Cutaneous reactions to carbamazepine in children with epilepsy

BACKGROUND: The main components in controlling and treating seizures are antiepileptic drugs (AEDs). Mostly, the systemic side effects of these drugs are regarded very important; however, these drugs can also cause serious mucocutaneous side effects. Carbamazepine is a drug which is used to treat epilepsy. Side effects of this drug can range from skin rash to toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). The purpose of this study was to evaluate skin complications of carbamazepine in children with epilepsy.METHODS: This study was performed on 99 children, aged 2 months to 11 years, with the diagnosis of skin complications after taking carbamazepine. Records were examined and their initial profiles including their medical skin conditions and rashes were recorded within the checklist. Data were entered into SPSS software. Measures of central tendency and dispersion were achieved. Finally, the relationship between the drug and the cutaneous reactions of these patients was analyzed using the chi-square test.RESULTS: The most common complications among the patients were maculopapular lesions and skin erythroderma, with the prevalence of 37.4% for each. Other types of skin lesions included papules with 14.1%, macules with 8.1%, and SJS with 3.0%. A significant association (P = 0.02) between the types of the skin lesion and the dose of carbamazepine was observed; the more the dosage was, the more severe skin lesions were.CONCLUSION: The most common cutaneous reactions to carbamazepine were erythroderma and maculopapular rash in the patients. The findings of this study also revealed that the lack of drug compliance was of high importance

Development of a novel nanoemulgel formulation containing cumin essential oil as skin permeation enhancer

Essential oils have been proposed as promising non-toxic transdermal permeation enhancers. Their use is limited because of their low water solubility. The use of nanotechnology-based strategies is one of the ways to overcome this limitation. This study aimed to explore the transdermal permeation enhancing capability of cumin essential oil in nanoemulgel systems containing diclofenac sodium. Cumin essential oil nanoemulsion was produced by high-pressure homogenization technique. The formulation was optimized by changing HLB values in a range of 9.65–16.7 using different surfactant mixtures, namely, Tween 20, Tween 80, and Span 80. Preparations were characterized by polydispersity index, droplet size, and zeta potential. Nanoemulsion with concentrations of 2 and 4% essential oil was incorporated into 0.75% Carbopol gel matrix to make nanoemulgel formulation, and its permeation enhancing effect was performed through Franz diffusion cells. Antinociceptive activities of the formulations were measured in thermal (tail-flick) and chemical (formalin) models of nociception in mice. Characterization exhibited that at HLB value of 9.65, the smallest particle size (82.20 ± 5.82 nm) was formed. By increasing the essential oil percentage in the nanoemulgel from 1 to 2%, the permeation of diclofenac increased from 28.39 ± 1.23 to 34.75 ± 1.07 µg/cm2 at 24 h. The value of permeation from the simple gel (21.18 ± 2.51 µg/cm2) and the marketed product (22.97 ± 1.92 µg/cm2) was lower than the formulations containing essential oil. Nanoemulgel of diclofenac containing essential oil showed stronger antinociceptive effects in formalin and tail-flick tests than simple diclofenac gel and marketed formulation. In conclusion, the study proved that nanoemulgel formulation containing cumin essential oil could be considered as a promising skin enhancer to enhance the therapeutic effect of drugs. Graphical abstract: [Figure not available: see fulltext.]

Preparation and In-Vitro Evaluation of Ketoconazole-Loaded Niosome (Ketosome) for Drug Delivery to Cutaneous Candidiasis

Background: Recently, niosomes are becoming popular in drug delivery. The current work aimed to investigate the characteristics, cellular safety, and antifungal activity of ketoconazole-loaded niosome (ketosome). Methods: Ultrasonic approach was employed to prepare ketosome including cholesterol, nonionic surfactant and ketoconazole. The size characteristics and morphological features of ketosome and physicochemical properties of ketoconazole in ketosomes were evaluated using dynamic light scattering (DLS), differential scanning calorimetry (DSC), powder x-ray diffractometer (PXRD), scanning electron microscopy (SEM), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. Also, the dissolution rate, cellular safety test and antimycotic properties of ketosome were examined. Results: According to the results, the particle size of the ketosome decreased from 491.400±10.622 to 121.300±7.274 nm by the increment of cholesterol. According to further research, changes in the cholesterol:surfactants ratio can modulate the zeta potential from -27.866±1.069 to -12.500±1.153 mV. The highest entrapment of ketoconazole was about 87% when the cholesterol concentration in the ketosome was high. Ketosome with the maximum cholesterol:surfactants ratio showed the fastest drug release. Furthermore, the cell viability assay revealed that the ketosome had lower cytotoxicity in comparison with pure drug. The cell viability of the ketosome was estimated to be about 90% (HGF cell line). The ketosome had a lower MIC than the pure drug when tested against Candida albicans. Conclusion: The results of this study revealed that the optimized ketoconazole-loaded niosome could be used as a possible nanovesicle for ketoconazole drug delivery, potentially opening up new ways for the management of cutaneous candidiasis complaints

Encapsulation of bacteriophage cocktail into chitosan for the treatment of bacterial diarrhea

The therapeutic effectiveness of a chitosan encapsulated bacteriophage cocktail as a smart biocontrol agent was evaluated in this study to be used as a preventative and treatment option for gastrointestinal infections. To evaluate the effect of the bacteriophage formulation on the treatment of gastrointestinal infection, rats were infected with Salmonella enterica, Shigella flexneri, and Escherichia coli. The rats were weighed and their stools cultured. The results showed that the group which had the chitosan encapsulated bacteriophage cocktail did not lose weight after 3 days and had significantly lower group weight changes. Weight loss was significant in the rats that had cefixime administered instead. Positive cultured stools were reduced after 4 days compared to 2 days in the treated group with the chitosan encapsulated bacteriophage cocktail. The chitosan encapsulated bacteriophage cocktail can therefore be effective in the treatment of gastrointestinal infections

Adolescent transport and unintentional injuries: a systematic analysis using the Global Burden of Disease Study 2019

Background: Globally, transport and unintentional injuries persist as leading preventable causes of mortality and morbidity for adolescents. We sought to report comprehensive trends in injury-related mortality and morbidity for adolescents aged 10–24 years during the past three decades. Methods: Using the Global Burden of Disease, Injuries, and Risk Factors 2019 Study, we analysed mortality and disability-adjusted life-years (DALYs) attributed to transport and unintentional injuries for adolescents in 204 countries. Burden is reported in absolute numbers and age-standardised rates per 100 000 population by sex, age group (10–14, 15–19, and 20–24 years), and sociodemographic index (SDI) with 95% uncertainty intervals (UIs). We report percentage changes in deaths and DALYs between 1990 and 2019. Findings: In 2019, 369 061 deaths (of which 214 337 [58%] were transport related) and 31·1 million DALYs (of which 16·2 million [52%] were transport related) among adolescents aged 10–24 years were caused by transport and unintentional injuries combined. If compared with other causes, transport and unintentional injuries combined accounted for 25% of deaths and 14% of DALYs in 2019, and showed little improvement from 1990 when such injuries accounted for 26% of adolescent deaths and 17% of adolescent DALYs. Throughout adolescence, transport and unintentional injury fatality rates increased by age group. The unintentional injury burden was higher among males than females for all injury types, except for injuries related to fire, heat, and hot substances, or to adverse effects of medical treatment. From 1990 to 2019, global mortality rates declined by 34·4% (from 17·5 to 11·5 per 100 000) for transport injuries, and by 47·7% (from 15·9 to 8·3 per 100 000) for unintentional injuries. However, in low-SDI nations the absolute number of deaths increased (by 80·5% to 42 774 for transport injuries and by 39·4% to 31 961 for unintentional injuries). In the high-SDI quintile in 2010–19, the rate per 100 000 of transport injury DALYs was reduced by 16·7%, from 838 in 2010 to 699 in 2019. This was a substantially slower pace of reduction compared with the 48·5% reduction between 1990 and 2010, from 1626 per 100 000 in 1990 to 838 per 100 000 in 2010. Between 2010 and 2019, the rate of unintentional injury DALYs per 100 000 also remained largely unchanged in high-SDI countries (555 in 2010 vs 554 in 2019; 0·2% reduction). The number and rate of adolescent deaths and DALYs owing to environmental heat and cold exposure increased for the high-SDI quintile during 2010–19. Interpretation: As other causes of mortality are addressed, inadequate progress in reducing transport and unintentional injury mortality as a proportion of adolescent deaths becomes apparent. The relative shift in the burden of injury from high-SDI countries to low and low–middle-SDI countries necessitates focused action, including global donor, government, and industry investment in injury prevention. The persisting burden of DALYs related to transport and unintentional injuries indicates a need to prioritise innovative measures for the primary prevention of adolescent injury. Funding: Bill & Melinda Gates Foundation

Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021

This online publication has been corrected. The corrected version first appeared at thelancet.com on September 28, 2023BACKGROUND : Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050. METHODS : Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined; these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs; defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims; type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative risk assessment framework to estimate the risk-attributable type 2 diabetes burden for 16 risk factors falling under risk categories including environmental and occupational factors, tobacco use, high alcohol use, high body-mass index (BMI), dietary factors, and low physical activity. Using a regression framework, we forecast type 1 and type 2 diabetes prevalence through 2050 with Socio-demographic Index (SDI) and high BMI as predictors, respectively. FINDINGS : In 2021, there were 529 million (95% uncertainty interval [UI] 500–564) people living with diabetes worldwide, and the global age-standardised total diabetes prevalence was 6·1% (5·8–6·5). At the super-region level, the highest age-standardised rates were observed in north Africa and the Middle East (9·3% [8·7–9·9]) and, at the regional level, in Oceania (12·3% [11·5–13·0]). Nationally, Qatar had the world’s highest age-specific prevalence of diabetes, at 76·1% (73·1–79·5) in individuals aged 75–79 years. Total diabetes prevalence—especially among older adults—primarily reflects type 2 diabetes, which in 2021 accounted for 96·0% (95·1–96·8) of diabetes cases and 95·4% (94·9–95·9) of diabetes DALYs worldwide. In 2021, 52·2% (25·5–71·8) of global type 2 diabetes DALYs were attributable to high BMI. The contribution of high BMI to type 2 diabetes DALYs rose by 24·3% (18·5–30·4) worldwide between 1990 and 2021. By 2050, more than 1·31 billion (1·22–1·39) people are projected to have diabetes, with expected age-standardised total diabetes prevalence rates greater than 10% in two super-regions: 16·8% (16·1–17·6) in north Africa and the Middle East and 11·3% (10·8–11·9) in Latin America and Caribbean. By 2050, 89 (43·6%) of 204 countries and territories will have an age-standardised rate greater than 10%. INTERPRETATION : Diabetes remains a substantial public health issue. Type 2 diabetes, which makes up the bulk of diabetes cases, is largely preventable and, in some cases, potentially reversible if identified and managed early in the disease course. However, all evidence indicates that diabetes prevalence is increasing worldwide, primarily due to a rise in obesity caused by multiple factors. Preventing and controlling type 2 diabetes remains an ongoing challenge. It is essential to better understand disparities in risk factor profiles and diabetes burden across populations, to inform strategies to successfully control diabetes risk factors within the context of multiple and complex drivers.Bill & Melinda Gates Foundation.http://www.thelancet.comam2024School of Health Systems and Public Health (SHSPH)SDG-03:Good heatlh and well-bein

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed