Kappeljohnston4264

The adaptive seamless design combining phases II and III into a single trial has been shown growing interest for improving the efficiency of drug development, becoming the most frequent adaptive design type. It typically consists of two stages, the trial objectives being often different in each stage. The primary objectives are to select optimal experimental treatment group(s) in the first stage and compare the efficacy between the selected treatment and control groups in the second stage. In this article, we focus on a two-stage adaptive seamless design, for which treatment selection is based on the short-term binary endpoint and treatment comparison is based on the long-term binary endpoint. We thus propose an exact conditional test as a final analysis, based on the bivariate binomial distribution and given the selected treatment with the most promising short-term endpoint response rate from an interim analysis. Additionally, the mid- p $$ p $$ approach is incorporated to improve conservativeness for an exact test. Simulation studies were conducted to compare the proposed methods with a method based on the combination test. The proposed exact method controlled for type I error rate at the nominal level, regardless of the number of initial treatments or the correlation between short- and long-term endpoints. In terms of the treatment comparison power, the proposed methods are more powerful than that based on the combination test in the scenarios, with only one treatment being effective.

To evaluate the effects of an at-home artificial intelligence (AI)-assisted dental monitoring application on treatment outcomes in patients with periodontitis.

Participants with periodontitis were recruited and randomly assigned to an AI (n=16), AI and human counselling (AIHC; n=17), or control (CG; n=20) group. All participants received non-surgical periodontal treatment. We employed an AI-assisted tool called DENTAL MONITORING® (DM) intervention, a new technological AI monitoring product that utilizes smartphone cameras for intra-oral scanning and assessment. Patients in the AI and AIHC groups received additional (a) DM or (b) DM, respectively, with real-person counselling over 3 months. Periodontal parameters were collected at baseline and follow-ups. A mixed-design model analysed the follow-up effects over time.

The AI and AIHC groups, respectively, exhibited greater improvement in probing pocket depth (PPD) (mean diff=-0.9 ± 0.4 and -1.4 ± 0.3, effect size [ES]=0.76 and 1.98), clinical attachment level (mean diff=-0.8 ± 0.3 and -1.4 ± 0.3, ES=0.84 and 1.77), and plaque index (mean diff=-0.5 ± 0.2 and - 0.7 ± 0.2, ES=0.93 and 1.81) at 3-month follow-up than the CG did. The AIHC group had a greater reduction in PPD (ES=0.46) and clinical attachment level (ES=0.64) at the 3-month follow-up compared with the AI group.

Using AI monitoring at home had a positive effect on treatment outcomes for patients with periodontitis. Patients who received AI-assisted health counselling exhibited better treatment outcomes than did patients who received AI monitoring alone.

Using AI monitoring at home had a positive effect on treatment outcomes for patients with periodontitis. Patients who received AI-assisted health counselling exhibited better treatment outcomes than did patients who received AI monitoring alone.

To investigate an optimal composite score for disease activity in adult juvenile idiopathic arthritis (JIA) from the viewpoint of the subsequent changes in physical function.

Patients with JIA under the following conditions were enrolled 1) disease onset < 18 years; 2) registered in the Institute of Rheumatology, Rheumatoid Arthritis database by Tokyo Women's Medical University for the first time between 2000 and 2020; and 3) ≥18 years old at the time of registration. The baseline of each patient was their initial entry into the database. The Simplified Disease Activity Index (SDAI), Disease Activity Score using 28 joints (DAS28), and Juvenile Arthritis Disease Activity Score (JADAS)-27 were compared. Patients were stratified according to mean disease activity scores in each index during the first year from baseline. Trends of estimated mean change in Japanese-HAQ score (ΔJ-HAQ) from baseline to 2 years later was examined across the stratified groups of each index.

We included 294 eligible individuals (median age at onset, 14.0 years; rheumatoid factor positive in 64.7%). A significant increasing trend of the estimated mean ΔJ-HAQ at 2 years after baseline was observed along with an increase in the mean disease activity during the first year measured using DAS28 (p = 0.01) and SDAI (p = 0.018), but not using JADAS-27.

Disease activity measured using SDAI and DAS28, but not using JADAS27, was significantly associated with subsequent changes in physical function in transitional and adult patients with JIA.

Disease activity measured using SDAI and DAS28, but not using JADAS27, was significantly associated with subsequent changes in physical function in transitional and adult patients with JIA.A working memory (WM) deficit is a reliable observation in people experiencing anxiety. Whether the level of anxiety is related to the severity of WM difficulties is still an open question. In the present experiment, we investigated this aspect by testing the WM performance of people with different levels of anxiety symptoms. Participants were grouped according to self-report anxiety into a control group with low anxiety scores and an experimental group with clinically relevant anxiety. The experimental group was then divided into a high anxiety group and a severe anxiety group. Participants performed a battery of WM tasks tagging different WM processes. AZD1480 The results showed that, compared to participants with low anxiety, participants with clinically relevant anxiety scores had reduced accuracy in all the WM tasks. Interestingly, participants with high and severe anxiety did not present any significant difference. Anxious participants showed difficulties also in cognitive domains other than WM. Hence, these results supply reliable evidence that people with clinically relevant anxiety scores present WM difficulties, irrespective of symptoms severity. The observation that anxiety compromises performance also in cognitive domains other than WM suggests that the deficit might affect fluid cognition.Breast cancer treatment with poly(ADP‑ribose)polymerase (PARP) inhibitors is currently limited to cells defective in the homologous recombination repair (HRR) pathway. The chemical inhibition of many HRR deficiency genes may sensitize cancer cells to PARP inhibitors. In the present study, Rad51, a central player in the HRR pathway, was selected to explore additional low variation and highly representative markers for PARP inhibitor activity. A CRISPR/Cas9‑based saturated mutation approach for the Rad51 WALKER domain was used to evaluate the sensitivity of the PARP inhibitor olaparib. Five amino acid mutation sites were identified in olaparib‑resistant cells. Two Rad51 haplotypes were assembled from the mutations, and may represent useful pharmacogenomic markers of PARP inhibitor sensitivity.

Autologous bone grafts consolidate faster than bone graft substitutes (BGSs) but resorb over time, which compromises implant support. We hypothesized that differences in consolidation rates affected the mechanical properties of grafts and implant stability, and tested whether a pro-osteogenic protein, liposomal WNT3A (L-WNT3A), could accelerate graft consolidation.

A transgenic mouse model of sinus augmentation with immunohistochemistry, enzymatic assays, and histology were used to quantitatively evaluate the osteogenic properties of autografts and BGSs. Composite and finite element modelling compared changes in the mechanical properties of grafts during healing until consolidation, and secondary implant stability following remodelling activities. BGSs were combined with L-WNT3A and tested for its osteogenic potential.

Compared with autografts, BGSs were bioinert and lacked osteoprogenitor cells. While in autografted sinuses, new bone arose evenly from all living autograft particles, new bone around BGSs solely initiated at the sinus floor, from the internal maxillary periosteum. WNT treatment of BGSs resulted in significantly higher expression levels of pro-osteogenic proteins (Osterix, Collagen I, alkaline phosphatase) and lower levels of bone-resorbing activity (tartrate-resistant acid phosphatase activity); together, these features culminated in faster new bone formation, comparable to that of an autograft.

WNT-treated BGSs supported faster consolidation, and because BGSs typically resist resorption, their use may be superior to autografts for sinus augmentation.

WNT-treated BGSs supported faster consolidation, and because BGSs typically resist resorption, their use may be superior to autografts for sinus augmentation.

Comparison of grading according to radiographic bone loss (BL) or according to interdental clinical attachment loss (CAL).

In 100 periodontitis patients at the Department of Periodontology of Goethe-University Frankfurt, Germany, periodontitis grade was assigned by (i) indirect evidence using BL at the most affected tooth divided by root length and (ii) CAL at the most affected tooth divided by root length of the respective tooth type according to root length in German and Swedish cohorts. The resulting quotients were divided by age.

Patients (age 53.5± 10.4 years; 57 females; 16 smokers; no diabetes; stage 78 III, 22 IV) were by either method assigned to grade B or C (BL 35 B, 65 C; CAL [German] 23 B, 77 C; [Swedish] 29 B, 71 C). Using root length (German cohort), agreement was 76% (kappa 0.427; fair to good/moderate agreement) and 72% (Swedish cohort; kappa 0.359; poor/fair agreement). Molars were most frequently chosen (BL 64%; CAL 71%).

Assignment of periodontitis grade by indirect evidence using BL or CAL using standard root length of the German cohort showed fair to good/moderate agreement. Thus, grade assignment by CAL may be used in epidemiologic studies where radiographs are not available.

Assignment of periodontitis grade by indirect evidence using BL or CAL using standard root length of the German cohort showed fair to good/moderate agreement. Thus, grade assignment by CAL may be used in epidemiologic studies where radiographs are not available.

This research aimed to review the theoretical and methodological aspects of the quality-adjusted life year (QALY) which give rise to potential for bias against certain patient populations, including those with problems with walking or an inability to walk (ambulatory disabilities), when health technology assessment decisions rely on QALY gain to show cost-effectiveness. Societal preferences for treating ambulatory versus non-ambulatory patients were also investigated.

We reviewed published literature to identify information on theoretical underpinnings of the QALY, measurement of utilities for QALY assessment, and empirical evidence of societal preferences for the treatment of ambulatory and non-ambulatory patients.

Health states which represent mobility impairment and the inability to walk receive low valuation from general public preferences. Non-ambulatory patients, for example those with advanced neuromuscular disease, have lower utilities determined by standardized preference-based measurement (PBM) tools.