Low Switching Rates Research Articles

Real-world treatment switching and sequencing to next line of therapy of zanubrutinib, acalabrutinib, and ibrutinib in CLL/SLL.

e19022 Background: Evaluating use of Bruton tyrosine kinase inhibitors (BTKis) for the treatment of CLL/SLL is crucial to understand real-world outcomes of these therapies in diverse populations. The objective of this study was to evaluate real-world switching and sequencing to next line of therapy in patients (pts) initiating BTKis as first-line (1L) or second-line (2L) CLL/SLL treatment. Methods: A retrospective study was conducted using IntegraConnect PrecisionQ to identify adult pts with ≥1 diagnosis for CLL/SLL initiating zanubrutinib (zanu), acalabrutinib (acala), or ibrutinib (ibru) in 1L or 2L between 1/1/2020-2/28/2023 (index period). Index date was defined as date of BTKi initiation. Pts were required to be continuously enrolled for ≥30 days pre- and post-index date. Treatment switching was measured as pts initiating another treatment within same line or advancing to next line of therapy within 90 days. Sequencing to next line of therapy was calculated from time to next treatment Kaplan-Meier curve, censoring patients at end of follow-up, and reported as proportion of pts receiving next line of therapy at 180 days. Results: 2,816 pts initiated a 1L BTKi (zanu=157; acala=1,238; ibru=1,421) and 1,253 initiated a 2L BTKi (zanu=107; acala=672; ibru=474). No major differences were observed in baseline demographic and clinical characteristics among 1L and 2L BTKi cohorts. Median follow-up in 1L was 123 days for zanu, 406 days for acala, and 637 days for ibru. Regardless of line of therapy, switching rate at ≤60 days and 61-89 days was statistically significantly lower for pts receiving zanu vs acala and ibru (P<0.0001, both 1L and 2L) (Table). Proportion of pts receiving next line of therapy at 180 days was lower for zanu vs acala and ibru (1L P=0.2958; 2L P<0.0001) (Table). Conclusions: Zanu pts had significantly lower switching rate within 90 days and lower proportion of pts receiving next line of therapy at 180 days when compared with acala and ibru in 1L and 2L. Longer follow-up and larger zanu sample size are required for a comprehensive assessment of treatment outcomes associated with use of BTKis in CLL/SLL. [Table: see text]

Three-Year Outcomes of VEGF Inhibitors in Naive Branch Retinal Vein Occlusion: Fight Retinal Blindness!

To evaluate the 3-year outcomes of VEGF inhibitors in the treatment of cystoid macular edema due to branch retinal vein occlusion (BRVO) in an international multicenter cohort of eyes. Multicenter, international, BRVO database study. Seven hundred forty-seven patients (760 eyes) undergoing intravitreal therapy for BRVO for 3 years in a multicenter international setting. Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, central subfield thickness (CST), treatments, number of injections, and visits data was collected using a validated web-based tool. Visual acuity gain at 3 years in logarithm of the minimum angle of resolution letters. Secondary outcome measures included anatomical results, treatment pattern, and percentage of completers. A subgroup analysis by study drug was conducted for clinical outcomes. Mean adjusted VA change was+11 letters (95% confidence interval 9-13), mean adjusted change in CST was-176 μm (-193,-159). Median number of injections/visits was 16 of 24 at 3 years of follow-up. Most eyes received VEGF inhibitors exclusively (89%, n= 677) and as a monotherapy in 71% (n= 538). Few eyes were switched to steroids (11%, n= 83). Suspensions in treatment >180 days occurred in 26% of study eyes. Aflibercept showed greater CST reductions (-147 vs.-128 vs.-114 μm; P < 0.001) and significantly lower switching rates (14% vs. 38% vs. 33%; P < 0.001) compared with ranibizumab and bevacizumab, respectively. This international study of 3-year BRVO outcomes after starting treatment with VEGF inhibitors found adequate visual and anatomical results in routine clinical care. Visual outcomes were similar among the different initiating VEGF inhibitors, although eyes starting with aflibercept had better anatomical outcomes and a lower switching rate. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Functional hierarchies in brain dynamics characterized by signal reversibility in ferret cortex.

