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CNN and the BBC World Service which is copyright and cannot be reproduced AEST = Australian Eastern Standard Time which is 10 hours ahead of GMT (Greenwich Mean Time) Patrick Gaggiano / Photograph by Webb Chappell “This place is classic—every time I’m in the North End It’s this timeless basement that has awesome cigars and great brown spirits Leather couches and Italian guys talking about God knows what This is the place we all wished our basement was.” Stanza Dei Sigari, 292 Hanover St., Boston, 617-227-0295, stanzadeisigari.com right on the water outside by the Aquarium It’s this spot where beers come in buckets Right in my wheelhouse: You can watch all the boats come in and grab a suntan—if I was capable of getting one of those.” The Landing at Long Wharf, One Long Wharf, Boston, 617-227-4321, bostonharborcruises.com 3.Lone Star Taco Bar “This new spot [in Cambridge] for this company is my favorite Definitely feels like the neighborhood local Lone Star Taco Bar, 635 Cambridge St., Cambridge, 857-285-6179, lonestar-boston.com 4.Bogie’s Place, inside JM Curley “This spot is the one where I go for birthdays It’s the perfect Boston steak house—secluded You feel like you’re living inside a Sinatra song when you go here Makes me swap my flannel for a suit jacket every time and never disappoints.” JM Curley, 21 Temple Place, Boston, 617-338-5333, jmcurleyboston.com “Anyone who knows me knows this is my happy place Always the spot I call out when a group is asking where to go I love it—honky-tonk bar that has killer live music This is where I do rounds of Fireball and Coors Light This is where anyone who I bring here looks at me sideways then gets here and can’t wipe the smile off their face Loretta’s Last Call, 1 Lansdowne St., Boston, 617-421-9595, lorettaslastcall.com BONUSEastern Standard “I was going back and forth about putting ES on here because I know that everyone already has this place in mind There’s no one in the industry here in Boston that doesn’t have an ES story up their sleeve or a page out of their playbook in their back pocket This place has single-handedly influenced damn near every person in the restaurant/bar industry in a positive way It’s honestly a home away from home: where I go for last call It’s the first spot I ever stepped foot into when I first came to Boston and it’s the spot I’m continuously impressed by Eastern Standard, 528 Commonwealth Ave., Boston, 617-532-9100, easternstandardboston.com. Here’s Where to Find the Top Doughnuts in Boston We Can’t Wait for These Greater Boston Restaurant Openings in 2025 ©2025 Boston Globe Media Partners, LLC This paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet’s disease (BD). The project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry. Preliminary results from the AIDA for Patients BD registry were consistent with data available in the literature, confirming that PROs and PREs could be easily provided by the patient remotely to integrate physician-driven registries with complementary and reliable information. Volume 10 - 2023 | https://doi.org/10.3389/fmed.2023.1188021 This article is part of the Research TopicNew Insights into Autoinflammatory Diseases: From Bench to BedsideView all 13 articles Introduction: This paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet’s disease (BD) Methods: The project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet) in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry Results: Respondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%) The median value of the Behçet’s Disease Quality of Life (BDQoL) score was 14 (IQR 11 and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9 The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range – 1.8–4) showing that the registry participants prioritized necessity belief over concerns to a limited extent patients had to pay from their own pocket for medical exams required to reach the diagnosis The low family socioeconomic status (p < 0.001) the presence of any major organ involvement (p < 0.031) the presence of gastro-intestinal (p < 0.001) neurological (p = 0.012) and musculoskeletal (p = 0.022) symptoms and headache (p < 0.001) were associated to a higher number of accesses to the healthcare system Multiple linear regression showed that the BDQoL score could significantly predict the global socioeconomic impact of BD (F = 14.519 Discussion: Preliminary results from the AIDA for Patients BD registry were consistent with data available in the literature confirming that PROs and PREs could be easily provided by the patient remotely to integrate physician-driven registries with complementary and reliable information Patient-driven or patient self-reported registries are organized systems collecting uniform data directly from patients to evaluate specified outcomes in a defined population (1) They integrate the classical physician-driven data collection with patient-reported outcomes (PROs) and patient-reported experiences (PREs) adding invaluable contents to research studies They are also expected to improve the doctor-patient relationship building trust and mutual connection through the patient’s transition from passive to active participant in all the steps of clinical research When based on user-friendly electronical records accessible online via remote devices they allow the widest participation even among people with disabilities or living far from the research center ensuring that geographical and social inequalities are overcome international experts from the AIDA Network made strategic collaborations with national patient advocacy organizations (PAOs) sharing the programme goals and vision there is the development of a patient-driven registry named “AIDA for Patients” covering the whole spectrum of diseases under surveillance and declined in all the national languages spoken in the Network to complement data collection with PROs and PREs directly entered by patients This paper is aimed at describing methods and preliminary results of the AIDA for Patients pilot project, a patient-driven registry for Italian persons affected by Behçet’s disease (BD) and their caregivers, which has been developed in collaboration with the Italian PAO SIMBA (Associazione Italiana Sindrome e Malattia di Behçet, https://www.behcet.it/) The registry data were preliminarily analyzed to evaluate the quality of life fatigue level and therapeutic adherence of people affected by BD and the socioeconomic impact of the disease in Italy The AIDA for Patients registry is hosted by the REDCap platform (Research Electronic Data Capture, https://projectredcap.org) a secure web application designed to support data capture for research studies Data were entered into electronic forms directly by the participants recruited through SIMBA communication channels (mailing list and social media) and the AIDA Network affiliated clinical centers in Italy Participants were able to access the registry through their mobile devices or computers via a QR code or a web link to the REDCap homepage of the project They were initially screened for inclusion through a short survey addressing the respondents to 7 different profiles: (1) adult patient >17 year-old (2) pediatric patient 13- to 17 year-old (3) pediatric patient 8- to 12 year-old (4) 13- to 17 year-old patient’s parent (5) 8- to 12 year-old patient’s parent (6) 5- to 7 year-old patient’s parent and (7) 2- to 4 year-old patient’s parent Respondents were automatically excluded by the system if the diagnosis of BD was only suspected or under evaluation and in case of parents of <2 year-old patients Each profile comprised 3 to 5 data collection instruments appropriate to the age and role of the participant which overall required about 10 min for completion The BDQoL score has a 0–30 validity range where higher scores indicate lower quality of life in adults The PedsQLcore score has a 0–100 validity range with higher scores meaning better quality of life in children aged 2–18 years The BMQ questionnaire is made up of two sections: the BMQ concern (BMQc) which investigates the strength of concerns about the safety of specific medications taken by the subject for BD which measures how much the subject feels important to take the specific medications prescribed for BD Both sections have a 1–5 validity range with higher scores indicating stronger beliefs; the BMQ necessity-concern differential has a – 4–+4 validity range indicating that necessity exceeds concern if the differential is >0 or concern exceeds necessity if <0 The global fatigue index (GFI) resulting from the MAF questionnaire ranges 0–50 where a higher index indicates more severe fatigue in adults The PedQLfatigue score has a 0–100 validity range with a higher score meaning less severe fatigue in children aged 2–18 years a new questionnaire (including 10 to 20 items according to the age and role of the respondent) was specifically developed by the authors and approved by SIMBA representatives to investigate the patient’s diagnostic journey and socioeconomic impact of the disease the emergency department and the specialistic services in the last 3 months The social burden index (SBI) resulted from the sum of the days lost at work/school by the subject and by his/her relatives due to BD and the number of days of hospitalization in the previous 3 months The total socioeconomic impact for each subject was calculated as the sum of the total number of accesses to medical services and the SBI The study protocol conformed to the tenets of the Declaration of Helsinki and was approved by the local Ethics Committee of the University of Siena (Reference No Informed consent for using clinical data for research purposes was obtained electronically at the start of the pre-screening survey via the following statement in the Italian language “By clicking this button you are expressing your willing to participate in this survey study and voluntarily give your consent.” Patients were informed by the physician or through the accompanying message of invitation that their personal information would be separated from their clinical data by using a pseudonym The researcher who handled clinical data and performed statistical analysis had no access to the mailing list of the subjects invited by SIMBA nor to any personal information potentially capable to identify the subjects the representatives from SIMBA and the treating physicians who invited the possible candidates had no access to the clinical data entered by the participants Statistical analysis was performed by using JASP open-source statistics package version 0.16.3 Descriptive statistics included sample sizes mean and standard deviation or median and interquartile range (IQR) Shapiro–Wilk test was used to assess normality distribution of data Differences in continuous data between independent groups were compared by Mann–Whitney U test or Kruskal–Wallis H test with Dunn’s post-hoc test Relationships between continuous variables failing to meet parametric assumptions were tested through Spearman’s rho (ρ) Multiple regression analysis was used to predict outcomes of multiple continuous variables (95% CI) The threshold for statistical significance was set to p < 0.05 and all p-values were two-sided During the period from March to October 2022 200 participants (M:F = 1:2.5) entered the registry Respondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%) 187 fulfilled inclusion criteria and were able to enter data into the registry as patients (n = 180) or patients’ parents (n = 7); the remaining 13 respondents were excluded by the system because the diagnosis of BD in the participant (n = 4) or in the participant’s child (n = 3) was not confirmed by a physician or for other reasons (n = 6) The median age of affected subjects was 43 years (IQR 17 range 18–69) for adults and 15 years (IQR 3.5 The median disease duration was 13 years (IQR 15 the median diagnostic delay was 4 years (IQR 7.8 There was a negative correlation with large effect size between the diagnostic delay and the year of disease onset (ρ = −0.72 Descriptive clinical and socioeconomic information of the participants is provided in Table 1 the BMQn score (ρ = 0.19 p < 0.031) and the BMQc score (ρ = 0.38 Multiple linear regression using backward data entry showed that GFI (OR 0.43 [CI 0.17–0.68]) the number of accesses to medical services in the previous 3 months (OR 0.59 [CI 0.04–1.14]) and BMQn score (OR −3.01 [CI −6.36–0.33]) could significantly predict BDQoL (F = 12.95 Correlation of the quality-of-life variation – measured by Behçet’s Disease Quality of Life (BDQoL) questionnaire – and (A) sport habit (B) socioeconomic status of the family [0 = not disclosed; 1 = poorer than average; 2 = average; 3 = healthier than average] (C) fatigue level measured by Multidimensional Assessment of Fatigue (MAF) and (D) global socioeconomic impact of the disease range 1–50) and the mean PedQLFatigue total score was 63.9 ± 32.9 (range 31.9–100) The median value of GFI was higher in patients not practicing any sport (median 39 p = 0.022) and in patients complaining of gastro-intestinal (p < 0.001) neurological (p = 0.048) and musculoskeletal (p = 0.015) symptoms and headache (p < 0.001) Subjects estimating the socioeconomic status of their family as poorer than average had higher values of GFI (median 39.4 IQR 12.5) compared to average (median 37.1 p = 0.009) and healthier than average (median 35.9 participants who autonomously searched for information about their disease showed higher values of GFI than those receiving information from medical professionals (43.2 A positive correlation was also found between GFI value and the number of accesses to medical services in the previous 3 months (ρ = 0.43 the BMQn score (ρ = 0.24 and the BMQc score (ρ = 0.29 The mean BMQn score was 4.1 ± 0.7 (range 1.4–5) the mean BMQc score 3.2 ± 0.8 (range 1–5) and the mean BMQ necessity-concern differential 0.9 ± 1.1 (range – 1.8–4) Subjects with major organ involvement had higher values of BMQn score than those with only minor BD manifestations (median 4.2 Participants with more than 18 school years had higher values of BMQn score (median 4.6 IQR 1) than those with 14–18 school years (median 4 p = 0.003) and 9–13 school years (median 4 Subjects with a socioeconomic status defined as poorer than average had higher BMQc score (median 3.4 p = 0.003) and healthier than average (median 2.7 a positive correlation was found between both the BMQn and BMQc score and the number of accesses to medical services in the previous 3 months (ρ = 0.24 p = 0.006 and ρ = 0.20 respectively) and between the BMQn score and the SBI (ρ = 0.29 Socioeconomic impact of different clinical manifestations of Behçet’s disease: (A) number of medical service (MS) accesses in the last 3 months in patients with or without major organ involvement (OI); global socioeconomic impact of the disease in patients with or without gastro-intestinal (B) This paper describes the methodology and preliminary data of a patient-driven registry for Italian-speaking people affected by BD which can be easily accessed online by patients of different age groups and their caregivers the registry access link and QR code were emailed and posted on Facebook by SIMBA and advertised directly by physicians through an informative leaflet given to patients during routine follow-up visits Preliminary statistics of the registry enrolment clearly show that the most promising channel is the non-medical one with 83.5% of spontaneous enrolments via SIMBA channels versus 16.5% via medical professionals This can be explained by the fact that direct email/Facebook access to the screening survey is more immediate than access through the QR code or link printed on the leaflet the context of the hospital visit may not be ideal to capture the attention of the patient who naturally focuses on information about his/her health condition The physician may also find it challenging to recruit patients in the short timeframe of the follow-up visit the AIDA for Patients recruitment strategy should be remodulated in the future by boosting the role of national PAOs and running a wider internet and social-media campaign by generating automatic email invitations linked to the AIDA physician-driven registry records to match physician- and patient-reported data The diagnostic delay was around 4 years, similar to what has been observed in historical cohorts of both adults and children with BD (16, 17); however the timeliness of the diagnosis improved over the last decades reflecting the increasing awareness about BD and general improvement of rare diseases diagnostic paths we observed that most patients had to pay for clinical and instrumental exams from their own pocket to achieve the diagnosis of BD even though the public Italian healthcare system fully covers medical expenses within the rare diseases diagnostic journey This inconsistency sheds light on the existence of procedural pitfalls of the system which should be discussed among all the stakeholders to improve the efficacy of existing procedures and introduce new operative measures where required We also observed that major organ involvement low socioeconomic status and impaired quality of life are the major determinants of the social burden of BD in terms of number of accesses to the healthcare system days of hospitalization and days lost at work by affected people As for the specific disease manifestations and musculoskeletal manifestations were more likely to access medical services and lose days of work but also recurrent fever and headache had a remarkable impact on productivity the preliminary results of the AIDA for Patients registry confirmed that people complaining of BD-related articular headache and fatigue have lower quality of life the measurement of disease activity cannot be separated from the medical examination which makes necessary to align the patient-driven data collection with the physician-driven prospective records of the AIDA registry we found among factors associated to a lower quality of life and fatigue complaint a poor socioeconomic status a high frequency of medical services and a high work/school absenteeism rate Respondents with a more severe disease course characterized by major organ involvement had higher necessity belief than those with minor disease manifestations more educated participants had higher sense of necessity of treatment while lower-income people had higher concerns of possible harm from their therapies These aspects should be considered when applying the results of patient-driven registry-based studies to the general population participants were engaged with the mediation of physicians working in reference centers for BD and a patient advocacy group specifically devoted to BD via mailing list of the association subscribers and its Facebook page The respondents were directed to a landing page with detailed information on the study aims and inclusion criteria and instructions about how to complete the surveys in order to mitigate the aforementioned risks of bias participants were addressed to a screening survey directly asking whether a definite diagnosis of BD was made by a physician or the disease was under evaluation or merely suspected by the respondents themselves we cannot ascertain that all the respondents enrolled via SIMBA communication channels have BD because participants data were fully anonymized the results of the pilot study are consistent with the literature on BD regardless of the different methodology used which allowed a consistent sparing of resources in terms of time and dedicated medical personnel The preliminary analysis of data entered by BD participants suggests that PROs and PREs may be easily provided by the patient remotely integrating physician-driven registries with complementary and reliable information which represents one of the major strengths of the AIDA for patient action the AIDA for patients instrument will be integrated in the AIDA Network Behçet’s Syndrome Registry to complement it with PROs and PREs directly collected by patients making them available for clinical research on a wide international cohort it will be also possible to reach the critical numbers allowing comparisons between different recruitment channels to assess in a more comprehensive way the reliability and consistency of data entered by patients themselves The AIDA for patients pilot project represents the starting point of a broader initiative that is expected to involve patients affected by autoinflammatory diseases and ocular immune-mediated diseases Aimed at the development of four-handed registries for clinical research purpose the project will facilitate interactions among all the figures involved in the co-production of health in all the Countries where AIDA Network partner centers operate In the light of the AIDA for Patients pilot project experience the alliance with patient advocates proves itself crucial for the prioritization of the registry domains and getting people actively involved into research The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Requests to access these datasets should be directed to the corresponding author: LC, Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinics, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Y2FudGFyaW5pbHVjYUBob3RtYWlsLmNvbQ== The protocol of this study involving human participants was reviewed and approved by the Ethics Committee of Azienda Ospedaliero Universitaria Senese (protocol number: 14951) Written informed consent to participate in this study was provided by the participants or their legal guardian/next of kin electronically at the start of the survey performed statistical analysis with support from JS and wrote the first draft of the manuscript ABi was involved in the registry development as patient representative and enrolled participants via email and social media campaign and accounts for AIDA Registries Coordinator ABa was involved as bioengineer in the technical development of the registry platform and BF enrolled participants in the project during hospital visits and EBatu were included in the authorship as investigators from the top contributor centres of the AIDA Behçet’s syndrome registry The authorship was established based on the number of patients recruited in the AIDA registries up to Mar 9th All authors contributed to the article and approved the submitted version This study received funding from the patient advocacy organization S.I.M.B.A (Associazione Italiana Sindrome e Malattia di Behçet) Seventeen of the authors of this publication are members of the European Reference Network (ERN) for Rare Immunodeficiency Autoinflammatory and Autoimmune Diseases (RITA) The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher Recommendations for improving the quality of rare disease registries Outcome measures in rheumatology Behçet’s syndrome working group Core set of domains for outcome measures in Behçet’s syndrome Development of the BD-QoL: a quality of life measure specific to Behçet’s disease The utility of the necessity-concerns framework in explaining treatment non-adherence in four chronic illness groups in Italy The PedsQL: measurement model for the pediatric quality of life inventory CrossRef Full Text | Google Scholar A systematic review of studies using the multidimensional assessment of fatigue scale Paediatric Behçet’s disease in Iran: report of 204 cases Patient characteristics in Behçet’s syndrome and their associations with major organ involvement: a single-centre experience of 2118 cases Clinical manifestations of Behçet’s syndrome: a single-center cohort of 777 patients Behcet’s disease in Iran: analysis of 7641 cases Clinical phenotypes of Behçet’s syndrome in a large cohort of Italian patients: focus on gender differences Behçet’s syndrome: one year in review 2022 Epidemiology and treatment of Behçet’s disease in the USA: insights from the rheumatology informatics system for effectiveness (RISE) registry with a comparison with other published cohorts from endemic regions Women’s involvement in clinical trials: historical perspective and future implications 15. EURORDIS report February 2018 Rare disease patients’ participation in research: a rare barometer survey Available at: https://www.eurordis.org/publications/rare-disease-patients-participation-in-research/ Google Scholar Adult Behcet’s disease in Iran: analysis of 6075 patients Consensus classification criteria for paediatric Behçet’s disease from a prospective observational cohort: PEDBD Global systematic review and meta-analysis of health-related quality of life in Behcet’s patients The impact of multifactorial factors on the quality of life of Behçet’s patients over 10 years Quality of life and life satisfaction in patients with Behçet’s disease: relationship with disease activity Quality of life impairment in Behçet’s disease and relationship with disease activity: a prospective study Evaluation of treatment adherence in patients with Behçet's disease: its relation to disease manifestations Adherence to treatment in patients with Behçet’s disease Adherence to treatment in Behçet’s syndrome: a multi-faceted issue Treat to target in Behcet’s disease: should we follow the paradigm of other systemic rheumatic diseases Collecting behavioural data using the world wide web: considerations for researchers CrossRef Full Text | Google Scholar Balistreri A and Cantarini L (2023) A patient-driven registry on Behçet’s disease: the AIDA for patients pilot project Received: 16 March 2023; Accepted: 22 May 2023; Published: 16 June 2023 distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Luca Cantarini, Y2FudGFyaW5pbHVjYUBob3RtYWlsLmNvbQ== Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish Luminary of the Sacramento dining scene Biba Caggiano has died. The Bologna-born chef, author, and TV personality was 82. Her midtown Italian restaurant, Biba, opened in 1986 and is credited with invigorating the Sacramento food scene. The Sacramento Bee ran her obituary yesterday Caggiano’s many admirers included former SF mayor Willie Brown who said Caggiano “set a standard to which we should all aspire.” Caggiano moved to Sacramento with her American husband in 1978 with backing from a former owner of the Sacramento Kings and is still sought out for dishes Caggiano’s dishes like lasagne verdi alla bolognese a seven layered masterpiece of fresh pasta interspersed with rich bolognese and bechamel sauces “Caggiano became a symbol of Sacramento in her own right,” the Bee writes in its obituary Biba Caggiano remained a constant source of goodwill and community.” In recent years, Caggiano was diagnosed with Alzheimers. and has spent less and less time in the dining room at Biba. She is survived by her husband and children, and her namesake Biba, which is on Eater’s list of the 38 Essential Sacramento restaurants, is still going strong. The restaurant shared the following statement: Oops. Something went wrong. Please enter a valid email and try again. Volume 11 - 2024 | https://doi.org/10.3389/fmed.2024.1489092 Efficacy and safety of Janus kinase inhibitors in non-infectious inflammatory ocular diseases: a prospective cohort study from the international AIDA network registries A Corrigendum on Efficacy and safety of Janus kinase inhibitors in non-infectious inflammatory ocular diseases: a prospective cohort study from the international AIDA network registries by Vitale, A., Palacios-Olid, J., Caggiano, V., Ragab, G., Hernández-Rodríguez, J., Pelegrín, L., Mejía-Salgado, G., Zarate-Pinzón, L., Gentileschi, S., Sota, J., Fonollosa, A., Carreño, E., Gaggiano, C., Amin, R. H., Balistreri, A., Narváez, J., Tosi, G. M., Frediani, B., Cantarini, L., de-la-Torre, A., and Fabiani, C. (2024). Front. Med. 11:1439338. doi: 10.3389/fmed.2024.1439338 Flow-chart explaining the selection of patients included in this study starting from the total number of patients included in the AutoInflammatory Disease Alliance (AIDA) Network project In the published article, there was an error in Table 1 as published. In Table 1, there is a typographical error in the second to last row, “Extra ocular” was changed to “Extraocular”. The corrected Table 1 and its caption appear below clinical and therapeutic features describing the twelve patients enrolled There are four sentences in which there are either structural or typographical errors A correction has been made to Patients and methods “international AutoInflammatory Disease Alliance (AIDA) Network registries dedicated to uveitis scleritis and Behçet's disease” “International AutoInflammatory Disease Alliance (AIDA) Network registries dedicated to uveitis scleritis and Behçet's syndrome” “and one from the International AIDA Network registry dedicated to Behçet's disease (10)” “and one from the International AIDA Network registry dedicated to Behçet's syndrome (10)” A correction has been made to Treatment details “Four patients were receiving combination therapy with cDMARDs at the start of treatment with JAK inhibitors: two were on azathioprine The follow-up period while on combination therapy was three months and eleven months for the patients on azathioprine and seven months for the patient treated with sulfasalazine” seven months for the patient in therapy with sulfasalazine and six months for the patient treated with leflunomide” “The lack of Gas withdrawal in these two cases was either due to systemic disease activity or the short follow-up duration” “The lack of GCs withdrawal in these two cases was either due to systemic disease activity or the short follow-up duration” The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way de-la-Torre A and Fabiani C (2024) Corrigendum: Efficacy and safety of Janus kinase inhibitors in non-infectious inflammatory ocular diseases: a prospective cohort study from the international AIDA network registries Received: 31 August 2024; Accepted: 02 September 2024; Published: 13 September 2024 Edited and reviewed by: George E. Fragoulis *Correspondence: Luca Cantarini, Y2FudGFyaW5pbHVjYUBob3RtYWlsLmNvbQ==; Claudia Fabiani, Y2xhdWRpYS5mYWJpYW5pQGFpZGFuZXR3b3JrLm9yZw== †These authors have contributed equally to this work Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish. Play Duration: 3 minutes 19 seconds3m 19sPresented by North Queensland locals are preparing for flash flooding as more rainfall strikes the region. Its hampering clean up efforts, as locals attempt to repair the damage after weeks of flooding.  Featured:Matthew Chiesa, Ingham Butcher Felix Reitano, Ingham real estate agent Owen Menkens, Canegrowers chairmanJim Chalmers, Federal TreasurerMelanie Gaggiano, Gaggiano Custom Panel and PaintDavid Crisafulli, Queensland Premier  Flooding in Ingham in North Queensland, Wednesday, February 5, 2025(AAP: Adam Head) Download the ABC listen app to hear more of your favourite podcasts Background and Objectives: Few studies have reported the drug retention rate (DRR) of biologic drugs in juvenile idiopathic arthritis (JIA), and none of them has specifically investigated the DRR of interleukin (IL)-1 inhibitors on systemic JIA (sJIA). This study aims to describe IL-1 inhibitors DRR and evaluate predictive factors of drug survival based on data from a real-world setting concerning sJIA. Methods: Medical records from sJIA patients treated with anakinra (ANA) and canakinumab (CAN) were retrospectively analyzed from 15 Italian tertiary referral centers. Conclusions: Our findings suggest an excellent overall DRR for both ANA and CAN that might be further augmented by paying attention to AEs and employing these agents as first-line biologics in an early disease phase. Volume 9 - 2018 | https://doi.org/10.3389/fphar.2018.01526 Background and Objectives: Few studies have reported the drug retention rate (DRR) of biologic drugs in juvenile idiopathic arthritis (JIA) and none of them has specifically investigated the DRR of interleukin (IL)-1 inhibitors on systemic JIA (sJIA) This study aims to describe IL-1 inhibitors DRR and evaluate predictive factors of drug survival based on data from a real-world setting concerning sJIA Methods: Medical records from sJIA patients treated with anakinra (ANA) and canakinumab (CAN) were retrospectively analyzed from 15 Italian tertiary referral centers Results: Seventy seven patients were enrolled for a total of 86 treatment courses The cumulative retention rate of the IL-1 inhibitors at 12- without any statistically significant differences between ANA and CAN (p = 0.056) and between patients treated in monotherapy compared to the subgroup co-administered with conventional immunosuppressors (p = 0.058) significant differences were found between biologic-naive patients and those previously treated with biologic drugs (p = 0.038) and when distinguishing according to adverse events (AEs) occurrence (p = 0.04) patients pre-treated with other biologics (HR = 3.357 [CI: 1.341–8.406] p = 0.01) and those experiencing AEs (HR = 2.970 [CI: 1.186–7.435] p = 0.020) were associated with a higher hazard ratio of IL-1 inhibitors withdrawal The mean treatment delay was significantly higher among patients discontinuing IL-1 inhibitors (p = 0.0002) Conclusions: Our findings suggest an excellent overall DRR for both ANA and CAN that might be further augmented by paying attention to AEs and employing these agents as first-line biologics in an early disease phase while robust evidence from randomized clinical trials is available in the medical literature only a small amount of real-life data has been published so far especially in the context of early treatment and few of them have marginally investigated anti-IL-1 agents drug retention rate (DRR) on a relatively long-term follow-up we herein report our multicenter experience on a patients affected by sJIA treated with the anti-IL-1 agents anakinra (ANA) and canakinumab (CAN) focusing on their long-term effectiveness and predictive factors of discontinuation Medical records of 76 patients affected by sJIA enrolled from January 2008 until July 2016 in 15 Italian tertiary referral centers were retrospectively reviewed All patients were diagnosed according to the revised International League of Association for Rheumatology (ILAR) criteria (Petty et al., 2004) In accordance with the best standards of care they were systematically followed-up every 3 months and/or in case of necessity (disease flare and/or safety issues) Before starting anti-IL-1 treatment with ANA or CAN patients underwent a complete medical examination evaluation of hepatitis B and hepatitis C virus markers QuantiFERON test and chest X-ray to rule out active or latent infections ANA and CAN dosages ranged from 1 to 4 mg/kg and from 2 mg/kg every 8 weeks to 4 mg/kg every 4 weeks This study adhered to the tenets of the Declaration of Helsinki and the protocol was approved by the local Ethic Committee (reference number: 364-16OCT2013) Written informed consent was obtained from all patients’ legal guardians The primary aim of the study was to examine the overall DRR of IL-1 blockers in sJIA patients Secondary aims of our study were to: (i) explore the influence of biologic line of treatment and the concomitant use of cDMARDs on DRR; (ii) find eventual predictive factors associated with events leading to drug discontinuation The CS sparing effect and the impact of disease duration and treatment delay on survival constituted ancillary aims The primary endpoint was evaluated by Kaplan–Meier survival curve at 12- Secondary endopoints were as follows: (i) using limit estimators to compare survival curves according to AEs combination therapy with cDMARDs and significant differences on survival curves distinguishing between biologic-naive patients and those already treated with other biologics; (ii) to evaluate whether demographic and therapeutic variables could predict time to treatment discontinuation the ancillary aims were explored by any potential statistically significant differences in the mean disease duration and in the mean treatment delay subdividing our sample in patients continuing and those discontinuing the treatment as well as on CS-sparing effect Data were analyzed using IBMSPSS Statistics for Windows Descriptive statistics was employed to display mean and standard deviation (SD) or median and interquartile range (IQR) as appropriate Shapiro–Wilk test is the test by which we assessed the normality of our data Categorical variables were analyzed by Pearson’s chi-square test while differences in means were investigated with Mann–Whitney U test Survival analysis were carried out with Kaplan–Meier curves with the event being ANA or CAN discontinuation Patients discontinuing treatment due to remission were not included in the statistical analysis Survival curves were compared using both long-rank and Breslow test as limit estimators Event-free survival was assessed with a Cox proportional hazard model using 95% confidence interval for hazard ratios aiming to evaluate any relation of demographic The threshold for statistical significance was set to p < 0.05 and all p-values were two-sided We studied 86 treatment regimens administered in a cohort of 77 pediatric patients (34 males, 43 females) receiving anti-IL-1 agents from January 2008 to July 2016. Demographic, clinical and therapeutic data are shown in Table 1 ANA and CAN were used in 61 and 25 regimens The mean ± SD time of treatment duration was 22.67 ± 19.50 months The median age ± IQR at disease onset was 6.00 ± 7.10 years clinical and therapeutic data of our cohort of patients affected with sJIA while Cox regression analysis identified two variables associated with a higher hazard of treatment withdrawal: biologic line with a higher hazard for biologic-exposed patients (HR = 3.357 [CI: 1.341–8.406] p = 0.01) and the occurrence of AEs (HR = 2.970 [CI: 1.186–7.435] Kaplan–Meier curve related to the overall cumulative drug retention rate of interleukin-1 inhibitors in the whole cohort of patients with systemic onset-juvenile idiopathic arthritis Time 0 represents the beginning of therapy with the event being the treatment discontinuation Kaplan–Meier curves describing the cumulative survival of interleukin-1 (IL-1) inhibitors according to: (A) biologic line of treatment (D) concomitant use cDMARDs or monotherapy with biologic agents conventional disease modifying anti-rheumatic drugs the median disease duration was significantly higher among patients discontinuing IL-1 blockers (5.88 years ± 6.55) compared to the subgroup that was able to retain these biologic agents (3.17 years ± 3.68) (p = 0.011) This difference was also found with regard to treatment delay which was significantly higher in the subgroup of patients discontinuing anti-IL-1 agents (3.71 years ± 6.07) vs (1.18 years ± 2.53) of those still on treatment (p = 0.0002) a significant reduction in the number of patients requiring the support of CS was found (p = 0.025) Sixteen out of 63 patients (27%) were able to completely discontinue CS therapy The AEs occurred in 13 out of 77 patients (17.1%) (11 on ANA and 2 on CAN), with the most frequent being injection site-reactions (n = 7), followed by generalized skin rashes (n = 4), respiratory problems (n = 1), and abnormal level of liver enzymes (n = 1). Two patients exhibiting generalized skin rash presented also diarrhea. Overall, AEs were responsible for 10 cases of treatment discontinuation. Figure 3 shows the reasons for treatment discontinuation and none of our patients developed macrophage activation syndrome during the follow-up period Reasons for discontinuation in sJIA patients In the present study we have reported the real-life experience of 15 Italian tertiary referral centers with IL-1 inhibitors used in the treatment of sJIA focusing on long-term effectiveness expressed as DRR safety issues determined a significant decrease in DRR not only on the long-term but also in the beginning of anti-IL-1 therapy Timely treatment is imperative also for minimizing CS exposure and CS-related deleterious AEs we found a significant lower number of patients on CS at the last follow-up visit which is of crucial importance in the pediatric age We observed an excellent safety profile of ANA and CAN that were well-tolerated without any serious AEs and no case of macrophage activation syndrome Limitations of our study includes the not randomized retrospective design along with its inherent associated drawbacks and the difficulties for a valid comparison with the available literature due to different endpoints Although the vast majority of patients were treated with standard dosages a few subjects were administered with higher dosages the small sample size of patients administered with non-standard dosages did not allow to perform a reliable statistical analysis the decision on when to start the treatment was made by the local physician without any predefined criteria this is the first study to report the long-term effectiveness in terms of DRR of anti-IL-1 agents in a cohort of patients diagnosed with sJIA Despite remaining a major therapeutic challenge in pediatric rheumatology sJIA may be currently managed with new biotechnologic drugs which allow to improve long-term outcome as well as to minimize long-term exposure to CS our results have shown an excellent overall retention rate of the IL-1 inhibitors ANA and CAN and their survival was not affected by the concomitant use of cDMARDs These data highlight the effectiveness of these agents in sJIA patients as monotherapy A close attention on safety concerns is warranted especially in the 1st year after treatment initiation the retention rate of anti IL-1 agents was influenced by the different line of biologic therapy suggesting that ANA and CAN should be used as first-line biologics our results have displayed a significant impact of treatment delay in drug discontinuation early treatment may take advantage of the “windows of opportunity,” but this hypothesis is far from being proven and requires further studies for its corroboration JS and LC conceived and designed the study JS and LC wrote the first draft of the manuscript DR revised the overall data and revised the manuscript All authors critically reviewed the draft manuscript and approved the submitted version Bridging the gap between the clinician and the patient with cryopyrin-associated periodic syndromes Systemic-onset juvenile idiopathic arthritis Mortality rates are increased in patients with systemic juvenile idiopathic arthritis outcome and complications in children with systemic onset juvenile idiopathic arthritis Efficacy and safety of canakinumab in patients with still’s disease: exposure-response analysis of pooled systemic juvenile idiopathic arthritis data by age groups Anakinra: a safe and effective first-line treatment in systemic onset juvenile idiopathic arthritis (SoJIA) Systemic juvenile idiopathic arthritis: diagnosis and management Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France Investigational drugs for treatment of juvenile idiopathic arthritis Pathogenesis of systemic juvenile idiopathic arthritis: some answers and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational Review: is there a window of opportunity for treatment of systemic juvenile idiopathic arthritis Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series Effectiveness and safety of a second and third biological agent after failing etanercept in juvenile idiopathic arthritis: results from the Dutch National ABC Register Systemic juvenile idiopathic arthritis: new insights into pathogenesis and cytokine directed therapies Anakinra in systemic juvenile idiopathic arthritis: a single-center experience International league of associations for rheumatology classification of juvenile idiopathic arthritis: second revision placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial) A systematic approach to autoinflammatory syndromes: a spelling booklet for the beginner The broad-ranging panorama of systemic autoinflammatory disorders with specific focus on acute painful symptoms and hematologic manifestations in children 2013 update of the 2011 American college of rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis Clinical remission in patients with systemic juvenile idiopathic arthritis treated with anti-tumor necrosis factor agents Safety profile of the interleukin-1 inhibitors anakinra and canakinumab in real-life clinical practice: a nationwide multicenter retrospective observational study doi: 10.1007/s10067-018-4119-x [Epub ahead of print] Treatment of juvenile idiopathic arthritis: a revolution in care Tynjälä Drug survival of the first and second course of anti-tumour necrosis factor agents in juvenile idiopathic arthritis Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis: results of a prospective cohort study Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis Google Scholar Keywords: systemic juvenile idiopathic arthritis Rigante D and Cantarini L (2019) Drug Retention Rate and Predictive Factors of Drug Survival for Interleukin-1 Inhibitors in Systemic Juvenile Idiopathic Arthritis Copyright © 2019 Sota, Insalaco, Cimaz, Alessio, Cattalini, Gallizzi, Maggio, Lopalco, La Torre, Fabiani, Pardeo, Olivieri, Sfriso, Salvarani, Gaggiano, Grosso, Bracaglia, De Benedetti, Rigante and Cantarini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Jurgen Sota, Z2lvcmdpb3NvdGE4OUBnbWFpbC5jb20= Luca Cantarini, Y2FudGFyaW5pbHVjYUBob3RtYWlsLmNvbQ== Background: Aim of this study was to search for any difference in the outcome of patients with adult onset Still's disease (AOSD) treated with anakinra (ANK) in relation with the interval between disease onset and the start of anti-interleukin(IL)-1 treatment and according with the different lines of ANK treatment. Patients and Methods: One hundred and forty-one AOSD patients treated with ANK have been retrospectively assessed. Statistically significant differences (p < 0.05) were analyzed in the frequency of ANK effectiveness, primary or secondary inefficacy to ANK and rate of resolution of clinical and laboratory AOSD manifestations after 3, 6, and 12 months since ANK treatment according with different lines of treatment and different times between AOSD onset and start of ANK. Conclusions: Clinical and therapeutic outcomes are substantially independent of how early ANK treatment is started in AOSD patients. However, a faster ANK effectiveness in controlling systemic inflammation and resolving articular manifestations may be observed in patients benefiting from IL-1 inhibition as soon as after disease onset. Volume 7 - 2020 | https://doi.org/10.3389/fmed.2020.00042 Background: Aim of this study was to search for any difference in the outcome of patients with adult onset Still's disease (AOSD) treated with anakinra (ANK) in relation with the interval between disease onset and the start of anti-interleukin(IL)-1 treatment and according with the different lines of ANK treatment Patients and Methods: One hundred and forty-one AOSD patients treated with ANK have been retrospectively assessed Statistically significant differences (p < 0.05) were analyzed in the frequency of ANK effectiveness primary or secondary inefficacy to ANK and rate of resolution of clinical and laboratory AOSD manifestations after 3 and 12 months since ANK treatment according with different lines of treatment and different times between AOSD onset and start of ANK Results: No significant differences were identified in the ANK effectiveness and frequency of primary or secondary inefficacy for patients starting ANK within 6 months (p = 0.19 respectively) since AOSD onset compared with patients starting ANK thereafter; no significant differences were identified in ANK effectiveness and primary or secondary inefficacy according with different lines of ANK treatment (p = 0.06 Patients starting ANK within 6 and 12 months since AOSD onset showed a significantly quicker decrease of erythrocyte sedimentation rate and C-reactive protein than observed among patients undergoing ANK treatment after 6 and 12 months The number of swollen joints at the 3 month follow-up visit was significantly lower among patients undergoing ANK within 6 months since AOSD onset (p = 0.01) while no significance was identified at the 6 and 12 month assessments (p = 0.23 and p = 0.45 the number of swollen joints was significantly higher among patients previously treated with conventional and biological disease modifying anti-rheumatic drugs (DMARDs) compared with those formerly treated only with conventional DMARDs (p < 0.017) Conclusions: Clinical and therapeutic outcomes are substantially independent of how early ANK treatment is started in AOSD patients a faster ANK effectiveness in controlling systemic inflammation and resolving articular manifestations may be observed in patients benefiting from IL-1 inhibition as soon as after disease onset both clinical and laboratory manifestations resolve within a few days from the start of anti-IL-1 treatment in the majority of patients also when a monotherapy approach is followed Despite the promising clinical results, not all patients are responsive to this treatment choice. Therefore, the identification of clinical or laboratory predictors of response currently accounts for a primary need to establish when and to whom IL-1 inhibitors should be started. In this regard, an early treatment with IL-1 blockade has been associated with a better outcome in the pediatric context (25–28) The main aim of the present study is to identify any difference in the outcome of AOSD patients treated with ANK in relation with the interval between disease onset and start of the IL-1 inhibitor and according with the different lines of ANK treatment Patients included in this study have also been presented in other studies providing information about effectiveness of anti-IL-1 agents in AOSD patients, long-term drug retention rate of ANK, and predictive factors of response to ANK (24, 29) Patients have been enrolled in 18 Italian tertiary Centers and had been diagnosed with AOSD basing on Yamaguchi's criteria (9) all patients had undergone a careful laboratory and radiologic screening in order to exclude infections neoplasms and other rheumatologic disorders possibly inducing fever Patients treated with ANK have been closely monitored with daily or weekly clinical and laboratory evaluations during the first month of treatment and then every three months or in case of either disease relapse or safety concerns A retrospective analysis of medical charts related to patients with AOSD was performed to evaluate any differences in the outcome of AOSD after treatment with ANK in relation with the time interval between disease onset and start of the IL-1 inhibitor and according with the different lines of ANK treatment endpoints of the study were to identify any statistically significant difference in the frequency of global ANK effectiveness primary or secondary inefficacy to ANK and in the resolution rate of clinical and laboratory AOSD manifestations after 3 6 and 12 months of ANK treatment between: (i) patients starting treatment within 6 months since disease onset and patients undergoing treatment afterwards; (ii) patients starting ANK within 12 months since AOSD onset and patients undergoing treatment thereafter; (iii) patients treated with ANK before cDMARDs and/or other biologics; (iv) patients undergoing ANK after cDMARDs and before other biologics; (v) patients previously treated with both cDMARDs and other biologic agents A further endpoint was to identify any statistically significant difference in the drug retention rate of ANK between patients treated with ANK before cDMARDs and other biologic agents patients undergoing ANK after cDMARDs and before other biologics and patients previously treated with both cDMARDs and other biologics The time cut-offs at 6 and 12 months after AOSD onset were chosen in order to accommodate the retrospective design of the study (patients were generally seen every three months in routine clinical practice) and the assessment of treatment outcomes based on how early IL-1 inhibition had been introduced Clinical variables considered in the statistical computation were: presence of fever liver involvement (hepatomegaly with increased liver enzymes) lymphadenitis (laterocervical and/or inguinal and/or axillary) lung involvement (non-infectious pneumonia) disease activity score in 28 Joints-C-reactive protein (DAS28-CRP) baseline Pouchot score (hereinafter referred to as “systemic score”) daily corticosteroid dosage at the start of ANK decrease in daily steroid dosage at 3-month Laboratory variables considered for the statistical computations were: total white blood cell counts erythrocyte sedimentation rate (ESR) and CRP The study protocol was conformed to the tenets of the Declaration of Helsinki and was approved by the local Ethics Committee of the University of Florence (reference number: 364-16OCT2013) Informed consent was obtained from each patient for the retrospective evaluation of her/his medical chart fever was defined by a temperature higher than 39°C 6-month and 12-month follow-up visits patients were considered fever-free when body temperature was persistently lower than 37°C during the previous four weeks pericarditis and pneumonia was based on echographic-radiological documentation; hepatomegaly was documented by ultrasound CT scan or magnetic resonance imaging (MRI) ESR and CRP were considered normal or increased according with the local laboratory normal ranges Primary inefficacy was considered as “no satisfactory improvement of clinical manifestations during the first four weeks of ANK treatment according with physician's judgment” A secondary inefficacy was defined as “reappearance of AOSD manifestations for at least four weeks leading to ANK withdrawal despite a previous global response lasting at least 3 months” Descriptive statistics has included sample size After having assessed normality distribution with Shapiro-Wilk test three-group comparisons of quantitative variables were performed by using ANOVA or Kruskall-Wallis test as appropriate; qualitative variables were analyzed employing Chi-square test with 2x3 contingency tables Unpaired two-tailed t test or Mann-Whitney two tailed U test with Bonferroni correction were used for post-hoc analysis when global significance had been reached two-group comparisons were performed using two-tailed t test or Mann-Whitney two tailed U test for quantitative variables and by employing Chi-square test with 2x2 contingency tables for dichotomous data When expected frequencies were less than five Chi-square test was changed with Fisher exact test Drug retention rates (DRR) were assessed using the Kaplan-Meier plot with “time 0” corresponding to the start of ANK treatment and the “event” being the discontinuation of therapy because of primary or secondary inefficacy Log-rank (Mantel-Cox) test and Breslow test were used to compare differences in the initial and terminal part of different Kaplan-Meier curves In order to verify any role for the therapeutic interval between AOSD onset and the start of ANK and to search for confounding factors related to patients' features binary stepwise regression analysis was performed by using the following demographic clinical and therapeutic features at the start of IL-1 inhibition as independent variables: disease duration (in months) between AOSD onset and the start of ANK AOSD severity assessed with the systemic score the daily corticosteroid dosage (mg/day of prednisone or equivalent) The following outcomes were used as dependent variables: ANK effectiveness (established according to our definition) at 6- and 12-month follow-up visit; a systemic score equal to zero at 6 and 12 month follow-up visits; a DAS28-CRP <2.6 at 6- and 12-month assessments; the complete normalization of inflammatory markers (both ESR and CRP) at 6- and 12-month laboratory assessments Statistical Package for Social Science (SPSS) 24.0 package was used for statistical analysis Two tailed p-values < 0.05 were considered statistically significant One hundred and forty-one patients (48 males, 93 females) diagnosed with AOSD according with Yamaguchi criteria and treated with ANK were enrolled in the study. Tables 1, 2 summarize demographic clinical and therapeutic data of all patients recruited General features of patients with AOSD at the start of treatment with anakinra Treatment choices preceding and accompanying anakinra in the patients evaluated in our study Treatment with ANK was started in 40 patients (28.4%) within 6 months since AOSD onset and in 65 patients (46.1%) during the first 12 months of disease In 19 cases (13.5%) ANK represented the first treatment approach soon after NSAIDs and corticosteroids; in 93 cases (66%) ANK treatment had been introduced as first-line biologic agent soon after cDMARDs failure while other than anti-IL-1 biologic agents had been previously employed in 29 cases (20.6%) None of the patients had been treated with canakinumab before starting ANK The median disease duration at the start of ANK was: i) 2 (IQR = 3) months among patients starting ANK during the first 6 months of disease activity and 28.5 (IQR = 71.25) months among patients treated with ANK thereafter; ii) 5 (IQR = 7) months among patients starting ANK during the first 12 months from AOSD onset and 56 (IQR = 84) months among patients undergoing ANK afterward; iii) 3 (IQR=8) months among patients undergoing ANK as first treatment approach soon after NSAIDs and corticosteroids 15 (IQR = 51) months among subjects treated with ANK after cDMARDs introduction and 69.5 (IQR = 164.75) months among patients undergoing ANK after cDMARDs and other biologics Dosages employed corresponded to ANK standard posology of 100 mg/day in 128 (90.8%) patients while 4 (2.8%) patients were treated with higher dosages (200 mg/day) and 9 (6.4%) with lower than standard dosages (100 mg every other day or less) When analyzing differences in clinical outcome between patients starting treatment with ANK before and after 6 months of disease duration no significant differences were identified in ANK effectiveness (p = 0.19) and in the frequency of primary (p = 0.14) or secondary (p = 0.81) inefficacy The systemic score at the start of treatments was significantly higher among patients undergoing ANK within 6 months since AOSD onset (6.3 ± 1.8 vs. 5.23 ± 1.9, p = 0.006). The decrease of systemic score at 3-, 6- and 12-month assessment was significantly higher among patients presenting a less than 6 months disease duration at the start of ANK (p = 0.006, p < 0.001 and p = 0.001, respectively). As reported in Table 3 the systemic score at 6-month assessment was significantly higher among patients starting ANK within six months from AOSD onset (p = 0.06) while no statistically significant differences were identified in the systemic score at 3- and 12-month assessments between the two groups (p = 0.67 and p = 0.89 Information about different responses in the articular manifestations between patients treated with anakinra no later than 6 months (upper part) and no later than 12 months (lower part) since AOSD onset compared with those starting the treatment thereafter Baseline corticosteroid dosage was significantly higher among patients treated early with ANK (p < 0.0001) The decrease in the steroid dosage was not statistically significant between groups at the 3-month assessment (p = 0.064); conversely it was significantly higher at both 6- and 12-month visits (p = 0.002 and p = 0.011 respectively) among patients starting ANK as early as 6 months since AOSD onset no differences were identified in the number of patients showing increased ESR (p = 0.86) while CRP was significantly more frequently increased among patients undergoing ANK within 6 months since AOSD onset (p = 0.023) At the 3-month evaluation ESR normalized in a significantly higher number of patients treated with ANK within the first 6 months since AOSD onset (p = 0.004) A similar trend was identified also for CRP without reaching a statistical significance (p = 0.054) No statistically significant differences were identified in the frequency of serum ferritin normalization at the 3-month (p = 0.86), 6-month (p = 0.24) and 12-month (p = 0.47) assessments. No statistically significant differences were found between groups regarding leukocytosis at the 3-month (p = 0.30), 6-month (p = 0.16) and 12-month (p = 0.33) assessments. As detailed in Figure 1 no significant differences were identified in the frequency of resolution of specific clinical manifestations between the two groups of patients Radar graphics highlight the frequency of resolution of laboratory and clinical manifestations of adult onset Still's disease between patients starting anakinra (ANK) within the first 6 months since disease onset (<6 months) and those starting ANK thereafter (>6 months); (A–C) refer to the 3-month 6-month and 12-month follow-up assessments P-values were obtained by employing Chi square test Fisher exact test was employed when expected frequencies were less than 5 No statistically significant differences were identified in the effectiveness of ANK (p = 0.37) and in the frequency of primary (p = 0.23) or secondary (p = 0.81) inefficacy between patients starting ANK during the first year since AOSD onset and those treated with ANK afterward systemic score was significantly higher among patients treated with ANK as soon as the first 12 months since the start of AOSD (6.2 ± 1.8 vs the decrease of systemic score was significantly higher among patients treated with ANK as early as the first 12 months since disease onset at the 3-month visit (p = 0.012) 6-month visit (p = 0.001) and 12-month assessment (p = 0.002) The baseline corticosteroid dosage was significantly higher among patients treated with ANK as soon as the first 12 months since AOSD onset (p = 0.001) the decrease of steroid dosage was significantly higher among patients undergoing the earlier ANK treatment at the 3-month (p = 0.001) 6-month (p = 0.007) and 12-month (p = 0.032) follow-up visits Table 3 provides details about different responses in articular features between patients treated with ANK no later than 12 months since AOSD onset and those starting the treatment thereafter At the start of ANK no differences were identified in the number of patients showing increased ESR (p = 0.56) between the two groups of patients; conversely CRP was significantly more frequently increased among patients starting ANK during the first year of disease (p = 0.032) Among subjects treated with ANK during the first 12 months since AOSD onset ESR normalized in a significantly higher number of patients at the 3-month assessment (p = 0.017) while no statistically significant differences were identified at the 6-month (p = 0.19) and 12-month (p = 0.58) follow-up visits CRP normalized in a significantly higher number of patients at the 3-month (p = 0.03) and 6-month (p = 0.014) visits while no differences were found at the 12-month assessment (p = 0.83) No differences were disclosed in the frequency of leukocytosis resolution and serum ferritin normalization at the 3-month (p = 0.87 and p = 0.66 respectively) and 12-month (p = 0.92 and p = 0.13 no significant differences were identified in the frequency of resolution of specific clinical AOSD manifestations between the two groups of patients Radar graphics highlight the frequency of resolution of laboratory and clinical manifestations of adult onset Still's disease between patients starting anakinra (ANK) within the first 12 months since disease onset (<12 months) and those starting ANK thereafter (>12 months); (A–C) refer to the 3-month No statistically significant differences were identified in ANK effectiveness (p = 0.06) and in frequency of primary (p = 0.19) or secondary (p = 0.13) inefficacy between patients treated with ANK after NSAIDs and corticosteroids, patients undergoing ANK as first-line biologic agent after cDMARDs failure and those previously treated with cDMARDs and other biologics. Table 4 describes clinical outcomes about systemic score articular involvement and corticosteroid sparing effect between the three groups of patients Differences about Pouchot score modified by Rau et al articular involvement and corticosteroid sparing effect between patients undergoing anakinra (ANK) as first treatment approach and patients previously treated with conventional disease modifying anti-rheumatic drugs (cDMARDs) or with cDMARDs plus other biologic agents No differences were identified in the serum ferritin levels between the three groups of patients at the 3-month, 6-month, and 12-month assessments. Figure 3 describes the frequency of resolution of laboratory and clinical AOSD manifestations at the 3-month, 6-month and 12-month follow-up visits. Table 5 provides details about the clinical manifestations at the start of ANK among patients starting treatment before and after 6 months since AOSD onset before and after 12 months since AOSD onset and according with different lines of ANK employment Significances at the post-hoc analysis: A = “ANK first” group vs “cDMARDs → biologics → ANK” group; B = “cDMARDs → ANK” group vs “cDMARDs → biologics → ANK” group The sign “*” indicates a lack of significance at the Bonferroni correction (p>0.017) Clinical and laboratory manifestations at the start of anakinra (ANK) treatment among patients undergoing ANK within and after 6 months since adult onset Still's disease (AOSD) onset patients starting ANK within and after 12 months since AOSD onset patients treated with ANK before both conventional disease modifying anti-rheumatic drugs (cDMARDs) and biologics (ANK first) patients treated with ANK after cDMARDs failure and before any other biologic agent (cDMARDs→ANK) and patients previously administered both cDMARDs and other biologics (cDMARDs→biologics→ANK) Supplementary Table 1 provides details about the frequency of effectiveness to anakinra, primary and secondary inefficacy in the different subgroups of patients identified in the study. Similarly, supplementary Tables 2, 3 respectively add information about the mean values of the systemic score [according to Rau et al. (11)] and the mean daily corticosteroid dosage at 3- 6- and 12-month assessments in the different subgroups of patients identified in the study The mean decrease of the systemic score and of the daily corticosteroid dosage compared to the start of ANK are also reported Figure 4 shows the different drug retention rates of ANK obtained including patients discontinuing treatment because of primary or secondary inefficacy blue line) from patients treated with ANK after cDMARDs failure (green line) and patients previously administered both cDMARDs and other biologics (red line) (C) In order to focus attention to ANK efficacy survival analysis excluded patients discontinuing ANK because of adverse events (25 cases) lack/loss of compliance or other non-medical reasons (19 patients) One patient was also excluded owing to the lack of information about the overall treatment duration After excluding patients who discontinued ANK because of adverse events lack/loss of compliance or other non-medical reasons and 1 patient with no information about the overall treatment duration no differences were identified in the drug retention rate of ANK between: (i) 23 patients treated with ANK as soon as the first 6 months since the start of AOSD manifestations and 53 patients starting ANK afterward (Log-rank test p = 0.52); (ii) 38 patients treated with ANK as soon as the first 12 months since the start of AOSD manifestations and 38 patients starting ANK afterward (Log-rank test p = 0.44); (iii) 10 patients treated with ANK as first treatment approach soon after NSAIDs and/or corticosteroids 49 patients treated with ANK soon after cDMARDs failure and 15 patients treated with ANK after cDMARDs and other biologics failure (Log-rank test The median follow-up while on ANK treatment duration was: 4 (IQR = 34) months among patients undergoing ANK within 6 months from AOSD onset and 48 (IQR = 67) months among patients starting the treatment thereafter; 15.5 (IQR = 57) months among patients treated with ANK within 12 months from disease onset and 5.5 (IQR = 56) months in the group of patients starting the IL-1 inhibitor afterward; 7.5 (IQR = 62) months among patients treated with ANK as first treatment line 10.5 (IQR = 55) months among patients treated with ANK after cDMARDs failure and 4 (IQR = 33) months among patients starting ANK after cDMARDs and other biologics we conducted the present study to identify any effect on clinical and laboratory outcomes in relation with the time delay between disease onset and the start of the IL-1 inhibitor we searched for any difference in the therapeutic outcome of ANK administered in different timepoints of disease course with respect to other treatment choices no significant differences are recognized in both the overall ANK effectiveness and frequency of primary or secondary inefficacy on the basis of the different intervals analyzed (6 and 12 months) as well as according to the different treatment lines the time delay between AOSD onset and the start of ANK did not represent a predictor of treatment outcome considered as ANK effectiveness complete AOSD control according to the systemic score achievement of a DAS28-CRP <2.6 and complete resolution of inflammatory markers the decrease of the score was significantly higher at 3- and 12-month assessments among patients undergoing ANK as first treatment line compared to subjects previously treated with both cDMARDs and other biologics This could be related to a more resistant inflammatory condition among patients experiencing several treatment failures but it could also suggest a higher ANK effectiveness in controlling systemic disease activity when used early the significantly higher systemic score identified at 6-month visit among patients starting ANK within the first six months from AOSD onset is hardly clinically significant given the absence of statistical significances at both the previous and at the next time point as well as in relation to the very modest mean values assumed by the score in the two groups (0.64 vs patients starting ANK within six or twelve months since AOSD onset showed a quicker reduction of the inflammatory markers ERS and CRP than observed among patients undergoing ANK treatment after six and twelve months This finding is even more pronounced when the 12-month time point is considered statistical significance in the rate of ESR and CRP resolution between groups tends to disappear over time while increased inflammatory markers were significantly more frequent at the 3-month assessment among patients starting ANK after both 6 and 12 months of disease duration at the 6-month assessment the significance was solely limited to CRP which was found more frequently increased among patients starting ANK after one year of disease duration no differences among groups were observed at the 12-month assessment these results suggest a slower activity of ANK in controlling systemic inflammation when employed later A similar trend was observed in the ability of ANK to control articular involvement. This is especially interesting, as joint affection has been frequently found less responsive to IL-1 inhibition than other AOSD manifestations (22, 23). Moreover, we recently found that the risk for a loss of efficacy of ANK increases along with the number of swollen joints at the start of treatment (29) the number of swollen joints at the 3-month follow-up visit was significantly higher among patients starting ANK after 6 months of AOSD duration compared with patients starting the biologic agent earlier no statistically significant differences were observed in the number of swollen joints at the 6- and 12-month follow-up visits no statistical significances were observed about the number of tender joints and the DAS28-CRP at the three follow-up visits neither considering the 6-month nor the 12-month time points since a higher number of treatment lines generally reflects a longer disease history the results obtained in our study seem to highlight a faster resolution of articular involvement in patients undergoing ANK during the first months of treatment The DRR analysis did not disclose statistically significant differences between patients treated with ANK during the first 6 or 12 months of AOSD duration compared to those undergoing IL-1 inhibition thereafter no differences were observed between patients treated with ANK soon after NSAIDs and/or corticosteroids failure and those previously treated with other treatment choices No differences were identified in the DRR of ANK by stratifying patients according with ANK treatment line these findings support that long-term therapeutic outcome is independent of how early ANK treatment is started future studies will have to verify whether this finding reflects a more resistant joint disease in patients failing other treatment strategies or underlies the need for an earlier ANK introduction in order to better manage joint manifestations Beyond joint involvement, no other single AOSD manifestations showed significant difference in the rate of resolution at the three follow-up visits, as almost all statistical significances did not overcome Bonferroni correction at the post-hoc analysis (Figures 1–3) As regards stratification for different treatment lines these findings seem to contradict the higher decrease of the systemic score observed among patients treated with ANK as first line treatment approach compared to those previously treated with cDMARDs and other biologics no statistically significant differences were observed in the frequency of each clinical manifestation taken individually while the systemic score seems to highlight a general higher response to ANK administered early The main limitation of this study is represented by its retrospective nature initiation of ANK was not made at random and the groups of patients were essentially not comparable at baseline; actually our experience reflects the real-life world as more difficult cases probably started ANK earlier as suggested by the higher systemic score and the higher baseline daily corticosteroid dosages employed when IL-1 inhibition was started earlier baseline differences does not seem to compromise results as the overall ANK effectiveness did not change between groups despite initial differences while the frequency of resolution of systemic inflammation resulted faster especially in groups with more severe conditions (higher systemic score and corticosteroid dosage) at the start of ANK regression analysis did not identify any role for possible baseline confounding factors related to patients' features AOSD activity and concomitant treatments including the type of AOSD (systemic vs the systemic score and the severity of joint involvement assessed with the DAS28-CRP the number of tender joints and the number of swollen joints were only available as qualitative data (increased/not increased) radiographic progression could not be assessed because of the lack of information As no defined criteria are currently applicable for starting or stopping IL-1 inhibition in AOSD patients the real-life enrollment has allowed statistical analysis including data obtained from subjects treated with ANK in different therapeutic lines and at different moments from AOSD onset the study has been conducted using time cut-offs at 6 and 12 months from disease onset We could have chosen higher time limits (24 but this would not have been helpful in addressing how early IL-1 inhibition should be introduced for treating patients with AOSD our results highlight that clinical and therapeutic outcomes are substantially independent of how early ANK treatment is started a faster effectiveness of ANK in controlling systemic inflammation and resolving articular manifestations may be described in patients benefiting from IL-1 inhibition as soon as after AOSD onset a lower decrease in the systemic Pouchot score is observed in patients treated with ANK only after the use of cDMARDs and other biologics These findings could suggest an early introduction of treatment with ANK specifically in patients with articular involvement The datasets generated for this study are available on request to the corresponding author The study protocol was approved by the Ethics Committee of the University of Florence (reference number: 364-16OCT2013) Written informed consent was obtained from each patient for the retrospective evaluation of her/his medical chart AV and LC conceived and designed the study and wrote the first draft of the manuscript DR revised the final data and the manuscript collected data and critically reviewed the final draft of the manuscript and approved the submitted version The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmed.2020.00042/full#supplementary-material Adult onset Still's disease in northern India: comparison with juvenile onset Still's disease “Adolescent-onset Still's disease”: characteristics and outcome in comparison with adult-onset still's disease Is Still's disease an autoinflammatory syndrome Adult Still's disease: manifestations Preliminary criteria for classification of adult Still's disease Proposal for a new set of classification criteria for adult-onset Still disease Clinical manifestations but not cytokine profiles differentiate adult-onset Still's disease and sepsis Adult-onset Still's disease: evaluation of prognostic tools and validation of the systemic score by analysis of 100 cases from three centers Adult-onset Still's disease: clinical serological and therapeutic considerations Autophagy inhibition in adult-onset Still's disease: still more space for hydroxychloroquine The German etanercept registry for treatment of juvenile idiopathic arthritis Natural killer cell dysfunction: a common pathway in systemic-onset juvenile rheumatoid arthritis Does systemic-onset juvenile idiopathic arthritis belong under juvenile idiopathic arthritis New insights in systemic juvenile idiopathic arthritis: from pathophysiology to treatment Drug retention rate and predictive factors of drug survival for interleukin-1 inhibitors in systemic juvenile idiopathic arthritis Beneficial effect of interleukin 1 inhibition with anakinra in adult-onset Still's disease Anakinra in adult-onset Still's disease: long-term treatment in patients resistant to conventional therapy Efficacy of anakinra in refractory adult-onset Still's disease: multicenter study of 41 patients and literature review Efficacy and safety of biological agents in adult-onset Still's disease Response to interleukin-1 inhibitors in 140 Italian patients with adult-onset Still's disease: a multicentre retrospective observational study Predictors of effectiveness of anakinra in systemic juvenile idiopathic arthritis Treat-to-target using first-line recombinant interleukin-1 receptor antagonist monotherapy in new-onset systemic juvenile idiopathic arthritis: results from a five year follow-up study Long-term retention rate of anakinra in adult onset Still's disease and predictive factors for treatment response Remission in rheumatoid arthritis: agreement of the disease activity score (DAS28) with the ARA preliminary remission criteria Minimal disease activity for rheumatoid arthritis: a preliminary definition Tolerance and efficacy of off-label anti-interleukin-1 treatments in France: a nationwide survey Adult onset Still's disease (AOSD) in the era of biologic therapies: dichotomous view for cytokine and clinical expressions May anakinra be used earlier in adult onset Still disease Keywords: adult onset Still's disease systemic onset juvenile idiopathic arthritis Giacomelli R and Cantarini L (2020) Comparison of Early vs Delayed Anakinra Treatment in Patients With Adult Onset Still's Disease and Effect on Clinical and Laboratory Outcomes Received: 14 October 2019; Accepted: 28 January 2020; Published: 21 February 2020 Non-infectious inflammatory ocular diseases pose significant challenges in diagnosis and management, often requiring systemic immunosuppressive therapy. Since Janus kinase (JAK) inhibitors may represent a novel therapeutic option for these disorders, the present study aimed to expand current knowledge about their efficacy and safety in patients with these conditions. This prospective cohort study included 12 adult patients from the international AutoInflammatory Disease Alliance (AIDA) Network registries dedicated to non-infectious ocular inflammatory conditions. We assessed ocular flares, visual acuity, disease course, and complications before and after initiating JAK inhibitor therapy. JAK inhibitors demonstrate efficacy and safety in controlling ocular inflammatory relapses, confirming that they represent a valuable treatment option for patients with non-infectious inflammatory ocular diseases resistant to conventional treatments. Volume 11 - 2024 | https://doi.org/10.3389/fmed.2024.1439338 A correction has been applied to this article in: Corrigendum: Efficacy and safety of Janus kinase inhibitors in non-infectious inflammatory ocular diseases: a prospective cohort study from the international AIDA network registries Introduction: Non-infectious inflammatory ocular diseases pose significant challenges in diagnosis and management often requiring systemic immunosuppressive therapy Since Janus kinase (JAK) inhibitors may represent a novel therapeutic option for these disorders the present study aimed to expand current knowledge about their efficacy and safety in patients with these conditions Methods: This prospective cohort study included 12 adult patients from the international AutoInflammatory Disease Alliance (AIDA) Network registries dedicated to non-infectious ocular inflammatory conditions and complications before and after initiating JAK inhibitor therapy Results: Ocular inflammation was related to a systemic disease in 8 (66.7%) patients as follows: spondyloarthritis (n = 3) antinuclear antibodies (ANA) positive juvenile idiopathic arthritis (n = 1) and 7 patients underwent upadacitinib treatment The overall average duration of JAK inhibitors treatment was 8.6 ± 5.5 months (ranging from 3 to 20 months) ocular disease control was complete in 12/12 patients One patient discontinued baricitinib due to poor compliance after a 12-month relapse-free period The incidence of ocular flares was 125 episodes/1.000 person-months prior to the initiation of JAK inhibitors and 28.6 episodes/1.000 person-months thereafter The incidence rate ratio for experiencing a relapse before starting a JAK inhibitor compared to the following period was 4.37 (95% CI 1.3–14.7 Conclusion: JAK inhibitors demonstrate efficacy and safety in controlling ocular inflammatory relapses confirming that they represent a valuable treatment option for patients with non-infectious inflammatory ocular diseases resistant to conventional treatments Non-infectious inflammatory ocular diseases encompass a diverse group of conditions, including uveitis, scleritis, and keratitis, that can arise either independently or as part of systemic autoimmune disorders. These disorders have the potential to lead to various vision-threatening complications, posing significant challenges in both diagnosis and management due to their varied presentations and the need for precise therapeutic strategies (1, 2) The Janus kinase pathway plays a crucial role in regulating inflammatory cells, cytokine synthesis, and proinflammatory signal transduction. Dysregulation of this pathway is closely associated with the development of various inflammatory and autoimmune conditions. Consequently, JAK inhibitors hold promise for mitigating the inflammatory cascade typically observed in ocular inflammatory conditions (6, 7) the therapeutic application of JAK inhibitors particularly in immune-mediated ocular diseases and substantial research data on this specific area of interest remains limited to address this gap and explore the potential of JAK inhibitors we conducted a multicenter study aimed at assessing the efficacy and safety of JAK inhibitors in a cohort of adult patients with non-infectious inflammatory ocular diseases This is a prospective registry-based cohort study enrolling patients with non-infectious uveitis and scleritis receiving JAK inhibitors treatment during their adulthood. Patients’ demographic, clinical, ophthalmological and therapeutic data were drawn from the International AutoInflammatory Disease Alliance (AIDA) Network registries dedicated to uveitis, scleritis and Behçet’s syndrome (8–10) The index date was the time at the start of one of the following JAK inhibitors: baricitinib The follow-up period ranged between the start of JAK inhibitor and the last assessment into the AIDA Network inserted up to February 2024 infectious ocular diseases and traumatic ocular inflammation were excluded The primary aim of the study was to assess the effectiveness of JAK inhibitors in controlling intraocular inflammation The secondary aim was to report the safety profile of JAK inhibitors in patients with intraocular inflammation The primary endpoint was represented by the frequency of ocular inflammatory relapses observed during the 12 months preceding the start of JAK inhibitors and those observed during JAK inhibitor treatment Additional endpoints testing the effectiveness of JAK inhibitors on ocular inflammation consisted of the occurrence of retinal vasculitis and/or uveitic macular edema (UME) any changes in the best-corrected visual acuity (BCVA) variations in the daily dosage of glucocorticoids as prednisone (PDN) or equivalent and the identification of new ocular complications between the start of JAK inhibitors and the last follow-up visit The secondary endpoint was represented by the occurrence of any adverse event during JAK inhibitors treatment Ocular flares and relapses were classified according to the standardized uveitis nomenclature (SUN) Working Group criteria for uveitic flares (11) and according to Sen et al. (12) classification criteria for scleritis Chronic uveitis was defined as persistent ocular inflammation with relapse in < 3 months after discontinuing treatment; recurrent uveitis was defined as repeated episodes separated by periods of inactivity without treatment lasting > 3 months The diagnosis of UME and active retinal vasculitis was based on clinical BCVA was measured with Snellen chart in decimal fractions at any follow-up visit Glucocorticoids (GCs) were analyzed as mg/day of PDN or equivalent The study was performed according to the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of the Azienda Ospedaliero-Universitaria of Siena All patients provided their informed consent to participate in the study at the time of the enrollment into the AIDA Network registries standard deviations and interquartile range calculations Pairwise comparisons between the start of JAK inhibitors and the last assessment were performed by using the Student t-test or the Mann-Whitney U test according to data distribution assessed through the Shapiro–Wilk test The incidence rate of developing ocular inflammatory flares was calculated as number of ocular flares divided the total number of months of observation (person-months) both before starting the study treatment (the 12 months preceding the start of JAK inhibitors 144 months for 12 patients) and during the study period the corresponding 95% confidence interval (CI) and the p-value were calculated by using the RStudio software as for all the other statistics previously described All statistics were two-sided; the level of statistical significance was set at a p-value of 0.05 in all statistical computations Ocular inflammation was associated to a systemic disease in 8 (66.7%) patients as follows: spondyloarthritis (n = 3) One patient suffered from punctate inner choroidopathy and additional 3 patients suffered from idiopathic oculo-specific inflammation The ocular involvement was bilateral in 6 (50%) patients and unilateral in 6 (50%) patients: as a whole The mean age at ocular disease onset was 36.6 ± 20.7 years the mean age at diagnosis was 37.9 ± 20.7 years the mean age at the enrollment in this study was 49.2 ± 16.1 years The median duration of ocular inflammatory disease was 97.5 (IQR = 251) months there were 6 eyes affected by anterior uveitis insidious in 4 eyes; the remaining cases were not specified in the registry The course of inflammatory episodes was chronic in 7 eyes and recurrent in 5 eyes; information about ocular disease course was not available for 6 eyes Table 1 describes the demographic, clinical and therapeutic features of the 12 patients enrolled in the study; Table 2 clarifies the treatment approaches performed prior to the start of JAK inhibitors Treatment preceding the start of Janus kinases (JAK) inhibitors The usage of JAK inhibitors in our cohort was as follows: 4 patients received baricitinib The decision to initiate this treatment was based on ocular involvement in 7 cases and both ocular and extraocular involvement in 3 cases The average duration of JAK inhibitors treatment was 8.6 ± 5.5 months (ranging from 3 to 20 months) accounting for a total follow-up duration of 103 person-months the average duration of upadacitinib treatment was 7.4 ± 6.2 months baricitinib treatment lasted for 9.5 ± 4.8 months and tofacitinib treatment was administered for 8 months 3 eyes (2 patients) experienced a single relapse each which was effectively managed with both topical and systemic GCs resulting in complete control of ocular disease These relapses occurred within the three-month assessment and were considered extensions of the ocular inflammation observed at the start of JAK inhibitor therapy During the 12 months preceding the start of JAK inhibitors ocular inflammatory relapses were observed in all the patients enrolled the incidence of ocular flares was 125 episodes/1.000 person-months prior to the initiation of JAK inhibitors and decreased to 28.6 episodes/1.000 person-months thereafter; the three aforementioned relapses that occurred in the first three months were included in the JAK inhibitors treatment period The IRR of experiencing a relapse before starting a JAK inhibitor compared to the following period was 4.37 (95% CI 1.3–14.7 The number needed to treat ocular flares was 10.4 range 0.03–1.0) at the start of treatment and remained at 1.0 (IQR: 0.1 range: 0.06–1.0) at the last assessment with no statistically significant differences observed (p-value: 0.63) Prior to initiating treatment with JAK inhibitors UME had been observed in 3 patient (4 eyes) and retinal vasculitis in 1 patient (2 eyes) no episodes of UME or retinal vasculitis occurred during treatment with JAK inhibitors the following ocular complications were reported in 7 patients: rhegmatogenous retinal detachment (3 eyes) retinal pigment epithelial alterations (1 eye) choroidal neovascularization (1 eye) and chorioretinal scars (1 eye) At the last follow-up visit while on JAK inhibitors 3 patients (4 eyes) were on topical GCs upon initiation of JAK inhibitor therapy 2 patients (2 eyes) continued topical treatment one of which required bilateral peribulbar injection; one patient (2 eyes) continued the topical treatment up to the 6-month assessment 4 patients were on systemic GCs therapy with an average dose of 28.4 ± 15.7 mg of PDN or equivalent 2 patients were still on systemic GCs therapy with an average dose of 9.4 ± 8 mg of PDN or equivalent Four patients were receiving combination therapy with cDMARDs at the start of treatment with JAK inhibitors: two were on azathioprine and six months for the patient treated with leflunomide None of these patients discontinued treatment and there were no changes in cDMARDs dosage during JAK inhibitor treatment there were no new cases of cDMARDs initiation during treatment with JAK inhibitors complete ocular disease control was achieved in 12/12 patients All but one patient continued treatment for the whole follow-up period poor compliance was the reason for the JAK inhibitor (baricitinib) discontinuation after a 12-month treatment period this patient was followed for an additional 10-month period without experiencing any further ocular relapses no JAK inhibitor dose tapering was observed only one adverse event was reported during JAK inhibitor treatment consisting of episodes of myalgia that the patient attributed to drug intake The results obtained in this study support the effective use of JAK inhibitors in controlling non-infectious uveitis and scleritis there was a significant reduction in the risk of experiencing ocular inflammatory recurrences when comparing relapses occurring during the 12 months prior to the initiation of JAK inhibitors with those observed during the study treatments the efficacy of JAK inhibitors in managing ocular inflammatory diseases was corroborated by the absence of episodes of UME and vasculitis during the follow-up period as well as the absence of further ocular inflammatory complications at the last assessment This suggests the prevention of new inflammatory or treatment-induced ocular damage further supported by the preservation of visual acuity The effectiveness of JAK inhibitors was accompanied by an excellent safety profile in this cohort The results obtained from this prospective study are in line with the literature published to date and widens the evidence on the role of JAK inhibitors based on a relatively greater number of patients treated with different JAK inhibitors while all patients achieved complete control of ocular inflammatory disease at the last assessment two out of the four patients initially undergoing systemic GCs still required steroids at the last follow-up visit The lack of GCs withdrawal in these two cases was either due to systemic disease activity or the short follow-up duration a GCs sparing effect may be supposed when treating ocular inflammation with JAK inhibitors but a wider number of patients are required to ascertain this aspect on a statistical threeshold cDMARDs concomitantly used with JAK inhibitors were only sparingly employed in this study While this allows for a clearer analysis of the effectiveness of JAK inhibitors combination with cDMARDs may have potentially enabled a faster onset of action and even better outcomes this study cannot make any assumptions about the role of combination therapy versus mono therapy; similarly a cDMARD sparing effect cannot be evaluated Although this study faces with an intriguing topic These include the small sample size and the lack of a control group for comparisons the duration of follow-up may not be sufficient to fully evaluate the long-term safety and effectiveness of JAK inhibitors in our cohort our results contribute to the growing preliminary evidence supporting the effectiveness of JAK inhibitors in controlling ocular inflammation particularly in adult patients where data are lacking the study corroborates the potential role of these agents as a promising therapeutic option for cases refractory to conventional treatments this study provides further evidence of the potential benefit of JAK inhibitors in managing non-infectious inflammatory ocular diseases further studies are needed to confirm these findings in the long-term and establish the optimal role of JAK inhibitors in the treatment of these sight-threatening conditions The data analyzed in this study is subject to the following licenses/restrictions: data will be available upon reasonable request to the corresponding author. Requests to access these datasets should be directed to Y2FudGFyaW5pQHVuaXNpLml0 The studies involving humans were approved by the Azienda Ospedaliero Universitaria Senese The studies were conducted in accordance with the local legislation and institutional requirements Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin VC: Writing – review & editing GR: Writing – review & editing JH-R: Writing – review & editing LP: Writing – review & editing GM-S: Writing – review & editing LZ-P: Writing – review & editing SG: Writing – review & editing JS: Writing – review & editing AF: Writing – review & editing EC: Writing – review & editing CG: Writing – review & editing RA: Writing – review & editing AB: Writing – review & editing JN: Writing – review & editing GT: Writing – review & editing BF: Writing – review & editing Ad-l-T: Writing – review & editing CF: Writing – review & editing The authors declare that no financial support was received for the research This research is supported (not financially) by the European Reference Network (ERN) for Rare Immunodeficiency Nine of the authors of this publication (AV and LC) belong to institutes that are members of the ERN RITA (Azienda Ospedaliero-Universitaria Senese of Siena; Hospital Clínic of Barcelona) We thank the University of Siena for partially covering part of the open access publication fees The authors declared that they were an editorial board member of Frontiers This had no impact on the peer review process and the final decision disease modifying anti-rheumatic drugs; DRRs Ocular involvement in systemic autoimmune diseases Google Scholar Google Scholar Role of Janus kinase (JAK) Inhibitor in autoimmune ocular inflammation: A systematic review Adalimumab in Juvenile Idiopathic arthritis-associated uveitis: 5-year follow-up of the bristol participants of the SYCAMORE trial Rituximab therapy for refractory scleritis: Results of a phase I/II dose-ranging Google Scholar Tocilizumab for refractory uveitis associated with juvenile idiopathic arthritis: A report of two cases Google Scholar Cytokines in immune-mediated “Non-infectious” Uveitis Google Scholar Autoinflammatory diseases alliance (AIDA) network Development and implementation of the aida international registry for patients with non-infectious uveitis Development and implementation of the AIDA international registry for patients with non-infectious scleritis Autoinflammatory diseases alliance (AIDA) Network Development and implementation of the AIDA international registry for patients with Behçet’s disease Standardization of Uveitis Nomenclature (SUN) Working Group Standardization of uveitis nomenclature for reporting clinical data Results of the first international workshop A standardized grading system for scleritis Google Scholar The current status of biological treatment for uveitis Google Scholar Therapeutic potential of JAK inhibitors in juvenile idiopathic arthritis-associated uveitis Google Scholar Tofacitinib for refractory uveitis and scleritis in children: A case series JAK inhibitors in refractory juvenile idiopathic arthritis-associated uveitis Google Scholar Tofacitinib for refractory uveitis and scleritis Google Scholar Tofacitinib in Vogt-Koyanagi-Harada disease Google Scholar Tofacitinib citrate for ulcerative keratitis in a patient with rheumatoid arthritis de-la-Torre A and Fabiani C (2024) Efficacy and safety of Janus kinase inhibitors in non-infectious inflammatory ocular diseases: a prospective cohort study from the international AIDA network registries Copyright © 2024 Vitale, Palacios-Olid, Caggiano, Ragab, Hernández-Rodríguez, Pelegrín, Mejía-Salgado, Zarate-Pinzón, Gentileschi, Sota, Fonollosa, Carreño, Gaggiano, Amin, Balistreri, Narváez, Tosi, Frediani, Cantarini, de-la-Torre and Fabiani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Luca Cantarini, Y2FudGFyaW5pbHVjYUBob3RtYWlsLmNvbQ==; Claudia Fabiani, Y2xhdWRpYS5mYWJpYW5pQGFpZGFuZXR3b3JrLm9yZw== †These authors have contributed equally to this work Gabriella Gaggiano dipping a decadent chocolate strawberry The candy cases offer a ton of tempting treats Dolce Mare in Marco Walk invites you to indulge in 'forbidden pleasures' including wine and chocolate Lance Shearer/Eagle Correspondent (Photo: Lance Shearer/Eagle Corresponden) Lance Shearer/Eagle Correspondent Don Abraham from New Hampshire inspects the candy cases What does Miami Beach have in common with Marco Island Answer: An entrepreneurial family with a talent for sweets with locations on Ocean Drive and the Marco Walk The couple reside on Marco with their 9-month old daughter and sole business partner Chiara Benedetta (the couple are expecting another little bundle of joy soon) The products the family offers at Dolce Mare Dessert & Wine Lounge are tempting treats opulent concoctions designed to tempt your taste buds "There's nothing like chocolate and red wine," said Tabeek and they create most of their sweet desserts and bonbons on the premises "The dessert lounge concept is the perfect marriage of all the places we have enjoyed when traveling to Europe and abroad a place where we wanted to offer our guests a place where they could come relax and enjoy delicious desserts and wines outside of the typical restaurant setting," said Gaggiano numerous varieties of fudge including maple walnut and brown sugar Dolce Mare also offers a selection of white and red wines along with coffee and related specialty drinks including espresso and cappuccino "We came here for cappuccino," said Nina Engelstad visiting from Norway with her husband Einar on a cold morning — by local not Scandinavian standards — but they did agree to sample some fudge was another escapee from a frigid northern climate but he said he came down "to escape the presidential candidates." The boutique at the front of the store in Marco Walk the wine lounge in the back opens for business and doesn't close "until the last person leaves," said Tabeek with glass-fronted cases displaying racks of candies The name translates from Italian as "sweet sea," although "there are two interpretations," said Tabeek "It could also be 'a sea of sweets.' " The boutique opened at the end of May last year so this is the first winter season for both parts of the operation Opening any business on Marco just as summer starts particularly a visitor-centric eatery such as Dolce Mare but Tabeek said response from the community has been "very good — we're really happy." "Both Steven and I have extensive backgrounds and training in desserts," said Gaggiano "We owned a chocolate shop on world-famous Lincoln Road in South Beach for five years where I exclusively handled all the chocolate production and we then went on to open our first Dolce Mare in the Marriott Hotel on Ocean Drive." Tabeek is from Brooklyn and Gaggiano is from Ventnor Francis College and she received her bachelors in psychology with a minor in journalism from the University of Miami and her master's degree in Italian from Columbia University in New York City "I grew up in the restaurant business my whole life as my father was born and raised in San Giovanni Rotondo Italy; hence our love for all things Italian He has had a restaurant and beach bar on the world-famous Atlantic City Boardwalk for the last 30 years," said Gaggiano "We chose to move to Marco Island after 10 years in Miami Beach since we thought it would be the perfect place to raise our 9-month-old daughter," said Gaggiano "This May we will be celebrating a full year at our Marco Island location We love Marco Island and Dolce Mare is the perfect family-friendly vacation spot with for all people of all ages to relax Bexon Harrison recently focused full time on swimming after doing that and water polo for much of his high school career Breaststroke specialist Landry Liston has announced her commitment to continue both her academic and athletic careers at George Mason University Lennox is a six-time 4A CHSAA State Champion Texas sophomore Brayden Taivassalo has announced that he is transferring to Arizona State University for the next season Backstroker and redshirt sophomore JT Ewing has confirmed he will transfer from NC State to Arizona State for the 2025–2026 collegiate season January 06th, 2024 College, College Recruiting, NCAA Division I Mid-Major Fitter and Faster Swim Camps is the proud sponsor of SwimSwam’s College Recruiting Channel and all commitment news swimming in college is a lifelong dream that is pursued with dedication and determination Fitter and Faster is proud to honor these athletes and those who supported them on their journey has announced his commitment to further his education and swimming career at George Washington University Stratton is currently a senior at Bishop Kelly High School and trains year-round with Sawtooth Aquatic Club under coach Nick Gaggiano “I am pumped to announce my commitment to George Washington University Coach Thomas and the GWU team recognize the confidence and personality that I’m bringing to the program and I’m thankful for the opportunity to become a Revolutionary and a member of the Buff & Blue I can’t wait to get started in Foggy Bottom and share my many talents ranging from backstroke to the all important skill of blowing perfect circle bubbles I look forward to being part of an incredible team and I know that Coach Thomas and the GWU team will help develop my skills as a swimmer and beyond Stratton is a Summer Juniors Nationals qualifier in the 100 and 200 backstroke as well as a Futures qualifier in the 200 IM He recently defended his Idaho high school state championship titles in the 100 back and 200 IM Shortly following the high school state meet Stratton raced at Winter Juniors – West He advanced to the A-final in the 200 backstroke where he dropped over two seconds on the day to post a time of 1:45.33 for 6th He also notched best times in the 100 backstroke (48.42) and 200 IM (1:51.61) to take 17th and 51st Highlighting his long course season this past year was Summer Juniors He managed to drop in both of the backstroke races Over the course of the summer Stratton knocked off over a second in both events George Washington competes in the Atlantic 10 Conference where the men are now three-time defending champions Stratton should add depth to the backstroke group as his best time in the 100 and 200 backstroke would have earned him a spot in the A-final at A-10s George Washington swept the top three places in the 100 back last spring Młynarczyk was also the champion in the 200 back with a time of 1:43.10 Mlynarczyk will have graduated by the time Stratton arrives next fall Joining Stratton on campus next fall is Gage Boushee and Holden Thomas while Thomas is also a backstroker with best times of 48.61 and 1:48.90 If you have a commitment to report, please send an email with a photo (landscape, or horizontal, looks best) and a quote to [email protected] Δdocument.getElementById( "ak_js_1" ).setAttribute( "value" Δdocument.getElementById( "ak_js_2" ).setAttribute( "value" a great commit for GW but hopefully there is still an on-campus pool once he arrives – the administration must respect this program more More from Sidney ZachariasSee All Subscribe to our newsletter and receive our latest updates Internal zone-Apennine thrust system.The western (internal) portion