Clinical benefits of routine varicella vaccination for adults

Varicella is a highly contagious disease caused by varicella zoster virus. In children, it is generally a mild to moderate illness while it is often more severe in adults, with serious complications as dehydration, pneumonia, bleeding problems, infection or inflammation of the brain, secondary bacterial infections, sepsis, toxic shock syndrome, bone infections, joint infections and deaths. Some groups of adults are at major risk of complications, in particular immunocompromised persons as subjects with impaired humoral immunity and who is receiving systemic steroids, persons who live or work in environments in which transmission of varicella is likely, health-care personnel and pregnant women. After the introduction of Universal Mass Vaccination (UMV), the first mathematical models suggested that vaccination will lead to a shift in the average age at infection from children to adults with an increasing numbers of complicated forms, nevertheless new models predicted that, although an upward shift in the age at infection may occur, the overall morbidity due to varicella is likely to decrease. Current literature seems to suggest that for public health authorities the key action to prevent an increase of varicella incidence among adults is to achieve high vaccination coverage among babies and adolescents in countries who adopted UMV

Evaluation of a vaccination strategy by serosurveillance data: The case of varicella

Serological studies have many important epidemiologic applications. They can be used to investigate acquisition of various infections in different populations, measure the induction of an immune response in the host, evaluate the persistence of antibody, identify appropriate target groups and the age for vaccination. Serological studies can also be used to determine the vaccine efficacy. Since 1995 a varicella vaccine is available and it has been recommended in several countries (e.g. USA, Australia, Canada, Costa Rica, Ecuador, etc.). Nevertheless few varicella seroprevalence studies in countries that adopted an URV are available. It is related to the relatively recent introduction of the vaccination and to the lack of structured and collaborative surveillance systems based on serosurvey at national or regional level. Varicella seroprevalence data collected before the introduction of vaccination strategies allowed to establish the age of vaccination (e.g., indicated the opportunity to offer the vaccine to Italian susceptible adolescents). In the post-vaccination era, seroprevalence data demonstrated vaccine as immunogenic and excluded an increase of the age of infection linked to the vaccination strategy. New seroprevalence studies should be performed to answer to open questions, such as the long-term immunity and the change of the herpes zoster epidemiological pattern related to the vaccine

REDUCTION OF INVASIVE DISEASE IN CHILDREN TWO DECADES AFTER THE INTRODUCTION OF HAEMOPHILUS INFLUENZAE TYPE B CONJUGATE VACCINATION IN APULIA REGION, ITALY

Background Haemophilus influenzae type b conjugate (Hib) monovalent vaccination, consisting of 2p+1 doses at 3, 5, and 11 months of age, was introduced in the Italy’s infant immunization schedule in 1999 and included in the DTaP-HBV-IPV/Hib hexavalent vaccine since 2001. The estimated vaccination coverage was 83.4% in 2002, >90% by 2005, and >95% by 2011 [1-4]. In the Apulia region of Italy (about 4,000,000 inhabitants), vaccination coverage for 3 doses reached 75% in 2001, >90% by 2002, and >95% by 2007 (Graph. 1).Methods We considered annual age-specific hospitalization rates in infants <1 year and children 1-4 years as a proxy for incidence in the period 1996-2014. The attributable benefit was calculated as the reduction in incidence of Haemophilus influenzae invasive disease among vaccinated children attributable to the routine use of Hib monovalent vaccine during 1999-2000 (“Hib-monovalent period”) and of the hexavalent DTPa-HBV-IPV/Hib vaccine in the period 2001-2014 (“DTPa-HBV-IPV/Hib period”). The prevented fraction was calculated as the proportion of hypothetical total cases that were prevented by the use of monovalent and hexavalent vaccine, respectively (Panel A) [5]Results The hospitalization rate for Haemophilus influenzae invasive disease among infants decreased from 11.5 (95% CI= 1.4-21.6) per 100,000 in the 1996-1998 pre-vaccination period to 6 (95% CI= -1.4-13.3) per 100,000 in the “Hib-monovalent period”, with an estimated AleB of -5.5 per 100,000 and a PedF of 48.2%. It declined further to 1 (95% CI= -2.2-4.1) per 100,000 in the “DTaP-HBV-IPV/Hib period”, with an AleB of -10.5 per 100,000 and a PedF of 91.6% (Graph. 2). The rate of hospitalization among children aged 1-4 year remained stable at 2.4 per 100.000 from the pre- vaccination period through “Hib-monovalent period” (AleB=0; PedF=2%) and declined to 0.1 (95% CI= - 0.4-0.7) per 100,000 in the “DTaP-HBV-IPV/Hib period”, with an AleB of -2.3 per 100,000 and a PedF of 94.3% (Graph. 3)Conclusions * Hib-monovalent period - ** DTPa-HBV-IPV/Hib period In the Apulia region of Italy, the proportion of Haemophilus influenzae invasive disease requiring hospitalization in children aged <5 years presumably prevented by the introduction of Hib universal vaccination amounted to more than nine in ten cases. These findings are consistent with increased vaccine coverage rates as a result of the wide use of the hexavalent combination vaccines

