Manipulating the exposome to enable better ageing.

The sum total of life course exposures creates an exposome that has a significant impact on age-related health. Understanding the interplay between exposome factors and the (epi) genome, offers pertinent insights into the ageing process and its relationship with the accumulation of allostatic load. We propose to exploit this to develop a biomimetic approach that will provide insight into how evolution through natural selection in other species has solved many age related human health issues. In particular, we will emphasise the need to reconnect a more mechanistic approach to medical science with a broader natural sciences approach, using biomimetics to mitigate the global burden of age related ill health. In particular, we will discuss how such an approach indicates leverage of the activities of the Nrf 2 gene to enhance health span via reintroduction of the classical 'Food as Medicine' concept, including modulation of the microbiome and the creation of more salutogenic and biophilic environments. Additionally, we will discuss how this approach integrates with novel and developing senotherapies.

Whole-Genome Sequence Analysis of Antibiotic Resistance, Virulence, and Plasmid Dynamics in Multidrug-Resistant E. coli Isolates from Imported Shrimp.

We analyzed antimicrobial resistance and virulence traits in multidrug-resistant (MDR) E. coli isolates obtained from imported shrimp using whole-genome sequences (WGSs). Antibiotic resistance profiles were determined phenotypically. WGSs identified key characteristics, including their multilocus sequence type (MLST), serotype, virulence factors, antibiotic resistance genes, and mobile elements. Most of the isolates exhibited resistance to gentamicin, streptomycin, ampicillin, chloramphenicol, nalidixic acid, ciprofloxacin, tetracycline, and trimethoprim/sulfamethoxazole. Multilocus sequence type (MLST), serotype, average nucleotide identity (ANI), and pangenome analysis showed high genomic similarity among isolates, except for EC15 and ECV01. The EC119 plasmid contained a variety of efflux pump genes, including those encoding the acid resistance transcriptional activators (gadE, gadW, and gadX), resistance-nodulation-division-type efflux pumps (mdtE and mdtF), and a metabolite, H1 symporter (MHS) family major facilitator superfamily transporter (MNZ41_23075). Virulence genes displayed diversity, particularly EC15, whose plasmids carried genes for adherence (faeA and faeC-I), invasion (ipaH and virB), and capsule (caf1A and caf1M). This comprehensive analysis illuminates antimicrobial resistance, virulence, and plasmid dynamics in E. coli from imported shrimp and has profound implications for public health, emphasizing the need for continued surveillance and research into the evolution of these important bacterial pathogens.

Whole-genome high-fidelity sequencing: A novel approach to detecting and characterization of mutagenicity in vivo.

Direct DNA sequencing can be used for characterizing mutagenicity in simple and complex biological models. Recently we described a method of whole-genome sequencing for detecting mutations in simple models of cultured bacteria, mammalian cells, and nematode. In the current proof-of-concept study, we expand and improve our method for evaluating a more complex mammalian biological model in outbred mice. We detail the method by applying it to a small set of animals treated with a mutagen with known mutagenicity profiles, N-ethyl-N-nitrosourea (ENU), for consistency with the known data. Whole-genome high-fidelity sequencing (HiFi Sequencing) showed frequencies and spectra of background mutations in tissues of untreated mice that were consistent with normal ageing and characterized by spontaneous or enzymatic deamination of 5-methylcytosine. In mice treated with a single 40 mg/kg dose of ENU, the frequency of mutations in the genomic DNA of solid tissues increased up to 7-fold, with the greatest increase observed in the spleen and the smallest increase in the liver. The most common mutations detected in ENU-treated mice were T > A transitions and T > C transversions, consistent with the types of mutations caused by alkylating agents. The data suggest that HiFi Sequencing may be useful for characterizing mutagenicity of novel compounds in various biological models.

Unbiased whole genome detection of ultrarare off-target mutations in genome-edited cell populations by HiFi sequencing.

