas en las actividades cotidianas y acordar las estra tegias de intervención en el aula de clase.
There is a rising prevalence of attention deficit and hyperactivity disorder (ADHD) in educational institutions. Difficulties in academic development manifest as: slow information processing, difficulty in planning and working memory, difficulty staying focused, struggle selecting data or stimuli relevant to the implementation and completion of tasks. If adequate educational measures and specialized intervention are not established, the characteristics may affect instrumental learning. The aim of this study is to identify procedural motor skills that interfere with academic activities in a group of elementary school children, with signs and symptoms of ADHD.
Descriptive study including children from 2nd to 4th grade of elementary school in which teachers detected signs and symptoms of ADHD by using questionnaires and observing school behavior. Procedural motor skills were identified and it was evidenced which skills interfered in the execution of academic activities.
The population that showed inattention and hyperactivity behaviors manifested behavioral problems, low academic performance, and in turn, greater difficulty in postural skills and skill related with organization of space and objects, which interfered with the activities of daily living academic routine, as expected.
The assessment of procedural motor skills allowed to determine specific difficulties in routine activities, and to agree on intervention strategies in the classroom.
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