• Translational and Clinical Pharmacology
• /
• v.26 no.4
• /
• pp.155-159
• /
• 2018

For regulatory approval of a new drug, the most preferred and reliable source of evidence would be randomized controlled trials (RCT). However, a great number of drugs, being developed as well as already marketed and being used, usually lack proper indications for children. It is imperative to develop properly evaluated drugs for children. And expanding the use of already approved drugs for other indications will benefit patients and the society. Nevertheless, to get an approval for expansion of indications, most often with off-label experiences, for drugs that have been approved or for the development of pediatric indications, either during or after completing the main drug development, conducting RCTs may not be the only, if not right, way to take. Extrapolation strategies and modelling & simulation for pediatric drug development are paving the road to the better approval scheme. Making the use of data sources other than RCT such as EHR and claims data in ways that improve the efficiency and validity of the results (e.g., randomized pragmatic trial and randomized registry trial) has been the topic of great interest all around the world. Regulatory authorities should adopt new methodologies for regulatory approval processes to adapt to the changes brought by increasing availability of big and real world data utilizing new tools of technological advancement.

• Bulletin of the Korean Chemical Society
• /
• v.35 no.5
• /
• pp.1279-1284
• /
• 2014

The binding of TATA-binding protein (TBP) to the TATA-box containing promoter region is aided by many other transcriptional factors including TFIIA and TFIIB. The mechanistic insight into the assembly of RNA polymerase II preinitation complex (PIC) has been gained by either directly altering a function of target protein or perturbing molecular interactions using drugs, RNAi, or aptamers. Aptamers have been found particularly useful for studying a role of a subset of PIC on transcription for their ability to inhibit specific molecular interactions. One major hurdle to the wide use of aptamers as specific inhibitors arises from the difficulty with traditional assays to validate and determine specificity, affinity, and binding epitopes for aptamers against targets. Here, using a technique called the bio-layer interferometry (BLI) designed for a label-free, real-time, and multiplexed detection of molecular interactions, we studied the assembly of a subset of PIC, TBP binding to TATA DNA, and two distinct classes of aptamers against TPB in regard to their ability to inhibit TBP binding to TFIIA or TATA DNA. Using BLI, we measured not only equilibrium binding constants ($K_D$), which were overall in close agreement with those obtained by electrophoretic mobility shift assay, but also kinetic constants of binding ($k_{on}$ and $k_{off}$), differentiating aptamers of comparable KDs by their difference in binding kinetics. The assay developed in this study can readily be adopted for high throughput validation of candidate aptamers for specificity, affinity, and epitopes, providing both equilibrium and kinetic information for aptamer interaction with targets.

• Archives of Plastic Surgery
• /
• v.42 no.5
• /
• pp.532-543
• /
• 2015

Capsular contracture is the most common complication following implant based breast surgery and is one of the most common reasons for reoperation. Therefore, it is important to try and understand why this happens, and what can be done to reduce its incidence. A literature search using the MEDLINE database was conducted including search terms 'capsular contracture breast augmentation', 'capsular contracture pathogenesis', 'capsular contracture incidence', and 'capsular contracture management', which yielded 82 results which met inclusion criteria. Capsular contracture is caused by an excessive fibrotic reaction to a foreign body (the implant) and has an overall incidence of 10.6%. Risk factors that were identified included the use of smooth (vs. textured) implants, a subglandular (vs. submuscular) placement, use of a silicone (vs. saline) filled implant and previous radiotherapy to the breast. The standard management of capsular contracture is surgical via a capsulectomy or capsulotomy. Medical treatment using the off-label leukotriene receptor antagonist Zafirlukast has been reported to reduce severity and help prevent capsular contracture from forming, as has the use of acellular dermal matrices, botox and neopocket formation. However, nearly all therapeutic approaches are associated with a significant rate of recurrence. Capsular contracture is a multifactorial fibrotic process the precise cause of which is still unknown. The incidence of contracture developing is lower with the use of textured implants, submuscular placement and the use of polyurethane coated implants. Symptomatic capsular contracture is usually managed surgically, however recent research has focussed on preventing capsular contracture from occurring, or treating it with autologous fat transfer.

