Convergence and divergence in Kawasaki disease and multisystem inflammatory syndrome in children: results from the COVASAKI survey.

OBJECTIVES: To compare Kawasaki disease (KD) and multisystem inflammatory syndrome (MIS-C) in children. METHODS: Prospective collection of demographics, clinical and treatment data. Assessment of type 1 interferon (IFN) score, CXCL9, CXCL10, Interleukin (IL)18, IFNγ, IL6, IL1b at disease onset and at recovery. RESULTS: 87 patients (43 KD, 44 MIS-C) were included. Age was higher in MIS-C compared to KD group (mean 31±23 vs. 94±50 months, p<0.001). Extremities abnormalities (p=0.027), mucosal involvement (p<0.001), irritability (p<0.001), gallbladder hydrops (p=0.01) and lymphadenopathy (p=0.07) were more often recorded in KD. Neurological findings (p=0.002), gastrointestinal symptoms (p=0.013), respiratory involvement (p=0.019) and splenomegaly (p=0.026) were more frequently observed in MIS-C. Cardiac manifestations were higher in MIS-C (p<0.001), although coronary aneurisms were more frequent in KD (p=0.012). In the MIS-C group, the multiple linear regression analysis revealed that a higher IFN score at onset was related to myocardial disfunction (p<0.001), lymphadenopathy (p=<0.001) and need of ventilation (p=0.024). Both CXCL9 and CXCL10 were related to myocardial disfunction (p<0.001 and p=0.029). IL18 was positively associated to PICU admission (0.030) and ventilation (p=004) and negatively associated to lymphadenopathy (0.004). IFNγ values were related to neurological involvement and lymphadenopathy (p<0.001), IL1b to hearth involvement (0.006). A negative correlation has been observed between IL6 values, heart involvement (p=0.013) and PICU admission (p<0.001). CONCLUSIONS: The demographic and clinical differences between KD e MIS-C cohorts confirm previous reported data. The assessment of biomarkers levels at MIS-C onset could be useful to predict a more severe disease course and the development of cardiac complications.

Multidrug-Resistant Bloodstream Infections in Internal Medicine: Results from a Single-Center Study.

OBJECTIVES: Infections due to multidrug-resistant organisms (MDROs) are expanding globally and are associated with higher mortality rates and hospital-related costs. The objectives of this study were to analyze the trends of MDRO bacteremia and antimicrobial resistance rates in Internal Medicine wards of our hospital and to identify the variables associated with these infections. METHODS: During a 6-year period (July 1, 2011-June 30, 2017), patients with positive blood culture isolates hospitalized in the Internal Medicine wards in the Santa Croce and Carle Hospital in Cuneo, Italy, were assessed. We performed an analysis taking into consideration the time trends and frequencies of MDRO infections, as well as a case-control study to identify clinical-demographic variables associated with MDRO bacteremias. RESULTS: During the study period a total of 596 blood cultures were performed in 577 patients. The most frequently identified organism was Escherichia coli (33.7%), followed by Staphylococcus aureus (15.6%) and S epidermidis (7.4%). The percentage of resistance to methicillin among S aureus isolates showed a decreasing trend, whereas rates of extended-spectrum ß-lactamase-producing Enterobacteriaceae and carbapenemase-producing Klebsiella pneumoniae increased during the study period. Multivariate analysis showed that the nosocomial origin of the infection, hospitalization during the previous 3 months, residence in long-term care facilities, presence of a device, antibiotic exposure during the previous 3 months, and cerebrovascular disease were independently associated with bacteremia by resistant microorganisms. CONCLUSIONS: Our analysis reveals a concerning microbiological situation in an Internal Medicine setting, in line with other national and regional data. The risk variables for infection by MDRO identified in our study correspond to those reported in the literature, although studies focused on Internal Medicine settings appear to be limited.

Evolution of infectious bronchitis virus in the field after homologous vaccination introduction.

Despite the fact that vaccine resistance has been typically considered a rare phenomenon, some episodes of vaccine failure have been reported with increasing frequency in intensively-raised livestock. Infectious bronchitis virus (IBV) is a widespread avian coronavirus, whose control relies mainly on extensive vaccine administration. Unfortunately, the continuous emergence of new vaccine-immunity escaping variants prompts the development of new vaccines. In the present work, a molecular epidemiology study was performed to evaluate the potential role of homologous vaccination in driving IBV evolution. This was undertaken by assessing IBV viral RNA sequences from the ORF encoding the S1 portion of viral surface glycoprotein (S) before and after the introduction of a new live vaccine on broiler farms in northern-Italy. The results of several biostatistics analyses consistently demonstrate the presence of a higher pressure in the post-vaccination period. Natural selection was detected essentially on sites located on the protein surface, within or nearby domains involved in viral attachment or related functions. This evidence strongly supports the action of vaccine-induced immunity in conditioning viral evolution, potentially leading to the emergence of new vaccine-escape variants. The great plasticity of rapidly-evolving RNA-viruses in response to human intervention, which extends beyond the poultry industry, is demonstrated, claiming further attention due to their relevance for animal and especially human health.

Avian influenza epidemiology in semi-intensive free ranging duck flocks of the Moyingyi Wetland in Bago East District, Myanmar.

Highly pathogenic avian influenza virus subtype H5N1 first entered Myanmar in 2006 in the Mandalay District. Several H5N1 outbreaks followed and the one of Bago East District (2007) required post outbreak surveillance in the at-risk domestic duck population of the Moyingyi Wetland. A field epidemiological study based on a randomised prospective stratified study with five surveys provided the serological evidence that the avian influenza H5 subtype circulates in the domestic duck population and spreads to almost all the newly housed (and negative) flocks in the time span of a seasonal production cycle. Virological investigation was negative. The survival analysis showed that the probability of seroconversion increased rapidly over the study period, without significant difference among different agro-ecosystems. The analysis suggests that viral spread in the new cycle could be limited if control measures were adopted at the time new flocks are housed. The study recommends that future surveillance schemes for ducks are designed in a way to get as much information as possible from serological results which should drive virological sampling to determined farms.

Effects of oral anticoagulant therapy in older medical in-patients with atrial fibrillation: a prospective cohort observational study.

BACKGROUND: Uncertainties about efficacy and safety of oral anticoagulant therapy (OAT) among older and frail medical patients with atrial fibrillation (AF) largely contribute to under-prescription of these drugs. AIMS: In this prospective observational cohort study, we investigated mortality, and ischemic and hemorrhagic events, in hospital-discharged older patients with AF. METHODS: Stroke and bleeding risk were evaluated using CHA2DS2-VASC and HAS-BLED scores. Comorbidity, frailty, cognitive and nutritional status and functional autonomy were evaluated using standardized scales. Independent associations between clinical variables, including OAT use, and all-cause mortality, fatal and non-fatal ischemic and hemorrhagic events, were evaluated. Further clinical outcomes comparison between patients treated with OAT and those untreated was performed after adjustment for significant differences in patient baseline characteristics with propensity score matching. RESULTS: Of 452 patients included (mean age 81.6 years, 54.9 % women, roughly 30 % cognitively impaired and/or functionally dependent, mean CHA2DS2-VASC and HAS-BLED scores 4.6 and 2.8, respectively), 151 (33.4 %) died during a mean follow-up period of 300.5 days; ischemic and hemorrhagic stroke occurred in 4.0 and 0.4 % of patients, respectively, and major bleedings in 6.2 %. DISCUSSION: After multivariate analysis, OAT at discharge was associated with lower overall mortality and reduced occurrence of ischemic stroke, the first finding being confirmed in propensity score matched analysis. CONCLUSIONS: Among older vulnerable AF patients with high post discharge death rate, OAT was associated, among other multiple factors, with reduced mortality and lower occurrence of ischemic stroke.

Anaplasma, Ehrlichia and rickettsial pathogens in ixodid ticks infesting cattle and sheep in western Oromia, Ethiopia.

Although ticks are widely distributed in all agro-ecological zones of Ethiopia, information on tick-borne pathogens is scarce. This study was conducted to determine the presence of Anaplasma spp., Ehrlichia spp., and Rickettsia spp. in Rhipicephalus evertsi and Rhipicephalus (Boophilus) decoloratus collected from cattle and sheep at Bako, western Oromia, Ethiopia, using polymerase chain reaction and sequencing. Anaplasma ovis and Anaplasma spp., Ehrlichia ruminantium and Ehrlichia spp. were detected in Rh. decoloratus, whereas only A. ovis was detected in Rh. evertsi. Both tick species were found to harbor DNA belonging to Rickettsia spp., and Rickettsia africae. Our findings highlight the risk of infection of animals and humans with these zoonotic tick-borne bacteria in Ethiopia.

Molecular detection of piroplasms in ixodid ticks infesting cattle and sheep in western Oromia, Ethiopia.

In Ethiopia, ticks and tick-borne diseases are widely distributed and contribute to important economic losses. Several studies investigated the prevalence and species composition of ticks infesting ruminants; however, data on tick-borne pathogens are still scarce. During the study period from October 2010 to April 2011, a total of 1,246 adult ticks and 264 nymphs were collected from 267 cattle and 45 sheep in Bako District, western Oromia, Ethiopia. The study showed infestation of 228/267 (85.4 %) cattle and 35/45 (77.8 %) sheep with adult ticks. Overall, eight tick species, belonging to three genera (Amblyomma, Rhipicephalus, Hyalomma), were identified and Amblyomma cohaerens (n = 577), Rhipicephalus evertsi evertsi (n = 290), Rhipicephalus (Boophilus) decoloratus (n = 287), and Amblyomma variegatum (n = 85) were the more prevalent species. A statistically significant host preference in A. cohaerens for cattle and R. evertsi evertsi for sheep was noticed. Molecular detection of piroplasms, performed only for adult ticks of two species of the genus Rhipicephalus (R. evertsi evertsi and R. decoloratus), revealed an overall prevalence of 4 % (8/202) Theileria buffeli/sergenti/orientalis, 0.5 % (1/202) Theileria velifera, and 2 % (4/202) Theileria ovis. The study showed that tick infestation prevalence is considerably high in both cattle and sheep of the area, but with a low intensity of tick burden and a moderate circulation of mildly pathogenic piroplasm species.

First evidence of avian metapneumovirus subtype A infection in turkeys in Egypt.

Although avian metapneumovirus (aMPV) infection has been reported in most regions of the world, to date, only subtype B has been detected in Egypt. At the end of November 2013, dry oropharyngeal swabs were collected during an outbreak of respiratory diseases in a free-range, multi-age turkey dealer farm in Northern Upper Egypt. The clinical signs that appeared when turkeys were 3 weeks-old were characterized by ocular and nasal discharge and swelling of sinuses. aMPV of subtype A was detected by real-time reverse transcription-polymerase chain reaction. In order to confirm the results and obtain more information on the molecular characteristics of the virus, F and G protein genes were partially sequenced and compared with previously published sequences deposited in GenBank by using BLAST. Subtype of the strain was confirmed by sequencing of partial F and G protein genes. The highest percentages of identity were observed when G sequence of the Egyptian strain was compared with the sequence of an aMPV-A isolated in Nigeria (96.4 %) and when the F sequence was compared with strains isolated respectively in Italy and in UK (97.1 %). Moreover, the alignment of the sequences with commercial subtype A vaccine or vaccine-derived strains showed differences in the Egyptian strain that indicate its probable field origin. The detection of aMPV in the investigated turkey flock highlights some relevant epidemiological issues regarding the role that multi-age farms and dealers may play in perpetuating aMPV infection within and among farms. To our knowledge, this is the first report of aMPV subtype A in Egypt.

Learning from precedent: how the British Brexit experience shapes nationalist rhetoric outside the UK.

The liberal international order has recently come under increasing nationalist pressure, evidenced by a rise in nationalist demands to withdraw from international institutions. A growing literature examines the domestic economic, social, and political origins of this nationalist backlash against international institutions. However, less is known about the extent to which precedents of withdrawals of one country affect nationalist pressures for future withdrawals elsewhere. In this paper, we argue that initial withdrawal episodes provide new information about the feasibility and desirability of withdrawals to nationalist elites in other countries. Hence, we expect nationalists abroad to be either encouraged or deterred to follow a similar path - depending on the success of these precedents. We explore this argument in the context of the British withdrawal from the European Union (Brexit), which arguably marks the most significant withdrawal from an international institution to date. Based on a quantitative analyses of media reports in ten European countries, we show we show that nationalist parties in Europe increased or moderated the aggressiveness about their EU-related rhetoric as the ups and downs of the Brexit-drama unfolded. Our results suggest that precedents of nationalist withdrawals shape domestic politics well beyond the concerned countries themselves.

Epidemiology, therapy and outcome of hepatocellular carcinoma between 2010 and 2019 in Piedmont, Italy.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide. It is often diagnosed at an advanced stage and therefore its prognosis remains poor with a low 5-year survival rate. HCC patients have increasingly complex and constantly changing characteristics, thus up-to-date and comprehensive data are fundamental. AIM: To analyze the epidemiology and main clinical characteristics of HCC patients in a referral center hospital in the northwest of Italy between 2010 and 2019. METHODS: In this retrospective study, we analyzed the clinical data of all consecutive patients with a new diagnosis of HCC recorded at "Santa Croce e Carle" Hospital in Cuneo (Italy) between 1 January 2010 and 31 December 2019. To highlight possible changes in HCC patterns over the 10-year period, we split the population into two 5-year groups, according to the diagnosis period (2010-2014 and 2015-2019). RESULTS: Of the 328 HCC patients who were included (M/F 255/73; mean age 68.9 ± 11.3 years), 154 in the first period, and 174 in the second. Hepatitis C virus infection was the most common HCC risk factor (41%, 135 patients). The alcoholic etiology rate was 18%, the hepatitis B virus infection etiology was 5%, and the non-viral/non-alcoholic etiology rate was 22%. The Child-Pugh score distribution of the patients was: class A 75%, class B 21% and class C 4%. The average Mayo end-stage liver disease score was 10.6 ± 3.7. A total of 55 patients (17%) were affected by portal vein thrombosis and 158 (48%) by portal hypertension. The average nodule size of the HCC was 4.6 ± 3.1 cm. A total of 204 patients (63%) had more than one nodule < 3, and 92% (305 patients) had a non-metastatic stage of the disease. The Barcelona Clinic Liver Cancer (BCLC) staging distribution of all patients was: 4% very early, 32% early, 23% intermediate, 34% advanced, and 7% terminal. Average survival rate was 1.6 ± 0.3 years. Only 20% of the patients underwent treatment. Age, presence of ascites, BCLC stage and therapy were predictors of a better prognosis (P < 0.01). A comparison of the two 5-year groups revealed a statistically significant difference only in global etiology (P < 0.05) and alpha-fetoprotein (AFP) levels (P < 0.01). CONCLUSION: In this study analyzing patients with a new diagnosis of HCC between 2010-2019, hepatitis C virus infection was the most common etiology. Most patients presented with an advanced stage disease and a poor prognosis. When comparing the two 5-year groups, we observed a statistically significant difference only in global etiology (P < 0.05) and AFP levels (P < 0.01).

Comparison of two 2-D numerical models for snow avalanche simulation.

Snow avalanches are gravitational processes characterised by the rapid movement of a snow mass, threatening inhabitants and damaging infrastructure in mountain areas. Such phenomena are complex events, and for this reason, different numerical models have been developed to reproduce their dynamics over a given topography. In this study, we focus on the two-dimensional numerical simulation tools RAMMS::AVALANCHE and FLO-2D, aiming to compare their performance in predicting the deposition area of snow avalanches. We also aim to assess the employment of the FLO-2D simulation model, normally used in water flood or mud/debris flow simulations, in predicting the motion of snow avalanches. For this purpose, two well-documented avalanche events that occurred in the Province of Bolzano (IT) were analyzed (Knollgraben, Pichler Erschbaum avalanches). The deposition area of each case study was simulated with both models through back-analysis processes. The simulation results were evaluated primarily by comparing the simulated deposition area with the observed one through statistical indices. Subsequently, the maximum flow depth, velocity and deposition depth were also compared between the simulation results. The results showed that RAMMS::AVALANCHE generally reproduced the observed deposits better compared to FLO-2D simulation. FLO-2D provided suitable results for wet and dry snow avalanches after a meticulous calibration of the rheological parameters, since they are not those typically considered in avalanche rheology studies. The results showed that FLO-2D can be used to study the propagation of snow avalanches and could also be adopted by practitioners to define hazard areas, expanding its field of application.

The role of general practitioners in the EU: time to draw lessons from a too wide range?

Although the role played by general practitioners (GPs) is historically consolidated, continuous changes have been recently introduced in Europe because of the increasing multimorbidity and complexity of patients. Here we try to compare the roles played by GPs in the four major countries of Europe. In France GPs are self-employed medical doctors, and their remuneration consists of a payment scheme for the services provided. The weekly opening hours of French GPs are on average approximately 48. In Germany primary care is mainly provided by GPs and outpatient internists, and patients are free to choose the facility and the professional. German GPs are self-employed professionals mainly remunerated for each consultation, who work for an average of 50 opening hours per week. In Italy GPs are self-employed professionals mainly paid on per capita basis, who have their own list of patients and must guarantee a minimum number of clinical opening hours per week, which has often become the average number in practice. Accordingly, the patients' weekly access to Italian GPs' clinics is very limited. In Spain GPs are civil servants who work in multifunctional facilities with multi-professional teams. The weekly hours worked by Spanish GPs are 38 hours, as for any other civil servant. Trying to draw positive lessons from the comparison, the Spanish facilities seem to be the most advanced examples of horizontal-integrated organizations able to fulfil the expectations of a growing population of ageing people. The range of generalist professionals could be enlarged beyond GPs, as the German example shows.

Human herpes virus 8-negative effusion-based lymphoma in a patient with persistent serous effusions.

Diffuse large B-cell lymphoma is the most common histologic diagnosis among the aggressive lymphomas, accounting for 30% of all lymphomas. Human herpes virus 8-negative effusion-based lymphoma (HHV8-negative EBL) is a rare form of lymphoma, under recognized and still not well characterized in the literature. In contrast to primary effusion lymphoma (PEL), HHV8-negative EBL is characterized by malignant effusion in essentially serous body cavity with no detectable contiguous tumor masses and is no associated with human immunodeficiency virus and HHV8 infections. The presence of comorbid medical conditions can hide this type of lymphoma and made diagnosis more challenging. Here, we describe a rare case of an 82-year-old male suffering from peritoneal and pleural effusion and Hepatitis B virus related cirrhosis diagnosed with HHV8-negative EBL.

Four-Component Recombinant Protein-Based Vaccine Effectiveness Against Serogroup B Meningococcal Disease in Italy.

Importance: Population-based data on the 4-component recombinant protein-based (4CMenB) vaccine effectiveness and reduction in incidence rate ratios (IRRs) are continuously needed to assess vaccine performance in the prevention of serogroup B invasive meningococcal disease (IMD). Objective: To assess the effectiveness and reduction in IRRs associated with the 4CMenB vaccine in the pediatric population in 6 regions in Italy. Design, Setting, and Participants: This retrospective cohort screening study and case-control study included data from children aged younger than 6 years in 6 highly populated Italian regions from January 1, 2006, to January 1, 2020. Participants included children younger than 6 years diagnosed with serogroup B IMD without predisposing factors. Data were collected from regional surveillance and vaccination registries and were analyzed from September 2021 to January 2022. Exposures: Routine 4CMenB vaccination, per regional vaccination programs. Main Outcomes and Measures: The main outcome was the effectiveness of the 4CMenB vaccine in the prevention of serogroup B IMD in the population of children aged younger than 6 years in 6 Italian regions. The percentages of vaccine effectiveness (VE) were obtained through the concomitant use of a screening method and a case-control study. Secondary outcomes were the comparison of effectiveness results obtained using the 2 different computational methods, the description of serogroup B IMD incidence rates, and reduction in IRRs before and after 4CMenB introduction, as a proxy for vaccine impact. Results: The cohort screening study included a resident population of 587 561 children younger than 6 years in 3 regions with similar surveillance protocols, and the matched-case controls study assessed a resident population of 1 080 620 children younger than 6 years in 6 regions. Analyses found that 4CMenB VE in fully immunized children was 94.9% (95% CI, 83.1%-98.4%) using the screening method and 91.7% (95% CI, 24.4%-98.6%) using the case-control method. Overall reduction in IRR was 50%, reaching 70% in regions with early-start vaccination schedules. The case-control method involving 6 highly-populated Italian regions included 26 cases and 52 controls and found an estimated VE of 92.4% (95% CI, 67.6%-97.9%) in children old enough for the first vaccine dose and 95.6% (95% CI, 71.7%-99.1%) in fully immunized children. VE was more than 90% for partially immunized children. Even in regions where the first dose was administered at age 2 months, almost 20% of unvaccinated cases were among infants too young to receive the first 4CMenB dose. Conclusions and Relevance: This screening cohort study and matched case-controls study found high effectiveness of 4CMenB vaccination and greater reduction in IRR for early-start vaccination schedules in preventing invasive serogroup B meningococcal disease. The high proportion of children too young to be vaccinated among unvaccinated cases suggests that starting the vaccination even earlier may prevent more cases. Screening and case-control methods provided similar estimates of VE: either method may be used in different study settings, but concomitant use can provide more robust estimates.

