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Aims: To assess the impact of Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an enzymatic deficiency prevalent in individuals of African or Asian descent, on Hemoglobin A1c (HbA1c) levels, diabetes medication purchases, and the cumulative incidence of diabetes related complications., Methods: A large cohort study was conducted within a national health organization, comparing 3,913 G6PD-deficient patients to a matched control group without G6PD deficiency over two decades. The main measures and outcomes were the HbA1c levels, patterns of diabetes medication purchases, and the incidence of severe diabetes-related complications., Results: HbA1c levels significantly underestimated blood glucose concentrations in G6PD-deficient individuals. Individuals with diabetes and G6PD deficiency had lower rates of treatment with most diabetes medications, notably GLP-1 receptor agonists and SGLT2 inhibitors. Severe diabetes-related complications were more frequent among G6PD-deficient patients, with adjusted hazards ratios [95% confidence intervals] of 1.44 [1.16-1.81] for severe kidney insufficiency, 1.75 [1.23-2.49] for myocardial infarction, and 1.27 [1.02-1.58] for neuropathy., Conclusions: This research highlights serious gaps in the management of G6PD-deficient patients with diabetes, who suffer from insufficient medication management and higher rates of complications. These findings underscore the need to account for G6PD deficiency in diabetes treatment to ensure equitable and effective healthcare for this vulnerable population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Several studies have associated prenatal exposure to volatile organic compounds (VOCs) with adverse health outcomes among newborns. However, little is known about the associations of VOCs at relatively low concentrations with newborn outcomes. Hence, this study aimed to investigate the potential associations between prenatal exposure to VOCs and VOC mixtures with newborn anthropometric measures., Methods: In this cross-sectional study, 883 mother-term infant pairs who lived in urban areas in Israel and were admitted to the delivery rooms of two major hospitals between 2016 and 2020 were recruited. Associations between VOC metabolites detected in maternal urine samples on the day of delivery with weight, length, and head circumference at birth were estimated using single-exposure linear models and weighted quantile sum (WQS) approach., Results: Toluene, ethylbenzene/styrene, and xylene metabolites were detected in most samples at levels comparable to OECD populations. In male newborns, higher levels of phenylglyoxylic acid (PGA), a metabolite of ethylbenzene/styrene, were associated with lower birth weight (β = -0.08, 95% CI: 0.14, -0.01; P = 0.03). WQS models suggested PGA as the most prominent contributor to this association., Conclusion: This study suggests that moderate exposure to ethylbenzene/styrene may be associated with reduced birth weight in male newborns. The sex-specific finding requires further research for the potential endocrine-disrupting mechanisms of these compounds. While the effect size was small, these results highlight the need to better understand the associations of frequent VOC exposures in levels similar to those common in OECD countries with fetal and child development., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier GmbH.)

Introduction: Less invasive surfactant administration (LISA) involves delivering surfactant to a spontaneously breathing infant by passing a thin catheter through the vocal cords and has become the preferred method for surfactant delivery. However, the role of pre-LISA sedation remains unclear., Objective: The aim of this study was to describe the use of dexmedetomidine for LISA in preterm and early-term infants., Methods: This retrospective study evaluated preterm and early-term infants who received intravenous dexmedetomidine for LISA between December 2022 and March 2024. Primary outcomes included safety parameters such as the absence of bradycardia, hypotension, hypothermia, or respiratory depression, and the success rate of LISA, determined by the lack of endotracheal intubation within 72 h. Intergroup comparison based on a cutoff of 32 weeks post-menstrual age (PMA) was performed., Results: Thirty-seven infants were included. The mean ± SD PMA at birth, birth weight, and age at LISA were 32.2 ± 2.7 weeks, 1879 ± 698 g, and 13.9 ± 12.4 h, respectively. Mean dexmedetomidine dosage was 0.66 ± 0.26 μg/kg. Six patients (16.2%) developed mild hypothermia, and 10 (27%) experienced apnea/bradycardia within 24 h. The success rate of the procedure was 89.2%. Infants born before 32 weeks received lower doses of dexmedetomidine than those born at 32 weeks and above (0.54 ± 0.24 versus 0.76 ± 0.24 μg/kg, p < 0.01). Safety and success rates of LISA were similar across groups., Conclusion: This is the first report on dexmedetomidine as pre-LISA sedation, demonstrating its feasibility with comparable success rates regardless of PMA. These findings may inform future studies on sedation strategies for LISA., Competing Interests: Declarations. Funding: The authors have no relevant financial interests to disclose. This research received no specific grant from any funding agency. Conflict of interest: Sagee Nissimov, Amitai Kohn, Rimona Keidar, Ayelet Livne, Mazal Shemer, Ayala Gover, Calanit Hershkovich-Shporen, Matitiahu Berkovitch, and Iris Morag declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript. Ethics approval: Research ethics approval for the study was obtained from Shamir Medical Center in accordance with the Declaration of Helsinki (approval number 0056-24-ASF). Consent to participate: Due to the fact that dexmedetomidine has been utilized as a primary pre-LISA sedative in our unit since December 2022, informed consent for this retrospective study was waived. Data availability statement: Data analyzed during this study are included in this published article as supplementary information files. Additional patients’ data are available from the corresponding author on request. Author contributions: Dr Sagee Nissimov and Prof. Iris Morag conceived, designed, and planned the study, contributed to data extraction, and interpretation of results, wrote the first and final draft of the manuscript, and approved the final publication. Drs Amitai Kohn, Rimona Keidar, Ayelet Livne, and NP Mazal Shemer assisted in the extraction of data, and contributed to and approved the final publication. Drs Ayala Gover, Calanit Hershkovich-Shporen and Prof. Matitiahu Berkovitch contributed to study design and data analysis and contributed to and approved the final publication., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

To evaluate Tonsitin (10% DL-lactic acid) safety, tolerability, and efficacy, as a treatment for recurrent tonsillitis (RT) in children. This is a clinical prospective, randomized, double blind pilot study, to evaluate the safety, tolerability and efficacy of Tonsitin in healthy children with RT. Safety evaluated in terms of adverse events (AEs), tolerability in terms of compliance, and efficacy in terms of tonsils' size and frequency of tonsillitis, and quality of life. The study included 51 children. The treatment regimen was tolerable among the participants. Six children experienced AEs, but mostly mild. Tonsil size declined in both groups, but these results did not reach statistical significance. Tonsillitis episodes' frequencies were random and not significant. Tonsitin treatment was found to be feasible in the clinical setup and was well tolerated, and appears to be safe. Study efficacy results did not reach statistical significance., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Attention deficit hyperactive disorder (ADHD) medication use rises among women of childbearing age and during pregnancy. Little is known on the safety of amphetamine stimulants for ADHD treatment during breastfeeding. Most data on the safety of these medications are from recreational abuse of methamphetamine. This study followed children (N = 13) exposed to amphetamine stimulants during breastfeeding. Assessments by Pediatric Quality of Life and Denver Developmental Scale evaluated neurodevelopment and outcomes. Study results showed normal neurodevelopment with no significant adverse effects. Findings suggest amphetamines are likely compatible with breastfeeding; however larger studies are needed., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to evaluate associations between prenatal and childhood exposure to phthalates and prenatal exposure to polychlorinated biphenyls (PCBs) and the development of 4-year-old children. Urinary metabolites of five phthalates were measured in women upon delivery, as well as serum concentrations of four PCB congeners. Postnatal phthalate metabolites were measured from children's urine obtained at the time of developmental assessment. The primary outcome was cognitive function as evaluated by the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) administered at 4 years. Secondary outcomes were motor function and response to sensory stimuli as evaluated by the Developmental Coordination Disorder Questionnaire (DCDQ) and Short Sensory Profile (SSP) that the mothers filled out, respectively. The study included 57 mother-child pairs. Higher maternal phthalate metabolite concentrations were inversely associated with WPPSI-III scores among boys and not among girls. After using linear regression models and controlling for confounding variables, we found that higher levels of monobenzyl phthalate (MBzP) were the ones associated with lower WPPSI-III scores (p=0.004, 95 %CI [-14.18; -3.16]), lower DCDQ scores (p=0.007, 95 %CI [-6.08; -1.17] and lower SSP scores (p=0.004, 95 %CI [-7.47; -1.79]). No association was found between child urinary phthalate metabolite concentrations or maternal PCB blood concentrations and developmental function. These findings indicate that higher prenatal phthalate metabolite levels may be associated with deficits in neurologic development of young boys., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The literature supports the benefits of medical cannabis for core and comorbid symptoms in autistic individuals and anxiety-related symptoms in individuals without autism. However, no study has specifically investigated how cannabidiol (CBD)-rich cannabis affects anxiety subtypes in autistic children or its relationship with restricted and repetitive behaviors and interests (RRBI). Understanding the effects of CBD-rich cannabis treatment on anxiety subtypes and RRBI could offer more precise treatment approaches to managing anxiety symptoms and reducing RRBI frequency in autistic children. Objectives: To examine (1) the impact of CBD-rich cannabis treatment on autistic children's (1a) anxiety levels and subtypes and (1 b) RRBI and subtypes and (2) whether changes in anxiety explain changes in RRBI following cannabis treatment. Method: In this open-label study, we analyzed data from 65 autistic children (5-12 years) who had participated in research on the effects of CBD-rich cannabis on children with autism. Their parents completed the Repetitive Behavior Scale-revised to assess the frequency and severity of six subgroups of their children's recurrent behaviors and the Screen for Child Anxiety-Related Emotional Disorders for symptoms related to five types of anxiety disorders. They completed these assessments at three time points: (T1) before treatment, (T2) after 3 months, and (T3) after 6 months of treatment. Results: The results indicated reduced RRBI and symptoms related to various anxiety subtypes in autistic children following 6 months of CBD-rich cannabis treatment. Specifically, we observed significant differences in the autistic children's overall anxiety and in some anxiety subtypes (i.e., general, social, panic, and separation anxieties). Significant improvements were observed in RRBI, including the total score, and specifically in compulsive, ritualistic, and sameness behaviors. Our findings revealed that reduced anxiety, particularly within the panic- and separation-related subtypes, predicted a subsequent decrease in RRBI, specifically sameness behaviors, following cannabis treatment. Conclusions: The findings of the cannabis treatment's potential benefits for alleviating anxiety symptoms, leading to reduced RRBI, may provide evidence for the meaningful relationship between these variables and for the potential benefits of cannabis treatment for autistic children. We strongly recommend further double-blind, placebo-controlled studies using standardized assessments to validate these findings.

Background: In-utero phthalate exposure was shown to be associated with shortened anogenital distance (AGD) in male newborns, but findings among female are inconsistent. While phthalate exposure among pregnant women in Israel is widespread, no study has examined the association with offspring AGD. The objective of the current study was to investigate the association between maternal phthalates urinary concentration and offspring AGD at time of delivery among a birth cohort in Israel., Methods: We measured spot urinary concentration of monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-hydroxyhexylphthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) among women presenting to the delivery room at Shamir Medical Center in Israel. Birthweight, length and AGD were measured in all newborns using a standardized protocol. Each AGD measurement was adjusted to weight (ano-genital index). Confounders included socio-demographic characteristics, comorbidities and obstetrical history. Univariate and multivariate analyses assessed the associations between phthalates, confounders and AGD., Results: Overall, 193 mother and infant were analyzed. All newborns were born at term and had normal Apgar scores. Mean maternal age was 32 ± 4.7 years old. Mean birth weight and pregnancy week were 3183 ± 498 g and 39 ± 1.3, respectively. Median (IQR) urinary phthalate concentration adjusted to creatinine (ug/g) were 3.96 (2.2-6.6), 1.22 (0.7-2), 10.84 (7-20.4), 6.36 (3.3-11.2) and 0.64 (0.4-1.1) for MBP, MBzP, MECPP, MEHHP and MEOHP, respectively. Univariate comparison showed a significant association between higher than median MBzP concentration, higher Ano-Fourchetal index (AFI: 4.4 vs. 4.1, p = 0.037) and Ano-clitoral index (ACI: 11.5 vs. 10.4, p = 0.032) in infants. Total urinary phthalates concentration ≥26.25 μg/g was significantly associated with smaller penile width index (3.5 vs. 3.7, p = 0.022), higher ACI (11.6 vs. 10.3, p = 0.013) and a trend towards significance for higher AFI (4.3 vs. 4.1, p = 0.055). Following multivariate linear regression only PWI remained significantly associated with total phthalate urinary concentration., Conclusions: Maternal urinary phthalates concentration at delivery were not associated with female AGD, but total urinary phthalate concentration were inversely associated with penile width., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Matitiahu Berkovich reports financial support and equipment, drugs, or supplies were provided by Environment and Health Fund. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Introduction: Medical cannabis treatment for autistic children has recently become popular, and studies have focused on examining the treatment's effects on children's symptom presentation, reported side effects, and dropout rates. However, no previous study has investigated the factors influencing adherence and dropout rates in cannabis treatment., Method: This explanatory sequential mixed-methods study explored these factors by examining the characteristics of 87 autistic children and their families and deepening parents' perspectives and experiences of the 6-month CBD-rich cannabis treatment's benefits and barriers., Results: We found this treatment to have a high (75%) adherence rate, relatively mild side effects, and substantial reported benefits for the children and families. However, this treatment was not free of barriers; the intake regime, some side effects, and in some cases, unrealistic parental expectations made adherence difficult for some families., Conclusion: Our results highlight the importance of providing professional guidance and knowledge to parents of autistic children, enhancing their understanding of the impact of CBD-rich cannabis treatment on their children and expected related challenges, and coordinating realistic treatment expectations. We hope that addressing these important aspects will influence parents' ability to adhere to and enjoy the benefits of cannabis treatment for their autistic children., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Tramadol is primarily metabolized by the highly polymorphic CYP2D6 enzyme, leading to a large spectrum of adverse events and clinical response. Ample evidence pointed a reduced CYPD26 activity score in individuals harboring the CYP2D6*10/*10 genotype, nevertheless, there is scarce studies on the impact of CYP2D6 *10/*10 genetic polymorphism on long-term tramadol's adverse effects. Aim: To test the correlation between CYP2D6 *10/*10 expression and the risk for tramadol-associated adverse effects. Method: Using a database of Leumit Healthcare Services in Israel, we retrospectively assessed the occurrence of adverse events in patients who were prescribed tramadol. A binary logistic regression model was applied to model the relationship between CYP2D6*10/*10 genotype and the occurrence of adverse effects. Results: Data from four hundred ninety-three patients were included in this study. Only 25 (5.1%) patients were heterozygous for the CYP2D6*10 variant, while 56 patients (11%) were tested positive to the CYP2D6*10/*10 genotype. Compared to carriers of other variants, patients with the CYP2D6*10/*10 variant exhibited a higher occurrence of adverse events (odds ratio [OR] = 6.14, 95% confidence interval 3.18-11.83); the odds ratio for central nervous system adverse events and gastrointestinal adverse events were 5.13 (95% CI 2.84-9.28), and 3.25 (95% CI 1.78-5.93), respectively. Conclusion: Among the different CYP2D6 genotypes, CYP2D6*10/*10 genotype carries the higher risk of tramadol related adverse events. Appreciating the frequency of this specific allele it seems prudent to pharmacogenetically screen patients considered for long term tramadol treatment for better tolerability and efficacy outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Mahajna, Abu Fanne, Odeh, Berkovitch, Tannous, Eyal, Vinker, Green and Matok.)

Objective: Tourette's syndrome (TS) is a neurodevelopmental disorder characterized by vocal and motor tics and other comorbidities. Clinical recommendations for the use of medical cannabis are established, yet further guidance is needed. The aim of this study was to describe the experience of patients with TS with medical cannabis. Materials and Methods: TS patients were recruited from a registry of patients ("Tikun Olam" company). Questionnaires were answered before and after 6 months of treatment. Patients were divided into two groups: (A) patients who responded and (B) patients who did not respond to the follow-up questionnaire. In group A, an analysis was made to evaluate the presence and frequency of motor and vocal tics. The patients' general mood, employment status, quality of life, and comorbidities were also included in the analysis. Results: Seventy patients were identified. The tetrahydrocannabinol and cannabidiol mean daily dose was 123 and 50.5 mg, respectively. In group A, a statistically significant improvement was identified in quality of life ( p <0.005), employment status ( p =0.027), and in the reduction of the number of medications ( p <0.005). Sixty-seven percent and 89% of patients with obsessive-compulsive disorder and anxiety comorbidities, respectively, reported an improvement. No statistically significant improvement was identified in motor tics ( p =0.375), vocal tics ( p >0.999), tics frequency ( p =0.062), or general mood ( p =0.129). The most frequent adverse effects were dizziness ( n =4) and increased appetite ( n =3). Conclusion: Subjective reports from TS patients suggest that medical cannabis may improve their quality of life and comorbidities. More studies are needed to evaluate the efficacy and safety of medical cannabis. Registry in the MOH: https://www.moh.gov.sg/ (Trial number: 0185-19-ASF).

Background-Various antidepressant agents are metabolized by the CYP2C19 enzyme, including Citalopram and Escitalopram. Variation in CYP2C19 expression might give rise to different plasma concentrations of the active metabolites, potentially affecting both drugs' efficacy and tolerability. Aim-The aim of this study was to evaluate differences in the Escitalopram and Citalopram efficacy and tolerability between different CYP2C19 genotype-based metabolizing categories in outpatients suffering from major depressive disorder (MDD). Methods-In a retrospective, longitudinal cohort study of electronic medical-record data, 283 patients with MDD who were prescribed Escitalopram or Citalopram with the available CYP2C19-genotyping test were enrolled. The primary efficacy end point was adverse drug reactions recorded in the medical files. A proportional-odds, multilevel-regression model for longitudinal ordinal data was used to estimate the relation between the CYP2C19 genotype and adverse drug reactions, adjusting for potential confounding variables and other explanatory variables. Latent-class analysis (LCA) was utilized to detect the presence of clinically significant subgroups and their relation to an individual's metabolizing status for CYP2D6/CYP2C19. Results-With poor CYP2C19 metabolizers as a reference, for each unit difference in the activity score of the CYP2C19 phenotype, the odds ratio for drug intolerability was lowered by 0.73 (95% credible intervals: 0.56-0.89), adjusting for significant covariates. In addition, applying LCA, we identified two qualitatively different subgroups: the first group (61.85%) exhibited multiple side effects, low compliance, and frequent treatment changes, whereas the second group (38.15%) demonstrated fewer side effects, good adherence, and fewer treatment changes. The CYP2C19 phenotype was substantially associated with the group membership. Conclusions-We found a positive association between the CYP2C19 activity scores, as inferred from the genotype, and both the efficacy of and tolerability to both Es/Citalopram. LCA enabled valuable insights into the underlying structure of the population; the CYP2C19 phenotype has a predictive value that discriminates between low-adherence, low-drug-tolerance, and low-response patients and high-adherence, high-drug-tolerance, and high-response patients. Personalized medicine based on CYP2C19 genotyping could evolve as a promising new avenue towards mitigating Escitalopram and Citalopram therapy and the associated side effects and enhancing treatment success.

In this cohort study conducted in a national healthcare organization in Israel, we found that individuals with glucose-6-phosphate dehydrogenase deficiency had an increased risk of coronavirus disease 2019 (COVID-19) infection and severity, with higher rates of hospitalization and diagnosed long COVID., Competing Interests: Potential conflicts of interest . E. R. reports financial interests as a cofounder of MedAware and Metabomed, Ltd, and is a divested cofounder and unpaid scientific consultant of Pangea Biomed. E. M. reports honoraria for lectures from Teva, Medisone, and Astra Zeneca; participation on advisory boards for Merck and SK-Pharma; roles as a board member of the Israeli National Diabetes Council and the Israeli Society of ADHD; and a role as a committee member of the Israeli National Dementia Prevention Program. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Multidisciplinary expert team collaboration in the clinical setting, which includes clinical pharmacist involvement can facilitate significant improvements in outcomes and optimize patient management by preventing drug-related problems (DRP). This type of collaboration is particularly valuable in patients with multi-morbidity and polypharmacy such as diabetic foot patients. Evidence regarding the successful integration of a new clinical pharmacist, without previous experience into a unit is still scarce. Therefore, this study aimed to describe and evaluate the actual successful integration process of the clinical pharmacist into a diabetic foot unit by measuring the change in recommendation acceptance rate over time. Methods: A prospective, exploratory treatment effectiveness study based on the recommendation acceptance rate of a new clinical pharmacist introduced into the diabetic foot unit was conducted over a 9- month period. The clinical pharmacist identified medical and drug-related problems (DRP) or any discrepancies in the prescribing and administration of medications. Each identified DRP was documented and formulated as a recommendation by the clinical pharmacist. The main outcome measure was the acceptance rate of recommendations over time. Results: A total of 86 patients, of which 67% were men, averagely aged 66.5 (SD 11.8) years were evaluated. Calculated BMI was 30.2 (SD 6.2). The average number of medical diagnoses was 8.9 (SD3.2), and 11.1 (SD 3.7) prescribed drugs for each patient. Cardiovascular disease was presented by 95% ( n = 82) of the patients and 33% of them ( n = 28) had uncontrolled hyperglycemia. Averagely, 3.3 (SD 1.9) DRPs were identified pre patient. The efficacy-related DRP recommendation acceptance rate increased over the study period from 37.8% in the first 4 months to 79.4% after a period of 4.75 months. Safety-related DRP recommendation acceptance rate increased from 56% to 67.6%. Conclusion: Improved clinical outcomes and optimized pharmacologic patient management may be achieved by the successful integration of a clinical pharmacist into the team. This study provides evidence of the increasing recommendation acceptance rate of integrated, pharmacist-driven comprehensive medication management in an unexperienced unit. To overcome challenges, team members should collaborate to fully integrate the clinical pharmacist into the team-based structure and utilize proper strategies to minimize and transcend barriers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Peled, Vitzrabin, Beit Ner, Lazaryan, Berlin, Barchel, Berkovitch, Beer and Tamir.)

Introduction: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic disorder that is particularly prevalent in Africa, Asia, and the Middle East. This study aimed to assess the long-term health risks associated with G6PD deficiency., Methods: A retrospective cohort study was conducted using data from a national healthcare provider in Israel (Leumit Health Services). A total of 7,473 G6PD-deficient individuals were matched with 29,892 control subjects in a 1:4 ratio, based on age, gender, socioeconomic status, and ethnic groups. The exposure of interest was recorded G6PD diagnosis or positive G6PD diagnostic test. The main outcomes and measures included rates of infectious diseases, allergic conditions, and autoimmune disorders between 2002 and 2022., Results: Significantly increased rates were observed for autoimmune disorders, infectious diseases, and allergic conditions in G6PD-deficient individuals compared to the control group. Specifically, notable increases were observed for rheumatoid arthritis (odds ratio [OR] 2.41, p<0.001), systemic lupus erythematosus (OR 4.56, p<0.001), scleroderma (OR 6.87, p<0.001), pernicious anemia (OR 18.70, p<0.001), fibromyalgia (OR 1.98, p<0.001), Graves' disease (OR 1.46, p=0.001), and Hashimoto's thyroiditis (OR 1.26, p=0.001). These findings were supported by elevated rates of positive autoimmune serology and higher utilization of medications commonly used to treat autoimmune conditions in the G6PD-deficient group., Discussion: In conclusion, individuals with G6PD deficiency are at a higher risk of developing autoimmune disorders, infectious diseases, and allergic conditions. This large-scale observational study provides valuable insights into the comprehensive association between G6PD deficiency and infectious and immune-related diseases. The findings emphasize the importance of considering G6PD deficiency as a potential risk factor in clinical practice and further research is warranted to better understand the underlying mechanisms of these associations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Israel, Schäffer, Berkovitch, Ozeri, Merzon, Green, Golan-Cohen, Ruppin, Vinker and Magen.)

Objective: This study aimed to investigate the efficacy and tolerability of Lacosamide (LCM) in a pediatric population with epilepsy using LCM serum concentration and its correlation to the age of the participants and the dosage of the drug. Methods: Demographic and clinical data were collected from the medical records of children with epilepsy treated with LCM at Shamir Medical Center between February 2019 to September 2021, in whom medication blood levels were measured. Trough serum LCM concentration was measured in the biochemical laboratory using High-Performance Liquid Chromatography (HPLC) and correlated with the administered weight-based medication dosing and clinical report. Results: Forty-two children aged 10.43 ± 5.13 years (range: 1-18) were included in the study. The average daily dose of LCM was 306.62 ± 133.20 mg (range: 100-600). The average number of seizures per day was 3.53 ± 7.25 compared to 0.87 ± 1.40 before and after LCM treatment, respectively. The mean LCM serum concentration was 6.74 ± 3.27 mg/L. No statistically significant association was found between LCM serum levels and the clinical response ( p = 0.58), as well as the correlation between LCM dosage and the change in seizure rate ( p = 0.30). Our study did not find a correlation between LCM serum concentration and LCM dosage and the gender of the participants: males (n = 17) females (n = 23) ( p = 0.31 and p = 0.94, respectively). A positive trend was found between age and LCM serum concentrations (r = 0.26, p = 0.09). Conclusion: Based on the data that has been obtained from our study, it appears that therapeutic drug monitoring for LCM may not be necessary. Nonetheless, further research in this area is needed in the light of the relatively small sample size of the study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kohn, Lezinger, Daniel, Masarwi, Brandriss, Bar-Chaim, Berkovitch, Heyman and Komargodski.)