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Turkish Journal of Medical Sciences 2024Data on the prevalence of allergic diseases in children with proven drug allergies are limited. We aim to evaluate the frequency of allergic comorbidity in children with...
BACKGROUND/AIM
Data on the prevalence of allergic diseases in children with proven drug allergies are limited. We aim to evaluate the frequency of allergic comorbidity in children with proven common drug allergies.
MATERIALS AND METHODS
Children with drug hypersensitivity confirmed by diagnostic allergy tests at our center between January 2010 and December 2020 were screened retrospectively. Patients with the most common drug allergies (due to antibiotics, nonsteroidal antiinflammatory drugs [NSAIDs], and antiepileptic drugs) were selected for analysis. Age, sex, the culprit drug, initial reaction characteristics, diagnostic test results, and the study physician who diagnosed concomitant allergic diseases were noted.
RESULTS
A total of 168 patients (boys, 51.2%) with a median age of 12 years (IQR = 8-16.3) were included in the study. The culprit drug was an antibiotic in 63% (n = 106), NSAID in 25% (n = 42) and anticonvulsant in 11.9 % (n = 20) of the patients. Drug hypersensitivity reactions were immediate in 74.4 % (n = 125) and delayed in 25.6 % (n = 43) of the patients. Seventy-five patients (44.6 %) had at least one allergic disease, most commonly rhinitis (27.3 %, n = 46) or asthma (25 %, n = 42). Fifty-five patients underwent skin prick tests with aeroallergens, producing a positive result in 60% (n = 31). The prevalence of allergic disease was not differing according to the culprit drug. The frequency of developing at least one concomitant allergic disease was 47.2% (n = 50/106) for antibiotic hypersensitivity, 52.4% (n = 22/42) for NSAID hypersensitivity, and 15% (n = 3/20) for anticonvulsant hypersensitivity (p < 0.00).Immediate drug hypersensitivity reactions were more frequent in children who had allergic diseases (80 % vs. 64.5 %; p = 0.027).
CONCLUSION
Nearly half (44.6%) of the children with proven drug hypersensitivity had concomitant allergic diseases and immediate reactions were more common in this group. Children evaluated for drug hypersensitivity should be assessed for other allergic diseases.
Topics: Humans; Child; Male; Drug Hypersensitivity; Female; Retrospective Studies; Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Anti-Bacterial Agents; Prevalence; Asthma; Comorbidity
PubMed: 38812629
DOI: 10.55730/1300-0144.5793 -
Frontiers in Immunology 2024Due to comorbidities and associated safety risks, the management of severe atopic dermatitis (AD) in pediatric and adolescent patients poses significant challenges.
IMPORTANCE
Due to comorbidities and associated safety risks, the management of severe atopic dermatitis (AD) in pediatric and adolescent patients poses significant challenges.
OBJECTIVE
To examine the efficacy and safety of systemic therapies for the treatment of moderate-to-severe atopic dermatitis in children and adolescents.
EVIDENCE REVIEW
On Feb 29, 2024, a systematic literature search was conducted in Embase, PubMed, and the Cochrane Central Register of Controlled Trials (Central). No date restrictions were applied. Randomized clinical trials, cohort studies, large case series, and meta-analyses were assessed to evaluate the efficacy (or effectiveness) and/or safety of systemic treatments for moderate-to-severe atopic dermatitis in children and adolescents.
FINDINGS
A preliminary search yielded 1457 results, from which 19 unique articles with a total of 3741 patients were included in the analysis. Overall, the available data for each systemic medication are limited, and the overall quality of the included studies on conventional systemic treatments is relatively low. When Dupilumab was used as a standalone treatment, 30%-40% of infants and toddlers aged 6 months to 2 years achieved EASI-75, while 50% of patients aged 2 to 6 years achieved EASI-75. In children aged 6 to 12 years, 33.0%-59.0% of atopic dermatitis patients achieved EASI-75, and when combined with topical corticosteroids (TCS), 69.7%-74.6% achieved EASI-75. Long-term data showed EASI-75 rates ranging from 75.0% to 94.0% for this age group. For adolescents aged 12 to 18 years, 40%-71% of patients achieved EASI-75 within 12 to 16 weeks, and by week 52, 80.8% of patients achieved EASI-75.Abrocitinib treatment resulted in 68.5%-72.0% of patients achieving EASI-75. Omalizumab treatment at week 24 showed a percentage change in SCORAD scores of -12.4%. In the Methotrexate treatment group, there was a SCORAD change of -26.25% at week 12, while the Cyclosporine A group had a SCORAD change of -25.01%. Patients treated with IVIG (Intravenous Immunoglobulin) showed a -34.4% change in SCORAD percentage scores at week 4, which further decreased by 47.12% at week 24. Patients receiving 4mg of Baricitinib and TCS had a 52.5% rate of EASI-75 at 16 weeks, and patients receiving different doses of upadacitinib had a 63-75% rate of EASI-75 at 16 weeks. The rate of EASI-75 at 16 weeks was around 28% in patients who received various doses of Tralokinumab.The most common adverse events observed were nasopharyngitis, respiratory events and dermatitis atopic.
CONCLUSIONS AND RELEVANCE
Awareness of adverse events and concomitant medications is crucial, and appropriate dosing and frequent laboratory and clinical monitoring are also essential. More real-world evidence and prospective cohort studies analyzing the effectiveness and safety of systemic therapies in children and adolescents are of paramount importance for optimizing personalized, effective, and safe management of the growing population of patients with atopic dermatitis in this age group.
Topics: Humans; Dermatitis, Atopic; Child; Adolescent; Child, Preschool; Treatment Outcome; Severity of Illness Index; Infant; Female; Male; Dermatologic Agents; Antibodies, Monoclonal, Humanized
PubMed: 38812522
DOI: 10.3389/fimmu.2024.1367099 -
Diabetology & Metabolic Syndrome May 2024While oxidative stress is the key player driving diabetic nephropathy (DN), firm glycemic control remains the pillar prophylactic measure. Purslane was extensively...
Portulaca oleracea L seed extracts counteract diabetic nephropathy through SDF-1/IL10/PPARγ-mediated tuning of keap1/Nrf2 and NF-κB transcription in Sprague Dawley rats.
BACKGROUND & OBJECTIVE
While oxidative stress is the key player driving diabetic nephropathy (DN), firm glycemic control remains the pillar prophylactic measure. Purslane was extensively described as a potent hypoglycemic and hypolipidemic agent owing to its rich content of antioxidants. Therefore, this report aimed to assess the renoprotective potentials of methanol (MO) and methylene chloride (MC) fixed oil extracts of purslane seeds in a diabetic nephropathy (DN) model.
METHODS
Purslane seeds were extracted using absolute methanol and methylene chloride, and type-1 diabetes was induced with a single 55 mg/kg dose of Streptozotocin (STZ) dissolved in 100 mmol/L citrate buffer (pH 4.5), and then diabetic animals were received MO, MC, for 42 consecutive days to compare their antidiabetic effect relative to the reference drug "Losartan". Renal functions and DN biomarkers were weekly assessed, and the relative expression of different oxido-inflammatory mediators was quantified in diabetic kidneys by RT-PCR. Data were statistically analyzed using GraphPad Prism 9.0.2.
RESULTS
The oral administration of MO and MC extracts (250 mg/kg/day) significantly ameliorated the body weight loss (P < 0.0001 / each), fasting blood glucose levels (FBG) (P < 0.0001 / each), urine volume (P < 0.0001 / each), as well as serum creatinine (P < 0.0001 / each), uric acid (P = 0.0022, 0.0052), and blood urea nitrogen (BUN) (P = 0.0265, 0.0338); respectively, compared with the untreated diabetic rats. In addition, both extracts restored the effectuality of antioxidative machinery in diabetic kidneys as indicated by a significant reduction of ROS accumulation and lipid peroxidation; higher GSH content, and promoted activity of glutathione reductase and superoxide dismutase antioxidant enzymes (P < 0.0001 / each). Histologically, both extracts alleviated the DN-structural alterations including the glomerular congestion and tubular degeneration, with MC-treated kidneys showing near to normal architecture. The transcription profiles of all treated kidneys revealed a significantly downregulated expression of TNF-α, IL-6, Keap1 and NF-κB genes, concomitant with a significant upregulation of SDF-1, IL-10, Nrf2, HO-1, and PPARγ gene expression (P < 0.0001 / all).
