Síndrome de distrés respiratorio agudo en la pos-pandemia: una nueva definición global con extensión a regiones de menos recursos / Post-Pandemic Acute Respiratory Distress Syndrome: A New Global Definition with Extension to Lower-Resource Regions

El síndrome de dificultad respiratoria aguda (SDRA), inicialmente descrito en 1967, se caracteriza por insuficiencia respiratoria aguda con hipoxemia profunda, disminución de la distensibilidad pulmonar e infiltrados bilaterales en la Rx de tórax. En 2012 la definición de Berlín estableció tres categorías con base en la hipoxemia (SDRA leve, moderado y grave), precisando aspectos temporales y permitiendo el diagnóstico con ventilación no invasiva. La pandemia de COVID-19 llevó a reconsiderar la definición, enfocándose en el monitoreo continuo de la oxigenación y la oxigenoterapia de alto flujo. En 2021 se propuso una nueva definición global de SDRA, basada en la definición de Berlín, pero incluyendo una categoría para pacientes no intubados, permitiendo el uso de saturación periférica de oxígeno medida con oximetría de pulso/fracción inspirada de oxígeno (SpO2/FiO2) y la ecografía pulmonar para el diagnóstico, y sin ningún requerimiento de soporte especial de la oxigenación en regiones con recursos limitados. Aunque persisten debates, la evolución continua busca adaptarse a las necesidades clínicas y epidemiológicas, y personalizar tratamientos. (AU)

Acute respiratory distress syndrome (ARDS), first described in 1967, is characterized by acute respiratory failure causing profound hypoxemia, decreased pulmonary compliance, and bilateral CXR infiltrates. After several descriptions, the Berlin definition was adopted in 2012, which established three categories of severity according to hypoxemia (mild, moderate and severe), specified temporal aspects for diagnosis, and incorporated the use of non-invasive ventilation. The COVID-19 pandemic led to changes in ARDS management, focusing on continuous monitoring of oxygenation and on utilization of high-flow oxygen therapy and lung ultrasound. In 2021, a New Global Definition based on the Berlin definition of ARDS was proposed, which included a category for non-intubated patients, considered the use of SpO2, and established no particular requirement for oxygenation support in regions with limited resources. Although debates persist, the continuous evolution seeks to adapt to clinical and epidemiological needs, and to the search of personalized treatments. (AU)

Large variation in anti-factor Xa levels with nadroparin as thromboprophylaxis in COVID-19 and non-COVID-19 critically ill patients.

PURPOSE: Critically ill COVID-19 and non-COVID-19 patients receive thromboprophylaxis with the LMWH nadroparin. Whether a standard dosage is adequate in attaining the target anti-FXa levels (0.20-0.50 IU/ml) in these groups is unknown. METHODS: This study was a prospective, observational study in the ICU of a large general teaching hospital in the Netherlands. COVID-19 and non-COVID-19 patients admitted to the ICU who received LMWH in a prophylactic dosage of 2850 IU, 5700 IU or 11400 IU subcutaneously were eligible for the study. Anti-FXa levels were determined 4 h after administration. Relevant laboratory parameters, prespecified co-variates and clinical data were extracted from the electronic health record system. The primary goal was to evaluate anti-FXa levels in critically ill patients on a prophylactic dosage of nadroparin. The second goal was to investigate whether covariates had an influence on anti-FXa levels. RESULTS: A total of 62 patients were included in the analysis. In the COVID-19 group and non-COVID-19 group, 29 (96%) and 12 patients (38%) reached anti-FXa levels above 0.20 IU/ml, respectively. In the non-COVID-19 group, 63% of the patients had anti-FXA levels below the target range. When adjusted for nadroparin dosage a significant relation was found between body weight and the anti-FXa level (p = 0.013). CONCLUSION: A standard nadroparin dosage of 2850 IU sc in the critically ill patient is not sufficient to attain target anti-FXa levels in the majority of the studied patient group. We suggest a standard higher dosage in combination with body-weight dependent dosing as it leads to better exposure to nadroparin. CLINICAL TRIALS REGISTRATION: Retrospectively registered, ClinicalTrials.gov ID NTC 05926518 g, date of registration 06/01/23, unique ID 2020/1725.

Vaccine Safety: Assessing the Prevalence and Severity of Adverse Events Following COVID-19 Vaccination amongst Healthcare Workers in Tertiary Health Facilities in Nigeria.

