Discontinuation Period Research Articles

Does methotrexate influence the efficacy of vaccination against SARS-CoV-2?

Die Frage, ob eine laufende MTX(Methotrexat)-Therapie tatsächlich die protektive Immunantwort nach SARS-CoV-2-Impfung in relevanter Form abschwächt, lässt sich anhand der vorliegenden Daten definitiv nicht beantworten. In Kenntnis der Tatsache, dass ein kurzes z. B. 1‑ oder 2‑maliges Pausieren der wöchentlichen MTX-Gabe bei Patienten in stabiler Krankheitssituation mit einem vergleichsweise geringen Risiko der Auslösung eines Schubes der Grundkrankheit verbunden ist, kann eine solche kurze Unterbrechung der Therapie nach individueller Entscheidung zwischen Patient*in und behandelnder/m Rheumatolog*in durchaus erwogen werden. Zwingend notwendig erscheint sie aber nicht – zumal diese Pause bei den meisten Impfstoffen 2‑mal innerhalb relativ kurzer Zeit erfolgen müsste. Keinesfalls aber sollte eine längere Therapiepause gemacht werden – die Auslösung eines Schubes der Grundkrankheit wäre eine mögliche kritische Folge. Für eine ausführlichere Einschätzung der Datenlage und der Konsequenzen daraus (auch in Bezug auf weitere DMARD [„disease-modifying anti-rheumatic drugs“]) wird auf die demnächst erscheinenden aktualisierten Handlungsempfehlungen der DGRh (Deutsche Gesellschaft für Rheumatologie e. V.) für die Betreuung von Patienten mit entzündlich rheumatischen Erkrankungen im Rahmen der SARS-CoV-2/COVID-19-Pandemie verwiesen.

FIREFLY-1: A phase 2 study of the pan-RAF inhibitor DAY101 in pediatric patients with low-grade glioma.

TPS10056 Background: The mitogen-activated protein kinase (MAPK) signaling pathway is an essential pathway that regulates key cell functions such as growth, survival, and differentiation. Genomic alterations and dysregulation of the MAPK pathway including BRAF fusions, point mutations (e.g. BRAF V600) and in-frame deletions have been described in many different types of malignancies, including pediatric low-grade glioma (pLGG) and other pediatric cancers. The identification of the KIAA1549:BRAF fusion in 2008 led to deeper understanding of the genomic events driving growth of pLGG (Jones, Cancer Res 2008). Despite the low-grade histology and excellent long-term survival, pLGGs are often associated with tumor- and treatment-associated morbidity and significant late-effects that persist throughout the lifespan of the patient. DAY101 is an oral, highly selective, CNS-penetrant small-molecule, Type II pan-RAF kinase inhibitor that is being developed for patients with pLGG harboring an activating BRAF-alteration. DAY101 has demonstrated tumor inhibition in preclinical models and has achieved clinically meaningful and durable responses in 7/8 patients with RAF-altered LGG in a pediatric phase 1 trial, including 2 complete responses, 3 partial responses, 2 stable disease and 1 progressive disease with a median time to response of 10.5 weeks. Patients have been treated for up to two years with no discontinuations due to toxicity or disease progression (Wright, SNO 2020). Methods: FIREFLY-1 is an open-label, multi-center, international Phase 2 study with DAY101 in pediatric and young adult patients between the ages of 6 months and 25 years with LGG harboring a documented BRAF-alteration as determined by local laboratory testing. DAY101 is administered orally once a week on a continuous 28-day schedule. Patients who respond will be treated for a minimum of two years after which they may at any point, opt to enter a “drug holiday” discontinuation period. Dosing is based on body surface area. DAY101 is available in a pediatric-friendly oral liquid formulation and tablets. The primary endpoint is objective response rate based on Response Assessment for Neuro-Oncology (RANO) as determined by an independent review committee. Secondary endpoints include objective response rate based on Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group criteria, duration of response and safety. Exploratory endpoints include quality-of-life measurements as well as functional outcomes. Molecular abnormalities will be characterized through the analysis of archival tissue. Enrollment began in February 2021 and is ongoing. Clinical trial information: NCT03429804.

The Effect of Hypothalamic Involvement and Growth Hormone Treatment on Cardiovascular Risk Factors in Patients With Childhood-Onset Craniopharyngioma

Background: We evaluated cardiovascular risk factors at the time of growth hormone (GH) retesting after completion of linear growth in patients with childhood-onset craniopharyngioma (CP). We also investigated the effects of postoperative hypothalamic involvement (HI) and GH discontinuation during transition period on cardiovascular risk factors. Methods: Forty-two CP patients (24 males, mean age 17.7 years) who reached final adult height after GH therapy between 1995 and 2012 from a tertiary center were included. We measured anthropometric data and components of the metabolic syndrome at the time of GH retesting. The period of GH discontinuation was classified as < 6 months vs. ≥ 6 months. The extent of HI was categorized into “no”, “mild”, and “extensive” HI according to Puget grading system. Results: The mean age of initial operation after CP diagnosis was 7.5 ± 3.6 years, and 23 (54.8%) patients showed extensive HI. All patients were treated with GH during childhood for median 5.8 years (range 2.4-8.2years). Duration of GH discontinuation was median 1.5 years (range 0.5-3.2 years), and 32 (76.2%) had GH discontinuation ≥ 6 months. At the time of GH retesting, 13 (31.0%) were obese, and the proportion of patients with impaired fasting glucose (≥ 100 mg/dL), high triglycerides (≥ 150 mg/dL), low high-density lipoprotein (HDL) cholesterol (male, < 40 mg/dL; female, < 50 mg/dL), and hypertension (systolic blood pressure ≥ 130mmHg or diastolic blood pressure ≥ 85mmHg) was 5 (11.9%), 18 (42.9%), 24 (57.1%), and 5 (11.9%), respectively. When multivariate-adjusted models were constructed including age, sex, postoperative duration, extent of HI, duration of GH discontinuation, and family history of cardiovascular disease, the extent of HI was significantly predictive for increased body mass index z-score (β = 1.27, P = 0.017), fasting insulin levels (β = 7.1, P = 0.049), HOMA-IR (β = 1.61, P = 0.020), and decreased HDL cholesterol levels (β = -9.9, P = 0.012). GH discontinuation more than 6 months was significantly associated with decreasedHDL cholesterol levels (β = -10.23, P = 0.026). Conclusion: In this study, impaired fasting glucose or hypertension accounted for one-tenth, and dyslipidemia was detected in more than half of childhood-onset CP patients with GH deficiency at the time of GH retesting. The more extensive HI and the longer duration of GH discontinuation were associated with increased risk of metabolic disturbance during the transition period.

Caffeine-Induced Effects on Human Skeletal Muscle Contraction Time and Maximal Displacement Measured by Tensiomyography.

Studies on muscle activation time in sport after caffeine supplementation confirmed the effectiveness of caffeine. The novel approach was to determine whether a dose of 9 mg/kg/ body mass (b.m.) of caffeine affects the changes of contraction time and the displacement of electrically stimulated muscle (gastrocnemius medialis) in professional athletes who regularly consume products rich in caffeine and do not comply with the caffeine discontinuation period requirements. The study included 40 professional male handball players (age = 23.13 ± 3.51, b.m. = 93.51 ± 15.70 kg, height 191 ± 7.72, BMI = 25.89 ± 3.10). The analysis showed that in the experimental group the values of examined parameters were significantly reduced (p ≤ 0.001) (contraction time: before = 20.60 ± 2.58 ms/ after = 18.43 ± 3.05 ms; maximal displacement: before = 2.32 ± 0.80 mm/after = 1.69 ± 0.51 mm). No significant changes were found in the placebo group. The main achievement of this research was to demonstrate that caffeine at a dose of 9 mg/kg in professional athletes who regularly consume products rich in caffeine has a direct positive effect on the mechanical activity of skeletal muscle stimulated by an electric pulse.

Methylphenidate Treatment Adherence and Persistence in Children in the Netherlands.

Objectives: Numerous studies have examined determinants contributing to methylphenidate adherence and persistence, but these were mainly conducted in adults. These determinants are likely to be different in children as they usually rely on their parents to provide them with the care they need. The objective was to study child and family characteristics as determinants of methylphenidate adherence and persistence in children. Methods: The study population consists of 307 children from the Generation R Study in the Netherlands, who had at least one dispensing record of methylphenidate until the age of 16 years. Adherence was defined as a medication possession ratio ≥0.80 up to 2 years after treatment initiation. Persistence was defined as the duration of treatment until a discontinuation period of ≥6 months. Family and child characteristics were tested as determinants of adherence with multivariable logistic regression analysis. Persistence was evaluated using a Kaplan-Meier analysis. Results: Children of mothers with one child (adjusted odds ratio [OR]: 2.31, 95% confidence interval [CI]: 1.17-4.54) or of mothers with an average household income (compared to high) were more likely to be adherent (adjusted OR: 3.45, 95% CI: 1.43-8.31). Children who started treatment at the age of 12-16 years (compared to <12 years) (adjusted hazard ratio [HR]: 3.55, 95% CI: 2.54-4.98) and girls (adjusted HR: 1.44, 95% CI: 1.07-1.95) were more often nonpersistent. Conclusion: Both child and family characteristics may play a role in methylphenidate treatment adherence. Furthermore, gender and the start age of treatment were found to be associated with nonpersistence. These findings may be important for health care professionals when initiating methylphenidate treatment in children.

Pedagoško obrazovanje nastavnika u Srbiji - od nastavlenija do Centra za obrazovanje nastavnika

The paper provides an overview of key events relevant to the education of teachers of specific subjects in Serbia up until the founding of the Center for Teacher Education in 1971, and aims to establish the key stages in the development of this education. Taking into account the position of pedagogical knowledge relative to the initial education of teachers of specific subjects, the content, organization, initiators and practitioners of teacher education, four stages can be distinguished in the development of the education of subject teachers. The first begins in 1838 with the publication of the first set of instructions for secondary school teachers. The second stage was characterized by the introduction of pedagogy into the curriculum of the highest educational institution in Serbia and the passing of the law on teacher examinations. The third significant stage comprises the founding of the Department of Pedagogy at the Great School and the work of Vojislav Bakić. The fourth stage relates to the work of the General Pedagogical Seminar, which was founded in the interwar period and resumed its work in changed circumstances in 1948. The paper concludes that the development of teacher education in Serbia has followed a similar course to that in Europe, but that the process in Serbia has been characterized by long periods of discontinuity, which has slowed down the institutionalization of this type of education. In addition, it suggests that the reconstruction of the development of teacher education can lead to more detailed insight into the process of professionalization of the teaching profession, and also to a better understanding of the development of particular pedagogical disciplines, notably teaching methodology.

Massive hemorrhage and osteonecrosis of the jaw in the patient with methotrexate-associated lymphoproliferative disorder: Report of a case and review of literature

Introduction: Methotrexate-associated lymphopro-liferative disorder (MTX-LPD) is one of the adverse effects of methotrexate (MTX). We report a case of MTX-LPD that caused osteonecrosis and massive bleeding without regression following MTX withdrawal. Case Report: A 61-year-old woman was referred to our hospital because of delayed socket healing after dental extraction. She had been diagnosed with rheumatoid arthritis (RA) and received MTX treatment for six years. At the first visit, a 15 mm × 15 mm bone exposure and swelling of the surrounding gingiva in the right upper molar region were observed. We performed an incisional biopsy of the necrotic bone and surrounding mucosal tissue. The histopathological diagnosis was diffuse large B-cell lymphoma (DLBCL). Therefore, we referred the patient to the Department of Hematology in our hospital. She was diagnosed with MTX-LPD based on the history of MTX therapy for RA, and MTX was discontinued immediately. However, the lesion progressed and caused bleeding that required blood transfusion and hemostasis by microfibrous collagen and tie-over even after the withdrawal of MTX. Subsequently, rituximab, cyclophosphamide, vincristine, and prednisolone (R-COP) chemotherapy was initiated. After 3 courses of chemotherapy, sequestrectomy was performed under local anesthesia. She achieved complete remission after 8 courses of chemotherapy, and there was no recurrence of necrotic bone exposure or gingival swelling. Conclusion: Approximately 80% of MTX-LPD cases occurring in the oral region show regression after MTX discontinuation, but we experienced a case in which bleeding occurred with progression of the lesion after discontinuation. Careful follow-up is required during the MTX discontinuation period.

Carbonaceous Aerosols in PM1, PM2.5, and PM10 Size Fractions over the Lanzhou City, Northwest China

Carbonaceous particles have been confirmed as major components of ambient aerosols in urban environments and are related to climate impacts and environmental and health effects. In this study, we collected different-size particulate matter (PM) samples (PM1, PM2.5, and PM10) at an urban site in Lanzhou, northwest China, during three discontinuous one-month periods (January, April, and July) of 2019. We measured the concentrations and potential transport pathways of carbonaceous aerosols in PM1, PM2.5, and PM10 size fractions. The average concentrations of OC (organic carbon) and EC (elemental carbon) in PM1, PM2.5, and PM10 were 6.98 ± 3.71 and 2.11 ± 1.34 μg/m3, 8.6 ± 5.09 and 2.55 ± 1.44 μg/m3, and 11.6 ± 5.72 and 4.01 ± 1.72 μg/m3. The OC and EC concentrations in PM1, PM2.5, and PM10 had similar seasonal trends, with higher values in winter due to the favorable meteorology for accumulating pollutants and urban-increased emissions from heating. Precipitation played a key role in scavenge pollutants, resulting in lower OC and EC concentrations in summer. The OC/EC ratios and principal component analysis (PCA) showed that the dominant pollution sources of carbon components in the PMs in Lanzhou were biomass burning, coal combustion, and diesel and gasoline vehicle emissions; and the backward trajectory and concentration weight trajectory (CWT) analysis further suggested that the primary pollution source of EC in Lanzhou was local fossil fuel combustion.

Perioperative Coagulation Profile with Thromboelastography in Aspirin-Treated Patients Undergoing Posterior Lumbar Fusion

Background It has been generally recommended that platelet function may recover after the recommended 5-day discontinuation period prior to operation. The technique of thromboelastography has been demonstrated to monitor intraoperative platelet function in liver transplantation and coronary bypass surgery. However, there is a dearth of literature that addresses the utility of thromboelastography in aspirin-treated patients undergoing fusion. Objectives To introduce a functional method of monitoring coagulation and validate the effectiveness of thromboelastography perioperatively in assessing aspirin-treated patients undergoing posterior lumbar fusion. Study design This research used a retrospective study design. Setting Orthopedic Department of Changhai Hospital,Shanghai, China and Orthopedic and Anesthesia Department of Changzheng Hospital. Methods Eighty patients were divided into aspirin-naive and aspirin-treated groups in this study. They had equally undergone lumbar fusion surgery for at least one or more segments between January and June 2018. They matched for age, gender, number of fused segments, and surgical procedures. The coagulation profile, including the reaction time (R), kinetics (K), maximal amplitude (MA), alpha-angle, and coagulation index (CI), platelet inhibition ratio (PIR) was analyzed by thromboelastogram (TEG) prior to operation and on preoperative days 1, 3, and 5. Correlation analysis included parameters such as waiting time, intraoperative blood loss, and postoperative drainage. Results Perioperatively, the TEG values including R, K, MA, alpha-angle, and CI, PIR, and correlation analysis showed no significant difference between the 2 groups, respectively (P > 0.05). Limitations First, the relatively small number of patients recruited limits control over other factors; larger studies may need to confirm our findings. Second, the patients were objectively less healthy with more medication treatment, which may result in a variance in the amount of blood loss. Randomized controlled studies are needed to further confirm these results. Conclusions TEG may be a helpful method to monitor perioperative platelet function in aspirin-treated patients undergoing fusion. It may be comparatively safe to relax the restriction of the aspirin-discontinued therapeutic window to approximately 2 to 3 days prior to surgery.

Esophageal Pityriasis Lichenoides Chronica

Abstract Casestudy: Pityriasis Lichenoides is an uncommon inflammatory skin condition of unknown cause that ranges from mild chronic form to a more severe acute eruption. The mild form, pityriasis lichenoid chronica (PLC), is characterized by the gradual development of symptomless, small scaling papules that spontaneously flatten and regress over weeks. The acute form is characterized by the sudden eruption of small scaling papules that develops into blisters and crusted red brown spots. This acute form is called pityriasis lichenoides et varioliformis acuta (PLEVA). Both forms usually involve the skin of the trunk and proximal extremities. Visceral involvement is not a well described phenomenon. We report a case of a 69-year-old female with significant history of PLC controlled by immunosuppressive therapy. The patient presented with odynophagia and dysphagia that occurred after a period of discontinuation of her PLC treatment. She underwent endoscopy which showed distal esophageal narrowing and stricture. Biopsy revealed squamous esophageal mucosa with marked intraepithelial lymphocytosis along with basal cell hyperplasia, acanthosis, vacuolation and prominent apoptosis in the epithelial cells. PAS, CMV and HSV stains showed no fungal or viral organisms. The esophagus is commonly involved in a number of dermatologic conditions including pemphigus vulgaris, erythema multiforme, epidermolysis bullosa, lichen planus and lichen sclerosis. The pattern of involvement is often in the form of “lymphocytic esophagitis”. To our knowledge, there are no reported cases in the literature on PLC involving the esophagus. While the diagnosis heavily relies on clinical history of PLC, awareness of potential involvement of the esophagus and attention to certain endoscopic and morphological details may better help classify esophagitis biopsies.

Conditioned Place Preference (CPP) in Rats: From Conditioning to Reinstatement Test.

Opioid addiction in humans is a chronically relapsing disorder characterized by discontinuous periods of drug use and abstinence resulting in dependence. With time, the probability of falling into renewed drug consumption becomes particularly high and constitutes a considerable problem in the management of opioid addicts. Opioid addiction represents an important health concern and animal models have been crucial in understanding the neurobiology and pathophysiology of this complex disease. Although animal models of addiction do not fully reproduce the human condition, they do permit investigation of specific elements of the process as well as identification of potential therapeutic targets. In this chapter, we provide a step-by-step description of the morphine-conditioned place preference (CPP) model that represents a useful preclinical animal model extensively used to study the rewarding/aversive effect of drugs.

Work functioning impairment in the course of pharmacotherapy treatment for depression

This study investigated the association between the duration of pharmacotherapy treatment for depression, or discontinuation from treatment, and work functioning impairment. This was a retrospective cohort study examining 30,409 workers. Work functioning impairment was assessed using a questionnaire, and treatment status was assessed using medical claims data. Odds ratios (ORs) of workers with severe work functioning impairment compared with healthy workers (control group) were calculated using logistic regression analysis. Continuous medical treatment was associated with severely impaired work functioning regardless of treatment period [continuous medical treatment; 4 months <: OR = 3.2, 4 months ≥, 10 months <: OR = 2.6, 10 months ≥, 14 months <: OR = 2.3, 14 months ≥, 16 months <: OR = 2.3, which are all statistically significant (p < 0.05)]. Workers who initially received pharmacotherapy treatment but discontinued in < 11 months had a significantly higher OR (treatment discontinuation period; 3 months <: OR = 2.3, 3 months ≥, 8 months <; OR = 2.0, 8 months ≥, 11 months <; OR = 3.0), while those who discontinued at ≥ 11 months did not (OR = 1.4, 95% CI 0.6–3.5). The sensitivity analysis excluding participants with at least one psychiatric comorbidity other than depression did not change the final result. It is important for the occupational health practitioners and attending psychiatrists to follow up in cooperation with each other, paying attention to the decrease in work functioning in addition to the symptoms.

Periodic property of the time-fractional Kundu–Mukherjee–Naskar equation

The Kundu–Mukherjee–Naskar equation (KMN) can model the data transmission in birefringent fibers through molecules or pulses in a few Femto-seconds. A fractional modification with Riemann-Liouville time-fractional derivative is suggested to take into account the discontinuous period, and the wave-train description is used to reduce the equation to a fractional nonlinear Schrödinger equation, which is further converted to a damping Duffing equation. Effective modification of the homotopy perturbation method is suggested to deal with the damping term.

Anthropogenic Photolabile Chlorine in the Cold-Climate City of Montreal

Chlorine atoms play a key role in the oxidative potential of the atmosphere and biogeochemical cycling of selected elements. This study provides a decadal analysis (2010−2019) of chloride ions in PM2.5 particles in the city of Montreal, where these are most concentrated systematically in the winter (up to 1.6 µg/m3). We also herein present the measurement of photolabile chlorine, which includes chlorine-containing compounds (e.g., Cl2, HOCl, ClNO2, ClNO3, and BrCl) that release chlorine atoms upon interaction with radiation, in urban Montreal, Canada using Cl2-RPGE (Cl2 Reactive Phase Gas Extraction) tubes and quantifying the chlorinated product by GC-MS. Photolabile chlorine in urban Montreal was measured during a discontinuous period primarily in summer 2018 and winter 2019 with a time resolution of 30 min, with concentrations ranging from 3 to 545 ng/m3 expressed as Cl2. The reported values are considered lower limits, as compounds such as HOCl and ClNO2 can only be partially converted in the current setup. The largest peak of gaseous photolabile chlorine occurred in the winter, when significant sources of anthropogenic salt are used in snow removal in the city. This coincides with observed chloride ion measurements in airborne particles, implying that anthropogenic salt addition produces photoactive chlorine. The maximum chlorine signal was consistently obtained during the daytime, which is in accordance with the tropospheric radiation profile. Complementary photochemistry laboratory experiments indicated that upon tropospheric radiation (340 ≤ λ ≤ 400 nm; UVA), an increase (20–100%) was observed, confirming the formation of Cl atoms from photolabile chlorine compounds. Thus, this portable technique is adequate for Cl atoms and photolabile chlorine-containing compounds upon photolysis using UVA lamps. High-resolution S/TEM and energy-dispersive X-ray spectroscopy (EDS) were used to evaluate collected particle morphology and composition. The behavior of complementary pollutants (O3, CO, PM2.5, and NOx) was also briefly discussed. We herein discuss the measurement of photolabile halogens within a northern urban metropolitan environment and the impact of anthropogenic sources on chlorine concentrations.

Effects of enriched branched-chain amino acid supplementation on sarcopenia.

To evaluate the effects of short-term administration of enriched branched-chain amino acids (BCAAs) on subjects with pre-sarcopenia or sarcopenia, our quasi-experimental study enrolled 33 subjects (12 pre-sarcopenia/21 sarcopenia; 6 men/27 women; mean age 66.6 ± 10.3 years) to take one sachet (3.6 g) of enriched BCAA powder twice a day for five weeks followed by a discontinuation period of 12 weeks. We evaluated sarcopenic parameters, including grip strength, 6-meter gait speed, and bioelectrical-impedance-analysis-derived skeletal mass index (SMI), at baseline, 5 weeks, and 17 weeks. We found that both pre-sarcopenic and sarcopenic subjects showed improved SMI, gait speed, and grip strength at 5 weeks. However, all three parameters progressively declined at 17 weeks, especially SMI and grip strength in subjects aged < 65 years and gait speed and grip strength in subjects aged ≥ 65 years. It thus appears that supplementation with enriched BCAAs for 5 weeks correlates with short-term positive effects on sarcopenic parameters but attenuation of those effects following discontinuation for 12 weeks.