Brain signal irreversibility has been shown to be a promising approach to study neural dynamics. Nevertheless, the relation with cortical hierarchy and the influence of different electrophysiological features is not completely understood. In this study, we recorded local field potentials (LFPs) during spontaneous behavior, including awake and sleep periods, using custom micro-electrocorticographic (μECoG) arrays implanted in ferrets. In contrast to humans, ferrets remain less time in each state across the sleep-wake cycle. We deployed a diverse set of metrics in order to measure the levels of complexity of the different behavioral states. In particular, brain irreversibility, which is a signature of non-equilibrium dynamics, captured by the arrow of time of the signal, revealed the hierarchical organization of the ferret's cortex. We found different signatures of irreversibility and functional hierarchy of large-scale dynamics in three different brain states (active awake, quiet awake, and deep sleep), showing a lower level of irreversibility in the deep sleep stage, compared to the other. Irreversibility also allowed us to disentangle the influence of different cortical areas and frequency bands in this process, showing a predominance of the parietal cortex and the theta band. Furthermore, when inspecting the embedded dynamic through a Hidden Markov Model, the deep sleep stage was revealed to have a lower switching rate and lower entropy production. These results suggest functional hierarchies in organization that can be revealed through thermodynamic features and information theory metrics.

Real-World Switching Pattern, Persistence, and Associated Healthcare Resource Utilization of Bruton Tyrosine Kinase Inhibitors for the Treatment of Mantle Cell Lymphoma in the United States

Introduction: Mantle cell lymphoma (MCL) is an aggressive form of B-cell non-Hodgkin's lymphoma. While incurable, MCL can be controlled for a prolonged period of time, but typically becomes refractory or relapsed and requires additional treatment. Bruton tyrosine kinase inhibitors (BTKi) are approved for relapse/refractory MCL and recommended by the National Comprehensive Cancer Network (NCCN ®); However, it is unclear how BTKi are being utilized and switched in the real-world patient populations. This study aimed to examine treatment patterns, persistence, and associated healthcare resource utilization of BTKi use in patients with MCL in the US. Methods: A retrospective observational study was conducted using Symphony Integrated Dataverse (IDV ®), a comprehensive, longitudinal, open-claims database and integrated Electronic Medical Record (EMR) data. Patients aged ≥18 years with ≥1 diagnosis for MCL and initiated a BTKi between 1/1/20 and 12/31/22 were included in the study. Patients were required to be continuously enrolled for 365 days leading up to the index date and ≥90 days following the index date (date of BTKi initiation). The full patient history in the database was used to identify previous BTKi use and analyze switching patterns for each patient. Three mutually exclusive cohorts (ibrutinib, acalabrutinib, zanubrutinib) were developed based on first-initiated BTKi. Patients were followed until the end of the study period (3/31/23) or lost to follow-up. Treatment switching pattern, duration, persistence, time to discontinuation (TTD), and healthcare resource utilization (HCRU) were examined by each BTKi cohort. Treatment duration was defined as time from BTKi initiation to the end date of last BTKi prescription. TTD was defined as time from BTKi initiation to the end date of the BTKi prescription that had a gap of &amp;gt;60 days with a subsequent BTKi prescription. Treatment persistence was evaluated as the proportion of patients that were continually prescribed BTKi (≥80% proportion of days covered) across 30-day intervals. HCRU was measured by number of outpatient visits and inpatient services, per patient per month (PPPM), during the treatment regimen. Results: BTKi switching patterns were analyzed for the 1,674 patients that initiated any BTKi therapy during study period (acalabrutinib [n= 697]; ibrutinib [n=693]; zanubrutinib [n=284]). Switching rates were 23.8% for ibrutinib, 5.6% for acalabrutinib, and 2.8% for the zanubrutinib cohort. In the ibrutinib cohort, the majority of patients switched to acalabrutinib (72.7%). Of those who switched from acalabrutinib, more than half (59.9%) switched to zanubrutinib. Of those who switched in zanubrutinib cohort, they were equally switched to ibrutinib and acalabrutinib (Table 1). Mean outpatient visits PPPM were 1.39 for patients who initiated with ibrutinib then switched to zanubrutinib, and 1.49 for those who switched to acalabrutinib. Mean inpatient services PPPM were 0.39 for patients who switched from ibrutinib to zanubrutinib, and 0.59 for those who switched to acalabrutinib. The 3 BTKi cohorts were similar across sociodemographic characteristics. The zanubrutinib cohort had higher median TTD (days) (188.5) compared to ibrutinib (161.5) and acalabrutinib (179), as well as higher median treatment duration (200) compared to ibrutinib (171) and acalabrutinib (194). Among MCL patients continuously enrolled for ≥ 360 days, zanubrutinib patients consistently had higher persistence rates (p=0.0079. Figure 1). Persistence at 90-days was 66.9% for zanubrutinib compared to 56.3% for ibrutinib and 62.7% for acalabrutinib. After 360 days, zanubrutinib continued to have the highest persistence (16.9%) compared to ibrutinib (10.8%) or acalabrutinib (13.2%). Zanubrutinib had the least number of mean inpatient services PPPM (0.56) compared to ibrutinib (0.83) and acalabrutinib (0.71) and mean outpatient visits-zanubrutinib (1.53), ibrutinib (1.81), acalabrutinib (1.59). Conclusions: This real-world study suggested that US patients with MCL receiving zanubrutinib showed longer treatment persistence, treatment duration and TTD, as well as lower switching rates and HCRU compared to those receiving acalabrutinib and ibrutinib.

Ultra-low power resistive random-access memory based on VO2/TiO2 nanotubes composite film

In this study, a resistive random access memory (RRAM) based on VO2/TiO2 nanotubes was prepared. Compared with single VO2-based RRAM or TiO2 nanotube-based RRAM, the Ag/VO2/TiO2 nanotube/FTO RRAM device has advantages such as low power consumption (∼0.154 pJ), excellent stability (3000 DC cycles), and high switching rate (300 times). It still shows certain advantages compared with TiO2-based low-power RRAM (0.5 pJ). The device can also exhibit 20 consecutive long-term enhancement/suppression behaviors, which can be used to simulate brain-like activity and achieve recognition accuracy of 95% (8 × 8 pixels) and 88% (28 × 28 pixels) in artificial neural network identification field.

Decoding the Atomic Structure of Ga2Te5 Pulsed Laser Deposition Films for Memory Applications Using Diffraction and First-Principles Simulations.

Neuromorphic computing, reconfigurable optical metamaterials that are operational over a wide spectral range, holographic and nonvolatile displays of extremely high resolution, integrated smart photonics, and many other applications need next-generation phase-change materials (PCMs) with better energy efficiency and wider temperature and spectral ranges to increase reliability compared to current flagship PCMs, such as Ge2Sb2Te5 or doped Sb2Te. Gallium tellurides are favorable compounds to achieve the necessary requirements because of their higher melting and crystallization temperatures, combined with low switching power and fast switching rate. Ga2Te3 and non-stoichiometric alloys appear to be atypical PCMs; they are characterized by regular tetrahedral structures and the absence of metavalent bonding. The sp3 gallium hybridization in cubic and amorphous Ga2Te3 is also different from conventional p-bonding in flagship PCMs, raising questions about its phase-change mechanism. Furthermore, gallium tellurides exhibit a number of unexpected and highly unusual phenomena, such as nanotectonic compression and viscosity anomalies just above their melting points. Using high-energy X-ray diffraction, supported by first-principles simulations, we will elucidate the atomic structure of amorphous Ga2Te5 PLD films, compare it with the crystal structure of tetragonal gallium pentatelluride, and investigate the electrical, optical, and thermal properties of these two materials to assess their potential for memory applications, among others.