• Clinical and Experimental Reproductive Medicine
• /
• v.42 no.3
• /
• pp.126-129
• /
• 2015

Essure (Bayer) received approval from the U.S. Food and Drugs Administration as a permanent non-hormonal contraceptive implant in November 2002. While the use of Essure in the management of hydrosalpinx prior to in vitro fertilization (IVF) remains off-label, it has been used specifically for this purpose since at least 2007. Although most published reports on Essure placement before IVF have been reassuring, clinical experience remains limited, and no randomized studies have demonstrated the safety or efficacy of Essure in this context. In fact, no published guidelines deal with patient selection or counseling regarding the Essure procedure specifically in the context of IVF. Although Essure is an irreversible birth control option, some patients request the surgical removal of the implants for various reasons. While these patients could eventually undergo hysterectomy, at present no standardized technique exists for simple Essure removal with conservation of the uterus. This article emphasizes new aspects of the Essure procedure, as we describe the first known association between the placement of Essure implants and the subsequent development of fluid within the uterine cavity, which resolved after the surgical removal of both devices.

• Clinical and Experimental Pediatrics
• /
• v.60 no.8
• /
• pp.237-244
• /
• 2017

During the last 10 years, there have been major technological achievements in pediatric interventional cardiology. In addition, there have been several advances in cardiac imaging, especially in 3-dimensional imaging of echocardiography, computed tomography, magnetic resonance imaging, and cineangiography. Therefore, more types of congenital heart diseases can be treated in the cardiac catheter laboratory today than ever before. Furthermore, lesions previously considered resistant to interventional therapies can now be managed with high success rates. The hybrid approach has enabled the overcoming of limitations inherent to percutaneous access, expanding the application of endovascular therapies as adjunct to surgical interventions to improve patient outcomes and minimize invasiveness. Percutaneous pulmonary valve implantation has become a successful alternative therapy. However, most of the current recommendations about pediatric cardiac interventions (including class I recommendations) refer to off-label use of devices, because it is difficult to study the safety and efficacy of catheterization and transcatheter therapy in pediatric cardiac patients. This difficulty arises from the challenge of identifying a control population and the relatively small number of pediatric patients with congenital heart disease. Nevertheless, the pediatric interventional cardiology community has continued to develop less invasive solutions for congenital heart defects to minimize the need for open heart surgery and optimize overall outcomes. In this review, various interventional procedures in patients with congenital heart disease are explored.

• Journal of Dental Rehabilitation and Applied Science
• /
• v.29 no.4
• /
• pp.391-398
• /
• 2013

Botulinum toxin has been used for treating strabismus, blepharospasm, cerebral palsy, cervical dystonia, hyperhydrosis, facial wrinkle and chronic migraine under US Food and Drug administration approval. Also it has been tried spasticity-induced pain, post-herpetic neuralgia, myofascial pain and aphthous ulcer as off-label use. In this study, we reviewed recent studies that suggested effects of botulinum toxin on snoring and sleep apnea.

• Journal of Yeungnam Medical Science
• /
• v.38 no.3
• /
• pp.251-257
• /
• 2021

Vedolizumab (VDZ) has been approved for the treatment of inflammatory bowel diseases (IBDs) in patients aged ≥18 years. We report a case of a pediatric patient with Crohn disease (CD) who was successfully treated with VDZ. A 16-year-old female developed severe active pulmonary tuberculosis (TB) during treatment with infliximab (IFX). IFX was stopped, and TB treatment was started. After a 6-month regimen of standard TB medication, her pulmonary TB was cured; however, gastrointestinal symptoms developed. Due to the concern of the patient and parents regarding TB reactivation on restarting treatment with IFX, VDZ was started off-label. After the second dose of VDZ, the patient was in clinical remission and her remission was continuously sustained. Ileocolonoscopy at 1-year after VDZ initiation revealed endoscopic healing. Therapeutic drug monitoring conducted during VDZ treatment showed negative antibodies to VDZ. No serious adverse events occurred during the VDZ treatment. This is the first case report in Korea demonstrating the safe and effective use of VDZ treatment in a pediatric CD patient. In cases that require recommencement of treatment with biologics after recovery of active pulmonary TB caused by anti-tumor necrosis factor agents, VDZ may be a good option even in pediatric IBD.