of the Apennine system is composed of stacked imbricate thrust sheets containing rocks ranging in age from Late Triassic to Upper Miocene Oil and gas fields have been discovered in allochthonous Mesozoic carbonates throughout the length of the system The northernmost fields of the internal zone are Gaggiano and Villafortuna located just south of the intersection of the Apennine system with the Alps Gaggiano and Villafortuna produce light oil (34-42°) from thrusted Middle Triassic dolomites at depths of 4,650-6,200 m is currently Italy's most productive oil field (60,000 b/d) During the last decade attention has also been focused on the internal zone of the southern Apennines The discovery of several fields containing light to medium gravity oil during the 1970s sparked initial interest in the area are productive from stacked sections of allochthonous Mesozoic carbonates (Figs Hampering further progress was the poor quality of seismic data in the region the result of rough topography and the structural complexity of the subsurface led to the first discovery in the prolific Val D'Agri area in 1988 To date at least four major fields have been discovered in the area Characterizing these fields are high flow rates (3,000-12,000 b/d) and large oil columns (600-1,000 m) The total recoverable reserves for the four fields are estimated at 1.02 billion bbl of oil equivalent The Val D'Agri fields are discussed in more detail later in this the second part of this three-part article Allochthonous Miocene (flysch) sandstones are also productive within the internal Apennine system and condensate fields in the Emilian and Romagna nappes along the southern edge of the Tertiary Po basin of northern Italy External zone-Apennine and Maghrebian thrust systems Fields of the external zone are dominantly gas productive but also include several oil and condensate fields The main reservoirs are allochthonous Miocene flysch and Lower-Middle Pliocene foredeep turbidite sandstones The largest field of the external zone is Luna (Fig a gas field that lies along the west side of the Gulf of Taranto in southernmost Italy The field contains large reserves of dry gas in sandstones that lie at or immediately above the top of the allochthonous Miocene flysch section The structure is the product of both Upper Miocene and Lower Pliocene movements A thin section of Messinian evaporites is present on the flanks but absent over the crest of the Luna structure the result of Early Pliocene uplift and erosional truncation of the Messinian The gas from Luna is dry (99% methane) and biogenic in origin The field was discovered in 1971 and currently includes 35 wells Initial recoverable gas reserves were estimated at 1.3 tcf During the period 1994-97 gas production from offshore Zone D (which consists only of Luna and several small nearby fields) was 348 bcf and remained stable during 1998 at 70 bcf Gas fields with allochthonous Miocene reservoirs of the external zone of the Apennine thrust system are common throughout the length of the Italian peninsula The gas from most of these fields is dry and biogenic although the presence of heavier hydrocarbons in a few areas probably indicates limited mixing with thermogenic gases The Apennine system of peninsular Italy is replaced by the regional Maghrebian wrench-thrust system on Sicily The Maghrebian system extends southwest from Sicily through Tunisia and westward across northern Africa to the Atlantic The external zone of the Maghrebian thrust belt contains several significant structurally trapped fields in north-central Sicily as well as offshore to the west of the island and light oil in allochthonous Miocene flysch sandstones at depths of 2,800-3,000 m (Fig Nilde field produces 39° gravity oil from highly productive Middle Miocene organic limestones at rates of up to 10,000 bo/d liocene and younger sandstones of the foredeep contain the majority of Italy's proved gas reserves Most of these reserves are currently located in the north-central Adriatic and Po basin of northern Italy production from four of the larger offshore fields (Barbara biogenic gases lie in both stratigraphic and structural traps Reservoirs range from turbidite sandstones to gravel Several of the larger fields of the north-central Adriatic and central Italy are described below and Northeast Barbara gas field complex was discovered in 1971 in the north-central part of the Adriatic A total of 112 productive wells have been drilled to date Gas production is from an Upper Pliocene sandstone at an average depth of 1,400 m The trap is a simple low relief (less than 100 m) structure draped over a broad uplift in the underlying Mesozoic foreland and Pisticci fields produce gas from Lower and Middle Pliocene foredeep sandstones South Salvo is stratigraphically trapped by the updip pinch out of multiple Pliocene sandstones that are overlain by approximately 800 m of allochthonous Miocene flysch The field includes 74 productive wells with an average depth of 1,200 m Pisticci field also contains heavy oil in autochthonous foreland carbonates along the western side of the field (Fig produce both light oil (40°) and gas from Middle and Upper Pliocene foredeep reservoirs along the east coast of central Italy sandstones and limestones are stratigraphically trapped by updip olistostromes derived from the east flank of the southern Apennines Mesozoic carbonate foreland.Several large oil fields have been discovered in the relatively undisturbed platform carbonates of the Mesozoic foreland of southern Italy and Sicily various thicknesses of allochthonous Miocene flysch and in some cases a thin section of Plio-Pleistocene sediments overlie the fields Offshore the allochthonous Miocene section is generally absent and the Mesozoic foreland sequence is overlain by sediments of the Plio-Pleistocene foredeep is located along the southwestern coast of the island on a broad anticline in the autochthonous foreland section (Fig Productive Upper Triassic shelf carbonates are overlain and sealed by organic-rich black shales of the Triassic Streppenosa formation and Cretaceous-Eocene basinal limestones The southern feather-edge of the allochthonous olistostromal Gela nappe and a thin interval of Plio-Pleistocene sediments cap the section Gela was discovered in 1956 and includes 104 productive wells Depth to the reservoir averages approximately 3,300 m Gela oil is the heaviest (10°) produced from the foreland fields of southern Sicily All of the oils of the area are characterized by relatively low gravity oils (15-21°) and a significant sulfur content produces 19° gravity oil with a sulfur content of 2% Studies indicate that the relatively heavy oils of southern Sicily are immature the result of a low thermal gradient and the early expulsion of hydrocarbons from organic rich Upper Triassic shales Only Gela oils are believed to be additionally biodegraded Perla field is located offshore just south of Gela The reservoir lies at the top of an interval of Lower Jurassic shelf limestones (Siracusa formation) at depths of slightly less than 3,000 m The reservoir is overlain and sealed by marls and evaporite and underlain by rich source rocks of the Streppenosa shale Farther to the south Vega field produces similar oils (15-21°) from the same stratigraphic level The total proved recoverable reserves for the four fields are estimated at 1.02 billion BOE.3 Production from Monte Alpi and Tempa Rossa fields is expected to reach a combined 165,000 bo/d by 2002 Oil will be transported via a new pipeline (to be completed in 2001) to a refinery and marine oil terminal at Taranto Val D'Agri wells are productive from multiple zones in a variety of carbonate facies Although the specific type and character of the zones varies in general the reservoir properties of the productive limestones and dolomites are excellent The reservoirs include dolomites and leached The section is also characterized by large Flow rates in the recent South Apennines oil discoveries range from 3,000-12,000 bo/d plus associated gas The produced oils display a wide range of gravities Tempa Rossa fieldTempa Rossa was discovered in 1988 by a group of companies headed by Petrex To date six wells have been drilled in the field and 2; Tempa D'Emma 1; Gorgolione 1; and Perticara 1 All of the wells are oil productive from Miocene through Cretaceous limestones and dolomites The oil column in the field is estimated at 1,000 m gross and 700 m net Proved recoverable reserves are estimated at 420 million BOE with associated gas forming about 7% of the total.4 Production is expected to reach 45,000 bo/d by 2002 and long term test results from at least two wells have been published 2 well produced a total of 116,000 bbl of oil (17°) during a 135-day test The test produced no water and reflected no decrease in reservoir pressure 1 well tested oil rates of over 7,600 bo/d (17-22°) and had produced over 500,000 bbl of oil through December 1996 during "test" production As of the end of 1996 the well was producing at a rate of 3,700 bo/d Monte Alpi was discovered in 1988 by a group headed by Fina Italiana The field currently consists of nine wells (all productive) is produced from Upper Cretaceous limestone and dolomite reservoirs The oil column is 1,060 m gross and 702 m net Oil flows (constrained by gas flaring restrictions) range up to 6,793 bo/d The production of 45,000 bo/d is projected for the field by 2000 Monte Enoc was discovered in 1994 and currently consists of 8 wells 3 and 9; Monte Enoc NW 1 and 1A; Monte Enoc Ovest 1; and Al* 1A) Oil flows (constrained by gas flaring restrictions) range up to 7,717 b/d Oil (32-36°) has been tested at rates of up to 6,600 b/d along with significant volumes of associated gas (up to 4.4 MMcfd) The field produces from Miocene to Cretaceous carbonate reservoirs A total of 42 production wells are currently planned for Monte Alpi Production is expected to peak at 120,000 bo/d in 2002 Total recoverable reserves for the three fields are estimated at 600 MMBOE of which approximately 12% is associated gas.5 The oil and gas fields of southern Italy and Sicily contain a wide variety of hydrocarbon types all of which are believed to have been generated within three general source rock intervals The large volumes of heavy oil discovered in carbonate reservoirs of the Mesozoic foreland can be traced to the development of organic-rich carbonates in the narrow troughs between the Mesozoic carbonate platforms These include black shales and marls of the Upper Triassic-Lower Jurassic Streppenosa shale and Noto formation of Sicily and the Upper Triassic Meride limestone of northern Italy The oils generated from these intervals are relatively heavy (11-22°) contain significant amounts of sulfur and are thought to be thermally immature no significant sulfur) have been found in Miocene and Pliocene reservoirs in scattered fields of the Italian peninsula and in the allochthonous Mesozoic carbonates of northern Italy (Villafortuna field) and the Val D'Agri trend of the southern Apennines The characteristics of these oils indicate that they originated in source rocks within the Miocene flysch section although specific intervals have yet to be identified including the fields of the Po basin and Adriatic indicates that over 80% are biogenic in origin derived from terrestrial organic matter in the abundant clays of the foredeep section Add articles to your saved list and come back to them any time Elderly Melbourne grandmother Rachele Gaggiano died in "the blink of an eye" at the hands of a drunk driver with her husband watching helplessly from their driveway The 87-year-old didn't even have time to say goodbye to her daughter Maria and Luigi Gaggiano outside court on Thursday.Credit: AAP had crashed into the mother and daughter while speeding in his unregistered V8 ute Despite the fact he'd just killed someone Adams continued to "neck" a UDL can at the scene With an "extraordinary" history of flouting road rules including seven past convictions for driving while unlicensed or disqualified Adams was jailed on Thursday for a minimum of seven years he'd bought two 10-packs of UDL pre-mixed drinks with his 18-year-old son before the pair sped off and fishtailed onto Plenty Road had just taken her mother out shopping and they were nearly home killing the nonna instantly while her husband Luigi Maria Gaggiano was rescued from the car but suffered a fractured spine She now rarely drives after being diagnosed with post-traumatic stress disorder Adams refused to undergo a preliminary breath test at the scene admitting to police he'd "necked" three cans but they'd stopped him at the fourth witnesses saw you drinking from a can containing alcohol," County Court of Victoria Judge Richard Smith said while sentencing on Thursday saying it was "difficult to image a worse example of behaviour" in front of his son after drink driving speeding and driving while disqualified in an unregistered vehicle Maria Gaggiano said she was relieved the matter was over and that it was time "to put mum to rest" We have to – it's been two years," she told reporters We didn't even have time to say goodbye." Elderly Melbourne grandmother Rachele Gaggiano died in \\\"the blink of an eye\\\" at the hands of a drunk driver The 87-year-old didn't even have time to say goodbye to her daughter Adams continued to \\\"neck\\\" a UDL can at the scene With an \\\"extraordinary\\\" history of flouting road rules he'd bought two 10-packs of UDL pre-mixed drinks with his 18-year-old son before the pair sped off and fishtailed onto Plenty Road admitting to police he'd \\\"necked\\\" three cans but they'd stopped him at the fourth witnesses saw you drinking from a can containing alcohol,\\\" County Court of Victoria Judge Richard Smith said while sentencing on Thursday saying it was \\\"difficult to image a worse example of behaviour\\\" in front of his son after drink driving Maria Gaggiano said she was relieved the matter was over and that it was time \\\"to put mum to rest\\\" We have to \\u2013 it's been two years,\\\" she told reporters We didn't even have time to say goodbye.\\\" Park Hyatt Marrakech will bring a personalized luxury experience to the impressive Al Maaden residential and leisure development and will be the fourth Hyatt-branded hotel in Morocco For guests interested in rare and intimate experiences the 181-room hotel will be set against the spectacular backdrop of the Atlas Mountains The hotel will also feature a resort complex and Moroccan garden-inspired 18-hole golf course designed by award-winning golf course designer Cheong Yew Kuan and Patrick Genard will collaborate to design the development Hotel website Brand OwnerHyatt Hotels Corporation Since Cocktail Week is almost over and you've hopefully been drinking a lot of cocktails throughout the week One of those beers preferably in the shower And Underberg is surprisingly amazing at helping hangovers It’s the coconut water of the booze world." —Patrick Gaggiano "Hair of the dog...bubbles or beer." -Brittany Casos and a good sweat session outside or in the gym." —Brooke Vandecar "Michelada: essentially a beer based bloody maria concoction." —Greg Neises "Two Budweisers in rapid succession." —Patrick Sullivan executive director of bar operations for the Legal Sea Foods brands and maybe a shot of tequila later on in the day." —Paulo Pereira "Miller High Life and a shot of Green Chartreuse." —Nick Giannotti "I’m a certified yoga instructor and sometimes teach free classes for the Boston Rescue Mission "A spicy Bloody Mary loaded with bacon!" —Katie Mae Dell Isola food & beverage manager of all Burtons Grill locations I gave those up in college." —Kevin Murphy And once I can pry myself away from that: ginger ale and greasy breakfast food." —Ryan Lotz "Complaining and promising to "never drink again" usually works pretty well in conjunction with a filthy bacon egg and cheese sandwich." —Vikram Hegde Gatorade/water combo...in that order." —Jake Kress "I find the best hangover cure is probably sweating it out — going for a run or getting into the steam room at the gym — but I much prefer a good Bloody Mary." —Michael Cottens and cheese — from Sidewalk Café in South Boston." —Moira Toomey "It all starts the night before — a big glass of whole milk and Aspirin operations manager of Tavern in the Square there’s always the greasy breakfast and a beer cocktail Something about shandies makes the pain go away." —Lauren Hayes head bartender at Ten Tables in Jamaica Plain "A classic champagne cocktail always does the trick." —Molly Woodhouse general manager and beverage director of Vida Cantina in Portsmouth (and an alum of The Butcher Shop and Menton) Two glasses of water before bed." —Ian Nal general manager and beverage director of Fish Restaurant & Wine Bar in Marlborough "Normally a greasy slice of pizza." —Jenna Pollock "I sound like a nerd but if you can manage to get out of bed: light exercise lightly carbonated Italian red dessert wine that was possibly invented to be enjoyed for breakfast That and a whole pot of coffee." —Brian Mantz "Diet Coke on the rocks along with an Egg McMuffin and hash browns." —Tom Tellier beverage director for Restaurant dante and both locations of il Casale "The first thing I do when I am really hungover is try to find my phone and if there is nothing horribly wrong there bartender at Firebrand Saints and Brick & Mortar and a big plate of scrambled eggs!" —Gretchen Thomas wine and spirits director at Barcelona Wine Bar & Restaurant "Advice for prevention: Drinking Carpano Antica Formula on the rocks when everyone else is asking for Fernet at last call pizza of the meat-oriented variety with a combination of Red Bull and orange juice to wash it down." —Todd Lipman "A michelada is a Mexican cerveza prepared with beer take some vitamin C before going to bed along with a big glass of water." —Christine Gerow director of restaurant & bar at the Westin Waltham-Boston's Seventy at Third Avenue "Fried foods and lack of sleep." —Will Isaza I don’t fuck around with a hangover and cute bullshit I’m not going to wait around for someone to meet up with for Bloody Marys I’d much rather feel better 10 minutes after I wake up than an hour later when everyone finally gets together for brunch." —Sean Woods head bartender at Rosebud American Kitchen & Bar "Root beer and a hot dog." —Katie Emmerson Franz Liszt on Pandora and a large Gatorade." —Jared Sadoian head bartender and beverage director of Craigie on Main and The Kirkland Tap & Trotter "Bitters and soda and cold pizza." —Evan Kenney "Momo soup (Tibetan dumpling soup)." —Tenzin Konchok Samdo "Montecristo sandwich from The Breakfast Club in Allston." —Jonathan Mendez "A shot of apple cider vinegar and a pint of water before bed "Lots of water and whatever you were drinking the night before!" —Taso Papatsoris "Spicy Bloody Mary and a Diet Coke." —Erica Petersiel "My favorite hangover cure is confit duck or pulled pork hash accompanied with a mimosa followed by a nap and ideally some football on the television." —Rob Dunn Parents of the couple are Betsy and Matt Yarcho of Morton and Lindsey and John Puder of Marco Island The bride is a 2004 graduate of Morton High School and a 2008 graduate of University of Iowa She is employed as a by Rubbermaid Healthcare The groom is a 2004 graduate of Libertyville High School and a 2008 graduate of University of Colorado Sign In Register Jennifer Mae Everett passed away February 17 At an early age she moved with her parents to Thunder Bay/Port Arthur Jennifer was the third child of Edward/Ted and Marka Hawkins from Current River Jennifer attended Lakeview high school and Lakehead University where she was an assistant librarian While on staff at Lakehead University she graduated in library science.  Jennifer furthered her career as the assistant librarian at Confederation College in Thunder Bay.  at an early age and they moved to Tucson Arizona in 1969 as Lorne completed his doctoral program in 1972 and joined the Department of Hydrology as a young professor at the University of Arizona In 1974 Jennifer and Lorne moved to Santa Barbara California to join General Electric’s Think Tank She resided there in Bel Aire for the rest of her life.  She exuded sunshine and warmth with a smile that would light up every room She was a stunning model and loved playing tennis winning several local tennis club tournaments Jennifer was a member of the Cathedral Oaks Tennis club  From 2000 to 2009 Jennifer was the First Lady of Lakehead University during Lorne’s Chancellorship where she participated in all graduation events including dinners For 27 continuous years Jennifer and Lorne were invited by the Science Adviser to the Pope Dr Antonino Zichichi to attend Planetary Emergency meetings in Italy Over 124 Nobel Laureates attended the meetings over the years captivating the attendees with her beauty and grace On many occasions a second fall trip to Europe was requested Often the fall trip was held at CERN Geneva home of the Large Hadron Collider or at the Pontifical Academy of Sciences in the Vatican In 2007 Dr Everett and Jennifer were invited back to Rome to spend 11 days over Christmas in the Vatican Meetings were held in the Pontifical Academy of Sciences Dinners were held in rooms designed by Galileo Galilei.   Jennifer and Lorne traveled the world extensively with over 40 trips to Europe They were members of The Captain’s Table based on their numerous ocean cruises  Jennifer and Lorne were the Navy League big band dance champions and danced on every occasion as they travelled Lorne was a raconteur and featured speaker on many Crystal Cruise Line voyages and with Jennifer they travelled the seas Lorne’s presentations focused on the World Federation of Scientists’ Planetary Emergencies Whether it was road trips to Acapulco Mexico or the Amalfi coast the International Ballooning festival in Albuquerque or the Paleo (horse races) in Sienna Italy Jennifer and Lorne lived a life full of excitement.   Jennifer was a devoted and loving mother to her children Stephen and Lauren Some of Jennifer’s greatest pleasures also included watching her grandchildren play baseball  She is survived by her loving husband of six decades Lorne Everett her son Stephen Edward Everett of Buellton her daughter Jennifer Lauren Everett Smith and her husband Rudy Smith of Santa Paula She also leaves behind her loving niece Lesli Schelling She was preceded in death by her parents Edward (Ted) Hawkins and their son Deano; and her brother Teddy Hawkins and his wife Barbara.  The Everett family would like to thank Dr William Koonce for his decades of care and devotion to Jennifer A funeral service led by Dr Craig Juratsch for Jennifer Everett was held at the Historic Santa Barbara El Presidio Chapel on March 8 a Celebration of Life will be held in the early spring.  Dialogue and debate are integral to a free society and we welcome and encourage you to share your views on the issues of the day. We ask that you be respectful of others and their points of view, refrain from personal attacks and stay on topic. To learn about our commenting policies and how our community-based moderation works, please read our Community Guidelines the Ornella Vanoni's show and still free events and family-friendly activities What to do (also for free) in Milan for the April 25th long weekend The long weekend of the "April 25th Bridge" is a unique opportunity to experience Milan and its numerous events The first appointment along the Naviglio Grande the most anticipated monthly event for vintage and collectibles enthusiasts Flowers and Art on the Naviglio is instead the market exhibition at the Alzaia along the Naviglio in Gaggiano In the spaces of Mosso Milano, in the former Trotter Park Boarding School, the Flug Market returns the famous market with dozens of creatives Among the numerous gastronomic events of this new, long weekend, the Sagra dei Pizzoccheri in Senago stands out and pizzoccheri alla valtellinese (all weekend) In Poasco, a stone's throw from San Donato Milanese, Poasco Circus & Street Food arrives the first edition of the circus-themed event featuring jugglers Among the unmissable evenings of the weekend, there's the one at the terrace at Bar Bianco There are many free events during the April 25th Bridge, such as the Baratto Market at the Temple of the Lost Future where you bring a gift and take another (Sunday) The OrMe - Ortica Memoria Association presents the PASOS exhibition the Spanish Collection walks with the Contemporary at Spazio San Faustino 5 (all weekend) At the Auxological Polyclinic the Milan l'è on gran Milan photographic exhibition continues with images of the city seen with the sensitivity and gaze of different photographers and taken at different times (all weekend) At the Appartamento, last days to admire Be-Polar a dialogue between canvas works and comic strip-like drawings on paper by Mirko Leuzzi a Roman artist with an unconventional and provocative personality (all weekend) Finally, at the headquarters of the CDI - Centro Diagnostico Italiano - in via Saint Bon 20, the photographic exhibition Colpo di scena is a visual journey behind the scenes of a theater discovering those who contribute to the realization of a show (all weekend) Among the beautiful exhibitions to mark in the agenda for the April 25th Bridge, there's the Dolce & Gabbana exhibition at Palazzo Reale an unprecedented journey through craftsmanship but also innovation and theater (all weekend) Ukiyoe - Immersive Art continues at Tenoha with 3DCG animations and projections based on over 300 works by renowned artists such as Katsushika Hokusai At Palazzo Reale, the exhibition dedicated to Cézanne and Renoir continues, with 52 masterpieces from the Musée d'Orsay and the Musée de l'Orangerie in Paris, and the Brassaï exhibition Paris's Eye is a path of 200 photographs by the great French artist (both all weekend) Street art lovers cannot miss the works of Urban Art by numerous internationally renowned artists at Prologis Park Romentino Also, mark in your agenda Monet and the Impressionists - Digital Experience an immersive experience celebrating the 150 years since the first exhibition of the impressionists the exhibition welcomes visitors into interactive rooms for a true multisensory experience (all weekend) At Mudec, Picasso's works are an unprecedented journey dedicated to the great Spanish artist and his relationship with primitive art (all weekend) At the Next Museum in Sesto San Giovanni, Love, The Immersive Experience continues a real "selfie" exhibition dedicated to love and all lovers in a space of over 1500 square meters (all weekend) Space Dreamers continues instead under the Madonnina with a journey into space with 16 colorful and immersive installations In Piazza Napoli, The Prism Core Center is the interactive artistic space ready to welcome the public and accompany them in self-awareness (all the weekend) Color lovers cannot miss the beautiful works of Van Gogh in the immersive virtual reality exhibition at Lampo Scalo Farini a surprising journey through the brushstrokes of one of the greatest artistic geniuses of the 19th century among sunflower fields and blooming almond trees (all weekend) At the Museum of Science, finally, Karina Smigla-Bobinski's Kaleidoscope installation is a large luminous table where different layers of primary ink colors intertwine to touch and mix (all weekend) Among the unmissable shows in the theater, there's Ornella Vanoni's "Senza fine" show at the Arcimboldi a major event to celebrate her incredible career (Saturday and Sunday) Among the appointments for the little ones, there's La Casa di Meneghino at Cascina Cuccagna a permanent place dedicated to the symbol mask of Milan with numerous workshops for the little ones (Sunday) an entertainment format for both adults and children For science lovers, finally, it's impossible not to mention Scientopolis, The City of Science an exciting interactive journey at Spazio Ventura where visitors can experiment and deepen scientific concepts in an engaging way (all the weekend) National firm Holding Redlich has promoted 41 lawyers including appointments in the Brisbane and Cairns offices Brisbane-based Katherine Hammond (Corporate and Commercial) is one of two new Partners and was previously Special Counsel.Katherine Hammond Katherine has more than 12 years’ experience specialising in the areas of public and private mergers and acquisitions equity capital markets (IPOs and secondary raisings) Katherine is also a qualified and experienced ASX listed company secretary.  David Chambers (Workplace Relations and Safety)David Chambers David is experienced in employment and criminal law He has acted for a variety of clients and stakeholders in various industries across federal and state jurisdictions. Before his admission David performed duties as a police officer in two states Keisha Currie (Workplace Relations and Safety)Keisha Currie Keisha is a Special Counsel in the Workplace Relations and Safety group Keisha’s practice involves advising on all aspects of workplace health and safety including duties reviewing safety health management systems and managing risks Keisha previously worked at the Department of Justice and Attorney-General for Crown Law Tarin is a Special Counsel in the Construction focusing on project delivery and the provision of commercial advice Tarin has experience across several sectors including major commercial construction hospital and health infrastructure projects school infrastructure projects and LNG projects.  Jeanne Vallade (Corporate and Commercial)Jeanne Vallade Jeanne is qualified to practise in both Australia and France Jeanne has more than 15 years’ experience advising on complex transactional and regulatory matters including cross-border and domestic mergers and acquisitions; foreign investment in Australia including investment approvals; corporate governance and regulatory compliance; privacy and data law; international succession and estate planning Guy is a leasing lawyer with more than 11 years’ experience in commercial industrial and retail leasing across multiple jurisdictions A large part of Guy’s practice involves advice on national property portfolios drafting client-specific precedent documentation and advising on all aspects of leasing.  Paul Thompson (Dispute Resolution and Litigation)Paul Thompson Paul has more than five years’ experience in taxation primarily in matters involving the Australian Taxation Office (ATO) His experience in tax matters includes engaging with the ATO in respect of reviews and audits involving Division 7A Part IVA general anti-avoidance provisions Roslyn is an experienced property and projects lawyer providing advice on a range of property transactions and projects including high value capital transactions including hotels and resorts and commercial and retail properties; residential developments including off-the-plan projects and title structuring; renewable energy projects; approvals and variations of the Foreign Investment Review Board; transaction structuring including taxation implications; and general property advice Andrea is a Senior Associate with experience providing advice to clients on a range of matters across the building and construction Andrea has experience in providing advice over the entire lifecycle of a project and regularly acts on behalf of principals superintendents and contractors at all levels Planning and Development – Cairns)Sangeetha Badya Sangeetha is a Senior Associate in the Planning and Environment team She was previously an Associate to her Honour Judge Fantin of the District Court Children’s Court and Planning and Environment Court Planning and Development – Cairns)Kayla Greenwood Kayla practices in the commercial property area and specialises in all forms of retail As well as acting for landlords and tenants Kayla also assists clients with undertaking pre-acquisition due diligence Natasha Scott-Kilsby (Dispute Resolution and Litigation) Joseph Sherman (Workplace Relations and Safety) Nicola Howell (Workplace Relations and Safety – Cairns) We are keen to help firms and their teams celebrate promotions and new appointments. Please email details of any lawyer promotions or appointments to proctor@qls.com.au Ensure you include some details of their areas of expertise and achievements along with a quality head-and-shoulders image and website in this browser for the next time I comment Admission sittings were held on two days in Brisbane’s Banco Court last week Brothers capped off their centenary year in fine style with an emphatic 42-10 win over arch rivals Herbert River Crushers to claim the Townsville and Districts Rugby League A grade premiership on Sunday at Townsville Sports Reserve finished with a perfect record of five grand final wins from as many appearances Brothers came out of the blocks blazing when five-eighth Ty Carucci registered first points in the opening minutes of the decider Despite Brothers losing a player to the sin bin early in the game Having a man down proved no disadvantage for Brothers when soon after Pickering scored in the 12th minute and put them out to a 12-0 lead While Herbert River had their chances and at times looked set to score they were unable to convert them into points The points kept coming for Brothers in the half with tries to Bowman Samsen O'Neill and captain Nathaniel Norford and a penalty kick by Bowman on the buzzer saw the lead blow out to 30-0 as they headed to the sheds both teams couldn't find momentum in their attack and Herbert River weren't able to break through Brothers defensive line Ben Spina looked set to open up scoring for Herbert River but was denied by the referee who ruled a knock on Crushers hopes were dashed again when George Prior appeared to have dived over for a certain try in the corner but lost control before the ball was grounded With just over 15 minutes left in the game Herbert River fans finally had something to celebrate when Duarne Dempsey found the line close to the sticks top open up their account as Pickering plucked an intercept ball and sprinted 90 metres for his third try of the match Dylan Gaggiano scored a consolation try for the Crushers in the final minute of the match but the dominant win by Brothers saw them claim the premiership trophy for the second time in three years who was in the Brothers 2017 grand final winning team and a player in multiple premierships said the win was massive for him as coach and the team but it was even more special in the club's centenary year He praised his players and said he couldn't be prouder "They gave their all and had nothing left in the tank It's efforts like these in crucial games which reaps rewards and achieves positive results," Baira said Townsville and Districts Rugby League grand final results: goals : Nathaniel Bowman 7) defeated Herbert River 10 (tries: Dylan Gaggiano 1 Player of the Final: Ty Carucci - Brothers Cliff Beetham 1) defeated Brothers 12 (tries: Gresham Ross 1 Player of the Final: Jeremy Laumea - Centrals Ryan Kinsey 1) defeated Brothers 18 (tries: Mark Gardiner 1 Player of the Final: Hayden Saltner - Centrals Goals: Samille Pagden 2) defeated Brothers 12 (tries: Samara Luta 2 Player of the Final: Romy Teitzel - Western Lions Main image: Brothers have claimed the Townsville & District Rugby League A grade premiership after defeating Herbert River in the grand final Semi-Finals: Weekend Preview - Mal Meninga Cup Mackay and Cairns women eager to dethrone favourites Townsville in Foley Shield Everything you need to know: XXXX Foley Shield 2025