Proposal for a new therapeutic high dosage of Pidotimod in children with Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome: an interventional study.

Abstract Background. Despite to PFAPA syndrome is considered a benign and self-limited condition in childhood its impact on patients and families can be remarkable in many cases. Currently, the therapeutic options for managing are non-specific and no consensus exists about the best treatment to use. Pidotimod has been suggested as a new potential treatment in PFAPA syndrome for its immunodulatory effects. We conducted a preliminary, prospective, controlled, open, cross-over trial to assess the efficacy and the safety of Pidotimod in the treatment of children with PFAPA syndrome. Methods. 22 children with PFAPA syndrome were randomly allocated to treatment with pidotimod (with 2 vials of 400mg daily) in combination with betamethasone 0.5-1 mg on need, based on parents/caregivers' decision (group A) or betamethasone 0.5-1mg on need, based on parents/caregivers' decision (group B). Each treatment period was for 3 months (Phase 1), after that patients were switched to the other arm for other 3 months (Phase 2). Efficacy was expressed in terms of number of episodes of fever, pharyngitis, or aphthous stomatitis, as well as the additional use of betamethasone on need. Safety and tolerability of the Pidotimod were evaluated on the basis of the number and type of adverse events (AEs) recorded during the treatment.Results. Patients receiving Pidotimod and use betametasone showed a significant decrease in frequency of fevers (p=0.002); number of episodes of pharyngitis (p=0.049); aphthous stomatitis (p=0.036) as well as the betamethasone use on need (p=0.007). Overall, 19/22 (86.4%) showed benefits from Pidotimod administration. The safety profile of Pidotimod was excellent as no serious adverse events have been reported in the treated groups.Conclusions. We firstly showed that high dosage of Pidotimod could be an effective and safe to reduce the PFAPA attacks in children.

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Proposal for a new therapeutic high dosage of Pidotimod in children with Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome: a randomized controlled study.

10.21203/rs.3.rs-25144/v3 ◽

2020 ◽

Author(s):

Sara Manti ◽

Federica Filosco ◽

Giuseppe Fabio Parisi ◽

Giuseppe Germano Finocchiaro ◽

Maria Papale ◽

...

Keyword(s):

Adverse Events ◽

Periodic Fever ◽

Phase 1 ◽

Aphthous Stomatitis ◽

Controlled Study ◽

Serious Adverse Events ◽

Group A ◽

Pfapa Syndrome ◽

Decision Group ◽

Group B

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Proposal for a new therapeutic high dosage of Pidotimod in children with Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome: an observational study.

10.21203/rs.3.rs-25144/v1 ◽

2020 ◽

Author(s):

Sara Manti ◽

Federica Filosco ◽

Giuseppe Fabio Parisi ◽

Giuseppe Germano Finocchiaro ◽

Maria Papale ◽

...

Keyword(s):

Adverse Events ◽

Periodic Fever ◽

Phase 1 ◽

Aphthous Stomatitis ◽

Potential Treatment ◽

Phase 2 ◽

Serious Adverse Events ◽

Group A ◽

Pfapa Syndrome ◽

Group B

Abstract Background. Despite to PFAPA syndrome is considered a benign and self-limited condition in childhood its impact on patients and families can be remarkable in many cases. Currently, the therapeutic options for managing are non-specific and no consensus exists about the best treatment to use. Pidotimod has been suggested as a new potential treatment in PFAPA syndrome for its immunodulatory effects. We conducted a preliminary, prospective, controlled, open, cross-over trial to assess the efficacy and the safety of Pidotimod in the treatment of children with PFAPA syndrome.Methods. 22 children with PFAPA syndrome were randomly allocated to treatment with Pidotimod (with 2 vials of 400 mg daily) in combination with betamethasone 0.5-1 mg on need (group A) or betamethasone 0.5-1 mg on need (group B). Each treatment period was for 3 months (Phase 1), after that patients were switched to the other arm for other 3 months (Phase 2). Efficacy was expressed in terms of number of episodes of fever, tonsillitis, and aphthous stomatitis, as well as the additional use of betamethasone on need. Safety and tolerability of the Pidotimod were evaluated on the basis of the number and type of adverse events (AEs) recorded during the treatment.Results. Patients receiving Pidotimod and betametasone showed a significant decrease in frequency of fevers (p = 0.002); number of episodes of tonsillitis (p = 0.049); aphthous stomatitis (p = 0.036) as well as the betamethasone use on need (p = 0.007). Overall, 19/22 (86.4%) showed benefits from Pidotimod administration. The safety profile of Pidotimod was excellent as no serious adverse events have been reported in the treated groups.Conclusions. We firstly showed that high dosage of Pidotimod is an effective and safe to reduce the PFAPA attacks in children.

