Virtual reality-based early neurocognitive stimulation in critically ill patients: A pilot randomized clinical trial

This study focuses on the application of a non-immersive virtual reality (VR)-based neurocognitive intervention in critically ill patients. Our aim was to assess the feasibility of direct outcome measures to detect the impact of this digital therapy on patients’ cognitive and emotional outcomes. Seventy-two mechanically ventilated adult patients were randomly assigned to the “treatment as usual” (TAU, n = 38) or the “early neurocognitive stimulation” (ENRIC, n = 34) groups. All patients received standard intensive care unit (ICU) care. Patients in the ENRIC group also received adjuvant neurocognitive stimulation during the ICU stay. Outcome measures were a full neuropsychological battery and two mental health questionnaires. A total of 42 patients (21 ENRIC) completed assessment one month after ICU discharge, and 24 (10 ENRIC) one year later. At onemonth follow-up, ENRIC patients had better working memory scores (p = 0.009, d = 0.363) and showed up to 50% less non-specific anxiety (11.8% vs. 21.1%) and depression (5.9% vs. 10.5%) than TAU patients. A general linear model of repeated measures reported a main effect of group, but not of time or group–time interaction, on working memory, with ENRIC patients outperforming TAU patients (p = 0.008, ¿p2 = 0.282). Our results suggest that non-immersive VR-based neurocognitive stimulation may help improve short-term working memory outcomes in survivors of critical illness. Moreover, this advantage could be maintained in the long term. An efficacy trial in a larger sample of participants is feasible and must be conducted. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Pathogenicity island cag, vacA and IS605 genotypes in Mexican strains of Helicobacter pylori associated with peptic ulcers

<p>Abstract</p> <p>Background</p> <p><it>Helicobacter pylori </it>is associated with chronic gastritis, peptic ulcers, and gastric cancer. Two major virulence factors of <it>H. pylori </it>have been described: the pathogenicity island <it>cag </it>(<it>cag </it>PAI) and the vacuolating cytotoxin gene (<it>vacA</it>). Virtually all strains have a copy of <it>vacA</it>, but its genotype varies. The <it>cag </it>PAI is a region of 32 genes in which the insertion of IS<it>605 </it>elements in its middle region has been associated with partial or total deletions of it that have generated strains with varying virulence. Accordingly, the aim of this work was to determine the <it>cag </it>PAI integrity<it>, vacA </it>genotype and IS<it>605 </it>status in groups of isolates from Mexican patients with non-peptic ulcers (NPU), non-bleeding peptic ulcers (NBPU), and bleeding peptic ulcers (BPU).</p> <p>Methods</p> <p>The <it>cag </it>PAI integrity was performed by detection of eleven targeted genes along this locus using dot blot hybridization and PCR assays. The <it>vacA </it>allelic, <it>cag </it>PAI genotype 1 and IS<it>605 </it>status were determined by PCR analysis.</p> <p>Results</p> <p>Groups of 16-17 isolates (n = 50) from two patients with NPU, NBPU, and BPU, respectively, were studied. 90% (45/50) of the isolates harbored a complete <it>cag </it>PAI. Three BPU isolates lacked the <it>cag </it>PAI, and two of the NBPU had an incomplete <it>cag </it>PAI: the first isolate was negative for three of its genes, including deletion of the <it>cagA </it>gene, whereas the second did not have the <it>cagM </it>gene. Most of the strains (76%) had the <it>vacA </it>s1b/m1 genotype; meanwhile the IS<it>605 </it>was not present within the <it>cag </it>PAI of any strain but was detected elsewhere in the genome of 8% (4/50).</p> <p>Conclusion</p> <p>The patients had highly virulent strains since the most of them possessed a complete <it>cag </it>PAI and had a <it>vacA </it>s1b/m1 genotype. All the isolates presented the <it>cag </it>PAI without any IS<it>605 </it>insertion (genotype 1). Combined <it>vacA </it>genotypes showed that 1 NPU, 2 NBPU, and 1 BPU patients (66.6%) had a mixed infection; coexistence of <it>H. pylori </it>strains with different <it>cag </it>PAI status was observed in 1 NBPU and 2 BPU (50%) of the patients, but only two of these patients (NBPU and BPU) had different <it>vacA </it>genotypes.</p

Autonomic nervous system assessment in critically ill patients undergoing a cognitive rehabilitation therapy

Recent clinical and electrophysiological studies reveal a high incidence of autonomic nervous system (ANS) dysfunction in patients treated in Intensive Care Units (ICUs). Cognitive rehabilitation (CR) is a behavioral therapy that has proven to be effective improving cognitive deficits in clinical populations with abnormalities in brain activation patterns. A total of 17 critically ill patients received CR aimed to improve the ANS status, which was quantified in terms of HRV. The CR included cognitive exercises aimed to improve prefrontal activation. HRV was obtained during pre-CR, CR and post-CR. Power in the low (PLF) and high (PHF) frequency bands related to sympathetic and parasympathetic systems was computed. PHF was obtained within a band centered at respiratory rate. Comparing with baseline values, 7 patients showed an increased PHF in post-CR, suggesting an increase of parasympathetic activity

