Osimertinib in poor performance status patients with T790M-positive advanced non-small-cell lung cancer after progression of first- and second-generation EGFR-TKI treatments (NEJ032B)

Background

Osimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown.

Methods

Enrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2–4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety.

Results

Thirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3–5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations.

Conclusion

Osimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs.

     

Atopic dermatitis disease registry in Japanese adult patients with moderate to severe atopic dermatitis (ADDRESS‐J): Baseline characteristics,treatment history and disease burden

Moderate to severe atopic dermatitis (AD) has a high disease burden and a significant effect on quality of life. Observational studies are necessary to determine the patient disease burden and long‐term disease control in the Japanese population. ADDRESS‐J is a non‐interventional, observational registry of adult Japanese patients with moderate to severe AD. Herein, we report baseline data from the ADDRESS‐J study describing disease characteristics and current treatment practices. At baseline, 300 adult AD patients with Investigator's Global Assessment (IGA) scores (range, 0–4) of 3 (moderate) or 4 (severe) whose treatments for AD were intensified, were assessed for clinical and patient‐reported outcomes and current AD treatments. The registry patients’ median age was 34.0 years; 60.7% were male and 71.7% had had AD for more than 20 years. At baseline, 220 study patients had an IGA score of 3 and 80 had an IGA score of 4. The median Eczema Area and Severity Index score was 21.7 (range, 0–72), the median body surface area involvement was 46.25%, and the median pruritus numerical rating scale score was 7.0 (range, 0–10); for each of these measures, higher scores represent greater severity. Most registry patients (86.7%) had recently used topical corticosteroids or topical calcineurin inhibitors as treatment for AD. This registry cohort represents a population of Japanese patients with moderate to severe AD and provides an important resource for characterizing the disease burden and evaluating the safety and effectiveness of various AD treatments.     

Changes in knee extensor strengths before and after medial patellofemoral ligament reconstruction

Objective: Quadriceps dysfunction has been suggested as a complication after medial patellofemoral ligament (MPFL) reconstruction. The purpose of this study was to investigate changes in knee extensor strength before and after MPFL reconstruction.

Methods: Twenty patients who underwent MPFL reconstruction for unilateral recurrent patellar dislocation (18 females and 2 males; mean age 20.8 ± 7.6 years) were examined. The peak isometric torque at 60° and 90° of knee flexion and isokinetic knee extensor strength at speeds of 60°/s and 90°/s in operated and non-operated legs were measured using a dynamometer preoperatively and 6 months, 1 year, and 2 years postoperatively. The following parameters were evaluated: (1) body weight-adjusted muscle strength, (2) improvement index (post-/preoperative value × 100) (%), and (3) extensor strength ratio (operated/non-operated value × 100) (%).

Results: The mean knee extensor strength in both operated and non-operated legs significantly increased 2 years after surgery compared with that before surgery. At 2 years postoperatively, the improvement indexes of the isometric knee extensor strength at 60° and 90° and of the isokinetic knee extensor strength at 60°/s and 90°/s were 237%, 192%, 318%, and 186%, respectively, in the operated legs and 144%, 124%, 140%, and 140%, respectively, in the non-operated legs. At 2 years postoperatively, the mean isometric knee extensor strength ratios at 60° and 90° and the isokinetic knee extensor strength ratios at 60°/s and 180°/s were 81%, 84%, 81%, and 82%, respectively.

Conclusions: Knee extensor strength was improved in most patients after MPFL reconstruction, at least compared with that before surgery, although an approximately 20% deficit against the non-operated legs remained even 2 years after surgery.     

Screening for musculoskeletal problems in children using a questionnaire

Background

On April 1, 2016, the Ministerial ordinance was enforced, and musculoskeletal examination of the extremities was made mandatory. From 2008, the University of us started musculoskeletal direct examination. To expand the examination, from 2016, we started to use the marksheet-type questionnaire. This study aimed to report the results of a musculoskeletal examination and investigate the association between musculoskeletal examination and age/gender and reports the reliability of the collected questionnaire data.

Dental floss use among elementary school children and environmental factors; a cross-sectional study

BackgroundThe onset of carious lesions and periodontal disease originates in plaque formed from dental bacteria. Appropriate plaque control is therefore important. Dental floss is one instrument used to control plaque. The influence of guardians is an important factor in whether children use dental floss regularly. However, the use of dental floss among school-age children and the relationship between use and family background has yet to be examined.AimIn this study, we conducted a questionnaire survey to examine rates of dental floss use and other related factors among elementary school children and their guardians.MethodsSurveys were sent to 298 guardians of children in grades 1–6 at an elementary school in Japan and 283 valid responses were received. Statistical analyses were carried out, with child’s use of dental floss as a dependent variable and grade, sex, guardian assistance with child's tooth brushing, frequency of child’s dental check-ups, and guardian's use of dental floss as independent variables.ResultsThe results revealed that 18.4% of children used dental floss compared with 52.7% of guardians, suggesting that the rate of usage among children is much lower than that among guardians. Logistic regression analysis further revealed that guardian's use of dental floss was significantly related to dental floss use among children.ConclusionThe guardian's use of dental floss was associated with dental floss use among their children in this group of Japanese elementary school.