scholarly journals Penetration of topical diclofenac into synovial tissue and fluid of osteoarthritic knees: a multicenter, randomized, placebo-controlled, pharmacokinetic study

2020 ◽  
Vol 12 ◽  
pp. 1759720X2094308
Author(s):  
Lothar Seefried ◽  
Mark Blyth ◽  
Rohit Maheshwari ◽  
Stephen M. McDonnell ◽  
Guillaume Frappin ◽  
...  
Keyword(s):  
Synovial Tissue ◽  
Geometric Mean ◽  
Primary Objective ◽  
Double Blind ◽  
Osteoarthritis Pain ◽  
Proven Efficacy ◽  
Secondary Objective ◽  
End Stage ◽  
Trained Nurse ◽  
Topical Diclofenac

Background: Topical diclofenac, a nonsteroidal anti-inflammatory drug, has proven efficacy and safety in the management of osteoarthritis pain. We investigated penetration of topical diclofenac into knee synovial tissue and fluid (primary objective) and evaluated relative exposure in the knee versus plasma (secondary objective). Methods: In this phase I, double-blind, multicenter study, patients scheduled for arthroplasty for end-stage knee osteoarthritis were randomly assigned 2:1 to 4 g diclofenac diethylamine 2.32% w/w gel (92.8 mg diclofenac diethylamine, equivalent to 74.4 mg diclofenac, per application) or placebo gel, applied to the affected knee by a trained nurse/designee every 12 h for 7 days before surgery. Diclofenac concentrations were measured in synovial tissue, synovial fluid and plasma from samples obtained during surgery ⩾12 h after last application. Treatment-emergent adverse events (TEAEs) were evaluated. Results: Evaluable synovial tissue or fluid samples were obtained from 45 (diclofenac n = 29; placebo n = 16) of 47 patients. All diclofenac-treated participants had measurable diclofenac concentrations in synovial tissue [geometric mean 1.57 (95% confidence interval (CI) 1.12, 2.20) ng/g] and fluid [geometric mean 2.27 (95% CI 1.87, 2.76) ng/ml] ⩾12 h after the last dose. Geometric mean (95% CI) ratio of diclofenac in synovial tissue:plasma was 0.32 (0.23, 0.45) and in synovial fluid:plasma was 0.46 (0.40, 0.54). TEAE rates were similar for diclofenac (55.2%) and placebo (58.8%); none were treatment related. Conclusions: Topical diclofenac diethylamine 2.32% w/w gel penetrated into the osteoarthritic knee after repeated application and remained detectable in synovial tissue and fluid at the end of the final 12 h dosing cycle.

Comparative double-blind randomized trial of 2 rituximab products in patients with CD20+ diffuse large B-cell lymphoma (DLBCL).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7550-7550 ◽  
Author(s):  
Sandip Shah ◽  
Auro Viswabandya ◽  
Asis Mukhopadhyay ◽  
Rajnish Vasant Nagarkar ◽  
Sonica Sachdeva Batra ◽  
...  
Keyword(s):  
B Cell ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Similarity Criterion ◽  
B Cell Lymphoma ◽  
Primary Objective ◽  
Double Blind ◽  
Secondary Objective ◽  
Grade 3

7550 Background: DRL-Rituximab (T) is a proposed biosimilar of the innovator reference rituximab (USA: Rituxan; EU: MabThera). Physicochemical analyses and nonclinical studies have shown T to be comparable with innovator Rituximab. This study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, safety and immunogenicity of T with EU sourced MabThera (R) in DLBCL patients. Methods: Multicentre randomized double-blind 2-arm parallel study conducted in patients aged 18-60 yrs, with a centrally confirmed newly diagnosed CD20+ DLBCL, as first line of treatment. Patients received 6 cycles (C), every 21 days, of either T or R at 375 mg/m2 + CHOP. Primary objective was to compare C1 PK (AUC0-21d & Cmax). Overall Response Rate (ORR) was the key secondary objective, with C6 PK parameters, PD parameters (B-cells measured as CD19+ positive cells in peripheral blood- depletion & repletion), treatment-emergent adverse events (TEAEs), and anti-drug antibodies (ADA) as other secondary objectives. PK similarity criterion was 90% CI of geometric mean ratios (GMRs) of AUC0-21d and Cmax in C1, within 80-125%. Results: 151 patients were randomized (T, 76; R, 75). PK similarity criterion was met. The GMR T/R ratios with 90% CIs for AUC0-21d & Cmax were 100.0% (87.7, 114.0) & 96.2% (88.7, 104.4), respectively. Per protocol, ORR with 95% CI was 82.1% (69.6, 91.1) with T and 87.1% (76.1, 94.3) with R. Trough concentration (C5/C6) GMR (90% CI) of 91.3% (86.3, 96.7) for T & 94.0% (88.9, 99.5) for R indicated steady state. C6 AUC0-21d & Cmax GMR (T/R [90% CI]) were 88.9% (80.3, 98.5) and 94.6% (88.1, 101.7), respectively. T and R led to comparable B-cell depletion and repletion. Incidence of all grades of TEAEs were comparable. TEAEs ≥Grade 3 were 80.3% in T (n = 61) and 88.0% R (n = 66). Neutropenia was the most common TEAE (overall: T, 75.0%; R, 73.3% & ≥ grade 3: T, 64.5%; R, 64.0%). No neutralizing antibodies were observed in either of the arms. Conclusions: These data demonstrate that DRL-Rituximab has comparable PK, PD, efficacy, safety and immunogenicity to MabThera. MabThera already has an established efficacy in longer term follow-up. Clinical trial information: CTRI/2012/11/003129.

A large multicenter, randomized, double-blind, crossover study in healthy volunteers, comparing pharmacokinetics and pharmacodynamics of Sandoz proposed biosimilar pegfilgrastim with European and United States reference pegfilgrastim.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23118-e23118
Author(s):  
Gordon P. Otto ◽  
Roumen Nakov ◽  
Steven Schussler ◽  
Stefanie Schier-Mumzhiu ◽  
Celine Schelcher ◽  
...  
Keyword(s):  
Single Dose ◽  
Phase I ◽  
Crossover Study ◽  
Healthy Volunteers ◽  
Phase I Study ◽  
Geometric Mean ◽  
Primary Objective ◽  
Local Tolerability ◽  
Pivotal Phase ◽  
Double Blind

e23118 Background: Similarity of the pharmacokinetic (PK)/pharmacodynamic (PD) profiles of Sandoz proposed biosimilar pegfilgrastim and EU-reference biologic was confirmed in a pivotal Phase I study. In order to confirm PK/PD similarity to the US reference biologic, and to bridge between the two references, a 3-way study was conducted. Methods: A randomized, double-blind, single-dose, 3-treatment, 6-sequence crossover Phase I study was performed in healthy volunteers (HVs) to demonstrate similarity in PK, PD, safety and immunogenicity between Sandoz proposed biosimilar, US reference, and EU reference pegfilgrastim administered subcutaneously (6 mg/0.6 mL) in each treatment period. The primary objective was to demonstrate PK (AUC0-inf, AUC0-last, Cmax) and PD similarity (ANC AUEC0-last, ANC Emax). The study was powered (90%) to achieve confidence intervals (CIs) within biosimilarity margins 0.8─1.25 in pairwise comparisons. Secondary objectives were additional PK/PD parameters, safety and immunogenicity. Results: The study included 577 male and female HVs. PK and PD similarity were demonstrated between Sandoz proposed biosimilar and US reference (Table), as well as EU reference and between both reference biologics since the 90% CIs of the geometric mean ratios were contained within the pre-defined margins of 0.80‒1.25. Safety, immunogenicity and secondary PK/PD parameters were also similar across treatment groups. Conclusions: This large randomized, double-blind, single-dose, 3-treatment, 6-sequence crossover study demonstrated PK and PD similarity between Sandoz proposed biosimilar, US reference and EU reference pegfilgrastim with similar safety, local tolerability and immunogenicity. Clinical trial information: 2016-003549-27. [Table: see text]

scholarly journals Assessment of Psychomotor Recovery after Etomidate and Propofol Induction: A Randomized Double-Blind Trial

2021 ◽  
Author(s):  
Jyoti Kale ◽  
Neha Panse ◽  
Ketki Maske ◽  
Pranali Nighukar
Keyword(s):  
Day Care ◽  
Enhanced Recovery ◽  
Postoperative Recovery ◽  
Primary Objective ◽  
Early Recovery ◽  
Double Blind ◽  
Psychomotor Tests ◽  
Early Ambulation ◽  
Secondary Objective ◽  
Operative Recovery

