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Purpose: There is a lack of real‐world data in Asian populations for brigatinib, a next‐generation anaplastic lymphoma kinase (ALK) inhibitor for patients with non‐small cell lung cancer (NSCLC). This study analysed real‐world outcomes and dosing patterns for brigatinib in patients with crizotinib‐refractory ALK+ NSCLC in South Korea. Methods: This retrospective, non‐interventional, cohort study used South Korean Health Insurance and Review Assessment claims data for adults with ALK+ NSCLC who initiated brigatinib between 19 April 2019 and 31 March 2021 after receiving prior crizotinib. Patients' characteristics, time to discontinuation (TTD), time to dose reduction, overall survival (OS) and treatment adherence were assessed. Results: The study included 174 patients (56.9% male; 27.0% with a history of brain metastases). Median duration of prior crizotinib was 17 (range 0.3–48) months. Median follow‐up after brigatinib initiation was 18 (range 0–34) months. Overall, 88.5% of patients received full‐dose brigatinib (180 mg/day) and 93.1% of patients were adherent (proportion of days covered ≥0.8). The median TTD was 24.9 months (95% CI 15.2–not reached). The probability of continuing treatment was 63.2% at 1 year and 51.5% at 2 years. The probability of continuing at full or peak dose was 79.7% at 1 year and 75.6% at 2 years. Median OS was not reached. The 2‐year OS rate was 68.7%. Conclusions: In this first nationwide retrospective study using national insurance claim data, brigatinib demonstrated real‐world clinical benefit as second‐line treatment after prior crizotinib in ALK+ NSCLC patients in South Korea. [ABSTRACT FROM AUTHOR]

In this paper, two observability measures are introduced for a discrete linear system. The degrees of observability of both the system and its subspaces can be examined with these measures. The measures are well conditioned to perturbation and applicable to multi-input/multi-output time-varying systems. The relations among observability, observability measures, error covariance, and the information matrix are presented. It is shown that the measures have direct connections with the singular value decomposition of the information matrix. In contrast to the error covariance, the measures are determined by the system model and independent of the initial error covariance. An example of the observability analysis of the Global Positioning System/Inertial Navigation System is given. The measures are confirmed to be less sensitive to the system model perturbation. It is also shown that the vertical component of the gyro bias can be considered unobservable with a tactical-grade inertial measurement unit for a horizontal constant-speed motion. Index Terms--Global Positioning System (GPS), inertial navigation, observability measure, singular value decomposition (SVD).

Lever-arm uncertainty can be an important error source in the integration of the Global Positioning System (GPS) and inertial navigation system (INS). This paper presents both numerical and experimental studies on the estimation of the lever arm in the integration of a very-low-grade inertial measurement unit (IMU) with an accurate single-antenna GPS measurement system. Covariance simulation results showed that maneuvers play an important role on the estimation of the lever arm and attitude. The length of the lever arm has a rather insignificant effect on the estimation of these. Experimental tests conducted with a low-cost microelectromechanical system (MEMS) IMU and a carrier-phase differential GPS (CDGPS) measurement system showed that the lever arm can be estimated with centimeter-level accuracy. The test results confirmed that angular motions and horizontal accelerations improve the estimates of the lever arm and yaw angle, respectively. Index Terms--Global positioning system (GPS), inertial measurement unit (IMU), inertial navigation, inertial navigation system (INS), lever arm, observability.

Observability properties of errors in an integrated navigation system are studied with a control-theoretic approach in this paper. A navigation system with a low-grade inertial measurement unit and an accurate single-antenna Global Positioning System (GPS) measurement system is considered for observability analysis. Uncertainties in attitude, gyro bias, and GPS antenna lever arm were shown to determine unobservable errors in the position, velocity, and accelerometer bias. It was proved that all the errors can be made observable by maneuvering. Acceleration changes improve the estimates of attitude and gyro bias. Changes in angular velocity enhance the lever arm estimate. However, both the motions of translation and constant angular velocity have no influence on the estimation of the lever arm. A covariance simulation with an extended Kalman filter was performed to confirm the observability analysis. Index Terms--Global Positioning System, GPS/INS, inertial measurement unit (IMU), inertial navigation, lever arm, observability.

Aims: We aimed to assess treatment persistence of tumor necrosis factor (TNF) inhibitors and non-TNF inhibitors in two groups of rheumatoid arthritis (RA) patients: biologic disease-modifying antirheumatic drug (bDMARD) initiators and switchers.Patients and methods: This retrospective cohort study utilized a national health insurance claims database. Patients aged ≥18 years initiating/switching bDMARD between 1 December 2013 and 31 December 2014, the index period, were followed for 12 months. Initiators who began treatment with a bDMARD during the index period were defined as having no bDMARD prescriptions for the previous year. Switchers who changed treatment from the previous bDMARD to the index bDMARD were defined as having different bDMARDs during the index period. Treatment persistence rates during the follow-up period were measured, and factors associated with non-persistence were assessed with the Cox proportional hazard model.Results: Of 2684 patients, treatment persistence rates were the highest for abatacept in initiators (69.3%) and tocilizumab in switchers (77.0%), while adalimumab showed the lowest persistence rates for both initiators and switchers (48.2%, 28.8%), followed by etanercept (51.3%, 41.0%). Adalimumab and etanercept were significantly more likely to show non-persistence (HR 1.58, 95% CI 1.27-1.96; HR 1.42, 95% CI 1.14-1.76) compared to infliximab for initiators, while tocilizumab was significantly more likely to show persistence (HR 0.411, 95% CI 0.206-0.819) in switchers.Conclusions: Non-TNF inhibitors showed higher persistence rates than TNF inhibitors in South Korean RA patients, and tocilizumab especially was associated with higher persistence in patients with inadequate response to TNF inhibitors. Good persistence with non-TNF inhibitors indicates the potential for long-term efficacy as first-line treatment. [ABSTRACT FROM AUTHOR]