DNA base editors (BEs) composed of a nuclease-deficient Cas9 fused to a DNA-modifying enzyme can achieve on-target mutagenesis without creating double-strand DNA breaks (DSBs). As a result, BEs generate far less DNA damage than traditional nuclease-proficient Cas9 systems, which do rely on the creation of DSBs to achieve on-target mutagenesis. The inability of BEs to create DSBs makes the detection of their undesired off-target effects very difficult. PacBio HiFi sequencing can efficiently detect ultrarare mutations resulting from chemical mutagenesis in whole genomes with a sensitivity ~1 × 10-8 mutations per base pair. In this proof-of-principle study, we evaluated whether this technique could also detect the on- and off-target mutations generated by a cytosine-to-thymine (C>T) BE targeting the LacZ gene in Escherichia coli (E. coli). HiFi sequencing detected on-target mutant allele fractions ranging from ~7% to ~63%, depending on the single-guide RNA (sgRNA) used, while no on-target mutations were detected in controls lacking the BE. The presence of the BE resulted in a ~3-fold increase in mutation frequencies compared to controls lacking the BE, irrespective of the sgRNA used. These increases were mostly composed of C:G>T:A substitutions distributed throughout the genome. Our results demonstrate that HiFi sequencing can efficiently identify on- and off-target mutations in cell populations that have undergone genome editing.

Draft Genome Sequences of 14 Fluoroquinolone-Resistant Escherichia coli Isolates from Imported Shrimp.

We report the draft genome sequences of 14 fluoroquinolone-resistant Escherichia coli strains that were isolated from imported shrimp. All isolates contained multiple point mutations in the quinolone resistance-determining regions (QRDRs) and non-QRDRs of gyrA, parC, and parE genes. The data improve the understanding of fluoroquinolone resistance and indicate resistance mechanisms.

Justice implications of health and food security policies for Indigenous peoples facing COVID-19: a qualitative study and policy analysis in Peru.

The spread of COVID-19 in Peru resulted in the declaration of a national health emergency, in which Indigenous peoples were identified as being particularly vulnerable due to their pre-existing poor health indicators and disadvantaged social conditions. The aim of this paper is to examine how the Peruvian government responded to the health and food needs of the Shawi and Ashaninka Indigenous peoples of Peru during the first 18 months of the pandemic (March 2020-August 2021). This study uses both official policy documents and real-world experiences to evaluate policy responses in terms of their immediate impact and their longer-term sustainability and contribution to the improvement of health, well-being and justice for Indigenous communities. Four health and food security responses were evaluated: the Amazon Health Plan and Indigenous Command; food aid; cash aid; and COVID-19 vaccination. We employed the Multidimensional Injustice Framework to analyse the justice implications of the design and implementation of responses. Data collection included 71 interviews with government officials (n = 7), Indigenous leaders (n = 31) and community members (n = 33). The results show how national and regional governments released policies to address the health and food needs of Indigenous peoples directly or indirectly, as part of a broader focus on vulnerable people. However, justice implications were not sufficiently addressed in the design or implementation of the responses. On the distributive dimension, Indigenous communities were prioritized to receive health goods and services, nevertheless, the distribution had shortcomings that impeded their collection and Indigenous food systems and livelihoods were largely overlooked. On the procedural dimension, Indigenous representatives were included to provide culturally sensitive feedback on health interventions, but without funding, and furthermore, the community members had only passive participation. This paper points out the importance of considering and addressing justice implications for more effective and fairer health and food policy responses to current and future health crises.

Evaluation of the mutagenic effects of Molnupiravir and N4-hydroxycytidine in bacterial and mammalian cells by HiFi sequencing.

Molnupiravir (MOV) is used to treat COVID-19. In cells, MOV is converted to the ribonucleoside analog N4-hydroxycytidine (NHC) and incorporated into the SARS-CoV-2 RNA genome during its replication, resulting in RNA mutations. The widespread accumulation of such mutations inhibits SARS-CoV-2 propagation. Although safety assessments by many regulatory agencies across the world have concluded that the genotoxic risks associated with the clinical use of MOV are low, concerns remain that it could induce DNA mutations in patients, particularly because numerous in vitro studies have shown that NHC is a DNA mutagen. In this study, we used HiFi sequencing, a technique that can detect ultralow-frequency substitution mutations in whole genomes, to evaluate the mutagenic effects of MOV in E. coli and of MOV and NHC in mouse lymphoma L5178Y cells and human lymphoblastoid TK6 cells. In all models, exposure to these compounds increased genome-wide mutation frequencies in a dose-dependent manner, and these increases were mainly composed of A:T → G:C transitions. The NHC exposure concentrations used for mammalian cells were comparable to those observed in the plasma of humans who received clinical doses of MOV.