Background: The very idea of faster recovery and early ambulation has prompted patients to opt for day care surgeries. The concept of ERAS (enhanced recovery after surgery) is the backbone to achieve this goal. We conducted this study with primary objective to compare the post-operative recovery with etomidate and propofol in terms of early recovery (awakening), intermediate recovery (psychomotor and cognitive recovery) and ambulation “home readiness” and secondary objective to study the adverse effects. Methods: 60 eligible patients scheduled for day care gynaecological procedures were randomised in two groups of 30 each. Group E received etomidate 0.2mg/kg and group P received propofol 2mg/kg. Early, intermediate and late postoperative recovery (ambulation) was studied in both groups. Results: Demography between the groups were comparable while hemodynamic fluctuations were more with propofol (p>0.05), early recovery was faster with etomidate (p = 0.07), psychomotor tests revealed better alertness with etomidate (p= 0.1) and patient could ambulate earlier in etomidate group. Conclusion: Both propofol and Etomidate facilitate early recovery but etomidate provides hemodynamic stability with early awakening, more alert patients and better ambulation and was found to be superior for day care surgeries.

scholarly journals A 12 weeks, randomized and double-blind evaluation of the efficacy of oral supplements of probiotics (Lactogut and Lactogut Kidz) on atopic dermatitis in adults and children

2020 ◽  
Vol 6 (5) ◽  
pp. 604
Author(s):  
B. S. Chandrashekar ◽  
Rashmi Agarwal ◽  
Preethi B. Nayak ◽  
S. Vijayraghavan ◽  
Atul A. Deshmukh
Keyword(s):  
Atopic Dermatitis ◽  
Patient Satisfaction ◽  
Conventional Therapy ◽  
Primary Objective ◽  
Double Blind Study ◽  
Life Questionnaire ◽  
Double Blind ◽  
Serum Ige ◽  
Adults And Children ◽  
Secondary Objective

<p class="abstract"><strong>Background:</strong> The primary objective of the study was to evaluate the efficacy and safety of oral probiotics in the treatment of atopic dermatitis (AD) using the scoring atopic dermatitis (SCORAD) index, serum IgE levels and absolute eosinophil count (AEC). The secondary objective of the study was to determine the association of oral probiotic therapy and improvement in AD using global photographs, dermoscopic images (fotofinder) and individual patient satisfaction.</p><p class="abstract"><strong>Methods:</strong> This was a randomized, double-blind study conducted on 70 patients (20 adults and 50 children) with moderate to severe AD. The participants were randomized into control arm and treatment arm. The treatment arm received conventional and probiotic therapy and only conventional therapy was provided to the control arm. The research was carried out in five visits. For each visit, SCORAD was calculated and response compared using clinical and videodermoscopic images. Patient satisfaction was documented using a quality of life questionnaire during each visit.<strong></strong></p><p class="abstract"><strong>Results:</strong> Across the treatment arm, the mean serum IgE levels were greatly decreased in contrast to the control arm over the 12 weeks period. SCORAD score was significantly lowered in the treatment arm (55.20%) compared with 18.95% in the control arm. Dermoscopic assessment, global photographic assessment and patient satisfaction in the treatment arm showed statistically significant improvement in AD compared to the control arm.</p><p class="abstract"><strong>Conclusions:</strong> The decrease in SCORAD scores demonstrated strong associations with the use of probiotics in patients with AD as an adjunct to conventional therapy. Thus, in both adults and children suffering from moderate to severe AD, probiotic supplement can be administered effectively as an adjunct therapy.</p><p class="abstract"> </p>

The Student Room Survey: Changes in the Post Graduate Study for Cardiothoracic Surgery

2020 ◽  
Vol 23 (2) ◽  
pp. 71-74
Author(s):  
Md Faizus Sazzad ◽  
Mohammed Moniruzzaman ◽  
Dewan Iftakher Raza Choudhury ◽  
Arif Ahmed Mohiuddin ◽  
Raafi Rahman ◽  
...  
Keyword(s):  
Thoracic Surgery ◽  
Retrospective Analysis ◽  
Primary Objective ◽  
Graduate Study ◽  
Postgraduate Students ◽  
Depth Interview ◽  
Secondary Objective ◽  
Cardio Vascular ◽  
The University ◽  
Day By Day

