Efficacy and tolerability of levetiracetam in people with and without intellectual disabilities: A naturalistic case control study.

INTRODUCTION: People with Intellectual Disabilities (PwID) are twenty times more likely than general population to have epilepsy. Guidance for prescribing antiseizure medication (ASM) to PwID is driven by trials excluding them. Levetiracetam (LEV) is a first-line ASM in the UK. Concerns exist regarding LEV's behavioural and psychological adverse effects, particularly in PwID. There is no high-quality evidence comparing effectiveness and adverse effects in PwID to those without, prescribed LEV. METHODS: Pooled casenote data for patients prescribed LEV (2000-2020) at 18 UK NHS Trusts were analysed. Demographics, starting and maximum dose, adverse effects, dropouts and seizure frequency between ID (mild vs. moderate-profound (M/P)) and general population for a 12-month period were compared. Descriptive analysis, Mann-Whitney, Fisher's exact and logistic regression methods were employed. RESULTS: 173 PwID (mild 53 M/P 120) were compared to 200 without ID. Mean start and maximum dose were similar across all groups. PwID (Mild & M/P) were less likely to withdraw from treatment (P = 0.036). No difference was found between ID and non-ID or between ID groups (Mild vs M/P) in LEV's efficacy i.e. >50 % seizure reduction. Significant association emerged between ID severity and psychiatric adverse effects (P = 0.035). More irritability (14.2 %) and aggression (10.8 %) were reported in M/P PwID. CONCLUSION: PwID and epilepsy have high rates of premature mortality, comorbidities, treatment resistance and polypharmacy but remain poorly researched for ASM use. This is the largest studied cohort of PwID trialled on LEV compared to general population controls. Findings support prescribing of LEV for PwID as a first-line ASM.

Microwave assisted regioselective halogenation of benzo[b][1,4]oxazin-2-ones via sp2 C-H functionalization.

A microwave assisted, palladium-catalyzed regioselective halogenation of 3-phenyl-2H-benzo[b][1,4]oxazin-2-ones has been demonstrated using inexpensive and readily available N-halosuccinimide. The reaction utilizes the nitrogen atom present in the heterocyclic ring as the directing group to afford regioselective halogenated products in good to moderate yields. The established protocol provides wide substrate scope, high functional group tolerance, and high atom and step economy. The reaction proved to be cost-effective and time-saving as it required only a few minutes for completion and is amenable to gram scale. The halogen atoms present in synthesized products provide further scope for post-functionalization. Several post-functionalized products have also been synthesised to demonstrate the high utility of the reaction in the field of drug discovery and late-stage functionalization.

Rhodium-catalyzed selenylation and sulfenylation of quinoxalinones 'on water'.

A rhodium-catalysed, regioselective synthetic methodology for selenylation and sulfenylation of 3-phenyl quinoxolinones has been developed through N-directed C-H activation in the presence of silver triflimide, and silver carbonate using dichalcogenides 'on water'. The methodology has been proven to be efficient, regioselective and green. Using this method, a range of selenylations and sulfenylations of the substrates has been carried out in good to excellent yields. Further, late-stage functionalisation produced potential anti-tumour, anti-fungal and anti-bacterial agents making these compounds potential drug candidates.

Sustainable C-H activation approach for palladium-catalyzed, regioselective functionalization of 1-methyl-3-phenyl quinoxaline-2(1H)-ones in water.

A sustainable and environment-friendly approach for the regioselective acylation of 1-methyl-3-phenyl quinoxaline-2(1H)-ones has been developed in water. The present protocol requires palladium acetate as a catalyst and exhibits a wide substrate scope by employing commercially available, non-toxic aldehydes, benzyl alcohols and toluenes as acyl surrogates. The mechanistic studies demonstrated the adoption of a free radical pathway for this transformation. Furthermore, the established protocol exhibits excellent regioselectivity and high functional group tolerance and is amenable to the gram scale. The established synthetic method also provides a practical and convenient route for the late-stage functionalization of some potential drug candidates.

Evidence of improved bond strength of resin-based sealer with the use of natural antioxidants on hypochlorite treated dentin: an in vitro study.

Aim: To evaluate the effect of natural antioxidants as final irrigants on the push-out bond strength of epoxy resin-based sealer to the hypochlorite treated dentin. Methods: Eighty single-rooted human mandibular incisors were prepared using ProTaper Gold (Dentsply, TN, USA) and an irrigation protocol including 3% NaOCl, followed by ethylenediaminetetraacetic acid (EDTA), and 3% NaOCl. The groups (n =20) were divided according to the final irrigant used: Group 1: None (Control); Group 2: 5% sodium ascorbate, Group 3: 5% grape seed extract (GSE); and Group 4: 5% pine bark extract. The obturation of root canals was performed using gutta-percha and AH Plus (Dentsply DeTrey, Germany). Bond strength was evaluated using the push-out test under the universal testing machine at a crosshead speed of 0.5 mm/min, and statistical analyses were performed using one-way ANOVA. The p-value significance was evaluated by Tukey's post hoc test (p<0.01). Results: Mean push-out bond strength values were compared in all the groups, and there was a statistically significant improvement in the experimental final irrigating groups. 5% pine bark extract had improved bond strength than the other groups, and the least bond strength was observed in the control group. Conclusion: The irrigation protocols and naturally derived antioxidants affected the resin-based sealer's bond strength to root dentin. It was observed that the use of antioxidants effectively reversed the compromised bond strength of resin-based sealers to root dentin. 5% pine bark extract application showed better bond strength.

Assessment of postoperative pain after single-visit root canal treatment using rotary and reciprocating file systems: an in vivo study.

Background: Various instrument kinematics used in single-visit endodontics influence the occurrence of pain after endodontic therapy. This study aimed to evaluate the occurrence of pain after mechanical instrumentation with Hyflex EDM (HEDM) and WaveOne Gold (WOG) during single-visit endodontic therapy. Methods: Sixty patients diagnosed with asymptomatic irreversible pulpitis and normal apical tissues in mandibular premolar teeth were included in the study for single-visit root canal therapy. The patients were divided into two groups (n = 30) according to the rotary instrument used during root canal preparation (group A [HEDM] and group B [WOG]). Pain was evaluated after endodontic therapy at 8, 24, and 48 h intervals using the visual analog scale (VAS). Data obtained were analyzed using the chi-square test, independent t-test, MannWhitney U test, and Wilcoxon matched-pairs test. Results: Statistically significant differences were observed between the two groups (P < 0.001) at 8, 24, and 48 h, with WOG exhibiting less pain than HEDM files. Conclusion: Postoperative pain was lower in the WOG file system than in the HEDM file system after single-visit root canal therapy at 8, 24, and 48 h.

Lacosamide in the general population and in people with intellectual disability: Similar responses?

PURPOSE: Epilepsy prevalence is significantly higher in people with Intellectual Disability (ID) compared to people with epilepsy (PWE) from the general population. Increased psychological and behavioural problems, healthcare costs, morbidity, mortality and treatment resistance to antiepileptic drugs (AEDs) is associated with epilepsy in ID populations. Prescribing AEDs for PWE and ID is challenging and influenced heavily by studies conducted with the general population. Our study compares Lacosamide (LCM) response for the ID population to those from the general population; using data from an UK based epilepsy database register (EP ID/PDD AED Register). METHODS: Pooled retrospective case notes data for PWE prescribed LCM at 11 UK NHS Trusts were analysed. Participants were classified as per WHO guidance into groups of moderate-profound ID, mild ID and General population. Demographics, concomitant AEDs, starting and maximum dosage, exposure length, adverse effects, dropout rates, seizure frequency were collected. Group differences were reported as odds ratios estimated from univariable logistic regression models. RESULTS: Of 232 consented participants, 156 were from the general population and 76 had ID (24 mild, 52 moderate-profound). Twelve month withdrawal rates and reasons, efficacy, side-effects, start and maximum doses were similar between the groups. Dose titration between baseline and three months was significantly slower in the ID group (p = 0.02). CONCLUSION: There were no differences for LCM outcomes between general and ID groups. Slower LCM titration in ID populations in the first 3 months was associated with higher retention and lower behavioural side effects as compared to similar European studies.

Scanning electron microscopy evaluation of chitosan and carboxymethyl chitosan as retrograde smear layer removing agents.

BACKGROUND: The smear layer acts as a physical barrier against penetration of root canal medicaments and sealers, thus compromising the seal leading to microleakage. OBJECTIVES: This study was conducted to evaluate the efficacy of 17% ethylenediaminetetraacetic acid (EDTA), 0.2% chitosan solution, and 0.2% carboxymethyl chitosan (CMC) used as smear layer removing agents in retrograde root canal preparation using scanning electron microscopy (SEM). MATERIALS AND METHODOLOGY: Eighty single-rooted teeth extracted for periodontal reasons were collected for the study. Root canals were prepared and obturated with gutta-percha coated with AH plus resin sealer. Apical 3 mm of each root resected and Class I retrograde preparation carried out using ultrasonic handpiece and ultrasonic retro tips to a depth of 3 mm along the root long axis. In Group 1 (control), normal saline solution alone was used for smear layer removal. In Group II, 17% EDTA, Group III and IV were treated with 5 ml of 0.2% chitosan and 0.2% carboxyl methyl chitosan, respectively, for 3 min. Blinded evaluation of specimens using SEM was performed independently by two operators who registered the amount of the smear layer present on the surface of the canal walls based on the score described by Hülsmann et al. RESULTS: Group I (saline) was least efficient in the removal of the smear layer. Group II (17% EDTA), Group III (0.2% Chitosan), and Group IV (0.2% CMC) efficiently removed the smear layer from the retrograde cavity with mean scores 1.35, 1.60, and 1.35, respectively. Statistically, no significant difference found in Group II (17% EDTA), Group III (0.2% Chitosan), and Group IV (0.2% CMC). CONCLUSIONS: About 0.2% CMC and 0.2% chitosan can be better alternatives to 17% EDTA for smear layer removal due to their biological advantages.

Unusual relapse of primary central nervous system lymphoma at site of lumbar puncture.

Primary CNS lymphoma (PCNSL) is a rare non-Hodgkin's lymphoma confined to the CNS. Local relapse of this disease is common, but extracranial or subcutaneous metastasis is rare with only a few cases being reported in literature. We report a 63-year-old male patient, who responded well to treatment for PCNSL but relapsed two and half years later with a lumbosacral nodule at the site of a previous lumbar puncture due to microscopic tumor seeding. Clinicians treating patients with PCNSL must remain alert to the possibility of extracranial solitary relapse even after the resolution of initial disease because prompt treatment can result in a good outcome.