Improved responsiveness for JKOOS+ compared to KOOS in Japanese patients undergoing total knee arthroplasty.

BACKGROUND: Existing knee related patient reported outcome measurements (PROMs) have overwhelmingly been developed and validated in western chair-based societies, suggesting a potential for a western bias in PROMs evaluation of patients with knee conditions. We, therefore, endeavor to evaluate the responsiveness of the previously developed culturally relevant Japanese version of the knee injury and osteoarthritis outcome score (JKOOS+). METHODS: We enrolled 114 patients scheduled for total knee arthroplasty (TKA) across 8 knee clinics in Japan. Patients completed the Oxford Knee Score (OKS) and JKOOS + both at the time of enrollment and again 1-year post-TKA. Responsiveness was evaluated using effect size and standardized response mean (SRM). An effect size or SRM >0.8 is considered adequately responsive. We further tested the difference in responsiveness between the original Japanese language KOOS activities of daily living (ADL) domain and the novel Japanese ADL (JADL) domain using the modified Jacknife test. RESULTS: All domains were adequately responsive with the exception of the KOOS sports and recreation domain, which has previously been ignored by TKA researchers due to its lack of applicability to elderly patients undergoing TKA. The JADL domain outperformed the ADL domain in both effect size (1.51 v. 1.45) and SRM (1.67 v. 1.57) (p < 0.001). The novel Knee Flexion (KF) domain was adequately responsive, though less responsive than other domains except sports and recreation (p < 0.01 v. all other PROMs domains). CONCLUSIONS: The JKOOS+ JADL domain is significantly more responsive than the Europe-developed ADL domain to TKA in Japanese knee patients suffering from knee osteoarthritis (OA). The KF domain, unique to the JKOOS+ and intended to assess difficulty with knee flexion, is adequately responsive to TKA in Japanese patients suffering from OA.

Development and validation of a culturally relevant Japanese KOOS.

INTRODUCTION: The Knee Injury and Osteoarthritis Outcomes Survey (KOOS) has been translated into 50 languages worldwide. These translations have adhered to guidelines for cross cultural adaptation of health surveys. However, after release of the Japanese KOOS (JKOOS) we discovered the JKOOS was not fully culturally relevant to Japanese patients. Therefore, we undertook the development and validation of the JKOOS+. METHODS: We completed this project in 2 phases across 9 hospitals. In Phase 1, 187 surgically naïve patients with knee pain were asked about activities limited by their knee pain. An expert panel reconciled these activities against existing KOOS items to identify novel items. In Phase 2, 241 surgically naïve patients with knee pain were administered the Japanese Oxford Knee Survey, JKOOS, and these novel items. An iterative Rasch analysis was used to test item fit of these novel items within the KOOS Activities of Daily Living (ADL) domain and a potential new domain. Unidimensionality was assessed using principle component analysis. Internal consistency (Cronbach's alpha) and external validity (Spearman's Correlations) were assessed for Japanese ADL (J-ADL) and the novel domain. RESULTS: Phase 1 identified 4 activities relevant to Japanese knee patients: sitting seiza, using a Japanese toilet, climbing hills, and getting on/off a bus/train. In Phase 2, climbing hills and bus/train were well fit in JADL. Seiza and using a Japanese toilet were not well fit in J-ADL, yet both require deep knee flexion so a knee flexion (KF) domain was constructed by considering all KOOS items that require knee flexion using an iterative Rasch model. An 8 item KF domain emerged. Both J-ADL and KF were deemed to be unidimensional with high internal consistency (Cronbach's alpha >0.92) and external validity (Spearman Correlations 0.723-0.929). CONCLUSIONS: We have successfully developed and validated JKOOS+, a more culturally relevant knee survey for Japanese patients.

Differentiation of the DnaA-oriC subcomplex for DNA unwinding in a replication initiation complex.

In Escherichia coli, ATP-DnaA multimers formed on the replication origin oriC promote duplex unwinding, which leads to helicase loading. Based on a detailed functional analysis of the oriC sequence motifs, we previously proposed that the left half of oriC forms an ATP-DnaA subcomplex competent for oriC unwinding, whereas the right half of oriC forms a distinct ATP-DnaA subcomplex that facilitates helicase loading. However, the molecular basis for the functional difference between these ATP-DnaA subcomplexes remains unclear. By analyzing a series of novel DnaA mutants, we found that structurally distinct DnaA multimers form on each half of oriC. DnaA AAA+ domain residues Arg-227 and Leu-290 are specifically required for oriC unwinding. Notably, these residues are required for the ATP-DnaA-specific structure of DnaA multimers in complex with the left half of oriC but not for that with the right half. These results support the idea that the ATP-DnaA multimers formed on oriC are not uniform and that they can adopt different conformations. Based on a structural model, we propose that Arg-227 and Leu-290 play a crucial role in inter-ATP-DnaA interaction and are a prerequisite for the formation of unwinding-competent DnaA subcomplexes on the left half of oriC. These residues are not required for the interaction with DnaB, nucleotide binding, or regulatory DnaA-ATP hydrolysis, which further supports their important role in inter-DnaA interaction. The corresponding residues are evolutionarily conserved and are required for unwinding in the initial complexes of Thermotoga maritima, an ancient hyperthermophile. Therefore, our findings suggest a novel and common mechanism for ATP-DnaA-dependent activation of initial complexes.