Effect of an early neurocognitive rehabilitation on autonomic nervous system in critically ill patients

Introduction Recent clinical and electrophysiological studies reveal a high incidence of autonomic nervous system (ANS) dys- function in patients treated in ICU [1]. ANS disturbances may produce diverse and unexpected consequences. For instance, critically ill patients are at risk of neurocognitive impairments that may persist after hospital discharge. Among various pathophysiological mechanisms proposed, ANS dysfunction leading cholinergic deficiency seems one of the most viable to explain the development of long-term sequelae. Heart rate variability (HRV) has been related to the activity of the prefrontal cortex [2] hence, prefrontal activation could help to strengthen the auto- nomic nervous system integrity. We are interested in assessing the improvement of the ANS dysfunction through neural circuits’ activation. Thus, we propose a novel therapy that could allow the reinforcing of ANS through an early neurocognitive intervention targeted to improve prefrontal activation. Objectives The aim of this study was to explore if the integrity of the ANS, via cardiac vagal tone, measured by the HRV can be modified after early neurocognitive rehabilitation in ICU patients. Methods A total of 17 critically ill patients received a 20-minute Early Neurocognitive Rehabilitation (ENR) session in their own bed in the ICU. HRV was derived from the recorded ECG signal during pre-session, session and post-session. Power in the specific frequency bands related to sympathetic and parasympathetic systems was computed (PLF and PHF for low and high frequency bands, respectively). PLF was computed within the clas- sic band, while PHF was computed within a band cen- tered at respiratory rate. Changes in the HRV parameters from pre-session to session, and from pre- session to post-session were studied using Wilcoxon signed-rank test. Results Clinical data of the sample are summarized in table 1. Comparing with baseline values, 9 patients (53%) showed a decreased PLF in post-session, while 8 patients (47%) presented a higher PLF (p = .759). In 12 patients (71%), PHF increased after the ENR session, suggesting an increase of parasympathetic activity (p = .836). Conclusions Diagnosis, severity of illness or medication could explain the differential effect in the evolution of the HRV para- meters among different patients. Despite differences, an early neurocognitive rehabilitation seems to increase parasympathetic activity after the session in the majority of the patients. Clinical characteristics of the critical ill patients should be further studied to determinate which patients could be the best candidates for early neurocog- nitive intervention

The age again in the eye of the COVID-19 storm: evidence-based decision making

Background: One hundred fifty million contagions, more than 3 million deaths and little more than 1 year of COVID-19 have changed our lives and our health management systems forever. Ageing is known to be one of the significant determinants for COVID-19 severity. Two main reasons underlie this: immunosenescence and age correlation with main COVID-19 comorbidities such as hypertension or dyslipidaemia. This study has two aims. The first is to obtain cut-off points for laboratory parameters that can help us in clinical decision-making. The second one is to analyse the effect of pandemic lockdown on epidemiological, clinical, and laboratory parameters concerning the severity of the COVID-19. For these purposes, 257 of SARSCoV2 inpatients during pandemic confinement were included in this study. Moreover, 584 case records from a previously analysed series, were compared with the present study data. Results: Concerning the characteristics of lockdown series, mild cases accounted for 14.4, 54.1% were moderate and 31.5%, severe. There were 32.5% of home contagions, 26.3% community transmissions, 22.5% nursing home contagions, and 8.8% corresponding to frontline worker contagions regarding epidemiological features. Age > 60 and male sex are hereby confirmed as severity determinants. Equally, higher severity was significantly associated with higher IL6, CRP, ferritin, LDH, and leukocyte counts, and a lower percentage of lymphocyte, CD4 and CD8 count. Comparing this cohort with a previous 584-cases series, mild cases were less than those analysed in the first moment of the pandemic and dyslipidaemia became more frequent than before. IL-6, CRP and LDH values above 69 pg/mL, 97 mg/L and 328 U/L respectively, as well as a CD4 T-cell count below 535 cells/?L, were the best cut-offs predicting severity since these parameters offered reliable areas under the curve. Conclusion: Age and sex together with selected laboratory parameters on admission can help us predict COVID-19 severity and, therefore, make clinical and resource management decisions. Demographic features associated with lockdown might affect the homogeneity of the data and the robustness of the results

Effectiveness of telephone monitoring in primary care to detect pneumonia and associated risk factors in patients with SARS-CoV-2

