Background/Aims: Fecal microbiota transplantation (FMT) represents a treatment option for recurrent Clostridioides difficile infection (CDI). Recently, FMT has been investigated in various clinical settings other than CDI. This study examined Korean physicians’ recognition of FMT and their attitudes toward this procedure Methods: An online questionnaire included questions on indications for FMT, the FMT process, physicians’ attitudes toward FMT for the treatment of CDI and non-CDI diseases, and possible concerns. Results: Finally, 107 physicians responded to this survey: 66 (61.7%) had experience of performing FMT, and 86 (80.4%) replied that they were willing to perform FMT for CDI. Two-thirds of physicians (63.6%, n = 68) would perform FMT for recurrent CDI on patients who had at least three recurrences. The most common obstacle to performing FMT for the treatment of CDI was the lack of regulations or guidelines (55.1%, n = 59). Seventy-seven (72.0%) physicians would consider FMT for non- CDI diseases when conventional treatment had failed. The most common obstacle for FMT for the treatment of non-CDI diseases was low treatment efficacy (57.0%, n = 61). Conclusions Two-thirds of Korean physicians had experience of performing FMT, and many performed FMT for recurrent CDI. The results of this study will prove useful to researchers and practitioners in FMT in Korea.

Chronic constipation is one of the most common digestive diseases encountered in clinical practice. Constipation manifests as a variety of symptoms, such as infrequent bowel movements, hard stools, feeling of incomplete evacuation, straining at defecation, a sense of anorectal blockage during defecation, and use of digital maneuvers to assist defecation. During the diagnosis of chronic constipation, the Bristol Stool Form Scale, colonoscopy, and a digital rectal examination are useful for objective symptom evaluation and differential diagnosis of secondary constipation. Physiological tests for functional constipation have complementary roles and are recommended for patients who have failed to respond to treatment with available laxatives and those who are strongly suspected of having a defecatory disorder. As new evidence on the diagnosis and management of functional constipation emerged, the need to revise the previous guideline was suggested. Therefore, these evidence-based guidelines have proposed recommendations developed using a systematic review and meta-analysis of the treatment options available for functional constipation. The benefits and cautions of new pharmacological agents (such as lubiprostone and linaclotide) and conventional laxatives have been described through a meta-analysis. The guidelines consist of 34 recommendations, including 3 concerning the definition and epidemiology of functional constipation, 9 regarding diagnoses, and 22 regarding managements. Clinicians (including primary physicians, general health professionals, medical students, residents, and other healthcare professionals) and patients can refer to these guidelines to make informed decisions regarding the management of functional constipation.

Fecal microbiota transplantation (FMT) is a highly efficacious and safe modality for the treatment of recurrent or refractory Clostridioides difficile infection (CDI), with overall success rates of 90%. Thus, FMT has been widely used for 10 years. The incidence and clinical characteristics of CDI, the main indication for FMT, differ between countries. To date, several guidelines have been published. However, most of them were published in Western countries and therefore cannot represent the Korean national healthcare systems. One of the barriers to performing FMT is a lack of national guidelines. Accordingly, multidisciplinary experts in this field have developed practical guidelines for FMT. The purpose of these guidelines is to aid physicians performing FMT, which can be adapted to treat CDI and other conditions.

Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

The equations on page 162 should be corrected.

The first-order conditional estimation (FOCE) method is more complex than the first-order (FO) approximation method because it estimates the empirical Bayes estimate (EBE) for each iteration. By contrast, it is a further approximation of the Laplacian (LAPL) method, which uses second-order expansion terms. FOCE without INTERACTION can only be used for an additive error model, while FOCE with INTERACTION (FOCEI) can be used for any error model. The formula for FOCE without INTERACTION can be derived directly from the extension of the FO method, while the FOCE with INTERACTION method is a slight simplification of the LAPL method. Detailed formulas and R scripts are presented here for the reproduction of objective function values by NONMEM.
Bays ; Methods ; Reproduction*

NONMEM(R) is the most-widely used nonlinear mixed effects modelling tool introduced into population PK/PD analysis. Even though thousands of pharmaceutical scientists utilize NONMEM(R) routinely for their data analysis, the various estimation methods implemented in NONMEM(R) remain a mystery for most users due to the complex statistical and mathematical derivations underlying the algorithm used in NONMEM(R). In this tutorial, we demonstrated how to directly obtain the objective function value and post hoc eta for the first order approximation method by the use of R. We hope that this tutorial helps pharmacometricians understand the underlying estimation process of nonlinear mixed effects modelling.
Hope ; Reproduction* ; Statistics as Topic