Genome-wide detection of ultralow-frequency substitution mutations in cultures of mouse lymphoma L5178Y cells and Caenorhabditis elegans worms by PacBio sequencing.

Many conventional genetic toxicology assays require specialized cell cultures or animals and can only detect mutations that inactivate the function of a reporter gene. These limitations make such assays incompatible with many toxicological models but could be overcome by the development of techniques capable of directly detecting genome-wide somatic mutations through DNA sequencing. PacBio sequencing can generate almost error-free consensus reads by repeatedly inspecting both DNA strands from circularized molecules (a method known as PacBio HiFi). In this study, we show that PacBio HiFi can detect genome-wide ultralow-frequency substitution mutations in cultures of mouse lymphoma L5178Y cells and Caenorhabditis elegans worms. The mutation frequencies (MFs) of unexposed samples in both models were ~1 × 10-7 mutations per base pair. Compared to these controls, PacBio HiFi detected MF increases of 23-fold in cultures of L5178Y cells exposed to 5 mM ethyl methanosulfonate (EMS) for 4 h, and 5-, 12-, and 29-fold in cultures of C. elegans worms exposed to 12.5, 25, and 50 mM EMS for 4 h, respectively. In both models, the mutation spectra of controls were diverse, while those derived from EMS-exposed samples were dominated by C:G → T:A transitions. To validate these results, clone sequencing analyses were performed on the same cultures of L5178Y cells. The results obtained by clone sequencing and PacBio HiFi were almost identical. Our results suggest that PacBio sequencing could be used for the detection, quantitation, and characterization of mutations in any DNA-containing sample, including those that are not compatible with conventional mutation detection approaches.

Consensus of the Liaison-Psychiatry Committee of the Colombian Psychiatric Association on the diagnosis and treatment of delirium in the context of the COVID-19 pandemic.

The pandemic caused by the new coronavirus named SARS-CoV-2 poses unprecedented challenges in the health care. Among them is the increase in cases of delirium. The severe SARS-CoV-2 disease, COVID-19, has common vulnerabilities with delirium and produces alterations in organs such as the lungs or the brain, among others, which have the potential to trigger the mental disorder. In fact, delirium may be the first manifestation of the infection, before fever, general malaise, cough or respiratory disturbances. It is widely supported that delirium increases the morbidity and mortality in those who suffer from it during hospitalization, so it should be actively sought to carry out the relevant interventions. In the absence of evidence on the approach to delirium in the context of COVID-19, this consensus was developed on three fundamental aspects: diagnosis, non-pharmacological treatment and pharmacological treatment, in patients admitted to the general hospital. The document contains recommendations on the systematic use of diagnostic tools, when to hospitalize the patient with delirium, the application of non-pharmacological actions within the restrictions imposed by COVID-19, and the use of antipsychotics, taking into account the most relevant side effects and pharmacological interactions.

Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial.

BACKGROUND: Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients. METHODS: This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919. FINDINGS: 10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97; p=0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077). INTERPRETATION: Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients. FUNDING: UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.

PacBio sequencing detects genome-wide ultra-low-frequency substitution mutations resulting from exposure to chemical mutagens.

Genetic toxicology uses several assays to identity mutagens and protects the public. Most of these assays, however, rely on reporter genes, can only measure mutation indirectly based on phenotype, and often require specific cell lines or animal models-features that impede their integration with existing and emerging toxicological models, such as organoids. In this study, we show that PacBio Single-Molecule, Real-Time (PB SMRT) sequencing identified substitution mutations caused by chemical mutagens in Escherichia coli by generating nearly error-free consensus reads after repeatedly inspecting both strands of circular DNA molecules. Using DNA from E. coli exposed to ethyl methanosulfonate (EMS) or N-ethyl-N-nitrosourea (ENU), PB SMRT sequencing detected mutation frequencies (MFs) and spectra comparable to those obtained by clone-sequencing from the same exposures. The optimized background MF of PB SMRT sequencing was ≤ 1 × 10-7 mutations per base pair (mut/bp).

Survey of psychiatrists and psychiatry residents in Colombia about their preventive and therapeutic practices in delirium.

