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BACKGROUND: Specialist early intervention (SEI) service models are designed to treat symptoms, promote social and vocational recovery, prevent relapse, and resource and up-skill patients and their families. The benefits of SEI over the first few years have been demonstrated. While early recovery can be expected to translate to better long-term outcomes by analogy with other illnesses, there is limited evidence to support this from follow-up studies. The current study involves the long-term follow-up of a sub-set of first episode psychosis (FEP) patients, with a range of diagnoses, who were first treated at Orygen's Early Psychosis Prevention and Intervention Centre (EPPIC) between 1998 and 2000. The aim of this paper is to present the methodology for this follow-up study. METHODS: Between January 1998 and December 2000, 786 patients between the ages of 15-29 years were treated at EPPIC, located in Melbourne, Australia. Our cohort consists of 661 people (82 were transferred/discharged and 43 were not diagnosed with a psychotic disorder at time of discharge). The 18-month treatment characteristics of this cohort have been extensively examined in the First Episode Psychosis Outcome Study (FEPOS). The ≥15 year outcomes of this cohort are being examined in this study, known as FEPOS15. RESULTS: Participant follow-up is ongoing. In order to extend and assess broader outcomes of the cohort, data linkage with health-related databases will be conducted. CONCLUSION: This study will provide a comprehensive evaluation of the long-term trajectory of psychotic disorders after treatment for FEP in a SEI service.

People with Bipolar Disorder (BD) consistently report a desire for employment; however, this is not reflected in employment figures. Individuals' perceptions of barriers to employment, along with endorsement of facilitators to employment remain under-investigated. We aimed to address this limitation by: (i) first examining differences in employed versus unemployed individuals (demographic, clinical, functioning); then (ii) identifying barriers and/or facilitators to employment, perception of same, and subsequent impact on employment. We assessed demographics, functioning, and illness-related characteristics in 35 participants with BD (19 employed, 16 unemployed). Participants were asked to indicate perception of common barriers and facilitators to employment. Groups did not differ regarding demographic or clinical variables. High levels of absenteeism, termination of last role and commonly perceived barriers were attributed to mental ill-health. 93.3% of unemployed participants reportedly desired employment, and more perceived barriers were observed in the unemployed group. Identified facilitators included increased support and flexible work strategies. A comprehensive understanding of perceptions of limiting and helpful factors related to employment for people with BD was obtained. These findings have implications for service provision, encouraging targeted discussion, and tailored treatment approaches to individual's unique perceptions of factors related to employment.

Introduction: Cystic fibrosis (CF) is the most common life-shortening recessive genetic disease in Caucasians, affecting primarily the lungs. The objective of our study was to investigate potential ophthalmologic involvement in adult patients with CF. Methods: Fifty adult patients with cystic fibrosis and 60 age- and sex-matched controls underwent complete ophthalmologic examination including tear-film Break-Up Time (BUT), Macular Thickness, and peripapillary Retinal Nerve Fiber Layer (pRNFL) thickness measurements using Spectral Domain-OCT. Results: CF patients had significantly lower nasal-inferior pRNFL thickness (median 82 IQR 67–102 vs 92.5 IQR 82–107, p = 0.005) and lower percentage of normal tear Break-Up Time (56.0% vs 96.7%, p = 0.001) than healthy controls. All CF patients with BUT Conclusions: Our study is, to the best of our knowledge, the largest ophthalmologic study of patients with cystic fibrosis. We found that CF patients had significantly decreased inferior-quadrant peripapillary retinal nerve fiber layer thickness and decreased tear-film break-up time compared to controls. We highlight the importance of careful regular ophthalmologic assessment and follow-up of these patients.

Aims: to determine the effect of NAC administration on hematological abnormalities in HIV/AIDS patients who are undergoing ARV treatment. Method: This was a pilot study using a double blind randomized clinical trial. A total of 32 subjects who met the inclusion and exclusion criteria were divided into 2 groups, namely placebo and NAC. Subjects in the NAC group were given NAC at a dose of 3x200 mg/day, while the placebo group was given lactose at a dose of 3x200 mg/day. Each group was given treatment for 12 weeks. Before and after treatment, subjects were examined for hematologic parameters. Results: Most of subjects had normal hematological features. NAC administration did not have a significant effect on the mean levels of Hb, Ht, number of erythrocytes, leukocytes and platelets (p> 0.05). However, NAC administration can reduce the degree of anemia and improve the condition of thrombocytopenia, leukopenia and lymphopenia. Conclusion: NAC administration can reduce hematological abnormalities HIV/AIDS patients undergoing ARV treatment. Keywords: ARV, Hematological abnormalities, HIV/AIDS, NAC.

Data available on possible associations of lipids, steroid levels, and depression are conflicting. This study investigated their possible associations in a sample of youth with depression. Ninety-eight youth with depression and individually matched healthy volunteers on the basis of age and sex were enrolled for the study. The two groups had nearly similar body mass index. After fasting overnight, they underwent blood sampling for triglycerides (TG), total cholesterol, low-density lipoprotein, high-density lipoprotein (HDL)-cholesterol, apolipoprotein A1 (apo A1) and B (apo B), lipoprotein A (LpA), morning cortisol, total testosterone (TT), estradiol (E2), and DHEAS measurements. All participants were evaluated with the semi-structured psychiatric K-SADS-PL interview and filled out the self-rating Children’s Depression Inventory (CDI). Salivary cortisol was also determined serially five times a day. Children with depression showed significantly higher levels of plasma TG (p = 0.006), lower apolipoprotein A1 (p = 0.043), higher morning cortisol (p = 0.011) and TT (p = 0.001), as well as lower E2 levels (p = 0.032) compared to those of controls. Positive correlations for the total sample was observed between TG (R = 0.24, p = 0.018), TT (R = 0.35, p

espanolLa afectacion hepatica en el contexto de un proceso infeccioso sistemico constituye un problema clinico frecuente, cuyo espectro comprende desde alteraciones analiticas con escasa expresion clinica hasta cuadros graves de hepatitis fulminante. La frecuencia con la que se presenta varia en funcion del estado de inmunocompetencia del huesped y del espacio geografico en el que nos encontremos. La etiologia de la enfermedad hepatica de origen infeccioso es variable, pudiendo estar implicadas bacterias, virus, hongos y parasitos. En esta actualizacion, se revisa la implicacion hepatica en el seno de las infecciones sistemicas por microorganismos no propiamente considerados germenes hepatotropos, incidiendo en las peculiaridades relevantes de cara al diagnostico y tratamiento en cada una de ellas. EnglishLiver involvement in systemic infectious disorder is a frequent condition, whose clinical spectrum ranges from subclinical biochemical change to even fulminant hepatic failure. Incidence varies depending on immunocompetence status and geographic situation of patient. Etiology of infectious liver disease is variable, bacteria, viruses, fungi and parasites can be involved. Current update reviews liver involvement in systemic infectious diseases caused by non-hepatotropic microorganisms, focusing on relevant peculiarities of each one facing the diagnosis and treatment.

espanolLas alteraciones hepaticas aparecen aproximadamente en el 3% de las gestaciones. La gravedad de estos procesos es variable, desde alteraciones analiticas asintomaticas hasta enfermedades graves con alta morbimortalidad. Por ello, es importante estudiar a cualquier gestante con sospecha de hepatopatia de forma precoz y reconocer los procesos potencialmente graves para iniciar las medidas terapeuticas necesarias. Dentro de las hepatopatias que pueden presentarse durante el embarazo se reconocen dos grandes grupos: enfermedades propias de la gestacion que no aparecen en otros contextos clinicos y enfermedades hepaticas que coinciden temporalmente con el embarazo. Este ultimo grupo engloba tanto hepatopatias agudas como enfermedades hepaticas cronicas. En ambos casos, debe tenerse en cuenta que la gestacion puede modificar el curso clinico habitual de la enfermedad, en ocasiones con importantes implicaciones pronosticas. EnglishLiver disorders appears approximately in 3% of pregnancies. Severity is variable and goes from asymptomatic to severe diseases with high morbi-mortality. Thus, early study of any pregnant woman suspected of liver disease has to be carried out, and potentially severe conditions have to be recognized in order to initiate therapeutic measures. We identify two large groups of liver diseases during pregnancy: gestational diseases not developed in other clinical contexts and liver diseases coinciding with pregnancy. The last group encompass both acute liver diseases as well as chronic liver diseases. In both cases, it is necessary to take in to account that pregnancy can modify the usual clinical course of the disease, with important prognostic implications at times.

espanolLa insuficiencia hepatica aguda grave (fallo hepatico agudo o fulminante) es una entidad poco frecuente caracterizada por un deterioro de la funcion hepatica en pacientes sin hepatopatia previa conocida, que se manifiesta por la presencia de coagulopatia de origen hepatico, ictericia y alteracion variable del nivel de consciencia (encefalopatia hepatica). La etiologia del cuadro es muy variable, desde causas mas frecuentes como hepatotoxicidad por diversas sustancias (como paracetamol) o la hepatitis isquemica o virica, hasta otras mucho menos habituales como la enfermedad de Wilson o el sindrome de Budd-Chiari. En otros casos (hasta el 40%) no se consigue identificar la causa desencadenante. Sin tratamiento, el pronostico de estos pacientes es pobre, con una mortalidad libre de trasplante incluso superior al 90% en algunos casos, por lo que el reconocimiento a tiempo del cuadro y su manejo de forma precoz resultan fundamentales. Ademas de medidas generales de soporte, debera iniciarse el tratamiento especifico de la causa (si esta se conoce) siempre que se disponga del mismo. Sin embargo, en muchos casos, ya sea por desconocimiento de la causa desencadenante, ausencia de tratamiento etiologico o de mejoria del paciente a pesar de la instauracion del mismo, el trasplante hepatico urgente sera la unica solucion posible para estos pacientes EnglishSevere acute liver failure (acute or fulminant hepatic failure) is a rare disorder characterized by hepatic function deterioration in patients without previous liver disease; it leads to hepatic coagulopathy, jaundice and hepatic encephalopathy (loss of consciousness in variable degree). Etiology varies from hepatoxicity (drug-induced injure, for example paracetamol) the commonest, to ischemic or viral hepatitis; including other causes much less frequent (Wilson's disease and Budd-Chiari syndrome). Triggering cause is not identified in other cases (up to 40%). Without treatment prognosis is poor, and transplant free mortality can exceed 90%; so, on-time diagnosis and early management are mandatory. Together with support measures, cause-specific treatment has to be stablished (if cause is known and treatment is available). However, urgent hepatic transplantation is the only possible treatment for such patients (unknowing triggering cause, etiologic treatment not available or lack of treatment response)

Background: Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). Methods: We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. Results: Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/10 0 0 pwCF. Incidence was higher in lung-transplanted patients (n = 23) versus non transplanted patients (n = 107) (8.43 versus 2.36 cases/10 0 0). Incidence was higher in pwCF versus the age-matched general population in the age groups < 15, 15-24, and 25-49 years (p < 0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p = 0.133). Conclusions: SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

The diagnosis of abortion in livestock is difficult. In this paper, Neospora caninumassociated abortion in cattle and buffaloes in India is reported for the first time. A total of 184 animals (cattle, n = 133; water buffaloes, n = 51) were randomly selected for seroprevalence studies from 28 farms with a history of abortion. Antibodies to N. caninum were detected using a commercial competitive enzymelinked immunosorbent assay (c-ELISA); the percentage seropositivity was 10.5% for cattle and 21.6% for buffaloes. Risk factors such as species, i.e. buffaloes in comparison to cattle (odds ratio [OR] = 2.33, calculated probability [p] = 0.05), disposal of foetus and foetal membranes by throwing them into the field, in comparison with burning/burial (OR = 2.63, p = 0.03), and origin of the animal, i.e. purchased from outside in comparison to born on the farm (OR = 4.69, p = 0.002), were significantly associated with N. caninum seropositivity in univariate logistic regression. In multivariate analysis, only two risk factors, animal purchased from outside (OR = 6.15, p = 0.001) and buffaloes (OR = 3.20, p = 0.01), were significantly associated with Neospora seropositivity at a p-value < 0.05. Histopathological examination of aborted foetal tissues (cattle, n = 13; buffaloes, n = 8) revealed N. caninum tachyzoites in the heart and liver of three foetuses, and the diagnosis was confirmed by positive immunoreactivity to anti-N. caninum polyclonal antibody in the placenta of one foetus. To the authors' knowledge, this is the first report of confirmed neosporosis abortion in cattle and buffaloes in India.

Purpose: Previously identified transcriptomic signatures have been based on primary and metastatic melanomas with relatively few American Joint Committee on Cancer (AJCC) stage I tumors, given difficulties in sampling small tumors. The advent of adjuvant therapies has highlighted the need for better prognostic and predictive biomarkers, especially for AJCC stage I and stage II disease. Experimental Design: A total of 687 primary melanoma transcriptomes were generated from the Leeds Melanoma Cohort (LMC). The prognostic value of existing signatures across all the AJCC stages was tested. Unsupervised clustering was performed, and the prognostic value of the resultant signature was compared with that of sentinel node biopsy (SNB) and tested as a biomarker in three published immunotherapy datasets. Results: Previous Lund and The Cancer Genome Atlas signatures predicted outcome in the LMC dataset (P = 10−8 to 10−4) but showed a significant interaction with AJCC stage (P = 0.04) and did not predict outcome in stage I tumors (P = 0.3–0.7). Consensus-based classification of the LMC dataset identified six classes that predicted outcome, notably in stage I disease. LMC class was a similar indicator of prognosis when compared with SNB, and it added prognostic value to the genes reported by Gerami and colleagues. One particular LMC class consistently predicted poor outcome in patients receiving immunotherapy in two of three tested datasets. Biological characterization of this class revealed high JUN and AXL expression and evidence of epithelial-to-mesenchymal transition. Conclusions: A transcriptomic signature of primary melanoma was identified with prognostic value, including in stage I melanoma and in patients undergoing immunotherapy.