A longitudinal study on thermophilic Campylobacter spp. in commercial turkey flocks in northern Italy: occurrence and genetic diversity.

Poultry are recognized as a main reservoir of thermophilic campylobacters, but few studies have been carried out on commercial meat turkeys. This study was aimed at assessing the occurrence of thermophilic Campylobacter spp., their genetic diversity, and the trend of the infection during the whole production cycle of three turkey flocks from different farms in Northern Italy. Flocks were monitored from the time of housing 1-day-old poults to slaughter time by collecting samples (meconium and cloacal swabs) at weekly intervals up to the recovery of Campylobacter spp. and then twice a month. A conventional culture method and a multiplex PCR assay were used for Campylobacter detection and identification. A subset of isolates was genetically characterized by random amplified polymorphic DNA-PCR (RAPD-PCR) and flagellin gene A short variable region (flaA-SVR) sequencing. Although at different times, all flocks became colonized by Campylobacter jejuni or Campylobacter coli (or both) that persisted throughout the entire production cycle. Overall, nine RAPD types and 14 flaA-SVR types were detected with differences in their distribution among flocks and sampling times. Moreover, changes in the Campylobacter genotypes colonizing turkeys were observed over time within each flock. These findings suggest that Italian commercial turkeys might be widely colonized by different genotypes of C. jejuni and C. coli and also suggest that differences in the distribution and epidemiologic dynamics of these microorganisms might occur among flocks.

[The European enigma of pharmaceutical pricing: still solvable?] / L'enigma europeo dei prezzi dei farmaci: è ancora risolvibile?

The attempt to regulate pharmaceutical pricing has a long tradition in Western European countries and various solutions have been experienced in recent decades to try to control public pharmaceutical spending. Nonetheless, drug prices have become increasingly out of control and unsustainable even in the richest European countries. In a situation of "market failure" such as the pharmaceutical one, in fact, two totally opposite needs collide: the main objective of the health authorities of universal access to essential drugs, versus the aim of the pharmaceutical industry to maximize turnover in order to guarantee high returns on investments. We are therefore convinced that the growing threat of drug prices that are too high must be solved with drastic solutions. The goal of this contribution is therefore to first summarize the current situation of pharmaceutical pricing in Western European countries, then debate the main issues currently discussed and finally propose a radically alternative scenario that moves from prices to the budget.

Integrated care in Western Europe: a wise solution for the future?

INTRODUCTION: IC is a term commonly adopted across the world underpinning a positive attitude against fragmentation of healthcare service provision. While the principles supporting IC are simple, their implementation is more controversial. AREAS COVERED: The growing number of IC definitions is related to the increasing domains of applications, which reflect the increasing demand induced by aging multi-morbid patients. A comprehensive definition of IC should now include the coordination of health and social services useful to deliver continuous care across organizational boundaries. The recent debate on IC is largely influenced by the mismatch between the increasing burden of health and social needs for chronic conditions from the demand side, and the design of health-care systems still focused on acute care from the supply side. EXPERT OPINION: The major reasons of persisting IC weakness in European countries stem from arguable choices of health policy taken in the recent past. The political creed in 'market competition' is probably the most emblematic. All initiatives encouraging health-care providers to compete with each other are likely to discourage IC. Since most European GPs are still self-employed professionals working in their own cabinets, the anachronistic professional status of GPs is another historically rooted reason of IC weakness.