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Feasibility of Non-Anesthesiologist-Administered Propofol Sedation for Emergency Endoscopic Retrograde Cholangiopancreatography

Gastroenterology Research and Practice ◽

10.1155/2015/685476 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Nobuhito Ikeuchi ◽

Takao Itoi ◽

Takuji Gotoda ◽

Chika Kusano ◽

Shin Kono ◽

...

Keyword(s):

Adverse Events ◽

Endoscopic Retrograde Cholangiopancreatography ◽

Acute Cholangitis ◽

Careful Monitoring ◽

Endoscopic Retrograde ◽

Serious Adverse Events ◽

Significant Difference ◽

Group A ◽

Group B ◽

Technical Safety

Background. The safety of non-anesthesiologist-administered propofol (NAAP) sedation in emergent endoscopic retrograde cholangiopancreatography (ERCP) has not been fully clarified. Thus, the aim of this study was to assess the safety of NAAP sedation in emergent ERCP.Materials and Methods. We retrospectively analyzed 182 consecutive patients who had obstructive jaundice and who underwent ERCP under NAAP sedation. The patients were divided into Group A (with mild acute cholangitis or without acute cholangitis) and Group B (moderate or severe acute cholangitis). And technical safety and adverse events were assessed.Results. The adverse events were hypoxia (31 cases), hypotension (26 cases), and bradycardia (2 cases). There was no significant difference in the rate of each adverse event of hypoxia and bradycardia in either group. Although the rate of transient hypotension associated in Group B was higher than that in Group A, it was immediately improved with conservative treatment. Moreover, there were no patients who showed delayed awakening, or who developed other complications.Conclusions. In conclusion, NAAP sedation is feasible even in emergent ERCP. Although some transient adverse events (e.g., hypotension) were observed, no serious adverse events occurred. Thus, propofol can be used in emergent ERCP but careful monitoring is mandatory.

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Treating gambling disorder with as needed administration of intranasal naloxone: a pilot study to evaluate acceptability, feasibility and outcomes

BMJ Open ◽

10.1136/bmjopen-2018-023728 ◽

2019 ◽

Vol 9 (8) ◽

pp. e023728 ◽

Cited By ~ 1

Author(s):

Sari Castrén ◽

Niklas Mäkelä ◽

Janne Haikola ◽

Anne H Salonen ◽

Roger Crystal ◽

...

Keyword(s):

Depressive Symptoms ◽

Pilot Study ◽

Alcohol Use ◽

Adverse Events ◽

Gambling Disorder ◽

Gambling Behaviour ◽

Serious Adverse Events ◽

Opioid Receptor Antagonists ◽

Group A ◽

Group B

Background and aimThere is growing interest in the use of medication-assisted treatments for gambling disorder (GD). Opioid receptor antagonists are hypothesised to blunt the craving associated with gambling. This study was designed to assess the feasibility of using an intranasal naloxone spray to treat GD.DesignAn 8-week, open-label, uncontrolled pilot study.SettingA single study site in the capital region of Finland.SubjectsTwenty problem gamblers (nine men) were randomised into two groups. Group A (n=10) took one dose into one nostril (2 mg naloxone), as needed, with a maximum of 4 doses/day (max. 8 mg/day). Group B (n=10) took one dose into each nostril (4 mg naloxone) as needed, with a maximum of 4 doses/day (max. 16 mg/day).InterventionNaloxone hydrochloride nasal spray.MeasuresAcceptability and feasibility of the intervention were assessed. Use of study medication, adverse events, gambling frequency and gambling expenditure were recorded in a mobile diary. Problem gambling: South Oaks Gambling Screen (SOGS), depressive symptoms: Beck Depression Inventory (BDI) and alcohol use: Alcohol Use Disorders Identification Test were recorded.ResultsStudy completion rate was 90%. Acceptability and feasibility scores were high. Group B used intranasal naloxone more frequently than group A, and consequently used more naloxone. No serious adverse events were reported. The postintervention SOGS scores were lower (median=4 (IQR=3.75) versus preintervention scores (median=12 (IQR=4.75)). Depressive symptoms were reduced during the trial (preintervention BDI median=9, IQR=9 vs postintervention BDI median=6, IQR=6).ConclusionsThe acceptability and feasibility of using intranasal naloxone were high, and no serious adverse events were reported. Preliminary results suggest mixed results in terms of gambling behaviour (ie, reduced frequency but not expenditure) and decreased depressive symptoms.Trial registration numberEudraCT2016-001828-56

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1288. Phase 1 First-in-Human Single- and Multiple-Ascending Dose Trial Demonstrates Pharmacokinetics (PK) and Tolerability of SPR720, an Oral DNA GyrB Inhibitor for Mycobacterial Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1471 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S659-S659

Author(s):

Angela Talley ◽

Archie Thurston ◽

Grayson Moore ◽

Myriah M Satterfield ◽

Erika L Manyak ◽

...

Keyword(s):

Adverse Events ◽

Healthy Volunteers ◽

Controlled Trial ◽

Phase 1 ◽

Safety Data ◽

Elderly Subjects ◽

Independent Contractor ◽

Serious Adverse Events ◽

Healthy Elderly ◽

Dose Proportional

Abstract Background SPR720 (phosphate pro-drug of SPR719) is a novel aminobenzimidazole bacterial DNA gyrase (GyrB) inhibitor in development for non-tuberculous mycobacterial lung disease (NTM-LD) and pulmonary tuberculosis. SPR719 has broad-spectrum activity versus clinically relevant mycobacteria in vitro and in murine and hollow fiber (HF) infection models. In this first-in-human single ascending dose (SAD) /multiple ascending dose (MAD) study, the safety, tolerability and pharmacokinetics (PK) of SPR720/SPR719 were evaluated in healthy volunteers. Methods This was a Phase 1 randomized, double-blind, placebo-controlled trial with 7 SAD cohorts (including a food effect cohort) and 5 MAD cohorts. Healthy volunteers (n=8/cohort, 3:1 randomization) received SPR720 or placebo in single oral doses of ranging from 100 mg to 2000 mg or repeat total daily doses ranging from 500 mg to 1500 mg for 7 or 14 days. Safety monitoring and PK sampling occurred throughout the trial. Plasma and urine concentrations of SPR720/SPR719 were measured by validated LC-MS/MS methods. PK parameters were calculated using non-compartmental analysis. Results A total of 96 subjects (including 8 healthy elderly subjects, age ≥ 65 years) were randomized and received study drug. SPR720 was well-tolerated at daily doses up to 1000 mg for up to 14 days. Across SAD/MAD cohorts, the most common adverse events were gastrointestinal (nausea, vomiting and diarrhea) and headache, all of mild or moderate severity and dose dependent. No serious adverse events were reported. Across SAD cohorts, a dose proportional and greater-than-dose proportional increase in SPR719 plasma Cmax and AUC0-24, respectively were observed. SPR720 was rapidly absorbed with a mean SPR719 t1/2 of 2.9-4.5 h. Dosing with food decreased SPR719 plasma AUC by ~20%. No clinically meaningful effect of age on plasma AUC was observed. In the MAD cohorts, SPR719 plasma exposure declined approximately 40% between Day 1 and Day 7, suggesting induction of an elimination pathway. However, plasma AUC0-24 was similar at Days 7 and 14. Conclusion Together with HF pharmacodynamic data, human PK and safety data for SPR720 suggest that predicted therapeutic exposures can be attained with a well-tolerated once-daily dose. Further evaluation in a Phase 2 NTM-LD trial is planned. Disclosures Angela Talley, MD, Spero Therapeutics (Employee, Shareholder) Archie Thurston, Jr., PhD, Spero Therapeutics (Consultant) Grayson Moore, BA, RN, Spero Therapeutics, Inc. (Shareholder, Independent Contractor) Vipul Kumar, PhD, Spero Therapeutics (Employee, Shareholder) Suzanne Stokes, PhD, Spero Therapeutics (Employee, Shareholder) Aaron Dane, MSc, Spero theraputics (Consultant) David Melnick, MD, Spero Therapeutics (Employee)Spero Therapeutics (Employee)

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Human Monoclonal Antibody Cocktail for the Treatment or Prophylaxis of Middle East Respiratory Syndrome Coronavirus

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab036 ◽

2021 ◽

Author(s):

Sumathi Sivapalasingam ◽

George A Saviolakis ◽

Kirsten Kulcsar ◽

Aya Nakamura ◽

Thomas Conrad ◽

...