Background Interventions early in the course of bipolar disorder (BD) may have the potential to limit its functional and symptomatic impact. However, the implementation of specific early interventions for BD has been limited which may at least partly be due to the lack of guidelines focused on the early illness stages. We therefore aimed to review the current recommendations for early stage BD from clinical practice guidelines. Methods We searched PubMED and PsychINFO for clinical guidelines for BD published in the ten years prior to 1 November 2018. Recommendations from identified guidelines that addressed early stage BD or first episode mania were consolidated and compared. We also reviewed the guidelines relating to adolescents with BD to complement the guidelines related to those in the early illness course. Results We identified fourteen international and national guidelines on BD or affective psychoses. Most guidelines contained a separate section on adolescents, but only a few referred specifically to early stage BD. There were no consistent recommendations for early stage disorder, except with respect to the indications for maintenance medication treatments. For adolescents, there was a consistent recommendation for the use of second generation antipsychotics for treating acute mania. Limitation The main limitation is that the identified guidelines did not include primary data that clearly separated illness and developmental stages. Conclusions There is a lack of emphasis on early BD among widely-respected current clinical guidelines, likely reflecting the dearth of primary data. Future evidence or consensus-based recommendations could significantly inform clinical practice for this population.

Aims: Social inclusion is increasingly understood to have positive and beneficial implications for the mental health outcomes of people with severe mental illness. The concept is plagued by definitional inconsistencies and a lack of consensus regarding what it means to be socially included, in particular for groups most vulnerable to social exclusion, such as people with mental illness. The aim of this study was to obtain a consensus regarding the key contributors to social inclusion from the perspective of people with and without a lived experience of mental illness (consumers of mental health services, carers, and general community members). Methods: Delphi methodology was employed to reach consensus agreement. The Delphi questionnaire was based on a previous review of the literature and consisted of 147 items categorized into 13 domains. It was presented to participants over three rounds. Participants ( N = 104) were recruited into three groups (32 consumers, 32 carers of people with a mental illness, and 40 members of the general community – neither consumers nor carers). Retention of participants from Round 1 to Round 3 was 79.8%. Results: Similarities and differences were observed between the groups. A number of items were very strongly endorsed as key contributors to social inclusion, relating to social participation, social supports, housing, neighbourhood, community involvement, employment and education, health and well-being and service utilization. Conclusion: Findings supported previous work, indicating the importance of having a strong sense of connection with others as well as the importance of safe and stable housing, support services and personal motivation and hope. We obtained a well-rounded perspective among groups regarding the key contributors to social inclusion, with a particular relevance to people living with mental illness. This perspective has significant clinical and research utility.

To assess the real-world impact of vaccines on COVID-19 related outcomes, we analysed data from over 7 million recipients of at least one COVID-19 vaccine dose in Italy. Taking 0–14 days post-first dose as reference, the SARS-CoV-2 infection risk subsequently decreased, reaching a reduction by 78% (incidence rate ratios (IRR): 0.22; 95% CI: 0.21–0.24) 43–49 days post-first dose. Similarly, hospitalisation and death risks decreased, with 89% (IRR: 0.11; 95% CI: 0.09–0.15) and 93% (IRR: 0.07; 95% CI: 0.04–0.11) reductions 36–42 days post-first dose. Our results support ongoing vaccination campaigns.

In Italy, the COVID-19 vaccination campaign started in December 2020 with the vaccination of healthcare workers (HCW). To analyse the real-life impact that vaccination is having on this population group, we measured the association between week of diagnosis and HCW status using log-binomial regression. By the week 22-28 March, we observed a 74% reduction (PPR 0.26; 95% CI 0.22-0.29) in the proportion of cases reported as HCW and 81% reduction in the proportion of symptomatic cases reported as HCW, compared with the week with the lowest proportion of cases among HCWs prior to the vaccination campaign (31 August-7 September). The reduction, both in relative and absolute terms, of COVID-19 cases in HCWs that started around 30 days after the start of the vaccination campaign suggest that COVID-19 vaccines are being effective in preventing infection in this group.

Control of Mycobacterium tuberculosis infection continues to be an issue, particularly in countries with a high tuberculosis (TB) burden in the tropical and sub-tropical regions. The effort to reduce the catastrophic cost of TB with the WHO’s End TB Strategy in 2035 is still obstructed by the emergence of drug-resistant TB (DR-TB) cases as result of various mutations of the MTB strain. In the approach to combat DR-TB, several potential antitubercular agents were discovered as inhibitors for various existing and novel targets. Host-directed therapy and immunotherapy also gained attention as the drug-susceptibility level of the pathogen can be reduced due to the pathogen’s evolutionary dynamics. This review is focused on the current progress and challenges in DR-TB treatment. We briefly summarized antitubercular compounds that are under development and trials for both DR-TB drug candidates and host-directed therapy. We also highlighted several problems in DR-TB diagnosis, the treatment regimen, and drug discovery that have an impact on treatment adherence and treatment failure.

OBJECTIVE: There is a lack of existing research regarding young people with bipolar I disorder (BD-I) and psychotic features, who are not in education, employment, and training (NEET). Thus, the aims of the study were to: (a) establish rates of NEET at service entry to a specialist early intervention service; (b) delineate premorbid and current variables associated with NEET status at service entry and (c) examine correlates of NEET status at discharge. METHOD: Medical file audit methodology was utilized to collect information on 118 patients with first episode psychotic mania treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. NEET status was determined using the modified vocation status index (MVCI). Bivariate and multivariable logistic variables were used to examine relationships between premorbid, service entry and treatment variables, and NEET status at service entry and discharge. RESULTS: The NEET rate was 33.9% at service entry, and 39.2% at discharge. Variables associated with NEET status at service entry were premorbid functioning and polysubstance use. NEET status at service entry was the only significant correlate of NEET status at discharge. When service entry NEET was taken out of the model, substance use during treatment was predictive of NEET status at discharge. CONCLUSIONS: NEET status at service entry was related to a history of premorbid decline, and risk factors such as substance use and forensic issues. NEET status can decline during treatment, and utility of vocational intervention programs specifically for BD, in addition to specialist early intervention, needs to be examined.

Background International literature suggests that disadvantaged groups are at higher risk of morbidity and mortality from SARS-CoV-2 infection due to poorer living/working conditions and barriers to healthcare access. Yet, to date, there is no evidence of this disproportionate impact on non-national individuals, including economic migrants, short-term travellers and refugees. Methods We analyzed data from the Italian surveillance system of all COVID-19 laboratory-confirmed cases tested positive from the beginning of the outbreak (20th of February) to the 19th of July 2020. We used multilevel negative-binomial regression models to compare the case fatality and the rate of admission to hospital and intensive care unit (ICU) between Italian and non-Italian nationals. The analysis was adjusted for differences in demographic characteristics, pre-existing comorbidities, and period of diagnosis. Results We analyzed 213 180 COVID-19 cases, including 15 974 (7.5%) non-Italian nationals. We found that, compared to Italian cases, non-Italian cases were diagnosed at a later date and were more likely to be hospitalized {[adjusted rate ratio (ARR)=1.39, 95% confidence interval (CI): 1.33–1.44]} and admitted to ICU (ARR=1.19, 95% CI: 1.07–1.32), with differences being more pronounced in those coming from countries with lower human development index (HDI). We also observed an increased risk of death in non-Italian cases from low-HDI countries (ARR=1.32, 95% CI: 1.01–1.75). Conclusions A delayed diagnosis in non-Italian cases could explain their worse outcomes compared to Italian cases. Ensuring early access to diagnosis and treatment to non-Italians could facilitate the control of SARS-CoV-2 transmission and improve health outcomes in all people living in Italy, regardless of nationality.

