Successful Switch Research Articles

Neonatal Diabetes Mellitus.

Neonatal Diabetes (ND) mellitus is a rare genetic disease (1 in 90,000 live births). It is defined by the presence of severe hyperglycaemia associated with insufficient or no circulating insulin, occurring mainly before 6 months of age and rarely between 6 months and 1 year. Such hyperglycaemia requires either transient treatment with insulin in about half of cases, or permanent insulin treatment. The disease is explained by two major groups of mechanism: malformation of the pancreas with altered insulin-secreting cells development/survival or abnormal function of the existing pancreatic β cell. The most frequent genetic causes of neonatal diabetes mellitus with abnormal β cell function are abnormalities of the 6q24 locus and mutations of the ABCC8 or KCNJ11 genes coding for the potassium channel in the pancreatic β cell. Other genes are associated with pancreas malformation or insufficient β cells development or destruction of β cells. Clinically, compared to patients with an ABCC8 or KCNJ11 mutation, patients with a 6q24 abnormality have lower birth weight and height, are younger at diagnosis and remission, and have a higher malformation frequency. Patients with an ABCC8 or KCNJ11 mutation have neurological and neuropsychological disorders in all those tested carefully. Up to 86% of patients who go into remission have recurrent diabetes when they reach puberty, with no difference due to the genetic origin. All these results reinforce the importance of prolonged follow-up by a multidisciplinary pediatric team, and later doctors specializing in adult medicine. 90% of the patients with an ABCC8 or KCNJ11 mutation as well as those with 6q24 anomalies are amenable to a successful switch from insulin injection to oral sulfonylureas.

A Plasmodium cysteine protease required for efficient transition from the liver infection stage

The transitions between developmental stages are critical points in the Plasmodium life cycle. The development of Plasmodium in the livers of their mammalian hosts bridges malaria transmission and the onset of clinical symptoms elicited by red blood cell infection. The egress of Plasmodium parasites from the liver must be a carefully orchestrated process to ensure a successful switch to the blood stage of infection. Cysteine protease activity is known to be required for liver-stage Plasmodium egress, but the crucial cysteine protease(s) remained unidentified. Here, we characterize a member of the papain-like cysteine protease family, Plasmodium berghei serine repeat antigen 4 (PbSERA4), that is required for efficient initiation of blood-stage infection. Through the generation PbSERA4-specific antisera and the creation of transgenic parasites expressing fluorescently tagged protein, we show that PbSERA4 is expressed and proteolytically processed in the liver and blood stages of infection. Targeted disruption of PbSERA4 results in viable and virulent blood-stage parasites. However, upon transmission from mosquitoes to mice, Pbsera4(-) parasites displayed a reduced capacity to initiate a new round of asexual blood-stage replication. Our results from cultured cells indicate that this defect results from an inability of the PbSERA4-deficient parasites to egress efficiently from infected cells at the culmination of liver-stage development. Protection against infection with wildtype P. berghei could be generated in animals in which Pbsera4(-) parasites failed to establish infection. Our findings confirm that liver-stage merozoite release is an active process and demonstrate that this parasite-encoded cysteine protease contributes to parasite escape from the liver.

PROFESSIONAL MOBILITY IN FUTURE PHILOSOPHY DOCTORS’ TRAINING

The article defines the essence of professional mobility and importance in future philosophy doctors' training in pedagogical universities. It was proved, that the basis of the sociological approach of determining professional mobility was based on changes in an individual position in the social structure of society. Features of individual personality were at the heart of the psychological approach. Pedagogical approach combines those two approaches, as it aims to ensure the movement of an individual in the social structure of society by future professionals’ appropriate training during their studies. Professional mobility was defined as a professional training component of future philosophy doctors; ability for successful switching from one activity to another during the process of thesis writing and for changing of activity types in the professional field; ability of efficient use of professional techniques system for implementation of any tasks in the field of thesis writing. The following factors have been proved to have positive influence on the development of future philosophy doctors professional mobility: organization of international relations and joint programs of international cooperation with foreign educational institutions, organizations, associations in the field of science and education; organization of participation in programs of bilateral and multilateral international exchange, internships and practices of postgraduate students, doctoral students, pedagogical staff and students of the university, organization and implementation of joint international educational programs with foreign partner universities considering obtaining diplomas of these universities.

Switching antiepileptic drugs to once-daily dosing regimens in epilepsy patients.

Antiepileptic drug (AED) non-adherence is an important factor contributing to poor seizure control in patients with epilepsy. The aim of this study is to investigate seizure improvement after switching AEDs to once-daily dosing regimens in patients with drug-resistant epilepsy related to AED non-adherence. We performed a 10-year retrospective analysis of drug-resistant epilepsy patients whom AED non-adherence attributed to drug resistance and switched AEDs to once-daily dosing regimens. Successful switching was defined by at least 70% reduction in seizure frequency without troublesome adverse events. Among 401 patients with drug-resistant epilepsy, 88 patients with AED non-adherence were switched to once-daily dosing regimens. Forty-six patients (52.3%) experienced successful seizure control following the switch. A higher chance of successful switch was found in patients without MRI abnormality (16/46 vs. 24/42; P=.04) and in patients who were switched to extended-release formulations or different AEDs with longer half-lives (33/46 vs. 19/42; P=.02). Our study shows that switching AEDs to once-daily dosing regimens was an effective therapeutic option in patients with poor seizure control related to AED non-adherence. Treatment with extended-release formulations or drugs with longer half-lives should be considered in these patients.

Role of eosinophilic chronic rhinosinusitis inswitching to benralizumab treatment in mepolizumab responders.

There are currently three anti-interleukin-5 (IL-5) pathway-directed therapies: mepolizumab, reslizumab, and benralizumab. Of these, benralizumab was most recently approved. Benralizumab is administered every 8weeks after an initial 3 doses given every 4weeks, whereas mepolizumab and reslizumab are administered every 4weeks. This convenience in benralizumab administration indicates that it is potentially beneficial for patients. Therefore, we potentially have an opportunity to change to benralizumab in patients who responded to mepolizumab or reslizumab. However, other than eosinophil levels, factors that could predict patients responding to anti-IL-5 pathway-directed therapies have been unknown. In this study, we examine the clinical characteristics of mepolizumab responders who achieved successful switching to benralizumab. A total of 18 consecutive severe asthmatic patients treated with sequential mepolizumab and benralizumab, each for at least 1year, were enrolled in this study. This study was a single-center case series. Patients were defined as having achieved successful switching to benralizumab if they satisfied either of the following for 1year before and after the benralizumab treatment: (1) they experienced no exacerbation; or (2) they experienced no exacerbation and discontinued oral corticosteroids. All 18 patients responded to mepolizumab treatment, and 11 of them achieved successful switching to benralizumab. The proportion of patients who achieved successful switching to benralizumab was higher in patients with eosinophilic chronic rhinosinusitis (ECRS) than in those without (76.9 vs. 20.0%; p=0.025). Our findings imply that in responders to mepolizumab, there may be a higher response rate to benralizumab in patients with ECRS than in those without.

A 580 nW Dual-Input Energy Harvester IC Using Multi-Task MPPT and a Current Boost Converter for Heterogeneous Source Combining

Herein, we present a multi-energy harvesting interface integrated circuit (IC) that enables the efficient combination of heterogeneous power sources. An electromagnetic vibration energy generator (EVG) and a thermoelectric energy generator (TEG) are the two energy sources, which have quite different internal resistance (tens and kilo-Ohms). To solve the challenge of combining heterogeneous sources, we propose a current boost converter (CBC), which achieves the resistance transformation as well as the source type conversion. The challenge of realizing maximum power point tracking (MPPT) for each source is tackled by using a multi-task MPPT controller, which is efficiently shared between the two sources. To achieve energy harvesting under uncertain and random source conditions, we propose an input ( $V_{\text {IN}}$ )-dependent clock generator (VCG) and a vibration pulse detector (VPD). The VCG tracks the change of source conditions to generate the clock for the MPPT controller. The VPD allows tracking of the random amplitude and frequency changes of the EVG. The energy harvester is fabricated in a 0.18 $\mu \text{m}$ process with a thick top-metal option. Measured results show successful source detection, switching, and MPPT operation. The proposed IC provides an output power of up to 119 $\mu \text{W}$ with an end-to-end peak efficiency of 82% by consuming 582 nW.

P61 Patient perspectives on switching to an infliximab biosimilar in paediatric inflammatory bowel disease (PIBD)

AimTo establish patient perspectives on switching to an infliximab biosimilar, which will enable the PIBD team to improve patient experience during future biosimilar switches.MethodsFamilies of patients receiving treatment with an Infliximab biosimilar (Remsima®) 2 years after switching from the originator (Remicade®) were selected from the active patient database for telephone interview. One family who chose not to switch was also included for interview. A 5-question interview was prepared, which asked parents to rate their overall experience according to a satisfaction rating scale from 1–5. Parents were asked about their knowledge of reasons for switching, if they needed to look up additional information resources and, finally, ways to improve the switching process.Results18 patients were identified, 16 parents were available for interview. 13 parents gave overall positive feedback with satisfaction scores of 4 or 5 on the numerical satisfaction scale. 3 parents were dissatisfied with the switching process, giving scores of 0, 1 and 3. This resulted in an average satisfaction score of 4.1. The majority of satisfied parents had little knowledge of the switch, not remembering details and indicating the switch was best performed this way. Nonetheless, most recognised costs as the reason for switching. The majority of parents did not need to look up additional information resources, 2 parents named The Crohn’s and Colitis Charity and Facebook support groups as useful resources. Two dissatisfied patients requested to switch back to Remicade® therapy due to side effects. The family of the patient who chose not to switch made this decision because Remsima® was not yet available in the United States, where they also received treatment.ConclusionBiosimilar biologics continue to be approved by the EMA as originators come off patent. Efficacy of infliximab biosimilars in paediatric IBD patients is extrapolated from adult rheumatology data, with limited long term outcome data.1 2 Successful switches for NHS trusts lead to financial benefits; these savings allow for NHS investment to enable more patients to be treated.3Patient autonomy and, in paediatrics, parental views must be respected during this switching process. The majority of interviews with parents were positive, re-affirming the process of this switch. Parental perceptions of side effects attributed to Remicade® highlight the importance of discussing realistic outcomes of therapy with both the originator and biosimilar. When questioned, the parent who refused to switch explained that they did not have faith in the efficacy of the biosimilar and had major concerns of treatment failure. A fear of treatment failure may be described as a ‘nocebo’ effect 4 which hypothesises that negative attitudes incur less effective results. Increasing our awareness of patient perceptions on switching biosimilars and monitoring reasons for switch failure will better inform us going forward with future biologic switches.ReferencesDanese S, Fiorino G, Raine T, et al. ECCO position statement on the use of biosimilars for inflammatory bowel disease—an update. J Crohn’s Colitis 2017;11:26–34.de Ridder L, Waterman M, Turner D, et al. Use of biosimilars in paediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2015;61:503–508.Healy M, Crook J, Chavda C, et al. P35 An experience of switching paediatric inflammatory bowel disease patients on infliximab therapy to the biosimilar ‘remsima.’Arch Dis Child 2018;103:e1.39–e1.Ordinet J, Day C, Cruz J, et al. The biosimilar nocebo effect? A systematic review of double-blinded versus open-label studies. J Manag Care Spec Pharm 2018;24:952–959.

P66 Standardising strengths of unlicensed medicines in a large London hospital trust

BackgroundA UK national position statement on standardised strengths of unlicensed liquid medicines recommend that when children require unlicensed liquid medications, they should receive the recommended strength. By standardising strengths of these medicines, the risk of errors being made in the doses given to children will be reduced and prevent accidental under and overdoses.1 Our Trust has 4 hospital sites since merging in 2012, we found the process of switching to a standard strength far from simple.MethodsThe strengths of unlicensed liquid medicines listed in the position statement available on the pharmacy dispensing system (JAC) were identified, along with the speciality users. Pharmacy and clinical leads were consulted for agreement to switching to the standardised strengths. Pharmacy procurement identified new products in standardised strengths and products were reviewed for suitability by paediatric pharmacist. A cost impact analysis was carried out. Communication was sent to stakeholders including, doctors, nurses, pharmacy and primary care.Results and DiscussionWe found the standardised strengths of azathioprine, clonazepam, ethambutol, isoniazid, melatonin, omeprazole, phenobarbitone and pyrazinamide strengths were on formulary. Clopidogrel, hydrocortisone, sertraline and tacrolimus liquids are not used. Different strengths of the listed unlicensed liquid medicines were used by different sites and specialties. Lead speciality pharmacists agreed with the standardisation. We identified use of unlicensed products where licensed products are available (sildenafil 20 mg/5 mL and furosemide 5 mg/5 mL). We added the use of these items to our review. We were not able to agree on a single standard strength for some items; the neonatal intensive care unit (NICU) have babies under 500 g who may require furosemide, spironolactone and sildenafil in doses that measure less than 0.1 mL using the recommended strengths. This volume is deemed less than satisfactory to be measured safely1. It has been agreed with the neonatal lead pharmacist that additional strengths of the sildenafil (unlicensed 20 mg/5 mL), spironolactone (unlicensed 10 mg/5 mL) and furosemide (20 mg/5 mL) be available for inpatient NICU use only. The potential for patients to be discharged on the non-standard strength is reduced by specifying ‘Not for discharge - inpatient use only’ on the pharmacy system as well as having them only as NICU stock from medicines distribution. Patients admitted on other strengths will be switched (with consent); to minimise risk pharmacists will ensure carers are aware of the change & correct dose volume to administer and endorse TTAs noting the change in concentration for the GP. Primary care have been engaged with the switch and invited the consultant pharmacist to discuss this at the interface meeting. We were not able to source the recommended midazolam 10 mg/5 mL. The switch to chloral hydrate to 1 g/5 mL was calculated to have a significant cost pressure therefore it was agreed that that we would not change from chloral hydrate 500 mg/5 mL at this time as it is mainly used in the in-patient setting within our Trust. Based on current usage there is an estimated cost saving of over £5 k based on the switch of sodium chloride, sildenafil, furosemide and spironolactone. The impact will be reviewed in 6 months.ConclusionA successful switch requires a team approach but will benefit patient safety and save money.ReferenceThe Neonatal and Paediatric Pharmacists Group (NPPG) and Royal College of Paediatric and Child Health (RCPCH). Position statement 18–01 Using Standardised Strengths of Unlicensed Liquid Medicines in Children. Version 2. May 2019.

Using airway resistance measurement to determine when to switch ventilator modes in congenital diaphragmatic hernia: a case report

BackgroundCongenital diaphragmatic hernia is a deficiency of the fetal diaphragm resulting in herniation of the abdominal viscera into the thoracic cavity. The best method of respiratory management of congenital diaphragmatic hernia is unclear, but high frequency oscillatory ventilation is often used as the initial ventilator mode for severe congenital diaphragmatic hernia. When it becomes impossible to maintain the pre-ductal saturations, the timing of successful switching of the ventilation mode from high frequency oscillatory ventilation to conventional mechanical ventilation remains unclear. Herein, we reported two cases in which airway resistance measurements based on pulmonary function tests were used for making the decision to switch the ventilator mode from high frequency oscillatory ventilation to conventional mechanical ventilation in patients with left isolated congenital diaphragmatic hernia.Case presentationTwo 0-day-old infants with congenital diaphragmatic hernia were admitted to our hospital. In both patients, high frequency oscillatory ventilation was started initially, and the levels of saturation gradually rose within a few hours after birth. After 24 h of high frequency oscillatory ventilation, the level of saturation decreased, and the dissociation of pre-ductal and post-ductal saturation re-occurred. The respiratory-system resistance was 515 and 403 cmH2O·kg/L/s, respectively. Because the respiratory-system resistance was elevated, we decided to change the ventilator mode from high frequency oscillatory ventilation to conventional mechanical ventilation. After switching to conventional mechanical ventilation, the patients’ heart rate and saturation increased immediately.ConclusionsIn patients with congenital diaphragmatic hernia, resistance levels of > 400 cmH2O·kg/L/s may indicate high airway resistance and suggest greater alveolar vibration attenuation. When respiratory-system resistance reaches over 400 cmH2O·kg/L/s, it may be an optimal time for switching from high frequency oscillatory ventilation to conventional mechanical ventilation.

Molecular and clinical characteristics of monogenic diabetes mellitus in southern Chinese children with onset before 3 years of age

IntroductionA specific molecular diagnosis of monogenic diabetes mellitus (MDM) will help to predict the clinical course and guide management. This study aims to identify the causative genes implicated in Chinese...

O-19 Feasibility of switching to S-1 upon other fluoropyrimidine-related cardiotoxicity during chemotherapy for solid tumors

Fluoropyrimidines are the cornerstone of chemotherapy in many solid tumors and linked to cardiotoxicity in about 5% (Polk, Cancer Treat Rev 2013), often leading to its discontinuation. Cardiotoxicity may be less common with the fluoropyrimidine S-1 and successful switch from other fluoropyrimidines has been reported (Kwakman, EJC 2017).

Third-order exceptional point and successive switching among three states in an optical microcavity

One of the most intriguing topological features of open systems is exhibiting exceptional point (EP) singularities. Apart from the widely explored second-order EPs (EP2s), the explorations of higher-order EPs in any system requires more complex topology, which is still a challenge. Here, we encounter a third-order EP (EP3) for the first time in a simple fabrication feasible gain-loss assisted optical microcavity. Using scattering-matrix formalism, we study the simultaneous interactions between three successive coupled states around two EP2s, which yield an EP3. Following an adiabatic parametric variation around the identified EP3, we present a robust successive-state-conversion mechanism among three coupled states. The proposed scheme indeed opens a unique platform to manipulate light in integrated devices.

Hopf-Hopf bifurcation in the delayed nutrient-microorganism model

In view of time delay in the transport of nutrients, a delayed reaction-diffusion system with homogeneous Neumann boundary conditions is presented to understand the formation of the heterogeneous distribution of bacteria and nutrients in the sediment. With the effects of time delay and diffusion, the system will experience various dynamical behaviors, such as stability, the Turing instability, successive switches of stability of equilibria, the Hopf and the Hopf-Hopf bifurcations. To further understand the dynamics of the Hopf-Hopf bifurcation, the multiple time scale (MTS) technique is employed to derive the amplitude equations at this co-dimensional bifurcation point, and the dynamical classification near such bifurcation point is also identified by analyzing the obtained amplitude equations. Some numerical simulations are carried out to demonstrate the validity of the theoretical analysis.

Feasibility of switching to S-1 after other fluoropyrimidine-related cardiotoxicity during chemotherapy for solid tumors.

7037 Background: Fluoropyrimidines (FP) are the cornerstone of chemotherapy in many solid tumors and linked to cardiotoxicity (CarTx) in about 5% (Polk, Cancer Treat Rev 2013), often leading to FP discontinuation. CarTx may be less common with S-1 and successful switch from other FP has been reported (Kwakman, EJC 2017). Methods: This 6-country, 12-center, cohort study included patients with solid tumors (ICD10 C15-C21, C24-25, C50, C80) who experienced FP-related CarTx. Primary endpoint was recurrent (R) CarTx during S-1 therapy after switch from any other FP. Results: CarTx during capecitabine (n = 124), continuous (n = 13) or bolus 5-fluorouracil (n = 4) was reported for 141 patients who switched to S-1 therapy. CarTx was chest pain including vasospasm without cardiac findings (55%), acute coronary syndrome or myocardial infarction (32%), atrial fibrillation (4%), heart failure/cardiomyopathy (4%), tachy-/bradycardia (3%), and/or other (15%). CarTx was grade 3-4 in 55%, appeared on cycle 1-2 in 89%, and at median 4 days (range 0-466) from FP initiation (Table). Causality was judged related in 26%, probable in 60%, and possible in 14%. Action with FP causing CarTx was permanent discontinuation in 91%. Treatment intent was curative in 70%. Cumulative incidence of RCarTx with S-1 was 3.5% (CI95%, 1.2-8.4%) and median time to R-CarTx was 11 (range 6-195) days. Four (out of 141) had grade 1 and one grade 2 R-CarTx. Three were judged possibly related to S-1 and 2 not related. S-1 was discontinued in one patient and continued in 4 (for 63-252 days) without action (n = 2), with dose reduction (n = 1), or delay (n = 1). There were no differences in demographic or risk factors regarding R-CarTx on S-1 (Table). Conclusions: FP-related CarTx is often severe, occurs early, and leads to permanent FP discontinuation. Switching to S-1-based therapy is safe, with, at the most, grade 1-2 R-CarTx in only 3.5%, and rarely leads to treatment discontinuation (0.7%), allowing patients to continue on an FP-based regimen. Clinical trial information: NCT04260269 . [Table: see text]

Comparisons Between Successful Versus Unsuccessful Switches From Benzodiazepines or Zolpidem (Z-Drug) to Controlled-Release Melatonin in Patients With Major Depressive Disorder and Insomnia.

ObjectivesChronic use of benzodiazepines and zolpidem (BDZ/Z-drugs) leads to dependency, cognitive impairment, and falls. Although controlled-release melatonin (Melatonin CR) may be an alternative, a switch in clinical settings has proven difficult. We investigated the factors associated with successful switch to Melatonin CR in patients with major depressive disorder (MDD) and insomnia.MethodsThis retrospective observational study involved 170 patients diagnosed with MDD and insomnia, and aged older than 55 years, who were treated with BDZ/Z-drug for at least the past 90 days and never before exposed to Melatonin CR. All patients were treated with a standard antidepressant therapy and Melatonin CR for their insomnia. A successful switch was defined as three or more consecutive prescriptions of Melatonin CR separated by at least one-month interval, after discontinuation of the BDZ/Z-drug.ResultsSeventy-nine patients (46.5%) who switched successfully showed no significant differences in sex, age, education, and occupational status compared with the unsuccessful group. The types of antidepressants used or BDZ/Z-drug treatment did not differ significantly between the two groups. Fewer somatic symptoms were observed in the successful group. In the multivariate analysis, the successful group showed significantly less somatic anxiety, shorter duration from first BDZ/Z-drug use to the first antidepressant use, and shorter total duration of BDZ/Z-drug therapy.ConclusionsA successful switch from BDZ/Z-drug to Melatonin CR was associated with less baseline somatic anxiety, earlier use of antidepressants, and shorter total duration of BDZ/Z-drug use, but was less strongly associated with the type of antidepressants in MDD patients with insomnia.

Intracellular Delivery of Budesonide and Polydopamine Co‐Loaded in Endosomolytic Poly(butyl methacrylate‐co‐methacrylic acid) Grafted Acetalated Dextran for Macrophage Phenotype Switch from M1 to M2

AbstractIn this study, a rationally designed nanocomposite (BUDPDA@MAP) composed of polydopamine (PDA) nanoparticle and anti‐inflammatory drug budesonide (BUD) encapsulated in a pH‐responsive endosomolytic polymer (poly(butyl methacrylate‐co‐methacrylic acid) grafted acetalated dextran, denoted by MAP), is proposed. The uniform nanocomposite is prepared using a microfluidic device. At low endosomal pH (5.5), MAP destabilizes the endosomal membranes for the cytoplasmic delivery of PDA, and releases BUD simultaneously, resulting in a greater reactive oxygen species scavenging capability than both the free drug and PDA alone. The combined therapeutic efficacy from PDA and BUD also leads to a successful macrophage phenotype switch from pro‐inflammatory M1 to anti‐inflammatory M2.

The evidence for switching dibenzazepines in people with epilepsy.

The dibenzazepines particularly carbamazepine are associated with known adverse effects (AEs) and drug to drug interactions. Eslicarbazepine acetate (ESL) is structurally distinct from other members of the dibenzazepine family and has the advantage of once daily dosing. Observational and trial data report successful switching from older dibenzazepines to ESL. The evidence base for doing so is unclear and not standardized. This is a literature review following the PRISMA scoping guidelines identifying the evidence of switching dibenzazepines. Transition methods, ratios, tolerance to change, adverse effects and retention post-change were evaluated. Study quality was assessed using the Oxford Centre for Evidence Based Medicine levels of evidence. Seven studies investigated the outcome of transition between carbamazepine and or oxcarbazepine to ESL, with specific data on the transition dose ratio and scheduling. The available data suggest that the overnight transition between oxcarbazepine and ESL in a 1:1 ratio (most common) is generally well tolerated with high retention rates. The transition showed improvement in adverse events associated with oxcarbazepine across a variety of domains. Almost 60% transitioned because of adverse events experienced no further symptoms at 12months. There is less data on the transition from carbamazepine to ESL. The evidence available suggests an overnight transition in the ratio of 1:1.3-1.5. The retention rate following transition from carbamazepine to ESL was 69% (follow-up of 4months) with almost half of those transitioned because of adverse events experiencing no further symptoms. There is Grade C evidence available to help guide clinicians in the transition.

Shifting Valproic Acid to Levetiracetam in Women of Childbearing Age With Epilepsy: A Retrospective Investigation and Review of the Literature.

Objective: Valproic acid is the most high-risk teratogenic antiepileptic drug, and it may lead to fetal major congenital malformations. However, it is still used in women of childbearing age with epilepsy. The aim of this study was to report our experience of discontinuing or lowering valproic acid by adding levetiracetam, a low-risk teratogenic antiepileptic drug.Methods: We reviewed the medical records of childbearing age female patients with epilepsy who were treated with valproic acid initially and then switched to levetiracetam. The clinical profiles were recorded. The primary outcome was successful switching, which was defined as a decrease in the daily valproic acid dosage, after levetiracetam had been added.Results: Twenty-four female patients were enrolled (median age 22 years). The successful switching rate was 83.3% (20/24), and 55% (11/20) discontinued valproic acid after levetiracetam had been added. There were no significant differences between the successful and unsuccessful groups in etiology, electroencephalogram, and magnetic resonance imaging findings. Pharmacoresistant to levetiracetam was much higher in the unsuccessful group (45 vs. 100%). The median switching duration was 19.5 months in the successful group. There were improvements in metrorrhagia and alopecia in all of the patients in the successful group after valproic acid had been tapered.Conclusions: Our experience supports switching valproic acid to levetiracetam in childbearing age women with epilepsy as an effective strategy to lower the teratogenic rate and adverse effects. A long switching period was noted in this study. We suggest starting early in childbearing age women with epilepsy.