Untangling the role of temporal and spatial variations in persistence of populations

We consider a population distributed between two habitats, in each of which it experiences a growth rate that switches periodically between two values, 1−ɛ>0 or −(1+ɛ)<0. We study the specific case where the growth rate is positive in one habitat and negative in the other one for the first half of the period, and conversely for the second half of the period, that we refer as the (±1) model. In the absence of migration, the population goes to 0 exponentially fast in each environment. In this paper, we show that, when the period is sufficiently large, a small dispersal between the two patches is able to produce a very high positive exponential growth rate for the whole population, a phenomena called inflation. We prove in particular that the threshold of the dispersal rate at which the inflation appears is exponentially small with the period. We show that inflation is robust to random perturbation, by considering a model where the values of the growth rate in each patch are switched at random times: we prove that inflation occurs for low switching rate and small dispersal. We also consider another stochastic model, where after each period of time T, the values of the growth rates in each patch is chosen randomly, independently from the other patch and from the past. Finally, we provide some extensions to more complicated models, especially epidemiological and density dependent models.

Treatment patterns and healthcare costs among patients with psoriasis initiating apremilast or biologics: a retrospective claims database cohort analysis

ObjectiveThis study aimed to compare treatment patterns and healthcare costs for patients with psoriasis who initiate apremilast, tumor necrosis factor inhibitor, or interleukin inhibitor.MethodsThis retrospective cohort study used Optum Clinformatics® Data Mart to identify propensity score–matched patients initiating apremilast, tumor necrosis factor inhibitors, or interleukin inhibitors, with 12-month baseline and 24-month follow-up data. Switch, discontinuation, persistence, healthcare resource utilization, and total healthcare costs were assessed.ResultsTwenty-four-month switch rates were highest for tumor necrosis factor inhibitors (32%), followed by apremilast (21%) then interleukin inhibitors (14%). Mean (SD) per-patient-per-month costs for switchers were lowest for apremilast ($4213 [$2304]), higher for tumor necrosis factor inhibitors ($5274 [$2280]), and highest for interleukin inhibitors ($5539 [$2296]; p < .001), primarily attributable to pharmacy costs: $3466 (apremilast), $4432 (tumor necrosis factor inhibitor), and $4721 (interleukin inhibitor).LimitationsPsoriasis severity is absent from claims data; cost outcomes may be influenced by more severe psoriasis being more costly.ConclusionSwitching psoriasis treatment is common and increases over time. Apremilast initiators had lower switch rates and costs compared with tumor necrosis factor inhibitors, despite lower effectiveness reported in previous studies, perhaps indicating patient preference for oral treatment. Additional oral options may be desirable for this population.

Engineering superconducting qubits to reduce quasiparticles and charge noise

Identifying, quantifying, and suppressing decoherence mechanisms in qubits are important steps towards the goal of engineering a quantum computer or simulator. Superconducting circuits offer flexibility in qubit design; however, their performance is adversely affected by quasiparticles (broken Cooper pairs). Developing a quasiparticle mitigation strategy compatible with scalable, high-coherence devices is therefore highly desirable. Here we experimentally demonstrate how to control quasiparticle generation by downsizing the qubit, capping it with a metallic cover, and equipping it with suitable quasiparticle traps. Using a flip-chip design, we shape the electromagnetic environment of the qubit above the superconducting gap, inhibiting quasiparticle poisoning. Our findings support the hypothesis that quasiparticle generation is dominated by the breaking of Cooper pairs at the junction, as a result of photon absorption by the antenna-like qubit structure. We achieve record low charge-parity switching rate (<1 Hz). Our aluminium devices also display improved stability with respect to discrete charging events.

33172 Real-world treatment patterns of adults with psoriasis initiated on apremilast or biologics

Background: Patients with psoriasis (PsO) commonly switch treatments due to adverse events and declining efficacy. This study used real-world data to assess treatment switching, discontinuation, and persistence in biologic- and apremilast-naive patients with PsO. Methods: Optum Clinformatics Data Mart claims were used to identify adults with PsO who newly initiated (index) treatment with apremilast, tumor necrosis factor inhibitors (TNFi; infliximab, adalimumab, etanercept, certolizumab pegol), or interleukin inhibitors (ILi; ustekinumab, guselkumab, tildrakizumab, risankizumab, brodalumab, secukinumab, ixekizumab) between 7/1/2014 and 12/31/2019, and had continuous enrollment for ≥1 year pre-index and ≥2 years post-index. Patients were propensity score matched 1:1:1 to adjust for possible selection bias. Rates of treatment switch, discontinuation, and persistence were measured over 24 months (24 m) of follow-up. Results: 2535 patients were included (845 per cohort). At 24 m, switch rates were highest for TNFi (32%), followed by apremilast (21%) and ILi (14%), with the majority of patients switching to treatment with a different mechanism of action. Overall discontinuation rates at 24m were 59%, 42%, and 58% for apremilast, TNFi, and ILi, respectively. More patients reinitiated ILi after discontinuing (65%) than either apremilast (40%) or TNFi (37%). At 24m, 21%, 25%, and 28% of patients on apremilast, TNFi, and ILi, respectively, persisted with same index treatment. Conclusion: This retrospective study showed that switching PsO treatment is common and increases over time. Oral treatments had lower switch rates compared with TNFi despite lower effectiveness in biologic-naive patients. Discontinuation was higher and persistency was lower for apremilast than for more effective biologic treatments.

Viral load monitoring for people living with HIV in the era of test and treat: progress made and challenges ahead – a systematic review

BackgroundIn 2016, we conducted a systematic review to assess the feasibility of treatment monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in low and middle-income countries (LMICs), in line with the 90-90-90 treatment target. By 2020, global estimates suggest the 90-90-90 target, particularly the last 90, remains unattainable in many LMICs. This study aims to review the progress and identify needs for public health interventions to improve viral load monitoring and viral suppression for PLHIV in LMICs.MethodsA literature search was conducted using an update of the initial search strategy developed for the 2016 review. Electronic databases (Medline and PubMed) were searched to identify relevant literature published in English between Dec 2015 and August 2021. The primary outcome was initial viral load (VL) monitoring (the proportion of PLHIV on ART and eligible for VL monitoring who received a VL test). Secondary outcomes included follow-up VL monitoring (the proportion of PLHIV who received a follow-up VL after an initial elevated VL test), confirmation of treatment failure (the proportion of PLHIV who had two consecutive elevated VL results) and switching treatment regimen rates (the proportion of PLHIV who switched treatment regimen after confirmation of treatment failure).ResultsThe search strategy identified 1984 non-duplicate records, of which 34 studies were included in the review. Marked variations in initial VL monitoring coverage were reported across study settings/countries (range: 12–93% median: 74% IQR: 46–82%) and study populations (adults (range: 25–96%, median: 67% IQR: 50–84%), children, adolescents/young people (range: 2–94%, median: 72% IQR: 47–85%), and pregnant women (range: 32–82%, median: 57% IQR: 43–71%)). Community-based models reported higher VL monitoring (median: 85%, IQR: 82-88%) compared to decentralised care at primary health facility (median: 64%, IRQ: 48-82%). Suboptimal uptake of follow-up VL monitoring and low regimen switching rates were observed.ConclusionsSubstantial gaps in VL coverage across study settings and study populations were evident, with limited data availability outside of sub-Saharan Africa. Further research is needed to fill the data gaps. Development and implementation of innovative, community-based interventions are required to improve VL monitoring and address the “failure cascade” in PLHIV on ART who fail to achieve viral suppression.

Substrate Dependent Study of Mim Capacitors for Resistive Random-Access Memory Applications

The present study focusses on the fabrication of Metal/MOx/Metal for ReRAM application. We evaluated I-V characteristics using pressure contact with both substrates and found that the silicon substrate has a relatively low switching rate (nearly linear curve), whereas the ITO substrate has a resistance ratio of 10, which gives the optimum switching performance. The identical model was developed in COMSOL software and used for validation, and the metal rich characteristics enhancement is studied. The stoichiometry of metal oxide film has been measured by Resonant Rutherford back Scattering (RRBS) of ZnO coated Au deposited Silicon. X-ray diffraction (XRD) analysis was used to characterize the crystalline structures of Au-deposited ZnO on ITO samples. It was observed that the desired (002)-oriented ZnO wurtzite phase exists. Raman parameters like force constant and bond length is calculated corresponding to the wave number.

Clinical efficacy and tolerability of 1.5 g/day oral amoxicillin therapy without probenecid for the treatment of syphilis

ObjectivesIntramuscular benzathine penicillin G is not available in certain countries. In a previous report, 3 g/day amoxicillin with probenecid was shown to be effective in treating syphilis in patients with...

Health Care Cost Analysis of PPI or P-CAB-First Treatment in Patients With Gastroesophageal Reflux Disease.

The aim was to examine actual health care cost in patients with gastroesophageal reflux disease (GERD) who were initiated on proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) as first-line therapy in Japanese real-world clinical settings. To date, cost-utility evaluation of acid-suppressants treatment in Japan has only been conducted by model analysis. A cost utilization analysis was performed using a Japanese nationwide hospital-based claim database by extracting patients with GERD initiated on either PPI or P-CAB (242,102 pairs) and esomeprazole (EPZ) or P-CAB (241,825 pairs). Health care costs were compared in each comparison cohort with propensity-score matched pairs. The switching rates of initial acid-suppressants were also examined. Baseline characteristics were well-balanced after matching. The 3-year mean cumulative GERD-related and hospitalization costs per patient were ¥142,620 and ¥122,444 in PPI-first and P-CAB-first treatment groups, and ¥105,263 and ¥121,958 in EPZ-first and P-CAB-first treatment groups, respectively. Most hospitalization costs were non-GERD related in all the groups. The switching rates of PPI to P-CAB and P-CAB to PPI in 12 months were 7.5% and 20.2%, respectively. In this propensity-score matched analysis, health care cost was higher in patients with GERD initiated on PPI than in those initiated on P-CAB mainly owing to non-GERD-related hospitalization cost, whereas it was lower in those initiated on EPZ than in those initiated on P-CAB. When considering health care costs except hospitalization costs, PPI-first treatment was less expensive than P-CAB-first treatment. Low switching rate from PPI to P-CAB in the real-world practice may partially explain the discrepancy.

Who pays the loyalty tax? The relationship between socioeconomic status and switching in Australia's retail electricity markets

The liberalisation of retail electricity markets aimed to benefit consumers through innovation and lower electricity prices. However, well-functioning retail markets require active consumers who are motivated to switch between offers for financial savings or better tailored products. Policymakers did not adequately consider the behavioural biases, market complexities and switching costs that have led to customer disengagement. This can have significant welfare implications, particularly if many of the disengaged customers are also vulnerable. In this article, we investigate the relationship between socioeconomic status and customer engagement using household survey data covering the three largest cities in Australia. We find that lower socioeconomic status is associated with lower engagement. Unemployment, lower educational attainment, and lower income are all associated with lower switching rates. Solving this issue is complex and requires a suite of solutions however it is critical that vulnerable, disengaged customers are brought along because the costs of disengagement are likely to increase with digitalisation and the renewable energy transition.

Switching of oral anticoagulants in atrial fibrillation: a cohort study using Australian general practice data

ABSTRACT Background We assessed switching patterns of oral anticoagulants (OACs) in patients with atrial fibrillation (AF) in the period following widespread availability of the direct-acting oral anticoagulants (DOACs). Research design and methods A retrospective cohort study was conducted using NPS MedicineWise’s MedicineInsight dataset, collected from Australian general practices. Patients with AF who newly commenced an OAC between 1 January 2013 and 30 September 2017 were included. The switching rate was calculated within 12 months post-initiation. Switching rates between OACs were compared, and predictors of switching were identified. Results We included 15,020 patients who were recorded as having been commenced on warfarin or a DOAC. Overall, 5.7% of patients switched their OAC within 12 months. The switching rates from warfarin, apixaban, dabigatran and rivaroxaban were 9.4%, 2.6%, 8.9% and 4.0%, respectively. Compared to apixaban, commencement on warfarin, dabigatran or rivaroxaban was associated with a higher risk of switching to another OAC. Patients with an estimated glomerular filtration rate (eGFR) <30 mL/min were more likely to switch from DOACs to warfarin and less likely to switch from warfarin, compared to those with an eGFR >60 mL/min. Conclusion There was a low switching rate between OACs in Australian general practice patients with AF. A key determinant of switching appeared to be kidney disease.

The subjective evaluation of task switch cues is related to voluntary task switching

Task switching refers to the effortful mental process of shifting attention between different tasks. While it is well-established that task switching usually comes with an objective performance cost, recent studies have shown that people also subjectively evaluate task switching as negative. An open question is whether this affective evaluation of task switching is also related to actual decision making. In this pre-registered study, we therefore examined whether individual differences in the negative evaluation of task switch cues are related to less voluntary task switching. To this end, participants first performed a cued task switching paradigm where abstract cues signaled task transitions (repetition or alternation). In a second phase, these transition cues were used as prime stimuli in an affective priming procedure to assess participants' affective evaluation of task switching. In a third phase, participants were allowed to freely choose whether to switch or repeat tasks. We found that a more negative evaluation of task switching cues was related to lower switch rates in the voluntary task switching phase. This finding supports neuroeconomic theories of value-based decision making which suggest that people use their subjective value of control to decide whether to engage in (different) tasks.

Analysis of antiretroviral therapy switch rate and switching pattern for people living with HIV from a national database in Japan

To report the status of switch rates and time-to-switch of antiretroviral therapy (ART) regimens by evaluating anchor drug classes and common switching patterns in Japanese people living with human immunodeficiency virus (HIV, PLWH). This cross-sectional cohort study extracted data of 28,089 PLWH from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), which contains data representing the entire population of Japan. PLWH with first prescription records of ART administered between January 2011 and March 2019 were identified (n = 16,069). The median time-to-switch and switch rates of anchor drug classes were estimated by Kaplan–Meier analysis. Brookmeyer–Crowley and Greenwood methods were used to estimate 95% confidence intervals for switch rates and median days, respectively. Switch rates were compared between anchor drug classes by year using log-rank tests. A total of 3108 (19.3%) PLWH switched anchor drug classes from first to second regimens. Switch rates increased continuously over 8 years for non-nucleoside reverse transcriptase inhibitors (NNRTIs) (14.9–65.5%) and protease inhibitors (PIs) (13.2–67.7%), with median time-to-switch of 1826 and 1583 days, respectively. Integrase strand transfer inhibitors (INSTIs) maintained a low switch rate (3.0–7.6%), precluding median-days calculation. Overall, the majority of patients treated initially with NNRTIs and PIs switched to INSTIs regardless of switching times (< 1 year: 67.3% and 85.9%, respectively; ≥ 1 year: 95.5% and 93.6%, respectively). The foremost switching strategies for first-to-second ART regimens are from NNRTIs or PIs to INSTIs regimens that maintain low switch rates long term. There was no observable difference in trend between sex, age and status of AIDS disease at first ART regimen. INSTIs HIV agents may be the most durable anchor drug class for PLWH receiving ART.