* Abbreviation: COVID-19 — : coronavirus disease 2019 In Italy, 15.8% of the residents are children

Background Cystic fibrosis (CF) leads to pancreatic endocrine dysfunction with progressive glycemic disturbance. Approximately 30%–50% of people with CF eventually develop CF–related diabetes (CFRD). Pre-CFRD states progress from indeterminant glycemia (INDET) to impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Screening guidelines recommend inconvenient annual 2-hour oral glucose tolerance tests (OGTTs), beginning at age 10 years. More efficient methods, such as hemoglobin A1C (HbA1c), have been evaluated, but only limited, relatively small studies have evaluated the association between HbA1c and pre-CFRD dysglycemic states. Objective To determine whether HbA1c is an appropriate screening tool for identifying patients with pre-CFRD dysglycemia to minimize the burden of annual OGTTs. Methods This retrospective review evaluated medical records data of all University of Massachusetts Memorial Health System CF patients with an HbA1c result within 90 days of an OGTT between 1997 and 2019. Exclusion criteria were uncertain CF diagnosis, other forms of diabetes, or incomplete OGTT. In total, 56 patients were included and categorized according to OGTT results (American Diabetes Association criteria): normal glucose tolerance, INDET, IFG, or IGT. Associations were evaluated between HbA1c and OGTT results and between HbA1c and pre-CFRD dysglycemic states. Results Mean HbA1c was not significantly different between patients with normal glucose tolerance and those in the INDET (p = 0.987), IFG (p = 0.690), and IGT (p = 0.874) groups. Analysis of variance confirmed the lack of association between HbA1c and glycemia, as mean HbA1c was not significantly different amongst the four categories (p = 0.250). Conclusion There is increasing awareness of the impact of pre-CFRD states, including reduced pulmonary function and nutritional status. Unfortunately, our results do not support using HbA1c as a screening tool for pre-CFRD dysglycemia, specifically INDET, IFG, and IGT. Further studies are warranted to evaluate more efficient screening methods to reduce the burden of annual OGTTs.

Background and Aims The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16. Results A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusions Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

Background Most COVID-19-related deaths have occurred in older persons with comorbidities. Specific patterns of comorbidities related to COVID-19 deaths have not been investigated. Methods A random sample of 6085 individuals in Italy who died in-hospital with confirmed COVID-19 between February and December 2020 were included. Observed to expected (O/E) ratios of disease pairs were computed and logistic regression models were used to determine the association between disease pairs with O/E values ≥ 1.5. Results Six pairs of diseases exhibited O/E values ≥ 1.5 and statistically significant higher odds of co-occurrence in the crude and adjusted analyses: (1) ischemic heart disease and atrial fibrillation, (2) atrial fibrillation and heart failure, (3) atrial fibrillation and stroke, (4) heart failure and COPD, (5) stroke and dementia, and (6) type 2 diabetes and obesity. Conclusion In those deceased in-hospital due to COVID-19 in Italy, disease combinations defined by multiple cardio-respiratory, metabolic, and neuropsychiatric diseases occur more frequently than expected. This finding indicates a need to investigate the possible role of these clinical profiles in the chain of events that lead to death in individuals who have contracted SARS-CoV-2.

Background On 20 February 2020, a locally acquired coronavirus disease (COVID-19) case was detected in Lombardy, Italy. This was the first signal of ongoing transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the country. The number of cases in Italy increased rapidly and the country became the first in Europe to experience a SARS-CoV-2 outbreak. Aim Our aim was to describe the epidemiology and transmission dynamics of the first COVID-19 cases in Italy amid ongoing control measures. Methods We analysed all RT-PCR-confirmed COVID-19 cases reported to the national integrated surveillance system until 31 March 2020. We provide a descriptive epidemiological summary and estimate the basic and net reproductive numbers by region. Results Of the 98,716 cases of COVID-19 analysed, 9,512 were healthcare workers. Of the 10,943 reported COVID-19-associated deaths (crude case fatality ratio: 11.1%) 49.5% occurred in cases older than 80 years. Male sex and age were independent risk factors for COVID-19 death. Estimates of R0 varied between 2.50 (95% confidence interval (CI): 2.18–2.83) in Tuscany and 3.00 (95% CI: 2.68–3.33) in Lazio. The net reproduction number Rt in northern regions started decreasing immediately after the first detection. Conclusion The COVID-19 outbreak in Italy showed a clustering onset similar to the one in Wuhan, China. R0 at 2.96 in Lombardy combined with delayed detection explains the high case load and rapid geographical spread. Overall, Rt in Italian regions showed early signs of decrease, with large diversity in incidence, supporting the importance of combined non-pharmacological control measures.

BACKGROUND: Persons with Down syndrome (DS) are presumed to be at high risk of severe CoVID-19, due to immune dysregulation and often compromised cardiopulmonary function. Aim of the present study is to assess epidemiological and clinical characteristics of individuals with DS deceased in Italian hospitals with CoVID-19. METHODS: We used a nationwide database of 3,438 patients deceased with RT-PCR-confirmed SARS-CoV-2 infection in Italy (10.4% of all deaths with CoVID-19 in the country at the time of analysis). Data on demographics, pre-existing comorbidities and in-hospital complications leading to death were extracted from medical charts obtained from hospitals. Data on individuals with DS deceased with CoVID-19 were obtained from this sample. RESULTS: Sixteen cases of death in individuals with DS (0.5% of all charts analyzed) were identified. Acute respiratory distress syndrome occurred in all 16 cases. Compared with individuals without DS, those with DS deceased with CoVID-19 were younger (52.3 ± 7.3 vs. 78.1 ± 10.6 years, p < .001) and presented a higher incidence of superinfections (31.2 vs. 13.0%, p = .029). Autoimmune diseases (43.8 vs. 4%, p < .001), obesity (37.5 vs. 11%, p = .009), and dementia (37.5 vs. 16.3%, p = .012) were more prevalent in individuals with DS. ICU admissions was similar in both groups (25 vs. 18.8%, p = .129). CONCLUSIONS: Individuals with DS deceased with CoVID-19 are younger than individuals without DS. Comorbidity burden and increased risk of complications (i.e., bacterial superinfections) can influence CoVID-19 prognosis in individuals with DS. Specific strategies to prevent and mitigate the effects of CoVID-19 in the population with DS are needed.

Background National immunisation programmes depend on an adequate supply of vaccines but shortages have become more frequent globally in recent years. Vaccine shortages can lead to missed opportunities for vaccination and a greater risk of occurrence of vaccine-preventable diseases (VPD). Methods The EU-Joint Action on Vaccination is a European Commission-funded project* which aims to strengthen cooperation between European countries against VPDs, including improvement of vaccine supply and preparedness. In this context, from February to May 2019, we conducted a survey amongst persons in charge of national immunisation programmes or of vaccine supply/procurement in EU/EEA, to collect information on vaccine shortages in the previous three years. Results Twenty-one of 28 invited countries responded, of which 19 reported at least one shortage, for a total of 115 shortage events. The median number of shortages per country was 5 (range 0-15). At the time of survey completion, there were ongoing shortages in six countries. DT/dt-containing combination vaccines, hepatitis A, hepatitis B and BCG vaccines were the most frequently involved vaccines. Supply and production issues, and global shortage, were the most frequent causes. Median duration of shortages was five months; 34% caused a disruption in immunization services. Procurement and purchase methods varied by country. Only half of countries have recommendations or procedures in place to address shortages. Conclusions Vaccine shortages are a serious public health issue in the EU. Causes are complex and multifaceted and more research is needed to understand the economic and market-related causes. Improved communication between public health authorities, manufacturers and regulatory agencies is essential. Procurement and tender mechanisms should be improved. In case of vaccine shortages, all countries should have procedures or recommendation in place regarding the use of alternative vaccines or vaccination schedules. Key messages Vaccine shortages are a relevant public health issue in the EU. More research is needed on the complex and multifaceted causes of vaccine shortages. Timely communication between supply and demand is needed and procurement and tender mechanisms should be improved.