OBJECTIVE: To describe pharmacological and non-pharmacological practices for delirium, carried out by psychiatry residents and psychiatrists in Colombia. METHODS: An anonymous survey was conducted based on the consensus of experts of the Liaison Psychiatry Committee of the Asociación Colombiana de Psiquiatría [Colombian Psychiatric Association] and on the literature review. It was sent by email to the association members. RESULTS: 101 clinicians participated. Non-pharmacological preventive measures such as psychoeducation, correction of sensory problems or sleep hygiene are performed by 70% or more. Only about 1 in 10 participants are part of an institutional multi-component prevention programme. The preventive prescription of drugs was less than 20%. Regarding non-pharmacological treatment, more than 75% recommend correction of sensory difficulties, control of stimuli and reorientation. None of the participants indicated that the care at their centres is organised to enhance non-pharmacological treatment. 17.8% do not use medication in the treatment of delirium. Those who use it prefer haloperidol or quetiapine, particularly in hyperactive or mixed motor subtypes. CONCLUSIONS: The practices of the respondents coincide with those of other experts around the world. In general, non-pharmacological actions are individual initiatives, which demonstrates the need in Colombian health institutions to commit to addressing delirium, in particular when its prevalence and consequences are indicators of quality of care.

Occurrence and inequalities by education in multimorbidity in Brazilian adults between 2013 and 2019: evidence from the National Health Survey.

OBJECTIVE: The aims of this study were: 1) to estimate the prevalence of multimorbidity in 2013 and 2019 in adults aged 20-59 years; 2) to assess inequalities in the prevalence of multimorbidity in 2013 and 2019 according to educational level. METHODS: Data from two cross-sectional surveys from the Brazilian National Health Survey in 2013 and 2019 were used. Multimorbidity was assessed from 14 lifetime self-reported morbidities (except back problems) and defined using the cutoff point of ≥2 diseases. The prevalence of multimorbidity and individual morbidities were described according to gender, age, skin color, and education. For education, crude, and relative inequalities in prevalence of multimorbidity were calculated using the Slope Index of Inequality and the Concentration Index, respectively. RESULTS: The prevalence of multimorbidity increased from 18.7% (95%CI 18.0-19.3) in 2013 to 22.3% (95%CI 21.7-22.9) in 2019, being higher among women and adults between 30-59 years in both periods. Asthma/bronchitis, depression, and back problems were the conditions that increased the most in the study period. Absolute and relative inequalities by education status were observed in the study period, with worse multimorbidity profiles among the less educated. CONCLUSION: The prevalence of multimorbidity increased between 2013 and 2019. Inequalities in the prevalence of multimorbidity were observed according to educational level.

Consensus of the Liaison-Psychiatry Committee of the Colombian Psychiatric Association on the Diagnosis and Treatment of Delirium in the Context of the COVID-19 Pandemic. / Consenso del Comité de Psiquiatría de Enlace de la Asociación Colombiana de Psiquiatría sobre el diagnóstico y tratamiento del delirium en el contexto de la pandemia por COVID-19.

The pandemic caused by the new coronavirus named SARS-CoV-2 poses unprecedented challenges in the health care. Among them is the increase in cases of delirium. The severe SARS-CoV-2 disease, COVID-19, has common vulnerabilities with delirium and produces alterations in organs such as the lungs or the brain, among others, which have the potential to trigger the mental disorder. In fact, delirium may be the first manifestation of the infection, before fever, general malaise, cough or respiratory disturbances. It is widely supported that delirium increases the morbidity and mortality in those who suffer from it during hospitalization, so it should be actively sought to carry out the relevant interventions. In the absence of evidence on the approach to delirium in the context of COVID-19, this consensus was developed on three fundamental aspects: diagnosis, non-pharmacological treatment and pharmacological treatment, in patients admitted to the general hospital. The document contains recommendations on the systematic use of diagnostic tools, when to hospitalize the patient with delirium, the application of non-pharmacological actions within the restrictions imposed by COVID-19, and the use of antipsychotics, taking into account the most relevant side effects and pharmacological interactions.

Survey of psychiatrists and psychiatry residents in Colombia about their preventive and therapeutic practices in delirium. / Encuesta a psiquiatras y residentes de psiquiatría en Colombia sobre sus prácticas preventivas y terapéuticas del delirium.

OBJECTIVE: To describe pharmacological and non-pharmacological practices for delirium, carried out by psychiatry residents and psychiatrists in Colombia. METHODS: An anonymous survey was conducted based on the consensus of experts of the Liaison Psychiatry Committee of the Asociación Colombiana de Psiquiatría [Colombian Psychiatric Association] and on the literature review. It was sent by email to the association members. RESULTS: 101 clinicians participated. Non-pharmacological preventive measures such as psychoeducation, correction of sensory problems or sleep hygiene are performed by 70% or more. Only about 1 in 10 participants are part of an institutional multi-component prevention programme. The preventive prescription of drugs was less than 20%. Regarding non-pharmacological treatment, more than 75% recommend correction of sensory difficulties, control of stimuli and reorientation. None of the participants indicated that the care at their centres is organised to enhance non-pharmacological treatment. 17.8% do not use medication in the treatment of delirium. Those who use it prefer haloperidol or quetiapine, particularly in hyperactive or mixed motor subtypes. CONCLUSIONS: The practices of the respondents coincide with those of other experts around the world. In general, non-pharmacological actions are individual initiatives, which demonstrates the need in Colombian health institutions to commit to addressing delirium, in particular when its prevalence and consequences are indicators of quality of care.

Mortality profiles in a country facing epidemiological transition: an analysis of registered data.

BACKGROUND: Sub-national analyses of causes of death and time-trends help to define public health policy priorities. They are particularly important in countries undergoing epidemiological transition like Peru. There are no studies exploring Peruvian national and regional characteristics of such epidemiological transition. We aimed to describe Peru's national and regional mortality profiles between 1996 and 2000. METHODS: Registered mortality data for the study period were corrected for under-registration following standardized methods. Main causes of death by age group and by geographical region were determined. Departmental mortality profiles were constructed to evaluate mortality transition, using 1996 data as baseline. Annual cumulative slopes for the period 1996-2000 were estimated for each department and region. RESULTS: For the study period non-communicable diseases explained more than half of all causes of death, communicable diseases more than one third, and injuries 10.8% of all deaths. Lima accounted for 32% of total population and 20% of total deaths. The Andean region, with 38% of Peru's population, accounted for half of all country deaths. Departmental mortality predominance shifted from communicable diseases in 1996 towards non-communicable diseases and injuries in 2000. Maternal and perinatal conditions, and nutritional deficiencies and nutritional anaemia declined markedly in all departments and regions. Infectious diseases decreased in all regions except Lima. In all regions acute respiratory infections are a leading cause of death, but their proportion ranged from 9.3% in Lima and Callao to 15.3% in the Andean region. Tuberculosis and injuries ranked high in Lima and the Andean region. CONCLUSION: Peruvian mortality shows a double burden of communicable and non-communicable, with increasing importance of non-communicable diseases and injuries. This challenges national and sub-national health system performance and policy making.

Prevalence, awareness, treatment and control of hypertension in rural and urban communities in Latin American countries.

OBJECTIVES: The objective is to describe hypertension (HTN) prevalence, awareness, treatment and control in urban and rural communities in Latin America to inform public and policy-makers. METHODS: Cross-sectional analysis from urban (n = 111) and rural (n = 93) communities including 33 276 participants from six Latin American countries (Argentina, Brazil, Chile, Colombia, Peru and Uruguay) were included. HTN was defined as self-reported HTN on blood pressure (BP) medication or average BP over 140/90 mmHg, awareness as self-reported HTN, and controlled as those with BP under 140/90 mmHg. RESULTS: Mean age was 52 years, 60% were Female and 32% belonged to rural communities. HTN prevalence was 44.0%, with the lowest rates in Peru (17.7%) and the highest rates in Brazil (52.5%). 58.9% were aware of HTN diagnosis and 53.3% were receiving treatment. Prevalence of HTN were higher in urban (44.8%) than rural (42.1%) communities in all countries. Most participants who were aware of HTN were receiving medical treatment (90.5%), but only 37.6% of patients receiving medical treatment had their BP controlled (<140/<90 mmHg), with the rates being higher in urban (39.6%) than in rural (32.4%) communities. The rate of use of two or more drugs was low [36.4%, lowest in Argentina (29.6%) and highest in Brazil (44.6%)]. Statin use was low (12.3%), especially in rural areas (7.0%). Most modifiable risk factors were higher in people with HTN than people without HTN. CONCLUSION: HTN prevalence is high but BP control is low in Latin America, with marked differences between countries and between urban and rural settings. There is an urgent need for systematic approaches for better detection, treatment optimization and risk factor modification among those with HTN in Latin America.