BACKGROUND: Vaccines, including COVID-19 vaccines, are known to be cost-effective interventions for disease prevention and control. However, adverse events following immunisation (AEFI) may challenge the acceptance of these vaccines. This study assessed the prevalence and severity of COVID-19-related AEFI amongst healthcare workers at tertiary health facilities in Nigeria. MATERIALS AND METHODS: This descriptive, cross-sectional study was conducted among healthcare workers who had received the COVID-19 vaccine. A multi-stage sampling technique was used to select participants from six Tertiary Health Facilities in Nigeria. Ethical approval (NHREC/01/01/2007-19/07/2021) was obtained from NHREC. Data were analysed using IBM® SPSS version 25 and categorical variables were presented in tables/charts using frequencies and proportions. RESULTS: A total of 2130 respondents participated in the study, with a mean age of 37.4 ± 9.1 years. Most of the respondents, 1674 (78.6%), had two doses of the vaccine, and the overall prevalence of AEFI was 813 (38.2%). Common among the AEFI reported following the administration of the first dose of the vaccine were fever 649 (30.5%) and pain at the injection site 644 (30.2%), while it was pain at the injection site 216 (10.1%) and fever 173 (8.1%) for second dose. The higher proportions of AEFI were mostly mild to moderate. CONCLUSION: The study observed a relatively low prevalence of AEFI, with the commonly reported ones being fever and injection site pain. It is crucial that countries continuously collect the data on AEFI and establish causality as a way to improve quality and guarantee vaccine safety.

Profiles of Cough and Associated Risk Factors in Nonhospitalized Individuals With SARS-CoV-2 Omicron Variant Infection: Cross-Sectional Online Survey in China.

BACKGROUND: Cough is a common symptom during and after COVID-19 infection; however, few studies have described the cough profiles of COVID-19. OBJECTIVE: The aim of this study was to investigate the prevalence, severity, and associated risk factors of severe and persistent cough in individuals with COVID-19 during the latest wave of the Omicron variant in China. METHODS: In this nationwide cross-sectional study, we collected information of the characteristics of cough from individuals with infection of the SARS-CoV-2 Omicron variant using an online questionnaire sent between December 31, 2022, and January 11, 2023. RESULTS: There were 11,718 (n=7978, 68.1% female) nonhospitalized responders, with a median age of 37 (IQR 30-47) years who responded at a median of 16 (IQR 12-20) days from infection onset to the time of the survey. Cough was the most common symptom, occurring in 91.7% of participants, followed by fever, fatigue, and nasal congestion (68.8%-87.4%). The median cough visual analog scale (VAS) score was 70 (IQR 50-80) mm. Being female (odds ratio [OR] 1.31, 95% CI 1.20-1.43), having a COVID-19 vaccination history (OR 1.71, 95% CI 1.37-2.12), current smoking (OR 0.48, 95% CI 0.41-0.58), chronic cough (OR 2.04, 95% CI 1.69-2.45), coronary heart disease (OR 1.71, 95% CI 1.17-2.52), asthma (OR 1.22, 95% CI 1.02-1.46), and gastroesophageal reflux disease (GERD) (OR 1.21, 95% CI 1.01-1.45) were independent factors for severe cough (VAS>70, 37.4%). Among all respondents, 35.0% indicated having a productive cough, which was associated with risk factors of being female (OR 1.44, 95% CI 1.31-1.57), having asthma (OR 1.84, 95% CI 1.52-2.22), chronic cough (OR 1.44, 95% CI 1.19-1.74), and GERD (OR 1.22, 95% CI 1.01-1.47). Persistent cough (>3 weeks) occurred in 13.0% of individuals, which was associated with the risk factors of having diabetes (OR 2.24, 95% CI 1.30-3.85), asthma (OR 1.70, 95% CI 1.11-2.62), and chronic cough (OR 1.97, 95% CI 1.32-2.94). CONCLUSIONS: Cough is the most common symptom in nonhospitalized individuals with Omicron SARS-CoV-2 variant infection. Being female, having asthma, chronic cough, GERD, coronary heart disease, diabetes, and a COVID-19 vaccination history emerged as independent factors associated with severe cough, productive cough, and persistent cough.

Unmet needs in mental healthcare for women with clinically significant symptoms of perinatal depression and/or anxiety during the COVID-19 pandemic.

OBJECTIVE/BACKGROUND: Unmet needs in perinatal mental healthcare are an important public health issue particularly in the context of a stressful life event such as the COVID-19 pandemic but data on the extent of this problem are needed. AIM: The aim of this study is to determine the (1) proportion of women with clinically significant symptoms of perinatal depression, anxiety or comorbid symptoms of depression and anxiety, receiving mental healthcare overall and by country and (2) factors associated with receiving mental healthcare. METHOD: Women in the perinatal period (pregnancy or up to 6 months postpartum) participating in the Riseup-PPD-COVID-19 cross-sectional study, reported on sociodemographic, social support health-related factors, and COVID-19 related factors, and on symptoms of depression (Edinburgh Postnatal Depression Scale [EPDS]) and anxiety (Generalised Anxiety Disorder [GAD-7]) using self-report questionnaires. Clinically significant symptoms were defined as EPDS ≥ 13 for depression and GAD-7 ≥ 10 for anxiety. Mental healthcare was defined as self-reported current mental health treatment. RESULTS: Of the 11 809 participants from 12 countries included in the analysis, 4 379 (37.1%) reported clinically significant symptoms of depression (n = 1 228; 10.4%; EPDS ≥ 13 and GAD-7 ⟨ 10), anxiety (n = 848; 7.2%; GAD-7 ≥ 10 and EPDS ⟨ 13) or comorbid symptoms of depression and anxiety (n = 2 303; 19.5%; EPDS ≥ 13 and GAD-7 ≥ 10). Most women with clinically significant symptoms of depression, anxiety, or comorbid symptoms of depression and anxiety were not receiving mental healthcare (89.0%). Variation in the proportion of women with clinically significant symptoms of depression and/or anxiety reporting mental healthcare was high (4.7% in Turkey to 21.6% in Brazil). Women in the postpartum (vs. pregnancy) were less likely (OR 0.72; 95% CI 0.59-0.88), whereas women with previous mental health problems (vs. no previous mental health problems) (OR 5.56; 95% CI 4.41-7.01), were more likely to receive mental healthcare. CONCLUSION: There are high unmet needs in mental healthcare for women with clinically significant symptoms of perinatal depression and/or anxiety across countries during the COVID-19 pandemic. Studies beyond the COVID-19 pandemic and covering the whole range of mental health problems in the perinatal period are warranted to understand the gaps in perinatal mental healthcare.

Depression and fatigue six months post-COVID-19 disease are associated with overlapping symptom constellations: A prospective, multi-center, population-based cohort study.

BACKGROUND: Depression and fatigue are commonly observed sequelae following viral diseases such as COVID-19. Identifying symptom constellations that differentially classify post-COVID depression and fatigue may be helpful to individualize treatment strategies. Here, we investigated whether self-reported post-COVID depression and post-COVID fatigue are associated with the same or different symptom constellations. METHODS: To address this question, we used data from COVIDOM, a population-based cohort study conducted as part of the NAPKON-POP platform. Data were collected in three different German regions (Kiel, Berlin, Würzburg). We analyzed data from >2000 individuals at least six months past a PCR-confirmed COVID-19 disease, using elastic net regression and cluster analysis. The regression model was developed in the Kiel data set, and externally validated using data sets from Berlin and Würzburg. RESULTS: Our results revealed that post-COVID depression and fatigue are associated with overlapping symptom constellations consisting of difficulties with daily activities, perceived health-related quality of life, chronic exhaustion, unrestful sleep, and impaired concentration. Confirming the overlap in symptom constellations, a follow-up cluster analysis could categorize individuals as scoring high or low on depression and fatigue but could not differentiate between both dimensions. LIMITATIONS: The data presented are cross-sectional, consisting primarily of self-reported questionnaire or medical records rather than biometric data. CONCLUSIONS: In summary, our results suggest a strong link between post-COVID depression and fatigue, highlighting the need for integrative treatment approaches.

Machine learning versus multivariate logistic regression for predicting severe COVID-19 in hospitalized children with Omicron variant infection.

With the emergence of the Omicron variant, the number of pediatric Coronavirus Disease 2019 (COVID-19) cases requiring hospitalization and developing severe or critical illness has significantly increased. Machine learning and multivariate logistic regression analysis were used to predict risk factors and develop prognostic models for severe COVID-19 in hospitalized children with the Omicron variant in this study. Of the 544 hospitalized children including 243 and 301 in the mild and severe groups, respectively. Fever (92.3%) was the most common symptom, followed by cough (79.4%), convulsions (36.8%), and vomiting (23.2%). The multivariate logistic regression analysis showed that age (1-3 years old, odds ratio (OR): 3.193, 95% confidence interval (CI): 1.778-5.733], comorbidity (OR: 1.993, 95% CI:1.154-3.443), cough (OR: 0.409, 95% CI:0.236-0.709), and baseline neutrophil-to-lymphocyte ratio (OR: 1.108, 95% CI: 1.023-1.200), lactate dehydrogenase (OR: 1.993, 95% CI: 1.154-3.443), blood urea nitrogen (OR: 1.002, 95% CI: 1.000-1.003) and total bilirubin (OR: 1.178, 95% CI: 1.005-3.381) were independent risk factors for severe COVID-19. The area under the curve (AUC) of the prediction models constructed by multivariate logistic regression analysis and machine learning (RandomForest + TomekLinks) were 0.7770 and 0.8590, respectively. The top 10 most important variables of random forest variables were selected to build a prediction model, with an AUC of 0.8210. Compared with multivariate logistic regression, machine learning models could more accurately predict severe COVID-19 in children with Omicron variant infection.