BACKGROUND AND OBJECTIVES: Opioid misuse and overdose remains a leading US public health concern, and many youth are first exposed to opioids via medical use. In this study, we examine school-level prevalence and correlates of medical use and misuse of prescription opioids among US 12th-grade students. METHODS: A sample of 228 507 US 12th-graders in 1079 public and private schools from 2002 to 2017 from the Monitoring the Future study was used to identify school-level prevalence and correlates associated with medical use and misuse of prescription opioids. RESULTS: The past-year prevalence of prescription opioid misuse was 7.6% and ranged from 0% to 73% across US high schools. Lifetime medical use of prescription opioids was 16.9% and ranged from 0% to 85% across US high schools. The odds of prescription opioid misuse were higher at schools with higher proportions of male students, more white students, higher rates of marijuana use, and more medical use of prescription opioids. Students attending schools with the highest rates of medical use of prescription opioids had 57% increased odds of past-year prescription opioid misuse compared with schools with no medical use (adjusted odds ratio = 1.57, 95% confidence interval = 1.35–1.83); this association was found to weaken in recent years. CONCLUSIONS: Differences exist in the prevalence of prescription opioid misuse among US high schools. The association between greater school-level medical use of prescription opioids and higher prevalence of prescription opioid misuse, although declining, indicates a key risk factor to target for prevention efforts.

Aim Young people with bipolar disorder (BD) commonly experience reduced quality of life, persistent symptoms and impaired functional recovery despite often superior school performance. Compromised long-term functioning can ensue. There is evidence that psychological therapies alongside pharmacology may be more efficacious earlier in the course of the disorder. Intervention in the early stages may thus reduce the burden and risk associated with BD and mitigate the impact of the disorder on normal developmental trajectories. To date, however, the availability of evidence-based psychological therapies for young people with early BD is limited. Furthermore, there are no large-scale randomized controlled trials (RCTs) of such interventions. Methods The study is a prospective, single-blind, RCT examining the effectiveness of an adjunctive individualized and manualized psychological intervention, compared with treatment as usual within youth-specific early intervention services. The REsearch into COgnitive and behavioural VERsatility (RECOVER) intervention is delivered over a 6-month period. About 122 young people in the early stages of BD-I (at least one manic episode in the previous 2 years, with no more than five lifetime treated/untreated manic or hypomanic episodes) will be recruited. The assessments will occur at baseline, 3, 6 (primary endpoint, end of treatment), 9, 12, 15 and 18 months. Results Recruitment will commence in January 2019 and is anticipated to occur over a 3.5-year period. Conclusions To date, there are no evidence-based psychological therapies tailored to young people with early BD. We will test whether early psychological intervention in the course of BD can reduce the symptomatic, psychological, vocational and social impacts that are seen in entrenched disorder.

Background The impact of guideline concordance on naturalistic maintenance treatment outcomes in BD is not known. We sought to evaluate the effect of guideline-concordant care on symptomatic, course and functional outcomes in youth with early-stage BD-I. Methods In this file audit study, we examined the prospective course of 64 clients with first treatment seeking manic episode of BD-I. Eighteen-month outcome measures included Clinical Global Impressions Scale - Bipolar Version (CGI-BP), Social and Occupational Functioning Assessment Scale (SOFAS) and number of relapses. Correlations and hierarchical linear regressions were used to examine the relationships between guideline concordance and outcomes, while controlling for potential confounders. Results Although higher guideline-concordant care in the maintenance phase was associated with a higher discharge CGI-BP score and thus worse outcome, baseline CGI-BP and insight were more predictive of illness severity at follow-up than guideline concordance. There was no association with SOFAS and guideline-concordant care at follow-up. Greater concordance with maintenance medication guideline statements was also associated with greater number of relapses even after controlling for sex, medication adherence, duration of care and baseline illness severity. Limitations This study was limited by sample size and its single pool of clients which may limit generalizability. Conclusions Contrary to our hypotheses, higher guideline concordance was associated with worse outcomes, although this relationship was moderated by the client's illness characteristics, severity and insight. More unwell youth with poor insight, greater severity, and mixed/rapid cycling features may need other interventions or modified guidelines.

SUMMARYBackgroundIn February 2020, a locally-acquired COVID-19 case was detected in Lombardia, Italy. This was the first signal of ongoing transmission of SARS-CoV-2 in the country. The outbreak rapidly escalated to a national level epidemic, amid the WHO declaration of a pandemic.MethodsWe analysed data from the national case-based integrated surveillance system of all RT-PCR confirmed COVID-19 infections as of March 24th 2020, collected from all Italian regions and autonomous provinces. Here we provide a descriptive epidemiological summary on the first 62,843 COVID-19 cases in Italy as well as estimates of the basic and net reproductive numbers by region.FindingsOf the 62,843 cases of COVID-19 analysed, 71.6% were reported from three Regions (Lombardia, Veneto and Emilia-Romagna). All cases reported after February 20th were locally acquired. Estimates of R0 varied between 2.5 (95%CI: 2.18-2.83) in Toscana and 3 (95%CI: 2.68-3.33) in Lazio, with epidemic doubling time of 3.2 days (95%CI: 2.3-5.2) and 2.9 days (95%CI: 2.2-4.3), respectively. The net reproduction number showed a decreasing trend starting around February 20-25, 2020 in Northern regions. Notably, 5,760 cases were reported among health care workers. Of the 5,541 reported COVID-19 associated deaths, 49% occurred in people aged 80 years or above with an overall crude CFR of 8.8%. Male sex and age were independent risk factors for COVID-19 death.InterpretationThe COVID-19 infection in Italy emerged with a clustering onset similar to the one described in Wuhan, China and likewise showed worse outcomes in older males with comorbidities. Initial R0 at 2.96 in Lombardia, explains the high case-load and rapid geographical spread observed. Overall Rt in Italian regions is currently decreasing albeit with large diversities across the country, supporting the importance of combined non-pharmacological control measures.Fundingroutine institutional funding was used to perform this work.

In cystic fibrosis (CF), liver disease (LD) is the third leading cause of mortality. As liver biopsy was considered inconsistent in CFLD diagnosis, a combination of modalities were utilized in the conventional Debray criteria (DC). More recently, noninvasive liver fibrosis biomarkers were applied by Koh et al (New criteria-NC). In the current study, we aimed to evaluate noninvasive biomarkers for the CFLD diagnosis.Longitudinal data were collected from a cohort of genetically confirmed CF patients. CFLD was diagnosed by both DC and NC. Apart from transient elastography (TE) 6.8 kPa, biomarkers incorporated in the NC included AST/ALT-ratio (AAR) ≥ 1, FIB-4 index ≥3.25 and APRI0.50.62 patients with CF, [56.5% male, age at enrollment 25 (22-31) years], were prospectively followed-up for 33 (28-36) months. Sixteen (25.8%) and 27 (43.5%) patients met DC and NC, respectively. Twenty-four fulfilling NC had at least one positive biomarker (6 TE, 7 AAR, 6 both TE and AAR, 2 both APRI and AAR and 3 both APRI and TE). Thirteen (48.1%) had diffuse LD/cirrhosis by the NC and all had at least one additional parameter classifying them as CFLD. From the 14 (51.8%) with no-diffuse-LD, 64.3%, 14.3% and 21.4% had 2, 3 and 4 of the necessary modalities incorporated in NC, respectively, confirming their classification as CFLD. TE was 100% specific to rule in CFLD but had a moderate sensitivity.NC were able to identify 17.7% more CFLD patients compared to DC. The multiple biomarkers incorporated in NC may enhance the ability to detect CFLD.

BACKGROUND Levels of the angiogenic cytokines placental growth factor (PlGF) and soluble Fms-like tyrosine kinase-1 (sFlt-1) and the angiogenic balance, expressed by sFlt-1/PlGF ratio, are perturbed in sickle-cell disease and iron overload, but they have not been evaluated in non-transfusion-dependent thalassemia (NTDT). PATIENTS AND METHODS We measured levels of PlGF, sFlt-1 and vWF:antigen in patients with NTDT of beta-thalassemia genotype, and correlated them with erythrocytic indices and markers of iron overload, inflammation, and tissue hypoxia. Thirty-four NTDT patients with mean hemoglobin level of 8.4 g/dL were included in the study along with 20 apparently healthy individuals who served as controls. RESULTS Ferritin, LDH, and hs-CRP were higher in patients as compared to controls. We found significant differences between patients and controls in regard to levels of PlGF (52.2 vs 17.2 pg/mL, P

There is growing evidence for dysregulation of the stress system in individuals with Attention Deficit Hyperactivity Disorder (ADHD). The stress system includes neuroanatomical and functional components that function in concert to maintain homeostasis and its main effectors are the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic/adrenomedullary nervous system (SNS). As stress system activity demonstrates a distinct circadian variation, we aimed to describe simultaneously, diurnal rhythms of both the HPA axis and the SNS in children with ADHD and a comparison group. Moreover, we attempted to investigate stress responses to a physical stressor, venipuncture, in both groups. Sixty-two prepubertal children with ADHD combined (ADHD-C) or inattentive (ADHD-I) type and 40 typically developing children provided saliva samples at six specific time points during a day, as well as before and 10 min after a scheduled morning venipuncture. Salivary cortisol and α- amylase were selected as reliable noninvasive biomarkers for HPA axis and SNS function and were measured in the samples obtained. Results revealed that children with ADHD-C had lower mean cortisol values both 30 min after awakening and at 18:00 h than controls (p = 0.002 and p = 0.018 respectively), as well as lower mean Cortisol Awakening Response (CAR) and Area Under the Curve for “wake to bed” period (AUCi) values of cortisol (p = 0.004 and p = 0.001, respectively). Also, mean CAR and cortisol AUCi were lower in children with ADHD-I than the control group (p = 0.034 and p = 0.038 respectively). Alpha-amylase measurements showed an increase over time (p

In Italy, in 2016, we conducted a cross-sectional survey to estimate vaccine hesitancy and investigate its determinants among parents of children aged 16–36 months. Data on parental attitudes and beliefs about vaccinations were collected through a questionnaire administered online or self-administered at pediatricians’ offices and nurseries. Parents were classified as pro-vaccine, vaccine-hesitant or anti-vaccine, according to self-reported tetanus and measles vaccination status of their child. Multivariable logistic regression was used to investigate factors associated with hesitancy. A total of 3130 questionnaires were analysed: 83.7% of parents were pro-vaccine, 15.6% vaccine-hesitant and 0.7% anti-vaccine. Safety concerns are the main reported reason for refusing (38.1%) or interrupting (42.4%) vaccination. Anti-vaccine and hesitant parents are significantly more afraid than pro-vaccine parents of short-term (85.7 and 79.7% vs 60.4%) and long-term (95.2 and 72.3% vs 43.7%) vaccine adverse reactions. Most pro-vaccine and hesitant parents agree about the benefits of vaccinations. Family pediatricians are considered a reliable source of information by most pro-vaccine and hesitant parents (96.9 and 83.3% respectively), against 45% of anti-vaccine parents. The main factors associated with hesitancy were found to be: not having received from a paediatrician a recommendation to fully vaccinate their child [adjusted odds ratio (AOR): 3.21, 95% CI: 2.14–4.79], having received discordant opinions on vaccinations (AOR: 1.64, 95% CI: 1.11–2.43), having met parents of children who experienced serious adverse reactions (AOR: 1.49, 95% CI: 1.03–2.15), and mainly using non-traditional medical treatments (AOR: 2.05, 95% CI: 1.31–3.19). Vaccine safety is perceived as a concern by all parents, although more so by hesitant and anti-vaccine parents. Similarly to pro-vaccine parents, hesitant parents consider vaccination an important prevention tool and trust their family pediatricians, suggesting that they could benefit from appropriate communication interventions. Training health professionals and providing homogenous information about vaccinations, in line with national recommendations, are crucial for responding to their concerns.

Background Premorbid characteristics may help predict the highly variable functional and illness outcomes of young people with early stage Bipolar Disorder (BD). We sought to examine the relationships between premorbid adjustment and short to medium-term outcomes after a first treated episode of mania. Methods We examined the baseline and 18-month follow-up characteristics of 117 participants with first episode of mania, treated at two tertiary early intervention services in Melbourne, Australia. The baseline demographic, family history, diagnoses, comorbidity and clinical features were determined using unstructured questionnaires and structured diagnostic interviews. Premorbid adjustment was determined using the Premorbid Adjustment Scale (PAS), the components of which were identified using a principal component analysis. Eighteen-month follow-up outcome measures included the Clinical Global Impressions scale, Social and Occupational Functioning Assessment Scale and the Heinrichs’ Quality of Life Scale (QLS). Correlations and linear regressions were utilised to examine the relationships between component scores and outcomes, while controlling for baseline and follow-up confounders. Results The social adjustment component of the PAS correlated with the interpersonal relations ( r s = −0.46, p r s =−0.39, p = 0.004). Premorbid adjustment did not predict illness severity or objective functioning. Limitations Lack of information on cognition, personality factors and prodromal symptoms limited the assessment of their impact on outcomes. Conclusions Impairments in domains of premorbid adjustment may be early markers of persistent difficulties in social and vocational functioning and may benefit from targeted interventions.

The Lazio region is one of the Italian regions where sustained measles transmission continues to occur. We investigated measles cases reported by the emergency department (ED) of the largest pediatric hospital in Italy, located in Lazio. We reviewed clinical records of all measles cases from 0 to 18 years of age evaluated in the ED in 2008–2013. We compared demographic and clinical characteristics of patients admitted to the inpatient setting with those of patients discharged home to assess possible determinants of hospital admission. Of 248 patients with measles evaluated in the ED, 113 (45.6%) were admitted as inpatients. The number of measles cases peaked in 2011 (N = 122; 49.2%), when epidemics were reported in Lazio. Median age was 2.7 years (range: 21 days to 17.9 years), and 31 patients (13%) had an underlying chronic illness. The strongest independent predictor of hospitalization was having an underlying chronic illness [adjusted odd ratio (OR): 9.87; 95% confidence interval: 3.13–31.13]. Other factors independently and significantly associated with higher risk of hospitalization were taking medications at the time of ED visit, being younger than 1 year of age and having altered liver enzyme values. Eighty-five percent of children >15 months of age who were hospitalized were not vaccinated. One hundred six hospitalized children (94%) had at least 1 measles complication; 1 child required intensive care for respiratory insufficiency. Hospitalizations of children with measles continue to occur in European areas where elimination has not been achieved. Children with chronic diseases represent a vulnerable population that is at higher risk of hospitalization.

Risk perception has a significant impact on decisions people make when facing a threat: a mismatch between actual hazard and perceived risk can lead to inappropriate behaviours and suboptimal compliance to recommended public health measures. The present study was conducted in the aftermath of a tuberculosis (TB) outbreak that occurred in 2019 in a primary school in Italy. The aim was to evaluate the impact of communication measures implemented by local health authorities (including face-to-face meetings between LHAs and the local population, weekly press announcements, implementation of a telephone hotline and of an information desk, and social media communication), on risk perception among parents of schoolchildren and school staff, and to identify factors related to a change in risk perception before and after the said activities. An anonymous questionnaire was administered to parents of schoolchildren (n = 846) and to school staff (n = 70). Participants were asked about the level of risk they had perceived at two distinct times: when they first became aware of the outbreak and following implementation of communication activities. A significant reduction of perceived risk was found in both groups (p &lt, 0.001) following the communication activities. The largest reduction was found among participants who reported having appreciated the meetings with the LHA healthcare staff. Our findings suggest that keeping an open approach, explaining the actual threat to the population and adapting communication to different listening skills, are essential for health authorities to successfully manage a public health emergency.

Background: drug-induced pancreatitis is an unexplored entity. Methods: a retrospective cohort study was performed at a referral center. Patients with drug-induced acute pancreatitis between 2008 and 2018 were included. Baseline patient characteristics, involved drugs, clinical course and recurrence were analyzed. Results: drug-induced pancreatitis represented 2.8 % of acute pancreatitis (47/1,665) and 18 different drugs were involved (thiopurines 61.8 %). The latency period was less than one month in 87.2 % of cases. Pancreatitis was mild in 89.3 % and recurrence risk was 2.3 %. Conclusion: drugs are a rare cause of pancreatitis, which mostly occurs within the first month of treatment, is usually mild and is associated with a low risk of recurrence.

Background Aim of the present study is to describe characteristics of COVID-19-related deaths and to compare the clinical phenotype and course of COVID-19-related deaths occurring in adults ( Method Medical charts of 3,032 patients dying with COVID-19 in Italy (368 aged < 65 years and 2,664 aged ≥65 years) were revised to extract information on demographics, preexisting comorbidities, and in-hospital complications leading to death. Results Older adults (≥65 years) presented with a higher number of comorbidities compared to those aged Conclusions Individuals dying with COVID-19 present with high levels of comorbidities, irrespective of age group, but a small proportion of deaths occur in healthy adults with no preexisting conditions. Non-respiratory complications are common, suggesting that the treatment of respiratory conditions needs to be combined with strategies to prevent and mitigate the effects of non-respiratory complications.

Background Among the unknowns posed by the coronavirus disease 2019 (COVID-19) outbreak, the role of biological sex to explain disease susceptibility and progression is still a matter of debate, with limited sex-disaggregated data available. Methods A retrospective analysis was performed to assess if sex differences exist in the clinical manifestations and transitions of care among hospitalized individuals dying with laboratory-confirmed SARS-CoV-2 infection in Italy (February 27–June 11, 2020). Clinical characteristics and the times from symptoms’ onset to admission, nasopharyngeal swab, and death were compared between sexes. Adjusted multivariate analysis was performed to identify the clinical features associated with male sex. Results Of the 32,938 COVID-19-related deaths that occurred in Italy, 3517 hospitalized and deceased individuals with COVID-19 (mean 78 ± 12 years, 33% women) were analyzed. At admission, men had a higher prevalence of ischemic heart disease (adj-OR = 1.76, 95% CI 1.39–2.23), chronic obstructive pulmonary disease (adj-OR = 1.7, 95% CI 1.29–2.27), and chronic kidney disease (adj-OR = 1.48, 95% CI 1.13–1.96), while women were older and more likely to have dementia (adj-OR = 0.73, 95% CI 0.55–0.95) and autoimmune diseases (adj-OR = 0.40, 95% CI 0.25–0.63), yet both sexes had a high level of multimorbidity. The times from symptoms’ onset to admission and nasopharyngeal swab were slightly longer in men despite a typical acute respiratory illness with more frequent fever at the onset. Men received more often experimental therapy (adj-OR = 2.89, 95% CI 1.45–5.74) and experienced more likely acute kidney injury (adj-OR = 1.47, 95% CI 1.13–1.90). Conclusions Men and women dying with COVID-19 had different clinical manifestations and transitions of care. Identifying sex-specific features in individuals with COVID-19 and fatal outcome might inform preventive strategies.

OBJECTIVES: To describe the epidemiological and clinical characteristics of coronavirus disease (COVID-19) pediatric patients aged METHODS: Data from the national case-based surveillance system of confirmed COVID-19 infections until May 8, 2020, were analyzed. Demographic and clinical characteristics of subjects were summarized by age groups (0–1, 2–6, 7–12, 13–18 years), and risk factors for disease severity were evaluated by using a multilevel (clustered by region) multivariable logistic regression model. Furthermore, a comparison among children, adults, and elderly was performed. RESULTS: Pediatric patients (3836) accounted for 1.8% of total infections (216 305); the median age was 11 years, 51.4% were male, 13.3% were hospitalized, and 5.4% presented underlying medical conditions. The disease was mild in 32.4% of cases and severe in 4.3%, particularly in children ≤6 years old (10.8%); among 511 hospitalized patients, 3.5% were admitted in ICU, and 4 deaths occurred. Lower risk of disease severity was associated with increasing age and calendar time, whereas a higher risk was associated with preexisting underlying medical conditions (odds ratio = 2.80, 95% confidence interval = 1.74–4.48). Hospitalization rate, admission in ICU, disease severity, and days from symptoms onset to recovery significantly increased with age among children, adults and elderly. CONCLUSIONS: Data suggest that pediatric cases of COVID-19 are less severe than adults; however, age ≤1 year and the presence of underlying conditions represent severity risk factors. A better understanding of the infection in children may give important insights into disease pathogenesis, health care practices, and public health policies.

Management of delayed (within 30 days) postpolypectomy bleeding (DPPB) has not been standardized. Patients often undergo colonoscopies that do not provide any benefit. We aimed to identify factors associated with therapeutic intervention and active bleeding after DPPB.We performed a retrospective study of 548 patients with bleeding within 30 days after an index polypectomy (DPPB; 71.9% underwent colonoscopy, 2.6% underwent primary angiographic embolization, and 25.5% were managed without intervention) at 6 tertiary centers in Spain, from January 2010 through September 2018. We collected demographic and medical data from patients. The primary outcomes were the need for therapeutic intervention and the presence of active bleeding during colonoscopy.A need for therapeutic intervention was associated independently with the use of antithrombotic agents, hemoglobin decrease greater than 2 g/dL, hemodynamic instability, and comorbidities (P.05). The bleeding point during colonoscopy was identified in 344 patients; 74 of these patients (21.5%) had active bleeding. Active use of anticoagulants (odds ratio [OR], 2.6; 95% CI, 1.5-4.5), left-sided polyps (OR, 1.95; 95% CI, 1-3.8), prior use of electrocautery (OR, 2.6; 95% CI, 1.1-6.1), and pedunculated polyp morphology (OR, 1.8, 95% CI, 1-3.2) significantly increased the risk of encountering active bleeding. We developed a visual nomogram to estimate the risk of active bleeding. Overall, 43% of the cohort did not require any hemostatic therapy. Rebleeding (6%) and transfusion requirements were low in those managed without intervention.In a study of patients with DPPB, we found that almost half do not warrant any therapeutic intervention. Colonoscopy often is overused for patients with DPPB. We identified independent risk factors for active bleeding that might be used to identify patients most likely to benefit from colonoscopy.

