A randomized, double-blind, three-arm, parallel group, single-dose phase I study to evaluate the pharmacokinetic similarity between SB12 (a proposed eculizumab biosimilar) and eculizumab (Soliris) in healthy subjects.

OBJECTIVES: To compare the pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity between SB12 (a proposed eculizumab biosimilar) and the reference product (RP) eculizumab (i.e., European Union (EU)-sourced Soliris and United States (US)-sourced Soliris). MATERIALS AND METHODS: In this phase I study, healthy adult subjects were randomized to receive a 300-mg dose of SB12 or RP eculizumab via intravenous infusion. The PK endpoints were area under the serum concentration-time curve from time zero to infinity and to the last quantifiable concentration, and maximum serum concentration. Bioequivalence for the PK endpoints was determined if the 90% confidence intervals (CIs) for the ratio of geometric least squared means (Lsmeans) were within the pre-defined bioequivalence margins of 80.00 - 125.00%. PD, safety, and immunogenicity were also investigated. RESULTS: The 90% CIs of the geometric Lsmeans ratios of the PK endpoints were fully contained within the pre-defined bioequivalence margin. PD profiles and incidence of treatment-emergent adverse events across treatment groups were comparable. Incidence of anti-drug antibodies was also comparable between all groups, and a positive result for neutralizing antibodies was not detected. CONCLUSION: This study demonstrated PK bioequivalence and similar PD, safety, and immunogenicity profiles of SB12 to both reference eculizumab products.

Efficacy of ficin and peroxyacetic acid against Salmonella enterica serovar Thompson biofilm on plastic, eggshell, and chicken skin.

Salmonella is the leading cause of zoonotic foodborne illnesses worldwide and a prevalent threat to the poultry industry. For controlling contamination, the use of chemical sanitizers in combination with biological compounds (e.g., enzymes) offers a solution to reduce the chemical residues. The current study investigated the biofilm reduction effects of a food-grade enzyme-ficin-and a common sanitizer-peroxyacetic acid (PAA)-against an emerging pathogen, Salmonella enterica ser. Thompson, on plastic, eggshell, and chicken skin surfaces. Results showed that PAA could kill S. Thompson, but ficin cannot. Maximum biofilm reduction was 3.7 log CFU/cm2 from plastic after individual treatment with PAA. However, sequential treatment of ficin and PAA led to biofilm reductions of 3.2, 5.0, and 6.5 log CFU/cm2 from chicken skin, eggshell, and plastic, respectively. Fourier-transform infrared spectroscopy and microscopic analysis confirmed that ficin increased PAA action, causing biofilm matrix destruction. Moreover, the quality of the food surfaces was only altered by 12.5 U/mL ficin and was not altered by PAA. This combined use of enzyme and sanitizer solved major safety issues and proved promising against S. Thompson-associated contaminations in poultry and poultry processing lines.

Validation of the Korean Version of the Scales for Outcomes in Parkinson's Disease-Sleep.

BACKGROUND: Sleep problems commonly occur in patients with Parkinson's disease (PD), and are associated with a lower quality of life. The aim of the current study was to translate the English version of the Scales for Outcomes in Parkinson's Disease-Sleep (SCOPA-S) into the Korean version of SCOPA-S (K-SCOPA-S), and to evaluate its reliability and validity for use by Korean-speaking patients with PD. METHODS: In total, 136 patients with PD from 27 movement disorder centres of university-affiliated hospitals in Korea were enrolled in this study. They were assessed using SCOPA, Hoehn and Yahr Scale (HYS), Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Sleep Scale 2nd version (PDSS-2), Non-motor Symptoms Scale (NMSS), Montgomery Asberg Depression Scale (MADS), 39-item Parkinson's Disease Questionnaire (PDQ39), Neurogenic Orthostatic Hypotension Questionnaire (NOHQ), and Rapid Eye Movement Sleep Behaviour Disorder Questionnaire (RBDQ). The test-retest reliability was assessed over a time interval of 10-14 days. RESULTS: The internal consistency (Cronbach's α-coefficients) of K-SCOPA-S was 0.88 for nighttime sleep (NS) and 0.75 for daytime sleepiness (DS). Test-retest reliability was 0.88 and 0.85 for the NS and DS, respectively. There was a moderate correlation between the NS sub-score and PDSS-2 total score. The NS and DS sub-scores of K-SCOPA-S were correlated with motor scale such as HYS, and non-motor scales such as UPDRS I, UPDRS II, MADS, NMSS, PDQ39, and NOHQ while the DS sub-score was with RBDQ. CONCLUSION: The K-SCOPA-S exhibited good reliability and validity for the assessment of sleep problems in the Korean patients with PD.

Differential Progression of Midbrain Atrophy in Parkinsonism: Longitudinal MRI Study.

AIMS: To elucidate different patterns of progression of midbrain atrophy in patients with Richardson's syndrome (RS), progressive supranuclear palsy-parkinsonism (PSP-P), and Parkinson's disease (PD) using magnetic resonance imaging (MRI)-based visual rating indexes. METHODS: We recruited 12 patients with PSP-RS, 12 with PSP-P, and 23 with PD for whom MRIs had been followed up for at least 2 years (mean ± SD, 4.9 ± 1.6 years) after the initial MRI. MRI-based visual rating indexes were used to estimate midbrain atrophy, including the ratio of the pontine to midbrain tegmental areas (P/M ratio) on a midsagittal image, the length between the interpeduncular fossa and the center of the cerebral aqueduct at the midmammillary-body level (MTEGM) on axial images, and the morning glory sign. RESULTS: Initially, there were no differences in MRI-based visual rating indexes between PSP-P and PD, while PSP-RS showed a higher P/M ratio and lower MTEGM compared with PSP-P and PD. In PD, the P/M ratio and MTEGM remained stable with disease progression. However, the extent of changes between initial and follow-up indexes was similarly greater for both PSP-RS and PSP-P than for PD. Finally, PSP-P showed a higher P/M ratio and lower MTEGM compared with PD in the follow-up, while PSP-RS still exhibited the most profound changes. CONCLUSIONS: Midbrain atrophy progresses differentially in patients with PSP-RS, PSP-P, and PD. Longitudinal measurements of midbrain atrophy using MRI-based visual rating indexes can help distinguish patients with PSP-P from those with PSP-RS and PD.

Levodopa dose maintenance or reduction in patients with Parkinson's disease transitioning to levodopa/carbidopa/entacapone.

BACKGROUND: Levodopa bioavailability is enhanced by adding entacapone. However, the optimal dose of levodopa while transitioning to levodopa/carbidopa/entacapone (LCE) in Parkinson's disease (PD) during the wearing-off period is unclear. AIMS: The relative therapeutic efficacy and safety of different doses of levodopa were assessed when transitioning to the LCE combination for optimizing combined levodopa therapy. MATERIALS AND METHODS: A randomized, multicenter, double-arm, open-label study was conducted in Korea. The patients were randomly assigned to either a maintained levodopa dose (Group 1, n = 66) or a reduced levodopa dose by 15-25% (Group 2, n = 41). Treatment efficacy, safety, and tolerability were assessed during an 8-week treatment period. RESULTS: Eighty of the 107 (74.8%) participants completed the study (Group 1, n = 50; Group 2, n = 30). The patients' global impression of a change in scores indicated significant benefits of maintaining the levodopa dose (Group 1) compared to reducing the dose (Group 2). Although changes in the unified Parkinson's disease rating scale (UPDRS) scores, Hoehn and Yahr (H and Y) stages, and duration of ON, OFF and dyskinesia were not statistically different between the groups, an increased ON time and a reduced OFF time occurred in both the groups after LCE administration. Twenty-four participants (26.7%) experienced adverse events and 15 of them did not complete the study in the safety population (Group 1, n = 57; Group 2, n = 38). Significant drug-related withdrawal caused troublesome dyskinesia and aggravation of Parkinsonism in both Group 1 and Group 2, respectively. CONCLUSIONS: Direct transitioning to LCE, without levodopa dose reduction, is recommended in Asian patients with PD and wearing-off.

Accelerating Additive-Assisted Defect Passivation via the Structural Isomer Effect for Highly Efficient and Stable Perovskite Solar Cells.

Defects in hybrid perovskites have hindered the development of highly efficient and stable hybrid perovskite solar cells (PSCs). Therefore, researchers have used additives to passivate defects in hybrid perovskites; however, detailed studies on multifunctional group additives with structural isomers are limited. In this letter, we report the improved defect passivation ability of additives through the structural isomer effect and enhanced photovoltaic performance using this effect. l-Alanine methyl ester hydrochloride (l-AMECl) and its structural isomer, ß-AMECl, were used to understand the influence of structural variations in functional groups. The structural isomer ß-AMECl effectively reduced the trap density in the hybrid perovskite, thereby enhancing the photovoltaic parameters. Consequently, we achieved a power conversion efficiency of 24.25% with ß-AMECl, which is the best result among PSCs using additives. Additionally, the PSCs with ß-AMECl maintained an initial efficiency of 94% over 2500 h at 25 °C and 25% relative humidity, showing improved long-term stability.

Synthesis and Electrochemical Characterization of Nitrate-Doped Polypyrrole/Ag Nanowire Nanorods as Supercapacitors.

Polypyrrole (PPy)-capped silver nanowire (Ag NW) nanomaterials (core-shell rod-shaped Ag NW@PPy) were synthesized using a one-port suspension polymerization technique. The thickness of the PPy layer on the 50 nm thickness/15 µm length Ag NW was effectively controlled to 10, 40, 50, and 60 nm. Thin films cast from one-dimensional conductive Ag NW@PPy formed a three-dimensional (3D) conductive porous network structure and provided excellent electrochemical performance. The 3D Ag NW@PPy network can significantly reduce the internal resistance of the electrode and maintain structural stability. As a result, a high specific capacitance of 625 F/g at a scan rate of 1 mV/s was obtained from the 3D porous Ag NW@PPy composite film. The cycling performance over a long period exceeding 10,000 cycles was also evaluated. We expect that our core-shell-structured Ag NW@PPy composites and their 3D porous structure network films can be applied as electrochemical materials for the design and manufacturing of supercapacitors and other energy storage devices.

Evaluating the Validity and Reliability of the Korean Version of the Scales for Outcomes in Parkinson's Disease-Cognition.

OBJECTIVE: The Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog) was developed to assess cognition in patients with Parkinson's disease (PD). In this study, we aimed to evaluate the validity and reliability of the Korean version of the SCOPACog (K-SCOPA-Cog). METHODS: We enrolled 129 PD patients with movement disorders from 31 clinics in South Korea. The original version of the SCOPA-Cog was translated into Korean using the translation-retranslation method. The test-retest method with an intraclass correlation coefficient (ICC) and Cronbach's alpha coefficient were used to assess reliability. Spearman's rank correlation analysis with the Montreal Cognitive Assessment-Korean version (MOCA-K) and the Korean Mini-Mental State Examination (K-MMSE) were used to assess concurrent validity. RESULTS: The Cronbach's alpha coefficient was 0.797, and the ICC was 0.887. Spearman's rank correlation analysis revealed a significant correlation with the K-MMSE and MOCA-K scores (r = 0.546 and r = 0.683, respectively). CONCLUSION: Our. RESULTS: demonstrate that the K-SCOPA-Cog has good reliability and validity.

A phase III, randomised, double-blind, multi-national clinical trial comparing SB12 (proposed eculizumab biosimilar) and reference eculizumab in patients with paroxysmal nocturnal haemoglobinuria.

Treatment of paroxysmal nocturnal haemoglobinuria (PNH) includes the monoclonal antibody eculizumab. This randomised, double-blind, multi-national cross-over Phase III study in PNH patients aimed to demonstrate the equivalence of the proposed eculizumab biosimilar SB12 and reference eculizumab (Soliris, ECU). PNH patients with lactate dehydrogenase (LDH) ≥1·5× upper limit of normal were randomised into treatment sequences SB12-ECU or ECU-SB12. Four weekly infusions of 600 mg eculizumab were followed by fortnightly infusions of 900 mg until week 50 (ECU/SB12 cross-over at week 26). Primary endpoints were LDH at week 26 and the time-adjusted area under the effect curve (AUEC) of LDH over weeks 14‒26 and 40‒52. Among 46 patients (92%) who completed the study, the least squares mean (LSM) difference in LDH at week 26 (34·48; 95% confidence interval [CI] -47·66‒116·62 U/l) and geometric LSM ratio of time-adjusted AUEC of LDH (1·08; 90% CI 0·95‒1·23) were within pre-defined equivalence margins. Mean numbers of transfused red blood cell units, other secondary endpoints, pharmacokinetics, and pharmacodynamics were comparable. No patients developed anti-drug antibodies. Treatment-emergent adverse events were reported in 72% and 68% of patients in the SB12 and ECU treatment groups, respectively. The results demonstrate equivalence of SB12 to ECU and support SB12-use in PNH patients.

Lumbar Interbody Fusion and Osteobiologics for Lumbar Fusion.

Lumbar interbody fusion (LIF) is an excellent treatment option for a number of lumbar diseases. LIF can be performed through posterior, transforaminal, anterior, and lateral or oblique approaches. Each technique has its own pearls and pitfalls. Through LIF, segmental stabilization, neural decompression, and deformity correction can be achieved. Minimally invasive surgery has recently gained popularity and each LIF procedure can be performed using minimally invasive techniques to reduce surgery-related complications and improve early postoperative recovery. Despite advances in surgical technology, surgery-related complications after LIF, such as pseudoarthrosis, have not yet been overcome. Although autogenous iliac crest bone graft is the gold standard for spinal fusion, other bone substitutes are available to enhance fusion rate and reduce complications associated with bone harvest. This article reviews the surgical procedures and characteristics of each LIF and the osteobiologics utilized in LIF based on the available evidence.

Effects of interfacial layer on characteristics of TiN/ZrO2 structures.

To minimize the formation of unwanted interfacial layers, thin interfacial layer (ZrCN layer) was deposited between TiN bottom electrode and ZrO2 dielectric in TiN/ZrO2/TiN capacitor. Carbon and nitrogen were also involved in the layer because ZrCN layer was thermally deposited using TEMAZ without any reactant. Electrical characteristics of TiN/ZrO2/TiN capacitor were improved by insertion of ZrCN layer. The oxidation of TiN bottom electrode was largely inhibited at TiN/ZrCN/ZrO2 structure compared to TiN/ZrO2 structure. While the sheet resistance of TiN/ZrCN/ZrO2 structure was constantly sustained with increasing ZrO2 thickness, the large increase of sheet resistance was observed in TiN/ZrO2 structure after 6 nm ZrO2 deposition. When ZrO2 films were deposited on ZrCN layer, the deposition rate of ZrO2 also increased. It is believed that ZrCN layer acted both as a protection layer of TiN oxidation and a seed layer of ZrO2 growth.

Inhibitory effects of Flavourzyme on biofilm formation, quorum sensing, and virulence genes of foodborne pathogens Salmonella Typhimurium and Escherichia coli.

Salmonella enterica and Shiga toxin-producing (or verotoxin-producing) Escherichia coli are major foodborne pathogens, posing substantial food safety risks. Due to the negative effects of chemical treatment against foodborne pathogens, the application of enzyme-based techniques is currently receiving great attention. Here, we evaluated the inhibitory properties of Flavourzyme, a commercial peptidase, against these two foodborne pathogens. We noticed 4.0 and 5.5 log inhibition of biofilm formation by S. Typhimurium and E. coli, respectively, while treated with sub-minimum inhibitory concentrations of Flavourzyme for 24 h. For both bacteria, the enzyme exhibited quorum-quenching activity, preventing autoinducer-2 production completely by E. coli. In addition, Flavourzyme significantly suppressed the relative expression levels of biofilm-forming, quorum sensing, and virulence regulatory genes as measured by qRT-PCR. Based on our results, we suggest the use of Flavourzyme as a preventive agent against foodborne pathogens that possibly acts by inhibiting bacterial self-defense mechanisms following disruption of cellular proteins. This finding may shed light on how enzymes can be applied as a novel weapon to control foodborne illnesses to ensure food safety and public health.

