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American Journal of Clinical Dermatology Jul 2024Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care...
BACKGROUND
Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management.
OBJECTIVES
The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE.
METHODS
In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to < 15 kg: 200 mg; ≥ 15 kg to < 30 kg: 300 mg).
RESULTS
Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0-5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator's Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores.
CONCLUSIONS
Consistent with results seen in adults, adolescents, and older children (aged 6-11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population.
TRIAL REGISTRATION
ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B).
Topics: Humans; Dermatitis, Atopic; Antibodies, Monoclonal, Humanized; Female; Male; Child, Preschool; Infant; Treatment Outcome; Severity of Illness Index; Injections, Subcutaneous; Nasopharyngitis; Drug Administration Schedule; Time Factors; Double-Blind Method; Interleukin-4 Receptor alpha Subunit
PubMed: 38743155
DOI: 10.1007/s40257-024-00859-y -
The Israel Medical Association Journal... May 2024Group A Streptococcus (GAS) is the predominant bacterial pathogen of pharyngitis in children. However, distinguishing GAS from viral pharyngitis is sometimes difficult....
BACKGROUND
Group A Streptococcus (GAS) is the predominant bacterial pathogen of pharyngitis in children. However, distinguishing GAS from viral pharyngitis is sometimes difficult. Unnecessary antibiotic use contributes to unwanted side effects, such as allergic reactions and diarrhea. It also may increase antibiotic resistance.
OBJECTIVES
To evaluate the effect of a machine learning algorithm on the clinical evaluation of bacterial pharyngitis in children.
METHODS
We assessed 54 children aged 2-17 years who presented to a primary healthcare clinic with a sore throat and fever over 38°C from 1 November 2021 to 30 April 2022. All children were tested with a streptococcal rapid antigen detection test (RADT). If negative, a throat culture was performed. Children with a positive RADT or throat culture were considered GAS-positive and treated antibiotically for 10 days, as per guidelines. Children with negative RADT tests throat cultures were considered positive for viral pharyngitis. The children were allocated into two groups: Group A streptococcal pharyngitis (GAS-P) (n=36) and viral pharyngitis (n=18). All patients underwent a McIsaac score evaluation. A linear support vector machine algorithm was used for classification.
RESULTS
The machine learning algorithm resulted in a positive predictive value of 80.6 % (27 of 36) for GAS-P infection. The false discovery rates for GAS-P infection were 19.4 % (7 of 36).
CONCLUSIONS
Applying the machine-learning strategy resulted in a high positive predictive value for the detection of streptococcal pharyngitis and can contribute as a medical decision aid in the diagnosis and treatment of GAS-P.
Topics: Humans; Pharyngitis; Child; Pilot Projects; Streptococcal Infections; Child, Preschool; Male; Female; Machine Learning; Streptococcus pyogenes; Adolescent; Decision Support Systems, Clinical; Anti-Bacterial Agents; Acute Disease; Diagnosis, Differential; Algorithms
PubMed: 38736345
DOI: No ID Found -
The Lancet. Microbe May 2024Streptococcus pyogenes causes more than 500 000 deaths per year globally, which occur disproportionately in low-income and middle-income countries. The roles of S...
BACKGROUND
Streptococcus pyogenes causes more than 500 000 deaths per year globally, which occur disproportionately in low-income and middle-income countries. The roles of S pyogenes skin and pharyngeal carriage in transmission are unclear. We aimed to investigate the clinical epidemiology and household transmission dynamics of both S pyogenes asymptomatic carriage and infection in a high-burden setting.
METHODS
We did a 1-year prospective, longitudinal, household cohort study, recruiting healthy participants from households in Sukuta, The Gambia. Households were eligible if they comprised at least three members, including one child younger than 18 years, and were excluded if more than half of household members declined to participate. Households were identified by random GPS coordinates derived from census data. At monthly visits, pharyngeal and normal skin swabs were collected for S pyogenes culture, and sociodemographic data were recorded by interview. Incident pharyngitis and pyoderma infections were captured. Cultured isolates underwent emm genotyping. The primary outcome measures were incidence of S pyogenes carriage and disease. Additional outcomes were prevalence of S pyogenes skin and pharyngeal carriage, S pyogenes skin and pharyngeal clearance time, S pyogenes emm type, risk factors for carriage and disease events, household secondary attack rate, and emm-linked household transmission events. The study is registered on ClinicalTrials.gov, NCT05117528.
FINDINGS
Between July 27, 2021, and Sept 28, 2022, 442 participants were enrolled from 44 households. The median age was 15 years (IQR 6-28) and 233 (53%) were female. We identified 17 pharyngitis and 99 pyoderma events and 49 pharyngeal and 39 skin S pyogenes carriage acquisition events. Mean monthly prevalence was 1·4% (95% CI 1·1-1·9) for S pyogenes pharyngeal carriage and 1·2% (0·9-1·6) for S pyogenes skin carriage. Incidence was 120 per 1000 person-years (95% CI 87-166) for S pyogenes pharyngeal carriage, 124 per 1000 person-years (90-170) for S pyogenes skin carriage, 51 per 1000 person-years (31-84) for S pyogenes pharyngitis, and 263 per 1000 person-years (212-327) for S pyogenes pyoderma. Pharyngeal carriage risk was higher during the rainy season (HR 5·67, 95% CI 2·19-14·69) and in larger households (per additional person: 1·03, 1·00-1·05), as was pharyngitis risk (rainy season: 3·00, 1·10-8·22; household size: 1·04, 1·02-1·07). Skin carriage risk was not affected by season or household size, but was lower in female than in male participants (0·45, 0·22-0·92) and highest in children younger than 5 years compared with adults (22·69, 3·08-167·21), with similar findings for pyoderma (female sex: 0·34, 0·19-0·61; age <5 years: 7·00, 2·78-17·64). Median clearance time after carriage acquisition was 4·0 days for both skin (IQR 3·5-7·0) and pharynx (3·5-7·3). The mean household secondary attack rate was 4·9 (95% CI 3·5-6·3) for epidemiologically linked S pyogenes events and 0·74 (0·3-1·2) for emm-linked S pyogenes events. Of the 204 carriage and disease events, emm types were available for 179 (88%). Only 18 emm-linked between-visit household transmission events were identified. Pyoderma was the most common source of S pyogenes household transmissions in 11 (61%) of 18 emm-linked transmissions. Both pharynx to skin and skin to pharynx transmission events were observed.
INTERPRETATION
S pyogenes carriage and infection are common in The Gambia, particularly in children. Most events are non-household acquisitions, but skin carriage and pyoderma have an important role in S pyogenes household transmission and bidirectional transmission between skin and pharynx occurs.
FUNDING
Wellcome Trust, Chadwick Trust, Fonds National de la Recherche Scientifique (Belgium), European Society for Paediatric Infectious Diseases, and Medical Research Council (UK).
PubMed: 38735305
DOI: 10.1016/S2666-5247(24)00046-6 -
Journal of Ethnopharmacology Oct 2024Jiegeng decoction (JGD), consisting of Glycyrrhizae Radix et Rhizoma and Platycodonis Radix at the ratio of 2:1, is a classical Chinese medicine prescription firstly...
ETHNOPHARMACOLOGICAL RELEVANCE
Jiegeng decoction (JGD), consisting of Glycyrrhizae Radix et Rhizoma and Platycodonis Radix at the ratio of 2:1, is a classical Chinese medicine prescription firstly recorded in "Treatise on Febrile Diseases". JGD has been extensively utilized to treat sore throat and lung diseases for thousands of years in China. However, the pharmacological effect and mechanism of JGD on acute pharyngitis (AP) remain unclear.
AIM OF THE STUDY
Our research aimed to reveal the pharmacological effect of JGD on AP and its potential mechanisms.
MATERIALS AND METHODS
The chemical components of JGD were analyzed based on the UPLC-MS analysis. The anti-inflammatory effect of JGD was evaluated by NO production using the Griess assay in RAW 264.7 cells. The mRNA expression of iNOS, IL-1β, IL-10, TNF-α, IL-6 and MCP-1 was determined by qRT-PCR in vitro. A 15% ammonia-induced AP model was established. The histopathology, the inflammatory cytokines IL-6 and MCP-1 in serum and the apoptosis-related genes caspease-8 and caspease-3 were determined by H&E staining, ELISA and qRT-PCR, respectively. The expression levels of p-p65, p65, p-JNK, JNK, p-p38, p38, p-ERK1/2, ERK1/2, and COX2 were measured through western blotting.
RESULTS
Nine compounds, including liquiritin, liquiritin apiosde, liquiritigenin, platycodin D, platycoside A, licorice saponin J2, licorice saponin G2, glycyrrhizic acid, and licochalcone A, were identified. JGD significantly inhibited NO production and regulated the mRNA expression levels of cytokines in LPS-stimulated RAW 264.7 cells. The results of in vivo experiments confirmed that JGD ameliorated AP through improving the pathological state of pharyngeal tissue, decreasing the serum levels of IL-6 and MCP-1 and preventing the tissue mRNA expression of caspease-8 and caspease-3. Furthermore, JGD also inhibited the NF-κB and MAPK pathways in the AP model.
CONCLUSIONS
This study suggested that JGD could alleviate AP through its anti-inflammation via NF-κB and MAPK pathways, which supported the traditional application of JGD for the treatment of throat diseases.
Topics: Animals; Mice; RAW 264.7 Cells; Pharyngitis; NF-kappa B; Drugs, Chinese Herbal; Anti-Inflammatory Agents; Cytokines; MAP Kinase Signaling System; Male; Acute Disease; Signal Transduction
PubMed: 38734391
DOI: 10.1016/j.jep.2024.118328 -
Journal of Clinical Anesthesia Sep 2024Periodic fever syndromes are autoinflammatory disorders associated with recurrent fevers unrelated to infection. Little is known about the perioperative management of... (Review)
Review
Periodic fever syndromes are autoinflammatory disorders associated with recurrent fevers unrelated to infection. Little is known about the perioperative management of patients with these syndromes, and existing literature consists primarily of case reports and occasional case series. This narrative review discusses background information and diagnostic criteria for the three most common periodic fever syndromes: periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA), familial Mediterranean fever (FMF), and TNF receptor-associated periodic syndrome (TRAPS), and describes perioperative considerations for anesthesia providers when caring for the patient with a periodic fever syndrome. We include a systems-based framework in which to organize these considerations.
Topics: Humans; Perioperative Care; Hereditary Autoinflammatory Diseases; Anesthesia; Fever; Familial Mediterranean Fever; Pharyngitis
PubMed: 38728932
DOI: 10.1016/j.jclinane.2024.111497 -
Southern African Journal of Infectious... 2024Lemierre's syndrome is a rare clinical syndrome of septic thrombophlebitis following a bacterial oropharyngeal infection. Lemierre's syndrome can be difficult to...
UNLABELLED
Lemierre's syndrome is a rare clinical syndrome of septic thrombophlebitis following a bacterial oropharyngeal infection. Lemierre's syndrome can be difficult to recognise and has significant morbidity. We report the case of a young man with Lemierre's syndrome caused by , who responded well to 2 weeks of beta-lactam therapy.
CONTRIBUTIONS
This case report summarises the key presenting features of Lemierre's syndrome and provides a brief literature review considering the South African context.
PubMed: 38726019
DOI: 10.4102/sajid.v39i1.606 -
Frontiers in Pediatrics 2024Group A streptococcus (GAS) infections, such as pharyngitis and impetigo, can lead to rheumatic fever and rheumatic heart disease (RHD). Australian Aboriginal and Torres...
INTRODUCTION
Group A streptococcus (GAS) infections, such as pharyngitis and impetigo, can lead to rheumatic fever and rheumatic heart disease (RHD). Australian Aboriginal and Torres Strait Islander populations experience high rates of RHD and GAS skin infection, yet rates of GAS pharyngitis are unclear. Anecdotally, clinical presentations of pharyngitis, including tonsillar hypertrophy and sore throat, are uncommon. This study aimed to develop a standardised set of tonsil photographs and determine tonsil size distribution from an urban paediatric population.
METHODS
A prospective cohort of children aged 3-15 years were recruited at the public events "Discover Day" and "Telethon Weekend" (October 2017) in Perth, Western Australia, Australia. Tonsil photographs, symptomatology, and GAS rapid antigen detection tests (RADT) were collected. Tonsil size was graded from the photographs using the Brodsky Grading Scale of tonsillar hypertrophy (Brodsky) by two independent clinicians, and inter-rater reliability calculated. Pharyngitis symptoms and GAS RADT were correlated, and immediate results provided.
RESULTS
Four hundred and twenty-six healthy children participated in the study over three days. The median age was seven years [interquartile range (IQR) 5.9-9.7 years]. Tonsil photographs were collected for 92% of participants, of which 62% were rated as good-quality photographs and 79% were deemed of adequate quality for assessment by both clinicians. When scored by two independent clinicians, 57% received the same grade. Average Brodsky grades (between clinicians) were 11%, 35%, 28%, 22% and 5% of grades 0,1,2,3 and 4, respectively. There was moderate agreement in grading using photographs, and minimal to weak agreement for signs of infection. Of 394 participants, 8% reported a sore throat. Of 334 GAS RADT performed, <1% were positive.
DISCUSSION
We report the first standardised use of paediatric tonsil photographs to assess tonsil size in urban-living Australian children. This provides a proof of concept from an urban-living cohort that could be compared with children in other settings with high risk of GAS pharyngitis or rheumatic fever such as remote-living Australian Indigenous populations.
PubMed: 38725980
DOI: 10.3389/fped.2024.1367060 -
BMJ (Clinical Research Ed.) May 2024
Topics: Adult; Female; Humans; Diagnosis, Differential; Pharyngitis; Recurrence
PubMed: 38724082
DOI: 10.1136/bmj-2023-078481 -
International Journal of Pediatric... Jun 2024Coblation intracapsular tonsillectomy (ICT) is increasingly being used in the paediatric population because of the rapid recovery and low rates of complications...
OBJECTIVES
Coblation intracapsular tonsillectomy (ICT) is increasingly being used in the paediatric population because of the rapid recovery and low rates of complications associated with it. There is, however, a risk of symptomatic regrowth with this technique. The objective of our study is to establish the rate of, and risks for, revision surgery over time in a major tertiary referral centre with a large cohort of paediatric Coblation ICT cases.
METHODS
A retrospective review of all children (0-19 years) undergoing Coblation ICT from April 2013 to June 2022 was undertaken, using electronic databases and clinical records. Post-operative follow up was reviewed and revision cases were subsequently identified and examined. Statistical analysis was performed using a Chi-Squared test.
RESULTS
4111 patients underwent Coblation ICT during the studied period, with or without concomitant adenoidectomy. Of these, 135 (3.3 %) required revision tonsil surgery, primarily for recurrence of initial symptoms; two patients required two consecutive revision procedures (137 revision procedures in total). Eight-eight (n = 88) (64 %) of these were revised with a repeat Coblation ICT procedure and 49 (36 %) with bipolar diathermy extracapsular tonsillectomy (ECT) of remnant tonsil tissue. The revision rates after Coblation ICT declined steeply on a year-on-year basis since the commencement of this technique (from 10.6 % early on, to 0.3 % at the end of the study period P<0.001). A significantly higher revision rate was noted in children below the age of two at the time of primary surgery, compared to those older than two years of age (P<0.001).
CONCLUSIONS
This study demonstrates real-world departmental revision rates over a nine-year period from the technique's commencement of use. With Coblation ICT, symptomatic re-growth occurs rarely, but may be clinically significant, with higher rates of recurrent symptoms seen in children under two years of age at the time of primary surgery. The revision rate apparently drops over time in parallel with overall experience of surgeons and formalised training.
Topics: Humans; Tonsillectomy; Reoperation; Child; Retrospective Studies; Female; Male; Child, Preschool; Adolescent; Tertiary Care Centers; Infant; Tonsillitis; Young Adult; Recurrence; Treatment Outcome; Infant, Newborn
PubMed: 38723424
DOI: 10.1016/j.ijporl.2024.111942 -
JAC-antimicrobial Resistance Jun 2024Recent regulatory and reimbursement changes facilitated the development of teleconsultation within primary care. French guidance advises against antibiotic prescribing...
BACKGROUND
Recent regulatory and reimbursement changes facilitated the development of teleconsultation within primary care. French guidance advises against antibiotic prescribing in children in teleconsultation. We assessed paediatric antibiotic prescribing on a French teleconsultation platform.
METHODS
This cross-sectional observational study analysed paediatric (0-14 years) visits on a national direct-to-consumer teleconsultation platform between January 2018 and December 2021. Teleconsultations with complete information regarding diagnosis (ICD-10 coding) and prescriptions were included. We assessed antibiotic prescription rates per 100 visits across diagnoses and used logistic regression to identify factors associated with antibiotic prescribing.
RESULTS
In the 37 587 included paediatric teleconsultations (median age 3 years) performed by 713 general practitioners (GPs) and 89 paediatricians, antibiotics were prescribed for 12.1%. Respiratory tract infections (RTIs) accounted for 49.5% of antibiotic prescriptions. Antibiotic prescription rates per 100 visits were: sinusitis, 69.5%; urinary tract infections, 62.2%; pharyngitis, 59.0%; pneumonia, 45.5%; otitis, 46.6%; bronchitis, 19.6%; rhinitis, 11.6%; bronchiolitis 6.6%. Antibiotic prescription rates were higher in GPs than paediatricians [OR 2.21 (IC95% 2.07-2.35)], among physicians aged 45-54 and over 65 [OR 1.66 (1.48-1.85) and 1.48 (1.32-1.66), respectively], in female practitioners [OR 1.13 (1.05-1.21)], in children 3-6 years old [OR 1.41 (1.28-1.56)] and over 6 [OR 1.50 (1.35-1.66)], during winter [OR 1.28 (1.21-1.37)] and for RTIs [OR 1.99 (1.87-2.10)]. Antibiotic prescription rates were lower in doctors with extensive experience in teleconsultation [OR 0.92 (0.86-0.98)].
CONCLUSIONS
Despite current recommendations, paediatric patients were frequently prescribed antibiotics during acute care teleconsultations. Specific antibiotic stewardship campaigns should target paediatric teleconsultations.
PubMed: 38721410
DOI: 10.1093/jacamr/dlae070