• Korean Circulation Journal
• /
• v.53 no.3
• /
• pp.134-150
• /
• 2023

Ventricular septal defects (VSDs) are the most common kind of congenital heart disease and, if indicated, surgical closure has been accepted as a gold-standard treatment. However, as less-invasive methods are preferred, percutaneous device closure has been developed. After the first VSD closure was performed percutaneously by Lock in 1988, both techniques and devices have developed consistently. A perventricular approach for closure of muscular VSD in small patients and the closure of perimembranous VSD using off-label devices are key remarkable developments. Even though the Amplatzer membranous VSD occluder (Abbott) could not be approved for use due to the high complete atrioventricular conduction block rate, other new devices have shown good results for closure of perimembranous VSDs. However, the transcatheter technique is slightly complicated to perform, and concerns about conduction problems after VSD closure with devices remain. There have been a few reports demonstrating successful closure of subarterial-type VSDs with Amplatzer devices, but long-term issues involving aortic valve damage have not been explored yet. In conclusion, transcatheter VSD closure should be accepted as being as effective and safe as surgery but should only be performed by experienced persons and in specialized institutes because the procedure is complex and requires different techniques. To avoid serious complications, identifying appropriate patient candidates for device closure before the procedure is very important.

• Hip & pelvis
• /
• v.35 no.1
• /
• pp.40-46
• /
• 2023

Purpose: A variety of short Exeter stems designed specifically for use in performance of total hip arthroplasty (THA) in primary and revision settings have recently been introduced. Some have been used 'off label' for hip reconstruction. The aim of this study is to report clinical and radiological results from the Exeter V40 125 mm stem in performance of primary THA and revision THA. Materials and Methods: This study had a retrospective design. Insertion of 58 (24 primary, 34 revision) Exeter V40 125 mm stems was performed between 2015 and 2017. The minimum follow-up period was two years. Assessment of the Oxford hip score (OHS), EuroQol-5 Dimension (EQ-5D), and radiological follow-up was performed at one and two years. Results: In the primary group, the preoperative, mean OHS was 13.29. The mean OHS was 32.86 and 23.39 at one-year and two-year post-surgery, respectively. The mean EQ-5D-3L scores were at 0.14, 0.59, and 0.35, preoperatively, at one-year follow-up and two-year follow-up, respectively. In the revision group, the mean preoperative OHS was 19.41. The mean OHS was 30.55 and 26.05 at one-year and two-year post-surgery, respectively. The mean EQ-5D-3L scores were 0.33, 0.61, and 0.48 preoperatively, at one-year follow-up and two-year follow-up, respectively. No progressive or new radiolucent lines were observed around any stem at the time of the final follow-up in all patients in both groups. Conclusion: Encouraging results regarding use of Exeter V40 125 mm stems have been reported up to two years following surgery in primary and revision THA settings.

• Journal of Oral Medicine and Pain
• /
• v.38 no.4
• /
• pp.325-331
• /
• 2013

Botulinum neurotoxin(BoNT) is a protease exotoxin produced from Clostridium botulinum. It works by blocking the release of acetylcholine from cholinergic nerve endings causing inactivity of muscles or glands. Recently, the therapeutic use of BoNT have expanded to include a wide range of medical and dental conditions. Botulinum neurotoxin type A(BoNT/A) is used off-label in the orofacial region to treat primary and secondary masticatory and facial muscle spasm, severe bruxism, facial tics, orofacial dyskinesias, dystonias, and hypertrophy of the masticatory muscles. Local hematoma, infection, and persistent pain in the injection site are the site-of-injection side effects. Medication-related side effects are adjacent muscle weakness, slurred speech, an alteration in the character of the saliva, and severe headaches. In most cases, these complications are not persistent and bothersome. We reported a case report of a patient who had transient anterior open bite after BoNT/A injection on masseter muscles to treat the refractory myofascial pain.