Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

DataSheet1_The chemistry of gut microbiome-derived lipopolysaccharides impacts on the occurrence of food allergy in the pediatric age.PDF

Introduction: Food allergy (FA) in children is a major health concern. A better definition of the pathogenesis of the disease could facilitate effective preventive and therapeutic measures. Gut microbiome alterations could modulate the occurrence of FA, although the mechanisms involved in this phenomenon are poorly characterized. Gut bacteria release signaling byproducts from their cell wall, such as lipopolysaccharides (LPSs), which can act locally and systemically, modulating the immune system function.Methods: In the current study gut microbiome-derived LPS isolated from fecal samples of FA and healthy children was chemically characterized providing insights into the carbohydrate and lipid composition as well as into the LPS macromolecular nature. In addition, by means of a chemical/MALDI-TOF MS and MS/MS approach we elucidated the gut microbiome-derived lipid A mass spectral profile directly on fecal samples. Finally, we evaluated the pro-allergic and pro-tolerogenic potential of these fecal LPS and lipid A by harnessing peripheral blood mononuclear cells from healthy donors.Results: By analyzing fecal samples, we have identified different gut microbiome-derived LPS chemical features comparing FA children and healthy controls. We also have provided evidence on a different immunoregulatory action elicited by LPS on peripheral blood mononuclear cells collected from healthy donors suggesting that LPS from healthy individuals could be able to protect against the occurrence of FA, while LPS from children affected by FA could promote the allergic response.Discussion: Altogether these data highlight the relevance of gut microbiome-derived LPSs as potential biomarkers for FA and as a target of intervention to limit the disease burden.</p

Psychological Distress After Covid-19 Recovery: Reciprocal Effects With Temperament and Emotional Dysregulation. An Exploratory Study of Patients Over 60 Years of Age Assessed in a Post-acute Care Service

To study the long-term psychological effects of Covid-19 disease, we recruited 61 patients older than 60 years of age and administered the Kessler questionnaire K10 to assess psychological distress and classify them according to mental health risk groups. Patients' affective temperaments were assessed with the 39-item form of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-A-39) and emotional dysregulation with the Difficulties in Emotion Regulation Scale (DERS). Patients were divided in two samples according to their scores on the K10, i.e., a high likelihood of psychological distress group (N = 18) and a low likelihood of psychological distress group (N = 43). The two groups differed on their gender composition, in that more women (N = 11) were in the former and more men in the latter (N = 29) (χ2 = 4.28; p = 0.039). The high likelihood of psychological distress group scored higher on the Cyclothymic (3.39 ± 3.45 vs. 0.93 ± 1.08, p &lt; 0.001) and the Depressive (2.28 ± 2.82 vs. 0.65 ± 1.09, p = 0.01) affective temperaments of the TEMPS and on the lack of Impulse control (12.67 ± 4.04 vs. 9.63 ± 3.14, p = 0.003) and lack of Clarity (15.00 ± 5.56 vs. 9.85 ± 4.67, p = 0.004) scales of the DERS. Our results show that having had Covid-19 may be related with high likelihood for psychological distress in advanced-age people and this may in turn be associated with impaired emotional regulation and higher scores on depressive and cyclothymic temperaments

Residual respiratory impairment after COVID-19 pneumonia

Abstract Introduction: The novel coronavirus SARS-Cov-2 can infect the respiratory tract causing a spectrum of disease varying from mild to fatal pneumonia, and known as COVID-19. Ongoing clinical research is assessing the potential for long-term respiratory sequelae in these patients. We assessed the respiratory function in a cohort of patients after recovering from SARS-Cov-2 infection, stratified according to PaO2/FiO2 (p/F) values. Method: Approximately one month after hospital discharge, 86 COVID-19 patients underwent physical examination, arterial blood gas (ABG) analysis, pulmonary function tests (PFTs), and six-minute walk test (6MWT). Patients were also asked to quantify the severity of dyspnoea and cough before, during, and after hospitalization using a visual analogic scale (VAS). Seventy-six subjects with ABG during hospitalization were stratified in three groups according to their worst p/F values: above 300 (n = 38), between 200 and 300 (n = 30) and below 200 (n = 20). Results: On PFTs, lung volumes were overall preserved yet, mean percent predicted residual volume was slightly reduced (74.8 ± 18.1%). Percent predicted diffusing capacity for carbon monoxide (DLCO) was also mildly reduced (77.2 ± 16.5%). Patients reported residual breathlessness at the time of the visit (VAS 19.8, p &lt; 0.001). Patients with p/F below 200 during hospitalization had lower percent predicted forced vital capacity (p = 0.005), lower percent predicted total lung capacity (p = 0.012), lower DLCO (p &lt; 0.001) and shorter 6MWT distance (p = 0.004) than patients with higher p/F. Conclusion: Approximately one month after hospital discharge, patients with COVID-19 can have residual respiratory impairment, including lower exercise tolerance. The extent of this impairment seems to correlate with the severity of respiratory failure during hospitalization

European Multicenter Study of ET-COVID-19

International audienceBackground and Purpose: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19. Methods: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality. Secondary outcomes: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0–1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage. Results: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59–79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11–21) and 8 (interquartile range, 7–9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3–87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20–39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8–29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7–12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21–5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22–5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43–12.91] per SD-log increase in LDH). Conclusions: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient’s profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT04406090