Improved technology facilitates the acceptance of telemedicine. The aim was to analyze the effectiveness of telephone follow-up to detect severe SARS-CoV-2 cases that progressed to pneumonia. A prospective cohort study with 2-week telephone follow-up was carried out March 1 to May 4, 2020, in a primary healthcare center in Barcelona. Individuals aged =15 years with symptoms of SARS-CoV-2 were included. Outpatients with non-severe disease were called on days 2, 4, 7, 10 and 14 after diagnosis; patients with risk factors for pneumonia received daily calls through day 5 and then the regularly scheduled calls. Patients hospitalized due to pneumonia received calls on days 1, 3, 7 and 14 post-discharge. Of the 453 included patients, 435 (96%) were first attended to at a primary healthcare center. The 14-day follow-up was completed in 430 patients (99%), with 1798 calls performed. Of the 99 cases of pneumonia detected (incidence rate 20.8%), one-third appeared 7 to 10 days after onset of SARS-CoV-2 symptoms. Ten deaths due to pneumonia were recorded. Telephone follow-up by a primary healthcare center was effective to detect SARS-CoV-2 pneumonias and to monitor related complications. Thus, telephone appointments between a patient and their health care practitioner benefit both health outcomes and convenience. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

MVA.85A Boosting of BCG and an Attenuated, phoP Deficient M. tuberculosis Vaccine Both Show Protective Efficacy Against Tuberculosis in Rhesus Macaques

BACKGROUND: Continuous high global tuberculosis (TB) mortality rates and variable vaccine efficacy of Mycobacterium bovis Bacille Calmette-Guérin (BCG) motivate the search for better vaccine regimes. Relevant models are required to downselect the most promising vaccines entering clinical efficacy testing and to identify correlates of protection. METHODS AND FINDINGS: Here, we evaluated immunogenicity and protection against Mycobacterium tuberculosis in rhesus monkeys with two novel strategies: BCG boosted by modified vaccinia virus Ankara expressing antigen 85A (MVA.85A), and attenuated M. tuberculosis with a disrupted phoP gene (SO2) as a single-dose vaccine. Both strategies were well tolerated, and immunogenic as evidenced by induction of specific IFNgamma responses. Antigen 85A-specific IFNgamma secretion was specifically increased by MVA.85A boosting. Importantly, both MVA.85A and SO2 treatment significantly reduced pathology and chest X-ray scores upon infectious challenge with M. tuberculosis Erdman strain. MVA.85A and SO2 treatment also showed reduced average lung bacterial counts (1.0 and 1.2 log respectively, compared with 0.4 log for BCG) and significant protective effect by reduction in C-reactive protein levels, body weight loss, and decrease of erythrocyte-associated hematologic parameters (MCV, MCH, Hb, Ht) as markers of inflammatory infection, all relative to non-vaccinated controls. Lymphocyte stimulation revealed Ag85A-induced IFNgamma levels post-infection as the strongest immunocorrelate for protection (spearman's rho: -0.60). CONCLUSIONS: Both the BCG/MVA.85A prime-boost regime and the novel live attenuated, phoP deficient TB vaccine candidate SO2 showed significant protective efficacy by various parameters in rhesus macaques. Considering the phylogenetic relationship between macaque and man and the similarity in manifestations of TB disease, these data support further development of these primary and combination TB vaccine candidates

COVID-19 : Age, Interleukin-6, C-reactive protein, and lymphocytes as key clues from a multicentre retrospective study

Background: The SARS-CoV-2 infection has widely spread to become the greatest public health challenge to date, the COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized records being carried out by local health authorities. The Spanish case-fatality rate is 11.22%, far higher than those reported in Asia or by other European countries. A multicentre retrospective study of demographic, clinical, laboratory and immunological features of 584 Spanish COVID-19 hospitalized patients and their outcomes was performed. The use of renin-angiotensin system blockers was also analysed as a risk factor. Results: In this study, 27.4% of cases presented a mild course, 42.1% a moderate one and for 30.5% of cases, the course was severe. Ages ranged from 18 to 98 (average 63). Almost 60 % (59.8%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19, and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of angiotensin-converting enzyme inhibitors was associated with a better prognosis. The angiotensin II receptor blocker use was associated with a more severe course. Conclusions: Age and age-related comorbidities, such as dyslipidaemia, hypertension or diabetes, determined more frequent severe forms of the disease in this study than in previous literature cohorts. Our cases are older than those so far reported and the clinical course of the disease is found to be impaired by age. Immunosenescence might be therefore a suitable explanation for the hampering of immune system effectors. The adaptive immunity would become exhausted and a strong but ineffective and almost deleterious innate response would account for COVID-19 severity. Angiotensin-converting enzyme inhibitors used by hypertensive patients have a protective effect in regards to COVID-19 severity in our series. Conversely, patients on angiotensin II receptor blockers showed a severer disease

Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

Background. A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls. Methods. This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate. Results. ES-SCZ was associated with the GAF dimensions in patients (symptom: B = 1.53, p-value = 0.001; disability: B = 1.44, p-value = 0.001), siblings (symptom: B = 3.07, p-value < 0.001; disability: B = 2.52, p-value < 0.001), and healthy controls (symptom: B = 1.50, p-value < 0.001; disability: B = 1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group. Conclusions. Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p <0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p <0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p <0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p <0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p <0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders