Sustainability and switching of biologics for psoriasis and psoriatic arthritis at Fukuoka University Psoriasis Registry

Biologics are efficacious for treating psoriasis vulgaris (PsV) and psoriatic arthritis (PsA), but sometimes must be terminated or changed for various reasons including ineffectiveness or adverse events. To find the optimal choice of biologics for treating psoriasis, we analyzed the real‐world data on drug survival and the reason for terminating or switching biologics. Medical records from patients with PsV or PsA, who visited the Department of Dermatology, Fukuoka University Hospital from 2010 to 2017, were analyzed. Two hundred and eleven patients received biologics, and 147 patients (69.7%) were treated with only one biologic, while 64 patients (30.3%) were switched to different products. Frequently used biologics in PsV were ustekinumab (UST), infliximab and adalimumab when calculated by patient‐year. Tumor necrosis factor inhibitor (TNFi) use decreased while UST and interleukin (IL)‐17 inhibitors increased in newly introduced patients. UST showed the highest survival rate as a first‐line drug, but the advantage was lost in the second reagent's group. The major reasons for terminating/switching biologics were as follows: primary ineffectiveness (26.4%), secondary loss of efficacy (36.5%), patient's preference, including referral to nearby hospital, or stopped visiting (22.6%), side‐effects (7.7%), comorbidities (3.4%) and economic burden (2.4%). In PsA patients, TNFi are more frequently employed than in PsV patients, although switching to UST or IL‐17 inhibitors showed an increasing trend. Biologic reagents were changed mostly because of primary or secondary loss of efficacy, which affected drug survival. Further research is needed to find the optimal choice of biologics with larger samples at multiple facilities.     

Attention and basic literacy and numeracy in children with Autism Spectrum Disorder: A one-year follow-up study

Little is known about the link between Executive Functioning (EF) and academic performance in children with Autism Spectrum Disorder (ASD) and how such links develop over time. This study examined word reading, basic mathematics, attention switching, sustained attention and their development. Two age, gender and perceptual IQ matched groups of cognitively able 7–12 year olds (ASD N = 40; typical developing [TYP] N = 40) were assessed at baseline and one year later, completing Word Reading and Numerical Operations tests and computerized tasks tapping attention switching and sustained attention. Children with ASD had similar word reading and numerical operations performance and similar development of these skills relative to TYP children. A delay in attention switching but similar development was found in children with ASD relative to TYP children. The EF tasks were correlated with reading and mathematics in ASD children only, however, in regression analyses these factors were not significant predictors of Time 2 reading and mathematics after accounting for Time 1 reading and mathematics scores. These findings indicate similar word reading and mathematics development but atypical attention profiles in cognitively able children with ASD. Implications for educators are discussed.     

Dolutegravir plus rilpivirine as dual regimen in virologically suppressed HIV-1 infected patients in a clinical setting

Objectives: There are scarce data on the combination of dolutegravir (DTG) plus rilpivirine (RPV) in the real world, including patients with hepatitis C virus (HCV) coinfection, toxicity or previous failure, or at risk for severe drug–drug interactions (DDIs).

Methods: Prospective cohort study of virologically suppressed HIV-1 infected patients, without resistance to DTG or RPV, switched to this dual regimen because of toxicity or risk of DDIs (NCT02491242).

Results: Overall, 102 patients (mean age 54 years, 28% women) were included. Fifty-seven were coinfected with HCV (fibrosis grade 4 in 27 cases, 1 liver transplantation). Seven patients had chronic kidney disease (1 renal transplantation). At week 48, only 1 virologic failure occurred (<1%), and 6 patients (6%) left the regimen (3 with central nervous system adverse events, 1 each due to pregnancy, metformin interaction, and lost to follow up). Thus, the overall treatment success rates were 93% (95% CI, 88%–98%; ITT-e, snapshot analysis) and 96% (95% CI, 92%–99%; per protocol analysis). The CD4/CD8 ratio increased slightly (median, +0.03). Triglycerides levels improved significantly (?18.8%, p?<?0.01). The creatinine-based estimated glomerular filtration rate decreased by a mean of ?8.4?ml/min/1.73 m², but tubular renal parameters improved. A paired dual X-ray absorptiometry scan showed a mild improvement in spine (mean, +1.15%; ?0.57 to +3.3%) and in femoral neck bone mineral density (mean, +0.4%; ?3.3% to +2.57%).

Conclusions: In the clinical setting, switching to the combination of DTG plus rilpivirine in virologically suppressed HIV-1 patients is effective and safe, and improves lipid, renal and bone evolution.

Trial registration: ClinicalTrials.gov identifier: NCT02491242.     

Effect of platform switching on peri-implant bone levels: a randomized clinical trial

Objective: The concept of platform switching has been introduced to implant dentistry based on observations of reduced peri‐implant bone loss. However, randomized clinical trials are still lacking. This study aimed to test the hypothesis that platform switching has a positive impact on crestal bone‐level changes. Material and methods: Two implants with diameters of 4 mm were inserted epicrestally into one side of the posterior mandibles of 25 subjects. After 3 months of submerged healing, the reentry surgery was performed. On the randomly placed test implant, an abutment 3.3 mm in diameter was mounted, resulting in a horizontal circular step of 0.35 mm (platform switching). The control implant was straight, with an abutment 4 mm in diameter. Single‐tooth crowns were cemented provisionally. All patients were monitored at short intervals over the course of 1 year. Standardized radiographs and microbiological samples from the implants' inner spaces were obtained at baseline (implant surgery), and after 3, 4, and 12 months. Results: After 1 year, the mean radiographic vertical bone loss at the test implants was 0.53±0.35 mm and at the control implants, it was 0.58±0.55 mm. The mean intraindividual difference was 0.05±0.56 mm, which is significantly <0.35 mm (P=0.0093, post hoc power 79.9%). The crestal bone‐level changes depended on time (P<0.001), but not on platform switching (P=0.4). The implants' internal spaces were contaminated by bacteria, with no significant differences in the total counts between the test and the control at any time point (P=0.98). Conclusions: The present randomized clinical trial could not confirm the hypothesis of a reduced peri‐implant bone loss at implants restored according to the concept of platform switching. To cite this article:
Enkling N, Jöhren P, Klimberg V, Bayer S, Mericske‐Stern R, Jepsen S. Effect of platform switching on peri‐implant bone levels: a randomized clinical trial.
Clin. Oral Impl. Res. 22 , 2011; 1185–1192.
doi: 10.1111/j.1600‐0501.2010.02090.x     

Optimizing the performance of the feedback controller for state-based switching bilinear systems

This article is concerned with the design and performance optimization of feedback controllers for state-based switching bilinear systems (SBLSs), where subsystems take the form of bilinear systems in different state space polyhedra. First, by further dividing the subregions into smaller regions and designing region-dependent feedback controllers in the resulting regions, the SBLSs can be transformed into corresponding switching linear systems (SLSs). Then, for these SLSs, by imposing contractility conditions on the Lyapunov functions, an upper bound on the infinite horizon quadratic cost can be obtained. Optimizing this upper bound yields the controller design. The optimization problem is formulated as a linear matrix inequalities optimization problem, which can be solved efficiently. Finally, the stability of the close-loop system under the proposed controller is established step by step through a decreasing overall Lyapunov function.