Association between methylphenidate treatment and risk of seizure: A population-based self-controlled case series study

Background: Individuals with attention-deficit hyperactivity disorder (ADHD) are at increased risk of seizures. Stimulant medications such as methylphenidate are the most commonly prescribed treatment for ADHD, but the association between their therapeutic use and the risk of seizures is unclear. We aimed to investigate the association between methylphenidate treatment and the risk of seizure. Methods: For this population-based observational study, we used the electronic medical record database of the Hong Kong Clinical Data Analysis And Reporting System to identify individuals aged 6–25 years who received at least one methylphenidate prescription during the study period. Individuals with records of seizure or epilepsy before the study period were excluded. Individuals treated with methylphenidate who had seizures during the study period were included in the subsequent analyses, and a self-controlled case-series design was used to control for time-invariant individual characteristics. We did additional analyses using skin infection as a negative control outcome. We compared relative incidence of seizure during periods when individuals were exposed to methylphenidate with that during non-exposed periods. Findings: Of 29 604 individuals prescribed methylphenidate between Jan 1, 2001, and Dec 31, 2017, 269 (199 males and 70 females) had incident seizures. The mean age at baseline was 6·66 years (SD 2·01) and the median age at the incident seizure was 9·69 years (IQR 7·62–12·99). The overall incidence of seizure during methylphenidate treatment was 4·4 per 10 000 patient-years. We detected an increased risk of seizure during the first 30 days of methylphenidate treatment compared with that during non-exposed periods, with an incidence rate ratio of 4·01 (95% CI 2·09–7·68). No increase in risk was identified during the following 31–180 days of treatment (1·13, 0·56–2·25) or during subsequent treatment (1·38, 0·92–2·07). We did not identify an increased risk in any risk window for the negative control outcome analysis. No individuals died because of a seizure during the study period. Interpretation: The incidence of seizures was higher in the period immediately after the start of methylphenidate treatment than in the non-exposed period. No increased risk was observed during continuation of methylphenidate treatment. The association between methylphenidate treatment and seizures immediately after initiation of medication can be seen as a potential safety signal. Monitoring of neurological outcomes in individuals with ADHD is recommended when they first start methylphenidate treatment. Funding: Hong Kong Research Grants Council

Clinical utility gene card for : inherited optic neuropathies including next-generation sequencing-based approaches

Non peer reviewe

Paclitaxel induces immunogenic cell death in ovarian cancer via TLR4/IKK2/SNARE-dependent exocytosis

Emerging evidence shows that the efficacy of chemotherapeutic drugs are reliant on their capability to induce immunogenic cell death (ICD), thus transforming dying tumor cells into antitumor vaccines. We wanted to uncover potential therapeutic strategies that target ovarian cancer by having a better understanding of the standard-of-care chemotherapy treatment. Here, we showed in ovarian cancer that paclitaxel induced ICD-associated DAMPs (i.e. damage-associated molecular patterns, such as CALR exposure, ATP secretion and HMGB1 release) in vitro and elicited significant antitumor responses in tumor vaccination assays in vivo. Paclitaxel-induced TLR4 signaling was essential to the release of DAMPs, which lead to the activation of NF-κB-mediated CCL2 transcription and IKK2-mediated SNARE-dependent vesicle exocytosis, thus exposing CALR on the cell surface. Paclitaxel induced ER stress, which triggered PERK activation and eIF2α phosphorylation independent of TLR4. Paclitaxel chemotherapy induced T cell infiltration in ovarian tumors of the responsive patients; CALR expression in primary ovarian tumors also correlated with patients' survival and patient response to chemotherapy. These findings suggest that the effectiveness of paclitaxel relied upon the activation of antitumor immunity through ICD via TLR4 and highlighted the importance of CALR expression in cancer cells as an indicator of response to paclitaxel chemotherapy in ovarian cancer

Overview on the phenomenon of two-qubit entanglement revivals in classical environments

The occurrence of revivals of quantum entanglement between separated open quantum systems has been shown not only for dissipative non-Markovian quantum environments but also for classical environments in absence of back-action. While the phenomenon is well understood in the first case, the possibility to retrieve entanglement when the composite quantum system is subject to local classical noise has generated a debate regarding its interpretation. This dynamical property of open quantum systems assumes an important role in quantum information theory from both fundamental and practical perspectives. Hybrid quantum-classical systems are in fact promising candidates to investigate the interplay among quantum and classical features and to look for possible control strategies of a quantum system by means of a classical device. Here we present an overview on this topic, reporting the most recent theoretical and experimental results about the revivals of entanglement between two qubits locally interacting with classical environments. We also review and discuss the interpretations provided so far to explain this phenomenon, suggesting that they can be cast under a unified viewpoint.Comment: 16 pages, 9 figures. Chapter written for the upcoming book "Lectures on general quantum correlations and their applications

A new multistage lattice vector quantization with adaptive subband thresholding for image compression

Lattice vector quantization (LVQ) reduces coding complexity and computation due to its regular structure. A new multistage LVQ (MLVQ) using an adaptive subband thresholding technique is presented and applied to image compression. The technique concentrates on reducing the quantization error of the quantized vectors by "blowing out" the residual quantization errors with an LVQ scale factor. The significant coefficients of each subband are identified using an optimum adaptive thresholding scheme for each subband. A variable length coding procedure using Golomb codes is used to compress the codebook index which produces a very efficient and fast technique for entropy coding. Experimental results using the MLVQ are shown to be significantly better than JPEG 2000 and the recent VQ techniques for various test images

Interaction of Imidazole Containing Hydroxamic Acids with Fe(III): Hydroxamate Versus Imidazole Coordination of the Ligands

Solution equilibrium studies on Fe(III) complexes formed with imidazole-4-carbohydroxamic acid (Im-4-Cha), N-Me-imidazole-4-carbohydroxamic acid (N-Me-Im-4-Cha), imidazole-4-acetohydroxamic acid (Im-4-Aha), and histidinehydroxamic acid (Hisha) have been performed by using pH-potentiometry, UV-visible spectrophotometry, EPR, ESI-MS, and H1-NMR methods. All of the obtained results demonstrate that the imidazole moiety is able to play an important role very often in the interaction with Fe(III), even if this metal ion prefers the hydroxamate chelates very much. If the imidazole moiety is in α-position to the hydroxamic one (Im-4-Cha and N-Me-Im-4-Cha) its coordination to the metal ion is indicated unambiguously by our results. Interestingly, parallel formation of (Nimidazole, Ohydroxamate), and (Ohydroxamate, Ohydroxamate) type chelates seems probable with N-Me-Im-4-Cha. The imidazole is in β-position to the hydroxamic moiety in Im-4-Aha and an intermolecular noncovalent (mainly H-bonding) interaction seems to organize the intermediate-protonated molecules in this system. Following the formation of mono- and bishydroxamato mononuclear complexes, only EPR silent species exists in the Fe(III)-Hisha system above pH 4, what suggests the rather significant “assembler activity” of the imidazole (perhaps together with the ammonium moiety)

Metalloporphyrin intercalation in liposome membranes: ESR study

Liposomes characterized by membranes featuring diverse fluidity (liquid-crystalline and/or gel phase), prepared from egg yolk lecithin (EYL) and dipalmitoylphosphatidylcholine (DPPC), were doped with selected metalloporphyrins and the time-related structural and dynamic changes within the lipid double layer were investigated. Porphyrin complexes of Mg(II), Mn(III), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), and the metal-free base were embedded into the particular liposome systems and tested for 350 h at 24°C using the electron spin resonance (ESR) spin probe technique. 5-DOXYL, 12-DOXYL, and 16-DOXYL stearic acid methyl ester spin labels were applied to explore the interior of the lipid bilayer. Only the 16-DOXYL spin probe detected evident structural changes inside the lipid system due to porphyrin intercalation. Fluidity of the lipid system and the type of the porphyrin complex introduced significantly affected the intermolecular interactions, which in certain cases may result in self-assembly of metalloporphyrin molecules within the liposome membrane, reflected in the presence of new lines in the relevant ESR spectra. The most pronounced time-related effects were demonstrated by the EYL liposomes (liquid-crystalline phase) when doped with Mg and Co porphyrins, whereas practically no spectral changes were revealed for the metal-free base and both the Ni and Zn dopants. ESR spectra of the porphyrin-doped gel phase of DPPC liposomes did not show any extra lines; however, they indicated the formation of a more rigid lipid medium. Electronic configuration of the porphyrin’s metal center appeared crucial to the degree of molecular reorganization within the phospholipid bilayer system

Suitability of databases in the Asia-Pacific for collaborative monitoring of vaccine safety

Introduction: Information regarding availability of electronic healthcare databases in the Asia-Pacific region is critical for planning vaccine safety assessments particularly, as COVID-19 vaccines are introduced. This study aimed to identify data sources in the region, potentially suitable for vaccine safety surveillance. This manuscript is endorsed by the International Society for Pharmacoepidemiology (ISPE). Methods: Nineteen countries targeted for database reporting were identified using published country lists and review articles. Surveillance capacity was assessed using two surveys: a 9-item introductory survey and a 51-item full survey. Survey questions related to database characteristics, covariate and health outcome variables, vaccine exposure characteristics, access and governance, and dataset linkage capability. Other questions collated research/regulatory applications of the data and local publications detailing database use for research. Results: Eleven databases containing vaccine-specific information were identified across 8 countries. Databases were largely national in coverage (8/11, 73%), encompassed all ages (9/11, 82%) with population size from 1.4 to 52 million persons. Vaccine exposure information varied particularly for standardized vaccine codes (5/11, 46%), brand (7/11, 64%) and manufacturer (5/11, 46%). Outcome data were integrated with vaccine data in 6 (55%) databases and available via linkage in 5 (46%) databases. Data approval processes varied, impacting on timeliness of data access. Conclusions: Variation in vaccine data availability, complexities in data access including, governance and data release approval procedures, together with requirement for data linkage for outcome information, all contribute to the challenges in building a distributed network for vaccine safety assessment in the Asia-Pacific and globally. Common data models (CDMs) may help expedite vaccine safety research across the region

Unregulated serving sizes on the Canadian nutrition facts table – an invitation for manufacturer manipulations

Abstract Background Serving sizes on the Nutrition Facts table (NFt) on Canadian packaged foods have traditionally been unregulated and non-standardized. The federal government recently passed legislation to regulate the serving sizes listed on the NFt. The objective of this study was to compare the serving sizes on food product NFts to the recommendations in the 2003 Nutrition Labelling regulation (Schedule M) reference amounts, the Canadian Food Inspection Agency (CFIA) ranges, and Canada’s Food Guide recommendations. An additional objective was to determine if food and beverage products that report smaller serving sizes have a higher calorie density, compared to similar products with a larger serving size. Methods Data for 10,487 products were retrieved from the 2010 Food Label Information Program (FLIP) database and categorized according to Schedule M categories. Correlations between calorie density and manufacturer stated serving size were tested and the proportion of products meeting recommendations were tabulated. Results 35% of products had serving sizes on the NFt that were smaller than the Schedule M reference amount and 23% exceeded the reference amount. 86% of products fell within the CFIA’s recommended serving size ranges; however, 70% were within the lower-half of the range. Several bread and juice categories exceeded CFG’s recommendations, while several dairy product categories were smaller than the recommendations. Of the 50 Schedule M sub-categories analyzed, 31 (62%) exhibited a negative correlation between serving size and calorie density. Conclusion While most products fell within the CFIA’s recommended serving size ranges, there was a tendency for products with a higher calorie density to list smaller serving sizes