Background: The number of postgraduate students in Cardiac surgical discipline is increasing day by day with incremental proportion are measurably suffering from the unnecessary lingering of the present course curriculum. The primary objective of this study was to find out the last 5 years’ of results of Masters in Surgery course under the University of Dhaka from a student room survey. A secondary objective was to find out positive changes that could show us the way of a step toward up-gradation. Methods: It is a retrospective analysis of all examination results of Cardio-vascular & Thoracic Surgery published since January 2008 to January 2013 from the University of Dhaka with in depth interview of 11 participants. Results: 85.24% students failed to pass part-I of Masters in Surgery for Cardio-vascular & Thoracic Surgery course while, 82.18% in part-II and 71.28% failed to pass the final part. Average 2.51 attempts needed to complete each part of the designed course resulted into lingering of course duration for 42.18 months/student. In the thoracic surgery discipline the number of students alarmingly reduced up to 0% in the recent academic sessions. Conclusions: Masters in Surgery is resulting in unnecessary prolongation of the course. We should step forward to meet the next generation challenge. Journal of Surgical Sciences (2019) Vol. 23(2): 71-74

Epidemiology of pheochromocytoma and paraganglioma: population-based cohort study

2021 ◽  
Vol 184 (1) ◽  
pp. 19-28
Author(s):  
Alexander A Leung ◽  
Janice L Pasieka ◽  
Martin D Hyrcza ◽  
Danièle Pacaud ◽  
Yuan Dong ◽  
...  
Keyword(s):  
Cohort Study ◽  
Administrative Data ◽  
Laboratory Data ◽  
Population Based ◽  
Incidence Rates ◽  
Primary Objective ◽  
Administrative Databases ◽  
Secondary Objective ◽  
True Frequency ◽  
Clinical Records

Objective Despite the significant morbidity and mortality associated with pheochromocytoma and paraganglioma, little is known about their epidemiology. The primary objective was to determine the incidence of pheochromocytoma and paraganglioma in an ethnically diverse population. A secondary objective was to develop and validate algorithms for case detection using laboratory and administrative data. Design Population-based cohort study in Alberta, Canada from 2012 to 2019. Methods Patients with pheochromocytoma or paraganglioma were identified using linked administrative databases and clinical records. Annual incidence rates per 100 000 people were calculated and stratified according to age and sex. Algorithms to identify pheochromocytoma and paraganglioma, based on laboratory and administrative data, were evaluated. Results A total of 239 patients with pheochromocytoma or paraganglioma (collectively with 251 tumors) were identified from a population of 5 196 368 people over a period of 7 years. The overall incidence of pheochromocytoma or paraganglioma was 0.66 cases per 100 000 people per year. The frequency of pheochromocytoma and paraganglioma increased with age and was highest in individuals aged 60–79 years (8.85 and 14.68 cases per 100 000 people per year for males and females, respectively). An algorithm based on laboratory data (metanephrine >two-fold or normetanephrine >three-fold higher than the upper limit of normal) closely approximated the true frequency of pheochromocytoma and paraganglioma with an estimated incidence of 0.54 cases per 100 000 people per year. Conslusion The incidence of pheochromocytoma and paraganglioma in an unselected population of western Canada was unexpectedly higher than rates reported from other areas of the world.

Incidência da utilização de protetores bucais em diversos esportes de contato

2020 ◽  
Vol 12 (45) ◽  
pp. 118-122
Author(s):  
Victor Paes Dias Gonçalves ◽  
Hugo Leonardo Matias Nahmias ◽  
Marcus Menezes Alves Azevedo
Keyword(s):  
Martial Arts ◽  
Rio De Janeiro ◽  
Dental Trauma ◽  
Primary Objective ◽  
Type Ii ◽  
Contact Sports ◽  
The Face ◽  
Secondary Objective ◽  
The City

Among contact sports, the practice of martial arts offers a greater risk of causing dental trauma and fractures as contact with the face is more frequent. The primary objective of the research is to evaluate the incidence of mouthguard use, and the secondary objective is to verify which type has a greater predominance and the difficulties in its use correlating to the type of mouthguard used. A documentary study was carried out with 273 athletes of different contact sports, among them: MMA, Boxing, Muay Thai, Jiu-Jitsu, and Taekwondo of the city of Campos dos Goytacazes, Rio de Janeiro, Brazil. It was concluded that the most commonly used mouthguard is PB Boils and Bites - Type II and its level of approval is poor, interfering with the athletes’ performance, mainly in relation to the breathing factor.

scholarly journals Efficacy and Safety of a 3-Antigen (Pre-S1/Pre-S2/S) Hepatitis B Vaccine: Results of a Phase 3 Randomized Clinical Trial in the Russian Federation