Diversity of Omicron sublineages and clinical characteristics in hospitalized patients in the southernmost state of Brazil.

BACKGROUND: Omicron has become the dominant variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since first reported in November 2021. From the initially detected Wuhan lineage, sublineages BA.2, BA.4, BA.5, BQ, XAG, and XBB have emerged over time and are dominant in many countries. Therefore, the aim is to evaluate which variants are circulating and the clinical characteristics of inpatients infected with the Omicron variant. METHODS: This retrospective cohort study selected hospitalized patients admitted with respiratory symptoms to a hospital in the state of Rio Grande do Sul, Brazil, between June and July 2022. SARS-CoV-2 results were analyzed together with clinical outcomes and vaccination status. A viral genome library was prepared and forwarded to the Illumina MiSeq Platform for sequencing. RESULTS: In total, 37 genomes were sequenced. Concerning the Omicron sublineages, our study detected: BA.1 (21 K), BA.2 (21 L), BA.4 (22A), BA.5 (22B), BA.2.12.1 (22C), BQ.1 (22E), XBB (22F), and XAG recombinant. Omicron BA.5 (30%), BA.2 (19%), and BQ.1 (19%) were the most frequent sublineages, respectively. In total, 38% of patients present hypertension, and the most common symptoms were coughing (62%). Analyzing the COVID-19 vaccination, 30% of patients were fully vaccinated, 49% had a partial vaccination status, and 21% were unvaccinated (no dose). CONCLUSIONS: BA.5 was the most prevalent sublineage in our study and surpassed the predominance of BA.2, as reported by the national genomic surveillance program. BQ.1 was diagnosed earlier in this study than it was officially reported in the state. Current data have demonstrated that the Omicron variant causes less severe infections, with the high rate of transmissibility and mutational landscape causing the rapid emergence of new sublineages.

Trajectories of mental health outcomes following COVID-19 infection: a prospective longitudinal study.

BACKGROUND: The COVID-19 pandemic has triggered a global mental health crisis. Yet, we know little about the lasting effects of COVID-19 infection on mental health. This prospective longitudinal study aimed to investigate the trajectories of mental health changes in individuals infected with COVID-19 and to identify potential predictors that may influence these changes. METHODS: A web-survey that targeted individuals that had been infected with COVID-19 was used at three time-points: T0 (baseline), T1 (six months), and T2 (twelve months). The survey included demographics, questions related to COVID-19 status, previous psychiatric diagnosis, post-COVID impairments, fatigue, and standardized measures of depression, anxiety, insomnia. Linear mixed models were used to examine changes in depression, anxiety, and insomnia over time and identify factors that impacted trajectories of mental health outcomes. RESULTS: A total of 236 individuals completed assessments and was included in the longitudinal sample. The participants' age ranged between 19 and 81 years old (M = 48.71, SD = 10.74). The results revealed notable changes in mental health outcomes over time. The trajectory of depression showed significant improvement over time while the trends in anxiety and insomnia did not exhibit significant changes over time. Younger participants and individuals who experienced severe COVID-19 infection in the acute phase were identified as high-risk groups with worst mental ill-health. The main predictors of the changes in the mental health outcomes were fatigue and post-COVID impairments. CONCLUSIONS: The findings of our study suggest that mental health outcomes following COVID-19 infection exhibit a dynamic pattern over time. The study provides valuable insights into the mental health trajectory following COVID-19 infection, emphasizing the need for ongoing assessment, support, and interventions tailored to the evolving mental health needs of this population.

Comparison of clinical characteristics, hospital treatment and outcomes in all four waves of Covid-19 patients at RTEH Muzaffargarh, Pakistan.

Background and Objective: The coronavirus pandemic followed a succession of COVID-19 waves globally, and had a varying pattern of frequency of cases and disease spectrum as each wave came with its distinct viral characteristics. The objective of this study was to compare clinical characteristics, treatments and outcomes of patients admitted with severe COVID -19 pneumonia in all four waves at Recep Tayyip Erdogan Hospital (RTEH). Methods: A cross sectional retrospective study was conducted at the COVID unit of Recep Tayyip Erdogan Hospital (RTEH), Muzaffargarh, from April 2020 to December 2021. Retrospective data was taken from Electronic Medical Records of patients of Covid pneumonia and divided into four groups according to four waves of Covid pandemic. The main objective was to compare disease spectrum, treatments and outcomes of patients admitted with severe COVID-19 pneumonia in all four waves at RTEH. Demographic characteristics, inflammatory markers such as C reactive protein (CRP), serum lactate dehydrogenase (LDH), serum ferratin and absolute lymphocyte counts, mortality, length of hospital and ICU stay and event of mechanical ventilation were compared between groups. The Kolmogorov-Smirnov test was applied to check the normality. P-value <0.05 was considered significance. Results: Of a total of 903 patients with covid pneumonia, 521(57.7%) were males and 382 (42.3%) females. Their mean age was 55.56±15.06 years. The mean length of stay (LOS) at the hospital was higher in first wave and least in fourth wave, 9.06±6.46 days and 6.56±5.34 days, respectively, (p<0.010). In first wave, LOS was generally >10 days with 21 (22.6%) while 33(26.8%) patients were shifted to ICU in first and second waves, respectively. Whereas, 35(8.2%) patients shifted to ICU in fourth wave (p<0.010). The use of mechanical ventilation was most common in first and second wave, 14 (15.1%) and 18 (14.6%), respectively. Mortality rate was highest in the third wave, 102 (38.9%, p<0.010) compared to the rest of the waves. Conclusion: Comparison of COVID-19 pneumonia patients across pandemic waves has revealed dynamic trends in patient outcomes. The initial waves had higher ICU admissions and mortality rate, suggesting a need for improved early response and resource allocation. Continuous adaptability in healthcare strategies was paramount for enhancing patient care during the ever-changing pandemic landscape.

The clinical manifestations and pregnancy outcomes of COVID-19 infection at a tertiary care hospital.

Objective: To evaluate clinical presentation and pregnancy outcomes in pregnant women with Covid-19 infection in our local tertiary care from lower middle-income country. Methods: A retrospective study was conducted at Obstetrics & Gynecology department, Sheikh Saeed Memorial Hospital (SSMH) of The Indus Hospital and Health Network (IHHN) from March 2020 to August 2021. Data of 422 admitted pregnant women with COVID-19 infection was retrieved for demographic and clinical information, laboratory tests, pregnancy outcome, and neonatal outcomes on RED-Cap and analyzed on SPSS 26. Univariate and multivariable logistic regression analyses were performed to estimate odds ratios (OR) for symptomology with categorical variables and feto-maternal outcome. Results: Of the total 422 pregnant women, 24.4% were symptomatic, 74.7% exhibiting mild symptoms. Largely reported symptoms were fever (71.8%), cough (36.9%) and body ache (35.0%); while odds of symptomatic COVID-19 infection was less in educated pregnant women (OR 0.3; 95% CI 0.1-0.9) compared to uneducated. Amongst maternal comorbidities, odds of having symptomatic COVID-19 infection were 3.8 times (95% CI 1.1-13.0) in women with chronic hypertension and 5.5 times (95% CI 2.9-10.4) in women with diabetes. Symptomatic women had significantly greater incidence of miscarriages (p= 0.009), PPROM (p= 0.001), preterm birth (p= 0.000), preeclampsia (p= 0.000), placental abruption (p= 0.006) and maternal ICU admission (p= 0.000) than asymptomatic patients. Still birth was higher (6.4% vs 1.3%, p-value= 0.013) in symptomatic group. The odds of having severe maternal outcome were higher (OR=3.5; 95% CI 1.9-6.0) in symptomatic pregnant women. Conclusion: Majority of pregnant women were asymptomatic. Symptomatic women with COVID-19 infection had an increased risk of adverse feto-maternal outcome.

Sleep and memory complaints in long COVID: an insight into clustered psychological phenotypes.

This study evaluated clinical features of individuals with long COVID (5-8 months after diagnosis) who reported sleep and memory problems (62 cases) compared to those without (52 controls). Both groups had a similar mean age (41 vs. 39 years). Around 86% of the participants were non-hospitalized at the time of infection, and none of them were vaccinated at that point. Subsequently, both cases and controls received the vaccine; however, the vaccination rates differed significantly between the groups (30.7% vs. 51.0%). Cases and controls had similar rates of symptoms at acute COVID phase. However, cases were more likely to experience coryza, dyspnea, headache, and nausea/vomiting during long COVID. Regarding new-onset symptoms in long COVID, 12.9% of cases had dyspnea, and 14.5% experienced nausea/vomiting, whereas in the control group there were only 1.9% and 0.0%, respectively. Cases also had a significantly higher prevalence of persistent headache (22.6% vs. 7.7%), and dyspnea (12.9% vs. 0.0). In addition, cases also showed an increased rate of mental health complaints: disability in daily activities (45.2% vs. 9.6%; P < 0.001); concentration/sustained attention difficulties (74.2% vs. 9.6%; P < 0.001); anxiety-Generalized Anxiety Disorder 2-item scale (GAD-2) ≥ 3 (66.1% vs. 34.6%; P = 0.0013); and "post-COVID sadness" (82.3% vs. 40.4%; P < 0.001). We observed a significant correlation between sadness and anxiety in cases, which was not observed in controls (P=0.0212; Spearman correlation test). Furthermore, the frequency of concomitant sadness and anxiety was markedly higher in cases compared to controls (59.7% vs. 19.2%) (P < 0.0001; Mann-Whitney test). These findings highlight a noteworthy association between sadness and anxiety specifically in cases. In conclusion, our data identified concurrent psychological phenotypes in individuals experiencing sleep and memory disturbances during long COVID. This strengthens the existing evidence that SARS-CoV-2 causes widespread brain pathology with interconnected phenotypic clusters. This finding highlights the need for comprehensive medical attention to address these complex issues, as well as major investments in testing strategies capable of preventing the development of long COVID sequelae, such as vaccination.

A Retrospective and Comparative Analysis of Clinical Outcomes of Kidney Transplant Recipients During First and Second COVID-19 Waves in North-West India.

Introduction Kidney transplant recipients (KTRs) are prone to coronavirus disease 2019 (COVID-19) disease secondary to chronic immunosuppressive therapy. There have been differences in mortality and morbidity amongst the general population with different COVID-19 waves. This study is done to understand the effects of different COVID-19 waves amongst KTRs. Methods This was a retrospective single-centre trial from a high-volume transplant centre in North India. The immunosuppression protocol was changed according to national guidelines, and predictors of survival were evaluated. Results A total of 62 patients got infected during the first COVID-19 wave (March 2020 to February 2021) and 50 patients during the second COVID-19 wave (March 2021 to December 2021). Analysis showed a higher incidence of severe COVID-19 disease (79% vs. 50%) in the first wave, while the rest of the baseline parameters were similar in both waves. Mortality was similar in both groups. In both groups, severe COVID-19 disease, the requirement of hospitalisation, invasive oxygen therapy, and CT score findings were significant predictors of survival. There was no change in survival with respect to immunosuppression modification. Allograft dysfunction was more common in the second wave (7 vs. 1). Baseline creatinine was significantly associated with allograft dysfunction in follow-up. Conclusion Patients had severe COVID-19 disease during the first wave; however, poor availability of healthcare services during the second wave led to more patients with allograft dysfunction. Though immunosuppression change is necessary to prevent flare-ups of COVID-19 infection, it is not associated with survival benefits.

Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial.

BACKGROUND: Obesity is a widespread and chronic condition that requires long-term management; research into additional targets to improve treatment outcomes remains a priority. This study aimed to investigate the safety, tolerability, and efficacy of glucagon receptor-GLP-1 receptor dual agonist survodutide (BI 456906) in obesity management. METHODS: In this randomised, double-blind, placebo-controlled, dose-finding phase 2 trial conducted in 43 centres in 12 countries, we enrolled participants (aged 18-75 years, BMI ≥27 kg/m2, without diabetes) and randomly assigned them by interactive response technology (1:1:1:1:1; stratified by sex) to subcutaneous survodutide (0·6, 2·4, 3·6, or 4·8 mg) or placebo once-weekly for 46 weeks (20 weeks dose escalation; 26 weeks dose maintenance). The primary endpoint was the percentage change in bodyweight from baseline to week 46. Primary analysis included the modified intention-to-treat population (defined as all randomly assigned patients who received at least one dose of trial medication and who had analysable data for at least one efficacy endpoint) and was based on the dose assigned at randomisation (planned treatment), including all data censored for COVID-19-related discontinuations; the sensitivity analysis was based on the actual dose received during maintenance phase (actual treatment) and included on-treatment data. Safety analysis included all participants who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov (NCT04667377) and EudraCT (2020-002479-37). FINDINGS: Between March 30, 2021, and Nov 11, 2021, we enrolled 387 participants; 386 (100%) participants were treated (0·6 mg, n=77; 2·4 mg, n=78; 3·6 mg, n=77; 4·8 mg, n=77; placebo n=77) and 233 (60·4%) of 386 completed the 46-week treatment period (187 [61%] of 309 receiving survodutide; 46 [60%] of 77 receiving placebo). When analysed according to planned treatment, mean (95% CI) changes in bodyweight from baseline to week 46 were -6·2% (-8·3 to -4·1; 0·6 mg); -12·5% (-14·5 to -10·5; 2·4 mg); -13·2% (-15·3 to -11·2; 3·6 mg); -14·9% (-16·9 to -13·0; 4·8 mg); -2·8% (-4·9 to -0·7; placebo). Adverse events occurred in 281 (91%) of 309 survodutide recipients and 58 (75%) of 77 placebo recipients; these were primarily gastrointestinal in 232 (75%) of 309 survodutide recipients and 32 (42%) of 77 placebo recipients. INTERPRETATION: All tested survodutide doses were tolerated, and dose-dependently reduced bodyweight. FUNDING: Boehringer Ingelheim.

Obesity care for youth during the COVID-19 pandemic: Challenges youth healthcare nurses experienced in providing obesity care in the Netherlands.

The COVID-19 pandemic deeply affected the lives of children and young people; studies report adverse effects on mental, physical, and social well-being. However, the impact of the pandemic on obesity care for children received little attention. The aim of this study was to gain insight into the challenges youth healthcare nurses experienced and to describe implications for future obesity care and policy. We conducted interviews, participant observations, and a group session with youth healthcare nurses during the pandemic in Amsterdam, the Netherlands. Youth healthcare nurses reported a deterioration in the problems of children and young people who were already in the highest classification for pediatric obesity, such as increased weight gain, mental health problems, and socio-economic problems. The nurses experienced immense challenges while trying to provide obesity care, such as a decrease in face-to-face contact with youth and their families, as well as loss of continuity of care. It is important to reconnect with these families, invest in a trusted relationship with youth receiving obesity care, and prioritize available and accessible obesity care for those who need it the most.

Differences in psychiatric comorbidity patterns in patients diagnosed with chronic stress-induced exhaustion disorder and depression - A cohort study in the total population of Region Stockholm.

The high prevalence of stress-related disorders and depression underscores the urgent need to unravel their impact on individual well-being. This study aim to investigate common psychiatric and stress-related diagnoses, along with postviral fatigue, in individuals with prior stress-induced exhaustion disorder (SED) and prior depression compared to those without prior SED or depression, and to study whether the psychiatric comorbidity patterns differ. The study includes individuals in Region Stockholm who, in 2011, did not have a diagnosis of SED or depression. ICD-10 diagnosis of SED, depression, or both, recorded in 2012-2013, were compared to individuals without prior SED or depression in a cohort (n = 1,362,886), aged 18 to 65. Odds ratios (OR) with 99 % confidence intervals, adjusted for age and neighborhood socioeconomic status, were calculated for psychiatric disorders and post-viral fatigue in 2014-2022. Patients with prior SED showed associations primarily with stress related diagnoses, including acute stress reaction, reaction to severe stress, as well as post-COVID-19 and post-viral fatigue syndrome. These ORs were all larger for SED than depression. Depression was primarily associated with post-traumatic stress disorder (PTSD), alcohol related and substance use disorders, schizophrenia, schizotypal disorders, delusional disorders, manic episode, bipolar affective disorder, persistent mood disorder, neurotic disorder, borderline personality disorder, autistic disorder, Asperger's syndrome, attention -deficit hyperactivity disorder, attention-deficit disorders ADHD/ADD), and suicide attempt. These ORs were all higher for depression, although autistic disorders, ADHD/ADD and PTSD were also highly associated with prior SED (OR > 3.5). The divergent psychiatric comorbidity patterns suggest different underlying mechanisms and clinical prognosis.

In silico identification of viral loads in cough-generated droplets - Seamless integrated analysis of CFPD-HCD-EWF.

BACKGROUND AND OBJECTIVE: Respiratory diseases caused by respiratory viruses have significantly threatened public health worldwide. This study presents a comprehensive approach to predict viral dynamics and the generation of stripped droplets within the mucus layer of the respiratory tract during coughing using a larynx-trachea-bifurcation (LTB) model. METHODS: This study integrates computational fluid-particle dynamics (CFPD), host-cell dynamics (HCD), and the Eulerian wall film (EWF) model to propose a potential means for seamless integrated analysis. The verified CFPD-HCD coupling model based on a 3D-shell model was used to characterize the severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2) dynamics in the LTB mucus layer, whereas the EWF model was employed to account for the interfacial fluid to explore the generation mechanism and trace the origin site of droplets exhaled during a coughing event of an infected host. RESULTS: The results obtained using CFPD delineated the preferential deposition sites for droplets in the laryngeal and tracheal regions. Thus, the analysis of the HCD model showed that the viral load increased rapidly in the laryngeal region during the peak of infection, whereas there was a growth delay in the tracheal region (up to day 8 after infection). After two weeks of infection, the high viral load gradually migrated towards the glottic region. Interestingly, the EWF model demonstrated a high concentration of exhaled droplets originating from the larynx. The coupling technique indicated a concurrent high viral load in the mucus layer and site of origin of the exhaled droplets. CONCLUSIONS: This interdisciplinary research underscores the seamless analysis from initial exposure to virus-laden droplets, the dynamics of viral infection in the LTB mucus layer, and the re-emission from the coughing activities of an infected host. Our efforts aimed to address the complex challenges at the intersection of viral dynamics and respiratory health, which can contribute to a more detailed understanding and targeted prevention of respiratory diseases.