CONCLUSION
These findings highlight the remarkable DN-prophylactic potentials of purslane extracts mediated by neutralizing the hyperglycemia-induced ROS accumulation, and circumventing the downstream inflammatory cascades, surpassing the reference angiotensin receptor blocker; i.e. Losartan.
PubMed: 38811991
DOI: 10.1186/s13098-024-01330-y -
Journal of Atherosclerosis and... May 2024Oral anticoagulants (OACs) reduce the risk of ischemic stroke but may increase the risk of major bleeding in patients with non-valvular atrial fibrillation (NVAF)....
AIM
Oral anticoagulants (OACs) reduce the risk of ischemic stroke but may increase the risk of major bleeding in patients with non-valvular atrial fibrillation (NVAF). Various risk scores, such as HAS-BLED, ATRIA, ORBIT, and DOAC, have been proposed to assess the risk of major bleeding in patients with NVAF receiving OACs. However, limited data are available regarding bleeding risk stratification in Japanese patients with NVAF.
METHODS
Of the 16,098 NVAF patients from the J-RISK AF study, the combined data of the five major AF registries in Japan (J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and Hokuriku-Plus AF Registry), we analyzed 11,539 patients receiving OACs (median age, 71 years old; women, 29.6%; median CHADS-VASc score, 3).
RESULTS
During the 2-year follow-up period, major bleeding occurred in 274 patients (1.3% per patient-year). In a multivariate Cox proportional hazards analysis, an advanced age, hypertension (systolic blood pressure ≥ 150 mmHg), bleeding history, anemia, thrombocytopenia, and concomitant antiplatelet agents were significantly associated with a higher incidence of major bleeding. We developed a novel risk stratification system, HED-[EPA]-B score, which had a better predictive performance for major bleeding (C-statistics 0.67, [95% confidence interval, 0.63-0.70]) than the HAS-BLED (0.64, [0.60-0.67], P for difference 0.02) and ATRIA (0.63, [0.60-0.66], P for difference <0.01) scores. Furthermore, it was non-significantly higher than the ORBIT (0.65, [0.62-0.68], P for difference 0.07) and DOAC (0.65, [0.62-0.68], P for difference 0.17) scores.
CONCLUSION
Our novel risk stratification system, the HED-[EPA]-B score, may be useful for identifying Japanese patients receiving OACs at a risk of major bleeding.
PubMed: 38811233
DOI: 10.5551/jat.64842 -
Biological & Pharmaceutical Bulletin 2024Mogroside, the main component of Siraitia grosvenorii (Swingle) C. Jeffrey (Cucurbitaceae) is a natural product with hypoglycemic and intestinal microbiota regulating...
Mogroside, the main component of Siraitia grosvenorii (Swingle) C. Jeffrey (Cucurbitaceae) is a natural product with hypoglycemic and intestinal microbiota regulating properties. However, whether the alteration of intestinal microbiota is associated with the antidiabetic effect of mogroside remains poorly understood. This study investigated the mechanism underlying the hypoglycemic effect of mogroside in regulating intestinal flora and attenuating metabolic endotoxemia. Kunming mice with type 2 diabetes mellitus (T2DM) induced by high-fat diet and intraperitoneal injection of streptozotocin were randomly divided into model, pioglitazone (2.57 mg/kg) and mogroside (200, 100, and 50 mg/kg) groups. After 28 d of administration, molecular changes related to glucose metabolism and metabolic endotoxemia in mice were evaluated. The levels of insulin receptor substrate-1 (IRS-1), cluster of differentiation 14 (CD14) and toll-like receptor 4 (TLR4) mRNAs were measured, and the composition of intestinal microflora was determined by 16s ribosomal DNA (rDNA) sequencing. The results showed that mogroside treatment significantly improved hepatic glucose metabolism in T2DM mice. More importantly, mogroside treatment considerably reduced plasma endotoxin (inhibition rate 65.93%, high-dose group) and inflammatory factor levels, with a concomitant decrease in CD14 and TLR4 mRNA levels. Moreover, mogroside treatment reduced the relative abundance of Firmicutes and Proteobacteria (the inhibition rate of Proteobacteria was 85.17% in the low-dose group) and increased the relative abundance of Bacteroidetes (growth rate up to 40.57%, high-dose group) in the intestines of diabetic mice. This study reveals that mogroside can relieve T2DM, regulating intestinal flora and improving intestinal mucosal barrier, indicating that mogroside can be a potential therapeutic agent or intestinal microbiota regulator in the treatment of T2DM.
Topics: Animals; Gastrointestinal Microbiome; Male; Diabetes Mellitus, Type 2; Diabetes Mellitus, Experimental; Mice; Hypoglycemic Agents; Diet, High-Fat; Blood Glucose; Triterpenes; Toll-Like Receptor 4; Endotoxemia; Liver
PubMed: 38811190
DOI: 10.1248/bpb.b24-00124 -
Dermatology Practical & Conceptual Apr 2024Acquired perforating dermatosis (APD) is a disease group characterized by transepidermal elimination of dermal connective tissue materials such as collagen, elastic...
INTRODUCTION
Acquired perforating dermatosis (APD) is a disease group characterized by transepidermal elimination of dermal connective tissue materials such as collagen, elastic fibers, and keratin through the epidermis and observed with pruritic skin lesions.
OBJECTIVES
In this study, we aim to clarify the clinical, histopathological, and dermoscopic characteristics of APD, identify the associated systemic disease, and figure out treatment options.
METHODS
This study was designed as a single-center retrospective, observational, cross-sectional study. We evaluated all accessible APD cases between January 2004 and June 2022 in a tertiary care hospital.
RESULTS
A total of 95 patients with confirmed APD were included in the study. Sixty percent of the patients were women and 40% were men. The median age at diagnosis was 63.1 years (35-85 years). The most common site of lesions was the lower extremities which were detected in 86.31% of the patients. The concomitant systemic disease was identified in 84.21% of the patients. The most common systemic disease was type 2 diabetes mellitus (65.26%). Antihistamines and topical corticosteroids were the most commonly prescribed treatment agents.
CONCLUSIONS
Transepidermal elimination of dermal connective tissue components is a feature of APD and the disease usually presents with pruritic papules and nodules with central keratotic crust or plug. The diagnosis of APD requires a clinical examination and histological investigation. APD is usually accompanied by systemic comorbidities. There are several topical and systemic medications available for APD, however, sometimes the therapy might be challenging.
PubMed: 38810077
DOI: 10.5826/dpc.1402a100 -
RMD Open May 2024To assess the safety and efficacy of upadacitinib versus adalimumab from SELECT-COMPARE over 5 years. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
OBJECTIVES
To assess the safety and efficacy of upadacitinib versus adalimumab from SELECT-COMPARE over 5 years.
METHODS
Patients with rheumatoid arthritis and inadequate response to methotrexate were randomised to receive upadacitinib 15 mg once daily, placebo or adalimumab 40 mg every other week, all with concomitant methotrexate. By week 26, patients with insufficient response to randomised treatment were rescued; patients remaining on placebo switched to upadacitinib. Patients completing the 48-week double-blind period could enter a long-term extension. Safety and efficacy were assessed through week 264, with radiographic progression analysed through week 192. Safety was assessed by treatment-emergent adverse events (TEAEs). Efficacy was analysed by randomised group (non-responder imputation (NRI)) or treatment sequence (as observed).
RESULTS
Rates of TEAEs were generally similar with upadacitinib versus adalimumab, although numerically higher rates of herpes zoster, lymphopenia, creatine phosphokinase elevation, hepatic disorder and non-melanoma skin cancer were reported with upadacitinib. Numerically greater proportions of patients randomised to upadacitinib versus adalimumab achieved clinical responses (NRI); Clinical Disease Activity Index remission (≤2.8) and Disease Activity Score based on C reactive protein <2.6 were achieved by 24.6% vs 18.7% (nominal p=0.042) and 31.8% vs 23.2% (nominal p=0.006), respectively. Radiographic progression was numerically lower with continuous upadacitinib versus adalimumab at week 192.
CONCLUSION
The safety profile of upadacitinib through 5 years was consistent with the known safety profile of upadacitinib, with no new safety risks. Clinical responses were numerically higher with upadacitinib versus adalimumab at 5 years. Upadacitinib demonstrates a favourable benefit-risk profile for long-term rheumatoid arthritis treatment.
TRIAL REGISTRATION NUMBER
NCT02629159.
Topics: Humans; Arthritis, Rheumatoid; Adalimumab; Heterocyclic Compounds, 3-Ring; Female; Antirheumatic Agents; Male; Middle Aged; Treatment Outcome; Double-Blind Method; Adult; Methotrexate; Aged; Drug Therapy, Combination
PubMed: 38806190
DOI: 10.1136/rmdopen-2023-004007 -
Journal of Medical Case Reports May 2024All-trans retinoic acid (ATRA) is an indispensable part of the treatment of acute promyelocytic leukemia (APL). Although, mild cutaneous toxicities like mucocutaneous... (Review)
Review
A rare incidence of severe dermatological toxicities triggered by concomitant administration of all-trans retinoic acid and triazole antifungal in patients with acute promyelocytic leukemia: a case series and review of the literature.
BACKGROUND
All-trans retinoic acid (ATRA) is an indispensable part of the treatment of acute promyelocytic leukemia (APL). Although, mild cutaneous toxicities like mucocutaneous xerosis, rash, and pruritus are well reported, ATRA associated severe dermatological toxicities are extremely rare. ATRA is primary metabolized by cytochrome P450 (CYP450) enzyme system, and triazole antifungals are notorious for their strong inhibitory effect on CYP450.
CASE PRESENTATION
Three Asian APL patients experienced rare ATRA-induced severe dermatological toxicities: exfoliative dermatitis (ED) in cases 1 and 2, and necrotic scrotal ulceration in case 3. Both case 1 (33-year-old female), and case 2 (28-year-old male) landed in emergency department with dehydration, generalized skin erythema and xerosis during their induction chemotherapy. Both of these patients also developed invasive aspergillosis and required concomitant triazole antifungals during their chemotherapy. For ED, intravenous fluids and broad-spectrum antibiotics were started along with application of local emollients to prevent transdermal water loss. Although their general condition improved but skin exfoliation continued with complete desquamation of palms and soles. Dermatology was consulted, and clinical diagnosis of ED was established. Discontinuation of ATRA resulted in complete resolution of ED. Case 3 (15-year-old boy) reported two blackish mildly tender scrotal lesions during induction chemotherapy. He also had mucocutaneous candidiasis at presentation and was kept on triazole antifungal. Local bacterial & fungal cultures, and serological testing for herpes simplex virus were reported negative. Despite adequate local care and optimal antibiotic support, his lesions persisted, and improved only after temporary discontinuation of ATRA. After a thorough literature review and considering the temporal association of cutaneous toxicities with triazole antifungals, we speculate that the concomitant use of triazole antifungals inhibited the hepatic metabolism of ATRA, resulting in higher serum ATRA concentration, and markedly accentuated cutaneous toxicities in our patients.
CONCLUSION
By highlighting this crucial pharmacokinetic interaction, we want to caution the fellow oncologists to be mindful of the inhibitory effect of triazole antifungals on CYP450. We propose using a non-myelosuppressive combination of ATRA and arsenic trioxide for management of APL hence, obliterating the need of prophylactic antifungals. However, in the event of invasive fungal infection (IFI), we suggest using alternative class of antifungals.
Topics: Humans; Leukemia, Promyelocytic, Acute; Male; Antifungal Agents; Female; Tretinoin; Adult; Triazoles; Antineoplastic Agents; Aspergillosis; Drug Eruptions
PubMed: 38797854
DOI: 10.1186/s13256-024-04577-1 -
Scientific Reports May 2024Spontaneous intracerebral hemorrhage (SICH) remains a devastating form of stroke. Prior use of antiplatelets or warfarin before SICH is associated with poor outcomes,...
Spontaneous intracerebral hemorrhage (SICH) remains a devastating form of stroke. Prior use of antiplatelets or warfarin before SICH is associated with poor outcomes, but the effects of direct oral anticoagulants (DOACs) remain unclear. This study aimed to clarify trends in prior antithrombotic use and to assess the associations between prior use of antithrombotics and in-hospital mortality using a multicenter prospective registry in Japan. In total, 1085 patients were analyzed. Prior antithrombotic medication included antiplatelets in 14.2%, oral anticoagulants in 8.1%, and both in 1.8%. Prior warfarin use was significantly associated with in-hospital mortality (odds ratio [OR] 5.50, 95% confidence interval [CI] 1.30-23.26, P < 0.05) compared to no prior antithrombotic use. No such association was evident between prior DOAC use and no prior antithrombotic use (OR 1.34, 95% CI 0.44-4.05, P = 0.606). Concomitant use of antiplatelets and warfarin further increased the in-hospital mortality rate (37.5%) compared to warfarin alone (17.2%), but no such association was found for antiplatelets plus DOACs (8.3%) compared to DOACs alone (11.9%). Prior use of warfarin remains an independent risk factor for in-hospital mortality after SICH in the era of DOACs. Further strategies are warranted to reduce SICH among patients receiving oral anticoagulants and to prevent serious outcomes.
Topics: Humans; Hospital Mortality; Aged; Female; Male; Registries; Cerebral Hemorrhage; Warfarin; Japan; Aged, 80 and over; Anticoagulants; Fibrinolytic Agents; Middle Aged; Risk Factors; Platelet Aggregation Inhibitors; Prospective Studies
PubMed: 38796624
DOI: 10.1038/s41598-024-62717-5 -
Viruses May 2024Given the World Health Organization's target to eliminate the hepatitis C virus (HCV) by 2030, we assessed the impact of French public policies and the COVID-19 pandemic...
Given the World Health Organization's target to eliminate the hepatitis C virus (HCV) by 2030, we assessed the impact of French public policies and the COVID-19 pandemic on HCV testing and initiation of direct-antiviral agents (DAAs). Using the French National Health Data System, we identified individuals living in metropolitan France with at least one reimbursement for an anti-HCV test and those with a first delivery of DAAs between 1 January 2014 and 31 December 2021. During this period, the annual number of people tested increased each year between 3.3 (in 2015) and 9.3% (in 2021), except in 2020, with a drop of 8.3%, particularly marked in April (-55.0% compared to February 2020). A return to pre-pandemic testing levels was observed in 2021. The quarterly number of patients initiating DAAs presented an upward trend from Q1-2014 until mid-2017, with greater increases in Q1-2015, and Q1- and Q2-2017, concomitant with DAA access policies and availability of new therapies. Then, quarterly numbers decreased. A 65.5% drop occurred in April compared to February 2020. The declining DAA initiations since mid-2017, despite new measures improving access and screening efforts, could be due to the shrinking pool of patients requiring treatment and a need to increase awareness among undiagnosed infected people. Further action is needed to eliminate HCV in France.
Topics: Humans; France; COVID-19; Antiviral Agents; Hepatitis C; Public Policy; SARS-CoV-2; Male; Female; Middle Aged; Pandemics; Hepacivirus; Aged; Health Policy; Adult; Mass Screening
PubMed: 38793673
DOI: 10.3390/v16050792