2020 ◽  
Author(s):  
Elena V Esaulenko ◽  
Aleksey A Yakovlev ◽  
Genady A Volkov ◽  
Anastasia A Sukhoruk ◽  
Kirill G Surkov ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Geometric Mean ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Antigen Vaccine ◽  
Single Antigen ◽  
Antibody Titers ◽  
The Russian Federation ◽  
The Difference ◽  
Mean Concentration

Abstract Background This study compares the immunogenicity and safety of a 3-antigen (S/pre-S1/pre-S2) hepatitis B (HepB) vaccine (3AV), to a single antigen vaccine (1AV) in adults to support the registration of 3AV in Russia. Methods We conducted a randomized, double-blind, comparative study of 3-dose regimens of 3AV (10 μg) and 1AV (20 µg) in adults aged 18–45 years. We evaluated immunogenicity based on hepatitis B surface (HBs) antibody titers at days 1, 28, 90, 180, and 210, adverse and serious adverse events (SAEs) to study day 210. The primary outcome was based on the difference in rates of seroconversion at day 210 (lower bound 95% confidence interval [CI]: &gt; − 4%). Secondary outcomes were seroprotection rates (SPR), defined as anti-HBs ≥10 mIU/mL and anti-HBs geometric mean concentration (GMC). Results Rate of seroconversion in 3AV (100%) was noninferior to 1AV (97.9%) at study day 210 (difference: 2.1%, 95% CI: −2.0, 6.3%]) but significantly higher at study day 28. SPR at study day 210 was &gt;97% in both arms. Anti-HBs titers were significantly higher at study days 90 (P = .001) and 180 (P = .0001) with 3AV. Sex, age, and body mass index (BMI) had no impact on anti-HBs titers. The rates of local reactions related to vaccination were similar between vaccine arms (3AV vs 1AV) after the first (30% vs 18.8%, P = .15), second (20.0% vs 14.6%, P = .33), and third vaccination (14.9% vs 23.4%, P = .22). No SAEs were reported. Conclusions 3AV was noninferior to 1AV. 3AV induced high SPR, and there were no safety concerns. Clinical Trials Registration. NCT04209400.

scholarly journals Use of Ceftaroline in Hospitalized Patients with and without COVID-19: A Descriptive Cross-Sectional Study

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 763
Author(s):  
Daniele Roberto Giacobbe ◽  
Chiara Russo ◽  
Veronica Martini ◽  
Silvia Dettori ◽  
Federica Briano ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Bloodstream Infections ◽  
Cross Sectional Study ◽  
Primary Objective ◽  
Sectional Study ◽  
Cross Sectional ◽  
First Line Therapy ◽  
Large Teaching Hospital ◽  
Secondary Objective ◽  
Medical Wards

A single-center cross-sectional study was conducted to describe the use of ceftaroline in a large teaching hospital in Northern Italy, during a period also including the first months of the coronavirus disease 2019 (COVID-19) pandemic. The primary objective was to describe the use of ceftaroline in terms of indications and characteristics of patients. A secondary objective was to describe the rate of favorable clinical response in patients with bloodstream infections (BSI) due to methicillin-resistant Staphylococcus aureus (MRSA-BSI) receiving ceftaroline. Overall, 200 patients were included in the study. Most of them had COVID-19 (83%, 165/200) and were hospitalized in medical wards (78%, 155/200). Included patients with COVID-19 pneumonia were given empirical ceftaroline in the suspicion of bacterial co-infection or superinfection. Among patients with MRSA-BSI, ceftaroline was used as a first-line therapy and salvage therapy in 25% (3/12) and 75% (9/12) of cases, respectively, and as a monotherapy or in combination with daptomycin in 58% (7/12) and 42% (5/12) of patients, respectively. A favorable response was registered in 67% (8/12) of patients. Improving etiological diagnosis of bacterial infections is essential to optimize the use of ceftaroline in COVID-19 patients. The use of ceftaroline for MRSA-BSI, either as a monotherapy or in combination with other anti-MRSA agents, showed promising rates of favorable response.

scholarly journals Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ekaterina Alexeeva ◽  
Gerd Horneff ◽  
Tatyana Dvoryakovskaya ◽  
Rina Denisova ◽  
Irina Nikishina ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Controlled Trial ◽  
Randomized Study ◽  
Primary Objective ◽  
Disease State ◽  
Inactive Disease ◽  
Open Label ◽  
Standard Regimen ◽  
Double Blind ◽  
Early Combination Therapy

Abstract Background Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.

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