BACKGROUND: Antimicrobial surveillance is important for providing an up-to-date understanding of the epidemiology of antimicrobial resistance and for creating a forum for rational drug development. In this study, we analyzed antimicrobial test data generated in 2011 by hospitals and commercial laboratories participating in the Korean Nationwide Surveillance of Antimicrobial Resistance program (KONSAR). MATERIALS AND METHODS: Data on the results of susceptibility tests conducted in 32 hospitals and two commercial laboratories were analyzed. Data on isolates from patients admitted to an intensive care unit (ICU) and those admitted to other wards were compared. Intermediate susceptibility was not analyzed and duplicate isolates were excluded. RESULTS: Escherichia coli was the most prevalent organism identified in both the hospital and commercial laboratories. Among the hospital isolates, methicillin-resistant Staphylococcus aureus (MRSA), penicillin G-non-susceptible Streptococcus pneumoniae, and ampicillin-resistant Enterococcus faecium remained as prevalent as they were in 2009. The proportion of vancomycin-resistant E. faecium (VR-EFM) slightly decreased from 29% in 2009 to 23% in 2011. Resistance rates of Klebsiella pneumoniae to ceftazidime, cefoxitin, fluoroquinolone, and amikacin were 24%, 14%, 27%, and 8%, respectively. Resistance rates of Pseudomonas aeruginosa to fluoroquinolone, ceftazidime, imipenem, and amikacin were 33%, 20%, 22%, and 16%, respectively, whereas those of Acinetobacter spp. resistance were 71%, 66%, 64, and 51%, respectively. The prevalence of oxyimino-cephalosporin-resistant E. coli and K. pneumoniae, carbapenem-resistant Acinetobacter spp. and P. aeruginosa, MRSA, and VR-EFM among ICU isolates was higher than those among non-ICU isolates. Extended-spectrum beta-lactamase-producing E. coli and K. pneumoniae, imipenem-resistant P. aeruginosa, and VR-EFM were more prevalent among isolates from commercial laboratories than those from hospitals. Resistance rates of K. pneumoniae to ceftazidime and amikacin decreased from 32% and 24% in 2005 to 24% and 8% in 2011, respectively. The resistance rate of P. aeruginosa to amikacin decreased from 22% in 2005 to 16% in 2011. The proportion of imipenem-resistant Acinetobacter spp. increased from 16% in 2005 to 64% in 2011. CONCLUSIONS: The prevalence of MRSA, penicillin G-non-susceptible S. pneumoniae, and ampicillin-resistant E. faecium among clinical isolates tested in laboratories remained high. Multidrug resistance was more prevalent among isolates from ICUs. The prevalence of ceftazidime-resistant and amikacin-resistant K. pneumoniae and amikacin-resistant P. aeruginosa decreased after 2005, while the prevalence of imipenem-resistant Acinetobacter spp. increased.
Acinetobacter* ; Amikacin ; Cefoxitin ; Ceftazidime ; Drug Resistance, Multiple ; Enterococcus faecium ; Epidemiology ; Escherichia coli ; Humans ; Imipenem ; Intensive Care Units ; Klebsiella pneumoniae ; Korea ; Methicillin-Resistant Staphylococcus aureus ; Penicillins ; Pneumonia ; Prevalence* ; Pseudomonas aeruginosa ; Salmonella* ; Staphylococcus ; Streptococcus pneumoniae

PURPOSE: The purpose of this study is to investigate on the regenerative capacity by using different size of graft materials around bony defect around implant. MATERIAL AND METHODS: Dental implant fixtures(Bio-TIS, Korea) were placed into the tibia of 8 rabbits. After placement of implant, artificial defects were created for each group, and the size of bone graft materials were used according to each designated group. 4 weeks after surgery, 8 rabbits were sacrificed. The histologic and histomorphometrical study were done for comparison of the regenerative capacity using 80-90micrometer and 200~1000micrometer size of grafting materials of OCS-B(R). RESULT: Matured bone formation was significantly increased more in Group E1(80-90micrometer) than in Group E2(200~1000micrometer). Group E1(80-90micrometer) showed more significant augmentation in marginal length of graft material per unit area than Group E2(200~1000micrometer). Group E1(80-90micrometer) showed more interspace in graft material than Group E2(200~1000micrometer). Control group showed no new bone formation around and inside of implanted fixture. CONCLUSION: Small grafting material size has great influence on bone regeneration.
Bone Regeneration ; Dental Implants ; Osteogenesis ; Prostheses and Implants ; Rabbits ; Tibia ; Transplants