Validation of the Korean version of the composite autonomic symptom scale 31 in patients with Parkinson's disease.

PURPOSE: The composite autonomic symptom scale-31 (COMPASS-31) is a self-rated questionnaire that evaluates diverse autonomic symptoms. In the present study, we developed the Korean version of the COMPASS-31 (K-COMPASS-31) with appropriate translation, and verified its reliability and internal and external validity in patients with Parkinson's disease (PD). METHODS: The original COMPASS-31 was translated independently into Korean by two bilingual neurologists. Test-retest reliability was evaluated at a 2-week interval. We investigated the correlations between the K-COMPASS-31, the scale for outcomes in PD-autonomic (SCOPA-AUT), and the results of an autonomic function test (AFT), respectively. RESULTS: A total of 90 patients with PD (47 females; mean age, 63.4 ± 10.8 years) were enrolled. The K-COMPASS-31 showed excellent test-retest reliability (intra-class correlation coefficient = 0.874, p < 0.001) and internal validity (Cronbach's α-coefficient = 0.878). The COMPASS-31 was positively correlated with SCOPA-AUT (r = 0.609, p < 0.001) and the results of the AFT. CONCLUSIONS: In conclusion, the K-COMPASS-31 showed excellent reliability and validity for the assessment of autonomic symptoms in PD patients. The K-COMPASS-31 is an easy-to-repeat and widely used tool for investigating autonomic dysfunction in various neurologic disorders and enables comparison of autonomic dysfunction among neurologic disorders. We recommend the K-COMPASS-31 as a valid instrument for use in clinical practice for patients with PD.

Isolated fractures of the greater trochanter with occult intertrochanteric extension.

INTRODUCTION: Isolated fractures of the greater trochanter (GT) are relatively rare. The diagnosis can be done on routine radiographs, but it is difficult to fully define the geographic extent of these injuries. This study examined the pattern and extent of an injury shown by magnetic resonance imaging (MRI) and radionuclide bone scan (RBS) in patients whose plain radiographs revealed fractures limited to the GT. MATERIALS AND METHODS: Between July 2004 and October 2008, 25 patients who displayed an isolated GT fracture on plain radiograph examination were examined by both MRI and RBS due to a suspicion of an extension into the intertrochanteric (ITC) region. The patients were then divided into two groups. Group A patients had an isolated fracture of GT, and group B patients had an occult fracture of ITC. RESULTS: All 25 cases were caused by a low-energy injury and plain radiographs showed non-displaced or minimally displaced isolated GT fractures. For 22 of the 25 patients, the result agreed with MRI and RBS. However, three patients had focal increased uptake at the GT region only according to RBS and an extension of signal intensity into the ITC region according to MRI. Group A and B comprised 5 and 20 patients, respectively. Of the group B patients, 8 had fractures with MRI evidence of complete extension across the ITC region and 12 had incomplete extension. Eleven of the 12 incomplete types showed an extension more than half way to the medial cortex. Fifteen group B patients underwent an internal fixation using a two-hole dynamic hip screw. CONCLUSION: Patients with an isolated fracture of GT can have a broader fracture extending into the ITC region than that diagnosed by standard radiographs. We recommend that all patients presenting with an isolated GT fracture on the plain radiographs should undergo MRI examination.

Comparison of the Pharmacokinetics, Safety, and Tolerability of the Autoinjector (AI) and Pre-Filled Syringe (PFS) of SB4 in Healthy Subjects.

PURPOSE: SB4 is an etanercept biosimilar, approved by the European Commission (EC) and the US Food and Drug Administration (FDA) following a demonstration of equivalent efficacy and safety and comparable quality data to the reference product. This study aimed to demonstrate equivalent pharmacokinetic (PK) profiles, safety, and tolerability between SB4 autoinjector (AI) and SB4 pre-filled syringe (PFS). PATIENTS AND METHODS: This was an open-label, two-period, two-sequence, single-dose, cross-over study to evaluate bioequivalence of PK profiles, safety, and tolerability between SB4 AI and PFS in healthy adults. Treatment periods were separated by 14 days resulting in a 35-day washout between investigational product (IP) administration in Periods 1 and 2. RESULTS: A total of 50 subjects were randomized: 24 subjects in Sequence I and 26 in Sequence II, and 6 subjects discontinued from the study. The primary PK endpoints including area under the concentration-time curve from time zero to infinity (AUCinf) and to the last quantifiable concentration (AUClast), and maximum serum concentration (Cmax) were all within the equivalence margin of 80.00-125.00%. Safety and tolerability were comparable between the two treatments. CONCLUSION: PK profiles showed that SB4 AI and PFS were bioequivalent in healthy subjects. Safety assessment was also comparable between the two treatments.

Validation of the Korean Version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale.

BACKGROUND AND PURPOSE: Impulse-control disorder is an important nonmotor symptom of Parkinson's disease (PD) that can lead to financial and social problems, and be related to a poor quality of life. A nationwide multicenter prospective study was performed with the aim of validating the Korean Version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (K-QUIP-RS). METHODS: The K-QUIP-RS was constructed using forward and backward translation, and pretesting of the prefinal version. PD patients on stable medical condition were recruited from 27 movement-disorder clinics. Participants were assessed using the K-QUIP-RS and evaluated for parkinsonian motor and nonmotor statuses and for PD-related quality of life using a predefined evaluation battery. The test-retest reliability of the K-QUIP-RS was assessed over an interval of 10-14 days, and correlations between the KQUIP-RS and other clinical scales were analyzed. RESULTS: This study enrolled 136 patients. The internal consistency of the K-QUIP-RS was indicated by a Cronbach's α coefficient of 0.846, as was the test-retest reliability by a Guttman split-half coefficient of 0.808. The total K-QUIP-RS score was positively correlated with the scores for depression and motivation items on the Unified PD Rating Scale (UPDRS), Montgomery-Asberg Depression Scale, and Rapid-Eye-Movement Sleep-Behavior-Disorders Questionnaire. The total K-QUIP-RS score was also correlated with the scores on part II of the UPDRS and the PD Quality of Life-39 questionnaire, and the dopaminergic medication dose. CONCLUSIONS: The K-QUIP-RS appears to be a reliable assessment tool for impulse-control and related behavioral disturbances in the Korean PD population.

Subtypes of Sleep Disturbance in Parkinson's Disease Based on the Cross-Culturally Validated Korean Version of Parkinson's Disease Sleep Scale-2.

BACKGROUND AND PURPOSE: This study aimed to determine the clinimetric properties of the Korean version of Parkinson's Disease Sleep Scale-2 (K-PDSS-2) and whether distinct subtypes of sleep disturbance can be empirically identified in patients with Parkinson's disease (PD) using the cross-culturally validated K-PDSS-2. METHODS: The internal consistency, test-retest reliability, scale precision, and convergent validity of K-PDSS-2 were assessed in a nationwide, multicenter study of 122 patients with PD. Latent class analysis (LCA) was used to derive subgroups of patients who experienced similar patterns of sleep-related problems and nocturnal disabilities. RESULTS: The total K-PDSS-2 score was 11.67±9.87 (mean±standard deviation) at baseline and 12.61±11.17 at the retest. Cronbach's α coefficients of the total K-PDSS-2 scores at baseline and follow-up were 0.851 and 0.880, respectively. The intraclass correlation coefficients over the 2-week study period ranged from 0.672 to 0.848. The total K-PDSS-2 score was strongly correlated with health-related quality of life measures and other corresponding nonmotor scales. LCA revealed three distinct subtypes of sleep disturbance in the study patients: "less-troubled sleepers," "PD-related nocturnal difficulties," and "disturbed sleepers." CONCLUSIONS: K-PDSS-2 showed good clinimetric attributes in accordance with previous studies that employed the original version of the PDSS-2, therefore confirming the cross-cultural usefulness of the scale. This study has further documented the first application of an LCA approach for identifying subtypes of sleep disturbance in patients with PD.

Simultaneous double dislocation of the interphalangeal joint in a finger.

Isolated traumatic dislocation of the distal and proximal interphalangeal joints of the fingers is a common occurrence. However, simultaneous dislocation of both interphalangeal joints in a single finger appears to be a rare event. We report five cases of simultaneous dislocation of both interphalangeal joints in a single finger with a review of the literature.

Three-year follow-up from a phase 3 study of SB3 (a trastuzumab biosimilar) versus reference trastuzumab in the neoadjuvant setting for human epidermal growth factor receptor 2-positive breast cancer.

BACKGROUND: We assessed long-term cardiac safety and efficacy in patients with human epidermal growth factor receptor 2-positive early breast cancer treated with a trastuzumab biosimilar (SB3) or its reference product, trastuzumab (TRZ), in a phase 3 study. METHODS: Patients who completed the phase 3 study could be enrolled in this extension study. The outcomes included the incidence of symptomatic congestive heart failure (CHF), asymptomatic significant left ventricular ejection fraction (LVEF) decrease, incidence of other cardiac events, event-free survival (EFS), and overall survival. In post hoc analysis, the Cox proportional hazards regression model was used to assess factors associated with EFS. RESULTS: A total of 367 patients were enrolled in the study (SB3, n = 186; TRZ, n = 181). The median follow-up duration from the main study enrolment was 40.8 and 40.5 months for SB3 and TRZ, respectively. During the two-year follow-up after adjuvant therapy, incidence of asymptomatic significant LVEF decrease was rare (SB3, n = 1; TRZ, n = 2), with all patients recovering with LVEF ≥ 50%, and no cases of symptomatic CHF or other cardiac events were reported. At 3 years, the EFS was 91.9% with SB3 and 85.2% with TRZ. The number of patients with events was 17 (9.1%) with SB3 and 31 (17.1%) with TRZ [hazard ratio: 0.47, 95% confidence interval: 0.26-0.87]. Antibody-dependent cell-mediated cytotoxicity (ADCC) activity and the breast pathologic complete response rate were the factors associated with EFS. CONCLUSION: Cardiotoxicity was rare in this extension study. EFS was higher with SB3 versus TRZ, with post hoc analysis suggesting that a downward drift in ADCC activity was a contributing factor. CLINICAL TRIAL REGISTRATION NUMBERS: NCT02771795 (EudraCT 2015-005663-17).

Validity and Reliability Study of the Korean Tinetti Mobility Test for Parkinson's Disease.

OBJECTIVE: Postural instability and gait disturbance are the cardinal symptoms associated with falling among patients with Parkinson's disease (PD). The Tinetti mobility test (TMT) is a well-established measurement tool used to predict falls among elderly people. However, the TMT has not been established or widely used among PD patients in Korea. The purpose of this study was to evaluate the reliability and validity of the Korean version of the TMT for PD patients. METHODS: Twenty-four patients diagnosed with PD were enrolled in this study. For the interrater reliability test, thirteen clinicians scored the TMT after watching a video clip. We also used the test-retest method to determine intrarater reliability. For concurrent validation, the unified Parkinson's disease rating scale, Hoehn and Yahr staging, Berg Balance Scale, Timed-Up and Go test, 10-m walk test, and gait analysis by three-dimensional motion capture were also used. We analyzed receiver operating characteristic curve to predict falling. RESULTS: The interrater reliability and intrarater reliability of the Korean Tinetti balance scale were 0.97 and 0.98, respectively. The interrater reliability and intra-rater reliability of the Korean Tinetti gait scale were 0.94 and 0.96, respectively. The Korean TMT scores were significantly correlated with the other clinical scales and three-dimensional motion capture. The cutoff values for predicting falling were 14 points (balance subscale) and 10 points (gait subscale). CONCLUSION: We found that the Korean version of the TMT showed excellent validity and reliability for gait and balance and had high sensitivity and specificity for predicting falls among patients with PD.