Food Perceptions and Dietary Changes for Chronic Condition Management in Rural Peru: Insights for Health Promotion.

Peru is undergoing a nutrition transition and, at the country level, it faces a double burden of disease where several different conditions require dietary changes to maintain a healthy life and prevent complications. Through semistructured interviews in rural Peru with people affected by three infectious and noninfectious chronic conditions (type 2 diabetes, hypertension, and neurocysticercosis), their relatives, and focus group discussions with community members, we analyzed their perspectives on the value of food and the challenges of dietary changes due to medical diagnosis. The findings show the various ways in which people from rural northern Peru conceptualize good (buena alimentación) and bad (mala alimentación) food, and that food choices are based on life-long learning, experience, exposure, and availability. In the context of poverty, required changes are not only related to what people recognize as healthy food, such as fruits and vegetables, but also of work, family, trust, taste, as well as affordability and accessibility of foods. In this paper we discuss the complexity of introducing dietary changes in poor rural communities whose perspectives on food are poorly understood and rarely taken into consideration by health professionals when promoting behavior change.

Consenso del Comité de Psiquiatría de Enlace de la Asociación Colombiana de Psiquiatría sobre el diagnóstico y tratamiento del delirium en el contexto de la pandemia por COVID-19 / Consensus of the Liaison-Psychiatry Committee of the Colombian Psychiatric Association on the Diagnosis and Treatment of Delirium in the Context of the COVID-19 Pandemic

RESUMEN La pandemia por el nuevo coronavirus denominado SARS-CoV-2 plantea retos sin precedentes en la atención de la salud. Entre ellos se cuenta el aumento en los casos de delirium. La enfermedad grave por SARS-CoV-2, COVID-19, tiene vulnerabilidades comunes con el delirium y produce alteraciones en órganos como el pulmón o el cerebro, entre otros, que tienen potencial para precipitar el trastorno mental; de hecho, este puede ser la primera manifestación de la infección, antes de la fiebre, el malestar general, la tos o las alteraciones respiratorias. Está ampliamente sustentado que el delirium incrementa la morbilidad y la mortalidad de quienes lo padecen durante una hospitalización, por lo que se debe buscar activamente para realizar las intervenciones pertinentes. Ante la ausencia de evidencia sobre el abordaje del delirium en el contexto de la COVID-19, se elaboró este consenso sobre tres aspectos fundamentales: diagnóstico, tratamiento no farmacológico y tratamiento farmacológico, en pacientes ingresados en el hospital general. El documento contiene recomendaciones sobre uso sistemático de herramientas diagnósticas, cuándo hospitalizar al paciente con delirium, la aplicación de acciones no farmacológicas dentro de las restricciones que impone la COVID-19 y la utilización de antipsicóticos teniendo en cuenta los efectos secundarios más relevantes y las interacciones farmacológicas.

ABSTRACT The pandemic caused by the new coronavirus named SARS-CoV-2 poses unprecedented challenges in the health care. Among them is the increase in cases of delirium. The severe SARS-CoV-2 disease, COVID-19, has common vulnerabilities with delirium and produces alterations in organs such as the lungs or the brain, among others, which have the potential to trigger the mental disorder. In fact, delirium may be the first manifestation of the infection, before fever, general malaise, cough or respiratory disturbances. It is widely supported that delirium increases the morbidity and mortality in those who suffer from it during hospitalization, so it should be actively sought to carry out the relevant interventions. In the absence of evidence on the approach to delirium in the context of COVID-19, this consensus was developed on three fundamental aspects: diagnosis, non-pharmacological treatment and pharmacological treatment, in patients admitted to the general hospital. The document contains recommendations on the systematic use of diagnostic tools, when to hospitalize the patient with delirium, the application of non-pharmacological actions within the restrictions imposed by COVID-19, and the use of antipsychotics, taking into account the most relevant side effects and pharmacological interactions.