Tackling Inequalities in Oral Health: Bone Augmentation in Dental Surgery through the 3D Printing of Poly(ε-caprolactone) Combined with 20% Tricalcium Phosphate

Personalized medicine and overcoming healthcare inequalities have gained significant popularity in recent years. Polymers offer an ideal solution due to their cost-effectiveness, ease of customized 3D printing, and potential for wide-scale expansion. Poly- mers blended with β-tricalcium phosphate (TCP) have been found to synergize with the environ- mental tissues of maxillary bones and promote osteoconductivity. However, little is known about their properties after printing and their ability to maintain their biological role; additionally, limi- tations exist in 3D printing when high TPC concentrations are added. Our study demonstrated that poly ε-caprolactone (PCL)+β-TCP 20% composite can be successfully printed and is a suitable ma- terial for commercial 3D printing. The material also demonstrated biocompatibility, supporting osteoblast adhesion and promoting cell proliferation and differentiation. The composite can also sustain ISO14937:200935 sterilization procedures, which makes it an ideal material for printing medical devices that can be used by clinicians worldwide

Intradermal Tuberculin Test in Water Buffalo (Bubalus bubalis): Experimental use of Mycobacterial Antigens for the Diagnosis of Bovine Tuberculosis

The study aims to evaluate the potential use of mycobacterial ESAT6 and CFP10 antigens, Early Secretory Proteins (ESP) in the Skin Test used for bovine tuberculosis (TB) diagnosis in Water Buffalo. A pilot study was performed on 21 buffaloes from a TB outbreak and 11 buffaloes from a TB-free herd. Three concentrations of ESAT6-CFP10 (10, 20, and 30 mg) and two of ESP (50 and 100 µg) were inoculated in the Skin Test, along with PPDB, PPDA, and PBS as a negative control. Skin thickness was measured with calipers before the test and every 24 hours for 4 days. Then, to evaluate the specificity of the antigens, a field study was conducted, and 100 buffaloes from a TB-free herd were inoculated using the best antigens concentration derived from the pilot study. In the positive buffaloes, the strongest skin response was to PPDB at 24h, with some subjects becoming inconclusive at 72 and 96 h. A peak response to PPDA at 48 hours was detected, followed by a slight decrease. The response to ESP-100 µg remained high at 24 and 48 h, then decreased, remaining positive at 72 h. In the 100 TB-free buffaloes, the best specificity was observed using ESAT6-CFP10 and ESP. ESP yielded the best results, showing higher reactivity in infected animals and no reactivity in the healthy ones at 72 h. Therefore, ESP could be an excellent candidate for further extensive studies in the buffalo species to improve Skin Test performance

High incidence of severe cyclosporine neurotoxicity in children affected by haemoglobinopaties undergoing myeloablative haematopoietic stem cell transplantation: early diagnosis and prompt intervention ameliorates neurological outcome