Investigating anticipatory processes during sequentially changing reward prospect: An ERP study

Performance-contingent reward prospect modulates the stability-flexibility balance in voluntary task switching. High reward prospect typically increases stability, indicated by a low voluntary switch rate (VSR). But this effect depends on the immediate reward history: Only when a high reward repeats (reward remains high), stability is increased. In contrast, when reward increases (high reward following low reward) cognitive flexibility is promoted, indicated by a relatively high VSR. To investigate the underlying mechanisms of changing reward expectations during voluntary task choice, we conducted two experiments and measured reward cue-locked event-related potentials (P2, P3b, CNV). The experiments yielded consistent findings: The P2 was stronger in response to high vs. low reward reflecting an early attentional boost by high reward anticipation. The P3b was highest in increase, intermediate in remain-high, and lowest in low reward trials suggesting responsiveness to working memory updating and motivational arousal. Finally, the CNV increased over time and was sensitive to both reward magnitude and sequence with the lowest amplitude in reward remain-low trials suggesting that preparatory control only increases when worth the effort. Taken together, early attentional processes (P2) were boosted by mere reward magnitude, while later processes (P3b, CNV) were sensitive to both reward magnitude and its sequence.

Comparison of Real-World Treatment Patterns Among Biologic-Experienced Patients with Psoriasis Treated with Ixekizumab or Secukinumab Over 18Months.

IntroductionReal-world data comparing effectiveness of ixekizumab (IXE) and secukinumab (SEC) among biologic-experienced patients are limited. This study compared treatment patterns over 18 months among biologic-experienced patients with psoriasis receiving IXE or SEC in the USA.MethodsA retrospective observational study using administrative claims data from IBM® Watson Health MarketScan® Research Databases included adult patients with ≥ 1 inpatient or ≥ 2 non-diagnostic (≥ 30 days apart) outpatient claim/s with diagnosis of psoriasis between March 1, 2015 and October 31, 2019, and ≥ 1 claim/s for index drugs, IXE or SEC, between March 1, 2016 and October 31, 2019. Patients had to have ≥ 1 claim/s for biologics indicated for psoriasis in the 6-month pre-period. During the 18-month follow-up, treatment adherence (proportion of days covered [PDC]), high adherence (PDC ≥ 80%), persistence, discontinuation, reinitiation, and switching were assessed. To address cohort imbalances, inverse probability of treatment weighting was employed. Logistic regression was used to estimate odds ratio for high adherence. Cox proportional hazard models were used to estimate hazard ratio for non-persistence, discontinuation, and switching.ResultsOverall, 411 IXE and 780 SEC users were included. After weighting, IXE users had significantly higher rate of high treatment adherence (42% vs. 35%, p = 0.019), higher persistence rate (44.9% vs. 36.9%, p = 0.007), lower discontinuation rate (48.4% vs. 56.0%, p = 0.012), and lower switching rate (26.6% vs. 34.0%, p = 0.009) compared with SEC users. After multivariable adjustment, compared with SEC, IXE use was associated with 36% higher odds of high treatment adherence (OR 1.36, 95% CI 1.05–1.74), 20% lower risk of treatment non-persistence (HR 0.80, 95% CI 0.68–0.93), 19% lower risk of discontinuation (HR 0.81, 95% CI 0.68–0.96), and 25% lower risk of switching (HR 0.75, 95% CI 0.60–0.93).ConclusionThis study suggests that IXE treatment is associated with significantly higher adherence rates and significantly lower non-persistence, discontinuation, and switching compared with SEC treatment.