Italy is a low-incidence country for tuberculosis (TB). We describe a TB outbreak in a primary school in north-eastern Italy, involving 10 cases of active pulmonary disease and 42 cases of latent infection. The index case was detected in March 2019, while the primary case, an Italian-born schoolteacher, was likely infectious since January 2018. Administration of a pre-employment health questionnaire to school staff with sustained contact with children should be considered in low-incidence countries.

Background Specialist early intervention (SEI) service models are designed to treat symptoms, promote social and vocational recovery, prevent relapse, and resource and up skill patients and their families. While the immediate benefits of SEI are clear, and have been demonstrated, the long-term impact of SEI on illness course is less clear. The First Episode Outcome Study involves the long-term follow-up of a representative sample of first episode psychosis patients who were first treated at the Early Psychosis Prevention and Intervention Centre (EPPIC) between 1998 and 2000. In this presentation the preliminary data on physical health outcomes are reported. Methods Between January 1998 and December 2000, 661 patients between the ages of 15–29 years were treated at the Early Psychosis Prevention and Intervention Centre, Melbourne Australia. The 18-month treatment characteristics of this cohort have been extensively examined in the First Episode Psychosis Outcome Study (FEPOS). The long-term outcomes of this cohort are now being examined in a new study (known as FEPOS15). Results The rates of self-report physical health problems in 100 participants 15 years after being treated for a first episode psychosis were significant for high cholesterol (41%), asthma (33.7%), chronic pain (25.3%), allergies (19.3%), respiratory problems (16.9%) anemia (12.2%), arthritis (12.0%), hepatitis C (10.8%) and diabetes (6.3%). Cardiovascular problems were also noted including heart attack (2.4%), other heart problems (8.4%), and stroke (3.6%). Sexual health problems are explored. Physical health findings pertaining to Coroners’ findings on those who had died will be also used to describe the long-term impacts of psychotic disorder. Discussion This follow-up study is one of the longest, largest and most comprehensive studies of the multidimensional outcomes of a SEI service for psychosis. The physical health outcomes of individuals 15-years after the first episode psychosis are poor. The importance of monitoring and managing physical health problems in those with psychotic disorder is highlighted.

Brucellosis is one of the major reproductive tract diseases of swine and causes a huge economic loss to pig farmers. In this study, serological, gross pathological, histopathological, immunohistochemical and Polymerase Chain Reaction technique(s) have been applied for diagnosis of brucellosis in pig. Seroprevalence studies showed prevalence of brucellosis to be 16.7% by Rose Bengal Plate Test (RBPT) and 12.5% by competitive ELISA(c-ELISA). In this study, comparison was done between RBPT and c-ELISA for serological diagnosis of brucellosis which revealed substantial degree of agreement (Kappa= 0.676, 95% CI= 0.372-0.826) between two tests. Histopathological examination revealed focal to diffuse mixed infiltration of neutrophils or lymphocytesin the fetal organs like lung especially in bronchi and interstitial septa. Lesions in the placenta were characterized by diffuse lympho-mononuclear cell infiltration. Histopathological changes in female reproductive tracts were characterized by cellular infiltration of the endometrial stroma, endometrial glands and hyperplasia of periglandular connective tissue. Immunohistochemical (IHC) staining revealed intracytoplasmic immunostaining of Brucella in bronchial epithelial cells of lung, endothelial cells in spleen, hepatocytes of liver, cells within the lymph node, kidney of fetus and placenta. In addition, positive immunostaining to Brucella was also seen in lamina propria cells of uterus. By PCR, eight out of 34 samples (2 from stomach contents, 2 from placental cotyledons and 4 from pooled tissue(s) produced 193 bpsized ampliconspecific for Brucella genus. In the present study, PCR and IHC provide a reliable test for the diagnosis of brucellosis in abortion cases on aborted fetal tissue and placental cotyledons. However, serology is important for detection of Brucella positive animal in a farm .

Background Population aging and comorbidity are leading to an increase in patients unfit for cholecystectomy. Aims To evaluate whether endoscopic biliary sphincterotomy after a first episode of acute gallstone pancreatitis reduces the risk of pancreatitis recurrence and gallstone-related events in non-surgical candidates. Methods Retrospective study of patients admitted for a first episode of acute gallstone pancreatitis rejected for cholecystectomy between 2013–2018. The role of endoscopic sphincterotomy was evaluated by adjusting for age, severity of pancreatitis, and presence of choledocholithiasis. Results We included 247 patients (mean age 80 ± 12 years; Charlson index: 5; severity of pancreatitis: 72% mild). Sphincterotomy was performed in 23.9%. Recurrence of pancreatitis occurred in 17.4% patients (median follow-up: 426 days). The one-year cumulative incidence of a new episode of pancreatitis was 1.8% (95% confidence interval [CI]: 0.2–12%) and 23% (95% CI: 17–31%) in patients with and without sphincterotomy, respectively (p = 0.006). In multivariate analysis, sphincterotomy showed a protective role for recurrence of pancreatitis (adjusted hazard ratio [HR]: 0.29, 95% CI: 0.08–0.92, p = 0.037) and for any gallstone-related event (HR 0.46, 95% CI: 0.21–0.98, p = 0.043). Conclusions Endoscopic biliary sphincterotomy reduced the risk of gallstone pancreatitis recurrence and other biliary-related disorders in patients with a first episode of pancreatitis non-candidates for cholecystectomy.

High mobility group box 1 protein (HMGB1) has been suggested to be involved in the immune dysfunction and inflammation reported in autism spectrum disorder (ASD). We aimed to assess HMGB1 serum concentrations (SCs) in high-functioning ASD children compared to typically developing (TD) controls and to explore their associations with the autism spectrum quotient (AQ), the empathy quotient (EQ), and the systemizing quotient (SQ). The study involved 42 ASD children and 38 TD children, all-male, aged between 6.1 and 13.3 years old. HMGB1 SCs were measured by enzyme-linked immunosorbent assay (ELISA). Groups were comparable regarding age, general IQ, birth weight, and maternal age at birth. ASD children showed significantly higher HMGB1 SCs compared to TD children (1.25 ± 0.84 ng/mL versus 1.13 ± 0.79 ng/mL, respectively, p = 0.039). The Spearman’s rho revealed that HMGB1 SCs were positively correlated with the AQ attention to detail subscale (rs = 0.46, p = 0.045) and with the SQ total score (rs = 0.42, p = 0.04) in the ASD group. These results show that HMGB1 serum concentrations are altered in ASD children, and suggest that inflammatory processes mediated by HMGB1 may be associated with specific cognitive features observed in ASD.