P282 Outcome for PsA biologic switchers following primary inefficacy of TNFi therapy in a secondary care cohort: sequential TNFi versus switching mode of action

Abstract Background TNFi are the most used first line of biologic disease modifying anti-rheumatic drugs (bDMARDs) in PsA. In primary loss of response (PLR) to TNFi, there is no current evidence that directs the choice of second line bDMARDs. Our aim in this work was to compare drug survival for those who switched to a second TNFi versus alternative agents in real life. Methods Data was analysed retrospectively from a cohort of 400 PsA patients followed through from 2002-2019. Statistical analysis was carried out with descriptive statistics and t-test analysis using SPSS version 22. Results Out of 400 patients, 220 (55.0%) were started on bDMARD treatment. Of these 220, 212 (96.5%) were started on TNFi as initial therapy. PLR was seen in 42 of these patients (19.8%). The median drug survival of initial TNFi therapy was 7.1 months (interquartile range [IQR] 3.6 - 53.4 months). Of the 42 patients with PLR: 32 (76.2%) were switched to a second TNFi; 6 (14.3%) were switched to ustekinumab and 4 (9.5%) were switched to secukinumab. 21 of the 32 patients switched to a second TNFi were subsequently switched onto a third biologic due to treatment failure (65.6%). The median drug survival of the second TNFi in this group was 7.7 months (IQR 3.0 - 26.3 months). 3 out of the 6 (50%) patients who were switched to ustekinumab were then subsequently switched, this was due to primary inefficacy in 66.7% and adverse events in 33.3%. The median drug survival of ustekinumab in this group was 10.0 months (IQR 0.0 - 16.0 months). All 4 patients switched to secukinumab continue on this treatment with no drop outs, giving a median drug survival 12.3 months (IQR 6.5 - 19.5 months). Conclusion Our data suggests that patients with PLR to TNFi in PsA who switched mode of action to IL-17 inhibitor appeared to have better drug survival than subsequent TNFi or IL-12/23 inhibitors. Exploring the clinical biomarkers for those with successful switch to non-TNFi bDMARD in a larger cohort would help with targeting the most appropriate individuals and early disease control. Disclosures M. Naja None. L. R. Santos None. M. Shipa None. G. Mandy None. M. Castelino None.

Single-shot all-optical switching of magnetization in Tb/Co multilayer-based electrodes

Ever since the first observation of all-optical switching of magnetization in the ferrimagnetic alloy GdFeCo using femtosecond laser pulses, there has been significant interest in exploiting this process for data-recording applications. In particular, the ultrafast speed of the magnetic reversal can enable the writing speeds associated with magnetic memory devices to be potentially pushed towards THz frequencies. This work reports the development of perpendicular magnetic tunnel junctions incorporating a stack of Tb/Co nanolayers whose magnetization can be all-optically controlled via helicity-independent single-shot switching. Toggling of the magnetization of the Tb/Co electrode was achieved using either 60 femtosecond-long or 5 picosecond-long laser pulses, with incident fluences down to 3.5 mJ/cm2, for Co-rich compositions of the stack either in isolation or coupled to a CoFeB-electrode/MgO-barrier tunnel-junction stack. Successful switching of the CoFeB-[Tb/Co] electrodes was obtained even after annealing at 250 °C. After integration of the [Tb/Co]-based electrodes within perpendicular magnetic tunnel junctions yielded a maximum tunneling magnetoresistance signal of 41% and RxA value of 150 Ωμm2 with current-in-plane measurements and ratios between 28% and 38% in nanopatterned pillars. These results represent a breakthrough for the development of perpendicular magnetic tunnel junctions controllable using single laser pulses, and offer a technologically-viable path towards the realization of hybrid spintronic-photonic systems featuring THz switching speeds.