Keyword(s):

Middle East ◽

Adverse Events ◽

Phase 1 ◽

Human Monoclonal Antibody ◽

Preclinical Study ◽

Middle East Respiratory Syndrome ◽

Lung Pathology ◽

Phase 1 Study ◽

Serious Adverse Events ◽

Dipeptidyl Peptidase 4

Abstract Background REGN3048 and REGN3051 are human monoclonal antibodies (mAb) targeting the spike glycoprotein on the Middle East respiratory syndrome coronavirus (MERS-CoV), which binds to the receptor dipeptidyl peptidase-4 (DPP4) and is necessary for infection of susceptible cells. Methods Preclinical study: REGN3048, REGN3051 and isotype immunoglobulin G (IgG) were administered to humanized DPP4 (huDPP4) mice 1 day prior to and 1 day after infection with MERS-CoV (Jordan strain). Virus titers and lung pathology were assessed. Phase 1 study: healthy adults received the combined mAb (n = 36) or placebo (n = 12) and followed for 121 days. Six dose levels were studied. Strict safety criteria were met prior to dose escalation. Results Preclinical study: REGN3048 plus REGN3051, prophylactically or therapeutically, was substantially more effective for reducing viral titer, lung inflammation, and pathology in huDPP4 mice compared with control antibodies and to each antibody monotherapy. Phase 1 study: REGN3048 plus REGN3051 was well tolerated with no dose-limiting adverse events, deaths, serious adverse events, or infusion reactions. Each mAb displayed pharmacokinetics expected of human IgG1 antibodies; it was not immunogenic. Conclusions REGN3048 and REGN3051 in combination were well tolerated. The clinical and preclinical data support further development for the treatment or prophylaxis of MERS-CoV infection.

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Management of walled-off necrosis with nasocystic irrigation with hydrogen peroxide versus biflanged metal stent: randomized controlled trial

Endoscopy International Open ◽

10.1055/a-1480-7115 ◽

2021 ◽

Vol 09 (07) ◽

pp. E1108-E1115

Author(s):

Sudhir Maharshi ◽

Shyam Sunder Sharma ◽

Sandeep Ratra ◽

Bharat Sapra ◽

Dhruv Sharma

Keyword(s):

Hydrogen Peroxide ◽

Adverse Events ◽

Clinical Success ◽

Controlled Trial ◽

Procedure Time ◽

Metal Stent ◽

Technical Success ◽

Group A ◽

Group B ◽

Walled Off Necrosis

Abstract Background and study aims Walled-off necrosis (WON) is a known complication of acute necrotizing pancreatitis (ANP). There is no study comparing nasocystic irrigation with hydrogen peroxide (H2O2) versus biflanged metal stent (BMS) in the management of WON. The aim of this study was to compare the clinical efficacy of both the treatment strategies. Patients and methods This study was conducted on patients with symptomatic WON who were randomized to nasocystic irrigation with H2O2 (Group A) and BMS placement (Group B). Primary outcomes were clinical and technical success while secondary outcomes were procedure time, adverse events, need for additional procedures, duration of hospitalization, and mortality. Results Fifty patients were randomized into two groups. Group A (n = 25, age 37.8 ± 17.6 years, 16 men) and Group B (n = 25, age 41.8 ± 15.2 years, 17 men). There were no significant differences in baseline characteristics between the two groups. The most common etiology of pancreatitis was alcohol, observed in 27 (54 %) patients. Technical success (100 % vs 96 %, P = 0.98), clinical success (84 % vs 76 %, P = 0.76), requirement of additional procedures (16 % vs 24 %, P = 0.70) and adverse events (4 vs 7, P = 0.06) were comparable in both the groups. The duration to clinical success (34.4 ± 12 vs 14.8 ± 10.8 days, P = 0.001) and procedure time (36 ± 15 vs 18 ± 12 minutes, P = 0.01) were longer in Group A compared to Group B. Conclusions Nasocystic irrigation with H2O2 and BMS are equally effective in the management of WON but time to clinical success and procedure time is longer with nasocystic irrigation.

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THU0019 INTRON REGIONS OF PIK3AP1 (BCAP) AND SPON2 (SPONDIN-2) GENES ARE DIFFERENTIALLY METHYLATED IN PATIENTS WITH PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS AND ADENITIS (PFAPA) SYNDROME

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5512 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 223.3-223

Author(s):

E. Lovšin ◽

J. Kovac ◽

T. Tesovnik ◽

N. Toplak ◽

D. Perko ◽

...

Keyword(s):

Dna Methylation ◽

Pattern Recognition ◽

Periodic Fever ◽

Aphthous Stomatitis ◽

Extracellular Matrix Protein ◽

Inflammasome Activation ◽

Cervical Adenitis ◽

Pfapa Syndrome ◽

Pattern Recognition Molecule ◽

Recognition Molecule

Background:Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome is the most common autoinflammatory disease in children, often grouped together with hereditary periodic fever syndromes, although its cause and hereditary nature remain unexplained.Objectives:We investigated whether a differential DNA methylation was present in DNA from peripheral blood mononuclear cells (PBMC) in patients with PFAPA versus a group of healthy young individuals.Methods:A whole epigenome analysis (MeDIP and MBD) was performed using pooled DNA libraries enriched for methylated genomic regions. Of identified candidate genes, two with most significantly different methylation leves were further evaluated with methylation specific restriction enzymes coupled with qPCR (MSRE-qPCR).Results:The analysis showed thatPIK3AP1andSPON2intronic gene regions are differentially methylated in patients with PFAPA. MSRE-qPCR proved as a quick, reliable and cost-effective method to confirm results from MeDIP and MBD.Conclusion:Our findings indicate that B cell adapter protein (BCAP) as PI3K binding inhibitor of inflammation and spondin-2 (SPON2) as a pattern recognition molecule and integrin ligand could play a role in etiology of PFAPA. Their role and impact of changed DNA methylation in PFAPA etiology and autoinflammation need further investigation.References:[1]Wekell P. Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome – PFAPA syndrome. Press Medicale [Internet]. 2019;48(1):e77–87. Available from:https://doi.org/10.1016/j.lpm.2018.08.016[2]K. Theodoropoulou, F. Vanoni, and M. Hofer, “Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome: a Review of the Pathogenesis,”Curr. Rheumatol. Rep., vol. 18:18, 2016.[3]Carpentier SJ, Ni M, Duggan JM, James RG, Cookson BT, Hamerman JA. The signaling adaptor BCAP inhibits NLRP3 and NLRC4 inflammasome activation in macrophages through interactions with Flightless-1. Sci Signal. 2019;12(581).[4]He YW, Li H, Zhang J, Hsu CL, Lin E, Zhang N, et al. The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens. Nat Immunol. 2004;5(1):88–97.Disclosure of Interests:None declared

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Effectiveness and safety of secukinumab in 608 patients with psoriatic arthritis in real life: a 24-month prospective, multicentre study

RMD Open ◽

10.1136/rmdopen-2020-001519 ◽

2021 ◽

Vol 7 (1) ◽

pp. e001519

Author(s):

Roberta Ramonda ◽

Mariagrazia Lorenzin ◽

Antonio Carriero ◽

Maria Sole Chimenti ◽

Raffaele Scarpa ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Adverse Events ◽

Disease Activity ◽

Biological Treatment ◽

Retention Rate ◽

Real Life ◽

Drug Retention ◽

Group A ◽

Group B ◽

Drug Retention Rate

ObjectivesTo evaluate in a multicentric Italian cohort of patients with psoriatic arthritis (PsA) on secukinumab followed for 24 months: (1) the long-term effectiveness and safety of secukinumab, (2) the drug retention rate and minimal disease activity (MDA), (3) diﬀerences in the outcomes according to the biological treatment line: biologic-naïve patients (group A) versus multifailure (group B) patients.MethodsConsecutive patients with PsA receiving secukinumab were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical values were recorded at baseline (T0), 6(T6), 12(T12) and 24(T24) months. Effectiveness was evaluated overtime with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug-discontinuation and MDA at T6. Infections and adverse events were recorded.Results608 patients (41.28% men; mean (SD) age 52.78 (11.33)) were enrolled; secukinumab was prescribed as first-line biological treatment in 227 (37.34%) patients, as second (or more)-line biological treatment in 381 (62.66%). Effectiveness of secukinumab was shown with an improvement in several outcomes, such as Ankylosing Spondylitis Disease Activity Score (T0=3.26 (0.88) vs T24=1.60 (0.69) ;p=0.02) and Disease Activity Index for Psoriatic Arthritis (T0=25.29 (11.14) vs T24=7.69 (4.51); p<0.01). At T24, group A showed lower Psoriasis Area Severity Index (p=0.04), erythrocyte sedimentation rate and C reactive protein (p=0.03 ;p=0.05) and joint count (p=0.03) compared with group B. At T24, MDA was achieved in 75.71% of group A and 70.37% of group B. Treatment was discontinued in 123 (20.23%) patients, mainly due to primary/secondary loss of effectiveness, and in 22 due to adverse events. Retention rate at T24 was 71% in the whole population, with some difference depending on secukinumab dosage (p=0.004) and gender (p=0.05).ConclusionsIn a real-life clinical setting, secukimumab proved safe and effective in all PsA domains, with notable drug retention rate.

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