Search

Introduction: Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease that significantly reduces occupational productivity and quality-of-life in affected patients. Italy has an estimated FMF prevalence of 1 in 60,000 people. While colchicine is the primary treatment for FMF, biologics are administered to intolerant and non-responder patients. Anakinra and canakinumab are the only biologics approved and reimbursed for FMF in Italy. Both medicines have demonstrated efficacy in FMF patients yet differ in treatment costs. This study aimed to perform a budget impact analysis (BIA) following anakinra's reimbursement for FMF treatment, considering pharmaceutical costs from the Italian National Healthcare Service (NHS) perspective. Methods: A 'Reference scenario' (all patients treated with canakinumab) was compared to an 'Alternative scenario', with increased anakinra market shares. The target population was estimated based on the Italian population, epidemiological and market research data. Drugs costs were estimated based on Summary of Product Characteristics and net ex-factory prices. Sensitivity analyses were implemented to test results' robustness. Results:The base case analysis showed an overall cumulative expenditure of €30,586,628 for 'Reference scenario' and € 16,465,548 for 'Alternative scenario'. A cumulative savings of €14,121,080 (46.2%) was calculated over 3 years as a result of the reimbursement and increasing uptake of anakinra. The sensitivity analyses, even considering a discount of 50% for canakinumab, confirmed the base case results. Conclusions: Anakinra's introduction, in FMF treatment, provides a financially sustainable option for Italian patients, with savings increasing according to greater use of anakinra. [ABSTRACT FROM AUTHOR]

• In non-middle eastern patients FMF manifests in mild form. • Chromosomes bearing the R202Q variant might not be completely neutral. • The sensitivity of FMF scores is diminished in a homogenous italian population. Familial Mediterranean Fever (FMF) is linked with the MEFV gene and is the commonest among monogenic autoinflammatory diseases, with high prevalence in the Mediterranean basin. Although the clinical presentation of FMF has a major role in diagnosis, genotype/phenotype correlations and the role of "benign" gene variants (as R202Q) appear highly variable and incompletely clear, making difficult to select the most effective strategy in the management of patients. Aim of the present study was to investigate the clinical presentation and the genetic background in a homogenous cohort of patients from Apulia (south eastern Italy). We investigated 217 patients with a clinical suspect of autoinflammatory diseases, who were characterized for the occurrence of specific symptoms and with next generation sequencing by a 4-gene panel including MEFV, MVK, NLRP3 and TNFRSF1A. A genetic change was identified in 122 (53.7%) patients, with 161 different MEFV variants recorded in 100 individuals, 10 variants in NLRP3 , and 6 each in TNFRSF1A and MVK. The benign variant R202Q was largely prevalent (41.6% of all MEFV variants). When patients were selected according the number of pathogenic MEFV variants (0, 1, or 2 pathogenic variants), results failed to show significant links between the frequency of symptoms and the number of pathogenic variants. Only family history and Pras score (indicative for severity of disease) predicted the presence of pathogenic variants, as compared with carriers of variants considered of uncertain significance or benign. Fever >38 °C and arthralgias appeared more frequently in R202Q-positive patients than in non-R202Q carriers. These two subgroups showed comparable duration of fever, occurrence of myalgia, abdominal and chest pain, Pras, and IFFS scores. In conclusion, results confirm that FMF manifests in mild form in non-middle eastern patients. This possibility partly affects the reliability of clinical criteria/scores. Furthermore, the presence of the R202Q variant might not be completely neutral in selected groups of patients. [ABSTRACT FROM AUTHOR]

Introduction: Although familial Mediterranean fever (FMF) is a relevant disease in countries surrounding the Mediterranean Sea, there are still few reports from Italy.We retrospectively evaluated patients with FMF diagnosed according to the EuroFever/PRINTO classification criteria in three pediatric rheumatology referral centers in central-southern Italy. Logistic regression analysis assessed the associations between age at disease onset and symptoms.Overall, 48 patients were enrolled (28 females, 20 males), with a median age at onset of 3.3 [3.1] years, and a median follow-up period of 5.1 [10.8] years. The most common MEFV genotype was M694V/- (11 patients, 22.9%), followed by M694V/M694V (6 patients, 12.5%). At onset, recurrent fever was observed in 47 patients (97.9%), with a median time between attacks of 18 [11] days. Overall, recurrent fever was observed in all patients, abdominal pain in 44 (91.7%), and chest pain in 18 (37.5%). At the last follow-up visit, 24 patients were on colchicine (50%), 2 on biologic (4.2%), and 6 on both (12.5%). Canakinumab was the most used biologic drug, in 6 (12.5%) patients. MEFV genotype was associated with disease severity (p = 0.007) and the use of a biological drug (p = 0.01). FMF prevalence in the Abruzzo region was found highly than expected (at least 1:45,000). Differently, we found a relevant gap among FMF patients expected and observed in the Apulia and Sicily regions.FMF is a relevant issue in central-southern Italy. A large epidemiologic study should be performed to better define its prevalence in the country.Key Points• Italian children with familial Mediterranean fever tend to have an early age of onset, primarily manifesting with recurrent fever and characteristic associated symptoms.• Many MEFV gene variants are present in Italian children with familial Mediterranean fever, and these patients are most often heterozygous, exhibiting a mild to moderate phenotype.• The prevalence of familial Mediterranean fever in Italy is still unknown but recently estimated to be around 1:60,000, probably higher in central and southern Italy.• According to our cohort, the prevalence of FMF in the Abruzzo region is at least 1:45,000, higher than expected. Differently, we found lower prevalence rates of the disease in Apulia and Sicily.Key Points• Italian children with familial Mediterranean fever tend to have an early age of onset, primarily manifesting with recurrent fever and characteristic associated symptoms.• Many MEFV gene variants are present in Italian children with familial Mediterranean fever, and these patients are most often heterozygous, exhibiting a mild to moderate phenotype.• The prevalence of familial Mediterranean fever in Italy is still unknown but recently estimated to be around 1:60,000, probably higher in central and southern Italy.• According to our cohort, the prevalence of FMF in the Abruzzo region is at least 1:45,000, higher than expected. Differently, we found lower prevalence rates of the disease in Apulia and Sicily.Methods: Although familial Mediterranean fever (FMF) is a relevant disease in countries surrounding the Mediterranean Sea, there are still few reports from Italy.We retrospectively evaluated patients with FMF diagnosed according to the EuroFever/PRINTO classification criteria in three pediatric rheumatology referral centers in central-southern Italy. Logistic regression analysis assessed the associations between age at disease onset and symptoms.Overall, 48 patients were enrolled (28 females, 20 males), with a median age at onset of 3.3 [3.1] years, and a median follow-up period of 5.1 [10.8] years. The most common MEFV genotype was M694V/- (11 patients, 22.9%), followed by M694V/M694V (6 patients, 12.5%). At onset, recurrent fever was observed in 47 patients (97.9%), with a median time between attacks of 18 [11] days. Overall, recurrent fever was observed in all patients, abdominal pain in 44 (91.7%), and chest pain in 18 (37.5%). At the last follow-up visit, 24 patients were on colchicine (50%), 2 on biologic (4.2%), and 6 on both (12.5%). Canakinumab was the most used biologic drug, in 6 (12.5%) patients. MEFV genotype was associated with disease severity (p = 0.007) and the use of a biological drug (p = 0.01). FMF prevalence in the Abruzzo region was found highly than expected (at least 1:45,000). Differently, we found a relevant gap among FMF patients expected and observed in the Apulia and Sicily regions.FMF is a relevant issue in central-southern Italy. A large epidemiologic study should be performed to better define its prevalence in the country.Key Points• Italian children with familial Mediterranean fever tend to have an early age of onset, primarily manifesting with recurrent fever and characteristic associated symptoms.• Many MEFV gene variants are present in Italian children with familial Mediterranean fever, and these patients are most often heterozygous, exhibiting a mild to moderate phenotype.• The prevalence of familial Mediterranean fever in Italy is still unknown but recently estimated to be around 1:60,000, probably higher in central and southern Italy.• According to our cohort, the prevalence of FMF in the Abruzzo region is at least 1:45,000, higher than expected. Differently, we found lower prevalence rates of the disease in Apulia and Sicily.Key Points• Italian children with familial Mediterranean fever tend to have an early age of onset, primarily manifesting with recurrent fever and characteristic associated symptoms.• Many MEFV gene variants are present in Italian children with familial Mediterranean fever, and these patients are most often heterozygous, exhibiting a mild to moderate phenotype.• The prevalence of familial Mediterranean fever in Italy is still unknown but recently estimated to be around 1:60,000, probably higher in central and southern Italy.• According to our cohort, the prevalence of FMF in the Abruzzo region is at least 1:45,000, higher than expected. Differently, we found lower prevalence rates of the disease in Apulia and Sicily.Results: Although familial Mediterranean fever (FMF) is a relevant disease in countries surrounding the Mediterranean Sea, there are still few reports from Italy.We retrospectively evaluated patients with FMF diagnosed according to the EuroFever/PRINTO classification criteria in three pediatric rheumatology referral centers in central-southern Italy. Logistic regression analysis assessed the associations between age at disease onset and symptoms.Overall, 48 patients were enrolled (28 females, 20 males), with a median age at onset of 3.3 [3.1] years, and a median follow-up period of 5.1 [10.8] years. The most common MEFV genotype was M694V/- (11 patients, 22.9%), followed by M694V/M694V (6 patients, 12.5%). At onset, recurrent fever was observed in 47 patients (97.9%), with a median time between attacks of 18 [11] days. Overall, recurrent fever was observed in all patients, abdominal pain in 44 (91.7%), and chest pain in 18 (37.5%). At the last follow-up visit, 24 patients were on colchicine (50%), 2 on biologic (4.2%), and 6 on both (12.5%). Canakinumab was the most used biologic drug, in 6 (12.5%) patients. MEFV genotype was associated with disease severity (p = 0.007) and the use of a biological drug (p = 0.01). FMF prevalence in the Abruzzo region was found highly than expected (at least 1:45,000). Differently, we found a relevant gap among FMF patients expected and observed in the Apulia and Sicily regions.FMF is a relevant issue in central-southern Italy. A large epidemiologic study should be performed to better define its prevalence in the country.Key Points• Italian children with familial Mediterranean fever tend to have an early age of onset, primarily manifesting with recurrent fever and characteristic associated symptoms.• Many MEFV gene variants are present in Italian children with familial Mediterranean fever, and these patients are most often heterozygous, exhibiting a mild to moderate phenotype.• The prevalence of familial Mediterranean fever in Italy is still unknown but recently estimated to be around 1:60,000, probably higher in central and southern Italy.• According to our cohort, the prevalence of FMF in the Abruzzo region is at least 1:45,000, higher than expected. Differently, we found lower prevalence rates of the disease in Apulia and Sicily.Key Points• Italian children with familial Mediterranean fever tend to have an early age of onset, primarily manifesting with recurrent fever and characteristic associated symptoms.• Many MEFV gene variants are present in Italian children with familial Mediterranean fever, and these patients are most often heterozygous, exhibiting a mild to moderate phenotype.• The prevalence of familial Mediterranean fever in Italy is still unknown but recently estimated to be around 1:60,000, probably higher in central and southern Italy.• According to our cohort, the prevalence of FMF in the Abruzzo region is at least 1:45,000, higher than expected. Differently, we found lower prevalence rates of the disease in Apulia and Sicily.Conclusions: Although familial Mediterranean fever (FMF) is a relevant disease in countries surrounding the Mediterranean Sea, there are still few reports from Italy.We retrospectively evaluated patients with FMF diagnosed according to the EuroFever/PRINTO classification criteria in three pediatric rheumatology referral centers in central-southern Italy. Logistic regression analysis assessed the associations between age at disease onset and symptoms.Overall, 48 patients were enrolled (28 females, 20 males), with a median age at onset of 3.3 [3.1] years, and a median follow-up period of 5.1 [10.8] years. The most common MEFV genotype was M694V/- (11 patients, 22.9%), followed by M694V/M694V (6 patients, 12.5%). At onset, recurrent fever was observed in 47 patients (97.9%), with a median time between attacks of 18 [11] days. Overall, recurrent fever was observed in all patients, abdominal pain in 44 (91.7%), and chest pain in 18 (37.5%). At the last follow-up visit, 24 patients were on colchicine (50%), 2 on biologic (4.2%), and 6 on both (12.5%). Canakinumab was the most used biologic drug, in 6 (12.5%) patients. MEFV genotype was associated with disease severity (p = 0.007) and the use of a biological drug (p = 0.01). FMF prevalence in the Abruzzo region was found highly than expected (at least 1:45,000). Differently, we found a relevant gap among FMF patients expected and observed in the Apulia and Sicily regions.FMF is a relevant issue in central-southern Italy. A large epidemiologic study should be performed to better define its prevalence in the country.Key Points• Italian children with familial Mediterranean fever tend to have an early age of onset, primarily manifesting with recurrent fever and characteristic associated symptoms.• Many MEFV gene variants are present in Italian children with familial Mediterranean fever, and these patients are most often heterozygous, exhibiting a mild to moderate phenotype.• The prevalence of familial Mediterranean fever in Italy is still unknown but recently estimated to be around 1:60,000, probably higher in central and southern Italy.• According to our cohort, the prevalence of FMF in the Abruzzo region is at least 1:45,000, higher than expected. Differently, we found lower prevalence rates of the disease in Apulia and Sicily.Key Points• Italian children with familial Mediterranean fever tend to have an early age of onset, primarily manifesting with recurrent fever and characteristic associated symptoms.• Many MEFV gene variants are present in Italian children with familial Mediterranean fever, and these patients are most often heterozygous, exhibiting a mild to moderate phenotype.• The prevalence of familial Mediterranean fever in Italy is still unknown but recently estimated to be around 1:60,000, probably higher in central and southern Italy.• According to our cohort, the prevalence of FMF in the Abruzzo region is at least 1:45,000, higher than expected. Differently, we found lower prevalence rates of the disease in Apulia and Sicily. [ABSTRACT FROM AUTHOR]

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disease, which presents with recurrent episodes of fever, serositis, synovial inflammation and various different clinical features. In parallel with the geographical distribution of FMF, the prevalence is notably higher in some population groups including Turks, Jews, Armenians and Arabs. The aim of this study was to assess FMF articles published between 2010 and 2019 bibliometrically and to present up-to-date data. This bibliometric research was conducted on the Scopus database. The key term ''familial Mediterranean fever'' was utilized to generate the publication list. The number of articles, active countries journals, prolific authors and citation data were determined. Visualization maps that revealed collaboration networks were also created. The number of FMF articles displayed a stable trend between 2010 and 2019 (p > 0.05). The top five countries according to the number of articles were Turkey (n = 473; 52.90%), Israel (n = 86; 9.61%), Japan (n = 39; 4.36%), Italy (n = 38; 4.25%) and the USA (n = 37; 4.13%. Italy, the USA and France were ranked as the top three countries for the average number of citations per article. Rheumatology International, Clinical Rheumatology, Clinical and Experimental Rheumatology, Annals of Rheumatic Diseases and Pediatric Rheumatology were the top five journals according to the number of FMF articles. The geographical distribution of FMF was seen to affect the article production of countries. Although Turkey dominated the field in the number of articles, it was not at the forefront in the average number of citations. To increase the production of articles in the field of FMF, it is necessary to support researchers in countries other than those which are already strongly active. [ABSTRACT FROM AUTHOR]

We assessed the causes of polyserositis in pigs, categorized by causative agents and ages of animals affected. In a 3-y study, 246 pigs from 80 different farms with recurrent problems of polyserositis, in a high-density breeding area, were submitted for autopsy; 154 pigs with typical fibrinous serosal lesions were sampled for further bacterial and viral investigation. The most common gross lesions were pleuritis and pericarditis (141 of 154; 92%). The animals most affected were weaned pigs (139 of 154; 90%). Haemophilus parasuis and Mycoplasma hyorhinis were the most common bacteria detected and were present at the same rate (85 of 154; 55%). Other bacteria isolated were Streptococcus sp. (44 of 154; 29%), Pasteurella multocida (21 of 154; 14%), Escherichia coli (19 of 154; 12%), Actinobacillus pleuropneumoniae (7 of 154; 5%), and Trueperella pyogenes (4 of 154; 3%). Porcine reproductive and respiratory syndrome virus (PRRSV; 119 of 154; 77%) predominated among the viruses detected, followed, with lesser prevalence, by porcine circovirus 2 (40 of 154; 26%) and swine influenza A virus (19 of 154; 12%). Bacterial coinfection and coinfection of bacteria and viruses were common (128 of 154; 83%). A strong positive correlation was found between coinfection by H. parasuis and M. hyorhinis and also by H. parasuis with PRRSV. [ABSTRACT FROM AUTHOR]

Background: Inflammation is deemed to play a crucial role in the pathogenesis of Alzheimer’s disease (AD). We sought to determine whether the proinflammatory M694V mutation of pyrin, the gene responsible for familial Mediterranean fever, could lead to an increased risk for AD. Methods: We compared the M694V variant genotypes in 378 sporadic AD patients and 384 healthy control subjects of Italian descent. Results: After adjustment for potential confounders, the M694V mutation was found to be associated with an increased risk for AD in subjects with an age at onset of 65 years or younger (multivariate-adjusted odds ratio, OR: 3.01, 95% confidence interval, CI: 1.24–6.72, p = 0.021), but not in patients with an age at onset older than 65 years (multivariate-adjusted OR: 0.81, 95% CI: 0.34–1.99, p = 0.847). Kaplan-Meier analysis indicated that AD patients bearing the M694V mutation presented with disease onset 7 years earlier than carriers of the wild-type genotype (log rank = 41.61, p < 0.001). Conclusion: Our data indicate that the M694V sequence variant in the pyrin gene might influence the age at onset of AD in the Italian population. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Familial Mediterranean fever (FMF) is an autosomal recessive disorder, characterised by short, recurrent attacks of fever with abdominal, chest or joint pain and erysipelas-like erythema. It is an ethnically restricted genetic disease, found commonly among Mediterranean populations, as well as Armenians, Turks, Arabs and Jews. Traditionally, Italians have been considered little affected by FMF, despite the geographical position of Italy (northern Mediterranean basin) and the migratory changes in its population. The objective was to characterise the demographic, clinical and genetic features of FMF in Italy. Patients of Italian origin were recruited from those referred to Italian-French medical centres for FUO (Fever of Unknown Origin) or 'surgical' emergencies; clinical history, genealogy and physical examination were recorded; all other possible infectious, neoplastic, auto-immune and metabolic diseases were excluded. Mutational analysis of the gene responsible for FMF (MEFV on 16p13.3) was performed, after which geno-phenotypical correlations were established. Italian FMF patients, 40 women and 31 men, aged from 3 to 75 years, have shown all the clinical manifestations indicative of FMF described in the literature, but with a lower incidence of amyloidosis. The genetic tests have been contributive in 42% of cases. The frequency of each different mutation has been similar to that found in a series of 'endemic' countries. The geno-phenotypical correlations have suggested the existence of genetic and/or environmental modifier-factors. Among Italians FMF seems to be more frequent than was believed in the past. The data presented are consistent with their geographical location and their history. [ABSTRACT FROM AUTHOR]