Comparison of plasma inflammatory biomarkers between MIS-C and potentially serious infections in pediatric patients.

BACKGROUND: Inflammatory biomarkers have been used for the diagnosis and management of multisystemic inflammatory syndrome in children (MIS-C). We aimed to compare the clinical and laboratory findings of MIS-C cases versus other febrile cases cataloged as potentially suspected bacterial infection (non-MIS-C). METHODS: Unicentric ambispective observational cohort study (June 2020-February 2022). We analyzed demographics, clinical symptoms and laboratory findings in MIS-C cases and in non-MIS-C cases with febrile processes of patients under 15 years of age admitted to hospital. RESULTS: We enrolled 54 patients with potential suspected bacterial infection and 20 patients with MIS-C for analysis. Fever (100%), gastrointestinal (80%) and mucocutaneous findings (35%) were common in MIS-C patients, also hypotension (36.8%) and tachycardia (55%). Laboratory findings showed significantly elevated proBNP (70%), ferritin (35%), D-dimer (80%) and lymphopenia (55%) and thrombocytopenia (27.8%) in MIS-C cases. IL-6 values were high in non-MIS-C patients (92.6%). CONCLUSIONS: In the management of MIS-C patients, the dynamic monitoring of proBNP, ferritin, D-dimer, lymphocytes and platelets could be helpful to pediatricians to effectively evaluate the progress of MIS-C in the early phases, not IL-6 values. The applicability of the IL-6 level as a prognostic biomarker in MIS-C patients may require closer discussion. In addition, the optimal laboratory markers, as stated in our study, can help establish a biomarkers model to early distinguish the MIS-C versus non-MIS-C in patients who are admitted to febrile syndrome.

Sarcopenia and risk factors among Japanese community-dwelling older adults during the COVID-19 pandemic: A cross-sectional study.

The COVID-19 pandemic exposed older adults to high risk of sarcopenia. This study aimed to investigate the prevalence of sarcopenia and its risk factors among Japanese community-dwelling older adults during the COVID-19 pandemic. We collected data through questionnaires and physical measurements among 242 older adults. Sarcopenia was assessed using the Asian Working Group for Sarcopenia 2019 criteria. The results revealed that 14.5% had sarcopenia, which was significantly associated with age, nutritional status, number of prescription medications, body mass index, and self-rated health. On multivariate analysis, the risk of malnutrition was independently significantly associated with sarcopenia. Approximately 70% of participants reported decreased social interaction and going outside, but with no significant association with sarcopenia. In addition, approximately 65% of the participants had an exercise habit and went outside at least once a week, thus maintaining a good level of activity. These findings suggest that prevention of sarcopenia during the pandemic required provision of opportunities for older adults to remain active and positive assessment of nutritional status and well-being.

Clinical and Laboratory Characteristics of Fatigue-Dominant Long-COVID Subjects: A Cross-Sectional Study.

BACKGROUND: Long COVID is defined by persistent symptoms following COVID-19 infection. Approximately 71% of individuals with long COVID experience ongoing fatigue, postexertional malaise, and cognitive impairments, which share pathological similarities with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This similarity has prompted studies to explore the characteristics of long COVID to gain a better understanding of ME/CFS. To gain insights, we investigated the clinical and laboratory characteristics of individuals with fatigue-dominant long COVID. METHODS: We enrolled 100 subjects (36 males, 64 females) with long COVID who had a higher score than 60 in the modified Korean version of the Chalder Fatigue Scale (mKCFQ11) and higher than 5 in a fatigue-focused visual analogue scale. To investigate fatigue symptoms, the mKCFQ11, the Multidimensional Fatigue Inventory, a visual analogue scale for fatigue and brain fog, along with the Short-Form survey, were employed. We also measured 3 cytokines and cortisol levels for immunological and endocrinological indicators. As a cross-sectional observational study, the data were collected at a single point in time. RESULTS: The mean scores on the measurements showed severe fatigue, and these scores were significantly correlated, with no differences based on sex, the post-COVID period, or age. Among the laboratory tests, plasma cortisol levels had a significant negative correlation with fatigue scores and a positive correlation with living quality. The negative correlation between cortisol levels and mKCFQ11 scores appeared to be more specific to mental fatigue than physical, which conflicted with other measurements. CONCLUSION: Our findings provide the first insights into the characteristics of fatigue in individuals with long COVID, particularly in terms of fatigue severity and cortisol levels. These results serve as valuable reference data for clinicians dealing with fatigue symptoms in long-COVID patients and for researchers exploring postviral fatigue symptoms, including ME/CFS, in the future.