Modeling and application of discontinuous slow crack growth behaviors of high-density polyethylene pipe with various geometries and loading conditions

A slow crack growth model based on the crack layer theory for various geometries of a high-density polyethylene (HDPE) pipe is developed to investigate the discontinuous slow crack growth (SCG) behavior of HDPE pipes. Discontinuous SCG patterns, jump lengths, and periods can be accurately simulated using the proposed model. In addition, effects of soil embedding height, internal pressure, and ground pressure on the discontinuous SCG behavior and consequent lifetime are investigated. It is confirmed that the additional ground pressure increased the discontinuous SCG rates of the buried HDPE pipes, thereby reducing the final lifetime considerably.

Frontal electroencephalogram reveals emergence-like brain activity occurring during transition periods in cardiac surgery

BackgroundCardiac surgery has one of the highest incidences of intraoperative awareness. The periods of initiation and discontinuation of cardiopulmonary bypass could be high-risk periods. Certain frontal EEG patterns might plausibly occur with unintended intraoperative awareness. This study sought to quantify the incidence of these pre-specified patterns during cardiac surgery. MethodsTwo-channel bihemispheric frontal EEG was recorded in 1072 patients undergoing cardiac surgery as part of a prospective observational study. Spectrograms were created, and mean theta (4–7 Hz) power and peak alpha (7–17 Hz) frequency were measured in patients under general anaesthesia with isoflurane. Emergence-like EEG activity in the spectrogram during surgery was classified as an alpha peak frequency increase by 2 Hz or more, and a theta power decrease by 5 dB or more in comparison with the median pre-bypass values. ResultsData from 1002 patients were available for analysis. Fifty-five of those patients (5.5%) showed emergence-like EEG activity at least once during surgery with a median duration of 13.2 min. These patients were younger (median age, 59 vs 67 yr; P<0.001) and the median end-tidal isoflurane concentration before cardiopulmonary bypass was higher (0.82 vs 0.75 minimum alveolar concentration [MAC]; P=0.013). There was no significant difference between those with or without emergence-like EEG activity in sex, lowest core temperature, or duration of surgery. Forty-six of these EEG changes (84%) occurred within a 1 h time window centred on separation from cardiopulmonary bypass. ConclusionThe findings of this study suggest that approximately one in 20 patients undergoing cardiac surgery with a volatile anaesthetic agent have a sustained EEG pattern while surgery is ongoing that is often seen with emergence from general anaesthesia. Monitoring the frontal EEG during cardiopulmonary bypass may identify these events and potentially reduce the incidence of unintended awareness. Clinical trial registrationNCT 02976584.

Causal Effect of Honorary Titles on Physicians' Service Volumes in Online Health Communities: Retrospective Study.

BackgroundAn OHC online health community (OHC) is an interactive platform for virtual communication between patients and physicians. Patients can typically search, seek, and share their experience and rate physicians, who may be involved in giving advice. Some OHC providers provide incentives in form of honorary titles to encourage the web-based involvement of physicians, but it is unclear whether the award of honorary titles has an impact on their consultation volume in an OHC.ObjectiveThis study is designed to identify the differential treatment effect of the incentive policy on the service volumes for the subgroups of treatment and control in an OHC. This study aims to answer the following questions: Does an honorary title for physicians impact their service volumes in an OHC? During the period of discontinuity, can we identify the sharp effect of the incentive award on the outcomes of physicians’ service volumes?MethodsWe acquired the targeted samples based on treatment, namely, physicians with an honorary title or not and outcomes measured before and after the award of the 2 subgroups. A regression discontinuity design was applied to investigate the impact of the honorary titles incentive as a treatment in an OHC. There was a sharply discontinuous effect of treatment on physicians’ online health service performance. The experimental data set consisted of 346 physicians in the treatment group (with honorary titles). Applying the propensity score matching method, the same size of physicians (n=346) was matched and selected as the control group.ResultsA sharp discontinuity was found at the time of the physician receiving the honorary title. The results showed that the parametric estimates of the coefficient were significantly positively (P<.001) associated with monthly home page views. The jump in the monthly volumes of home page views was much sharper than that of the monthly consultations.ConclusionsThe changes in the volumes of monthly consultations and home page views reflect the differential treatment effect of honorary titles on physicians’ service volumes. The effect of the incentive policy with honorary titles is objectively estimated from both the perspective of online and offline medical services in an OHC. Being named with honorary titles significantly multiplied monthly home page views, yet it did not significantly impact monthly consultations. This may be because consultation capacity is limited by the physician's schedule for consultations.

Advances in Management of Food Allergy in Children

Food allergy is a potentially life-threatening medical condition and a significant public health concern worldwide. The current management consists of strict avoidance of the culprit food and treating any adverse reactions from unintended food ingestion. The increasing prevalence of food allergy encouraged research and clinical trials in the field of specific allergen immunotherapy (AIT) which represents an appealing approach, especially in pediatric age. AIT consists of the gradual administration of growing amounts of the offending allergen in order to induce food desensitization, which is an increase in the threshold for reactivity while continuing on regular exposure to the allergen. AIT can be administered through oral, sublingual, epicutaneous, and subcutaneous routes. Reports on oral immunotherapy (OIT) thus far have been more extensive. The desirable goal is to achieve "post desensitization effectiveness", that is the ability to introduce food without reaction even after a period of discontinuation of the offending food. Other therapeutic approaches are being studied alongside immunotherapy such as modified proteins, probiotics, Chinese herbal supplements, biologic therapies, and DNA vaccines.

The Impact of Reproductive Issues on Preferences of Women with Relapsing Multiple Sclerosis for Disease-Modifying Treatments.

Relapsing-remitting multiple sclerosis (RRMS) is an incurable disease characterised by relapses (periods of function loss) followed by full or partial recovery, and potential permanent disability over time. Many disease-modifying treatments (DMTs) exist that help reduce relapses and slow disease progression. Most are contraindicated during conception/pregnancy and some require a discontinuation period before trying to conceive. Although around three-quarters of people with RRMS are women, there is limited knowledge about how reproductive issues impact DMT preference. The aim of this study was to measure the preferences for DMTs of women with RRMS who are considering pregnancy. An online discrete choice experiment (DCE). Participants chose between two hypothetical DMTs characterised by a set of attributes, then indicated if they preferred their choice to no treatment. Attributes were identified from interviews and focus groups with people with RRMS and MS professionals, as well as literature reviews, and included the probability of problems with pregnancy, discontinuation of DMTs, and breastfeeding safety. In each DCE task, participants were asked to imagine making decisions in three scenarios: now; when trying to conceive; and when pregnant. Two mixed logit models were estimated, one to assess the statistical significance between scenarios and one in maximum acceptable risk space to allow comparison of the magnitudes of parameters between scenarios. Women with RRMS who were considering having a child in the future, recruited from a UK MS patient register. Sixty respondents completed the survey. Participants preferred no treatment in 12.6% of choices in the 'now' scenario, rising significantly to 37.6% in the 'trying to conceive' scenario and 60.3% in the 'pregnant' scenario (Kruskal-Wallis p < 0.001). This pattern corresponds with results from models that included a no-treatment alternative-specific constant (ASC) capturing differences between taking and not taking a DMT not specified by the attributes. The ASC was lower in the trying to conceive scenario than in the now scenario, and lower still in the pregnant scenario, indicating an intrinsic preference for no treatment. Participants also placed relatively less preference on reducing relapses and avoiding disease progression in the trying to conceive and pregnant scenarios compared with a lower risk of problems with pregnancy. In the trying to conceive scenario, participants' preference for treatments with shorter washout periods increased. Women with RRMS considering having a child prefer DMTs with more favourable reproduction-related attributes, even when not trying to conceive. Reproductive issues also influenced preferences for DMT attributes not directly related to pregnancy, with preferences dependent on the life circumstances in which choices were made. The design of the DCE highlights the benefits of considering the scenario in which participants make choices, as they may change over time.