<p>Abstract</p> <p>Background</p> <p>Neurotoxicity is a recognized complication of cyclosporine A (CSA) treatment. The incidence of severe CSA-related neurological complications following hematopoietic stem cell transplantation (HSCT) is 4-11%.</p> <p>Methods</p> <p>We describe 6 cases of CSA related neurotoxicity out of 67 matched related HSCT performed in paediatric Middle East patients affected by haemoglobinopaties (5 beta thalassemia major, 1 sickle cell disease-SCD). Conditioning regimen consisted of iv busulphan, cyclophosphamide and graft-versus-host-disease (GvHD) prophylaxis with CSA, methylprednisolone, methotrexate and ATG.</p> <p>Results</p> <p>All 6 patients presented prodromes such as arterial hypertension, headache, visual disturbances and vomiting, one to two days before overt CSA neurotoxicity. CSA neurotoxicity consisted of generalized seizures, signs of endocranial hypertension and visual disturbances at a median day of onset of 11 days after HSCT (range +1 to +40). Brain magnetic resonance imaging (MRI) performed in all subjects showed reversible leukoencephalopathy predominantly in the posterior regions of the brain (PRES) in 5/6 patients. EEG performed in 5/6 patients was always abnormal. Neurotoxicity was not explainable by high CSA blood levels, as all patients had CSA in the therapeutic range with a median of 178 ng/ml (range 69-250). CSA was promptly stopped and switched to tacrolimus with disappearance of clinical and radiological findings. All patients are symptoms-free at a median follow up of 882 days (range 60-1065).</p> <p>Conclusions</p> <p>Our experience suggests that paediatric patients with haemoglobinopaties have a high incidence of CSA related neurological events with no correlation between serum CSA levels and neurotoxicity. Prognosis is good following CSA removal. Specific prodromes such as arterial hypertension, headache or visual disturbances occurring in the early post-transplant period should be carefully evaluated with electrophysiological and MRI-based imaging in order to intervene promptly and avoid irreversible sequels.</p

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

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

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19)

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments

NOS1AP is a novel molecular target and critical factor in TDP-43 pathology

Cappelli et al. reported that Nitric Oxide Synthase 1 Adaptor Protein is a co-regulated transcript of the TAR DNA-binding protein 43 kDa, reduced in amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients with TAR DNA-binding protein 43 kDa pathology. Overall, their results highlight Nitric Oxide Synthase 1 Adaptor Protein as a novel druggable disease-relevant gene in TAR DNA-binding protein 43 kDa-related proteinopathies.Many lines of evidence have highlighted the role played by heterogeneous nuclear ribonucleoproteins in amyotrophic lateral sclerosis. In this study, we have aimed to identify transcripts co-regulated by TAR DNA-binding protein 43 kDa and highly conserved heterogeneous nuclear ribonucleoproteins which have been previously shown to regulate TAR DNA-binding protein 43 kDa toxicity (deleted in azoospermia-associated protein 1, heterogeneous nuclear ribonucleoprotein -Q, -D, -K and -U). Using the transcriptome analyses, we have uncovered that Nitric Oxide Synthase 1 Adaptor Protein mRNA is a direct TAR DNA-binding protein 43 kDa target, and in flies, its modulation alone can rescue TAR DNA-binding protein 43 kDa pathology. In primary mouse cortical neurons, we show that TAR DNA-binding protein 43 kDa mediated downregulation of Nitric Oxide Synthase 1 Adaptor Protein expression strongly affects the NMDA-receptor signalling pathway. In human patients, the downregulation of Nitric Oxide Synthase 1 Adaptor Protein mRNA strongly correlates with TAR DNA-binding protein 43 kDa proteinopathy as measured by cryptic Stathmin-2 and Unc-13 homolog A cryptic exon inclusion. Overall, our results demonstrate that Nitric Oxide Synthase 1 Adaptor Protein may represent a novel disease-relevant gene, potentially suitable for the development of new therapeutic strategies

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P &lt; 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria