Upper Respiratory Tract Infection Research Articles

COVID-19 infection and incident diabetes in American Indian and Alaska Native people: a retrospective cohort study

Evidence suggests an increased risk of new-onset diabetes following COVID-19 infection. American Indian/Alaska Native (AI/AN) people were disparately impacted by the COVID-19 pandemic and historically have had higher diabetes incidence than other racial/ethnic groups in the US. We measured the association between COVID-19 infection and incident diabetes in AI/AN people. We conducted a retrospective cohort study using de-identified patient data from the Indian Health Service's (IHS) National Patient Information Reporting System. We estimated age-adjusted diabetes incidence rates, incidence rate ratios, and adjusted hazard ratios among three cohorts spanning pre-pandemic (1/1/2018-2/28/2020) and pandemic (3/1/2020-12/31/2021) timeframes: 1) pre-pandemic cohort (1,503,085 individuals); 2) no-COVID-19 pandemic cohort (1,344,339 individuals); and 3) COVID-19 cohort (176,483 individuals). The COVID-19 cohort had an increased hazard of diabetes compared to the no-COVID-19 group (adjusted hazard ratio (aHR)=1.56; 95% CI: 1.50-1.62) and the pre-pandemic group (aHR=1.27; 95% CI: 1.22-1.32). The association between COVID-19 infection and new-onset diabetes was stronger in those with severe COVID-19 illness. A sensitivity analysis comparing the COVID-19 cohort to members of other cohorts that had acute upper respiratory infections showed an attenuated but higher risk of new-onset diabetes in those with COVID-19. AI/AN people diagnosed with COVID-19 had an elevated risk of a new diabetes diagnosis when compared to the no-COVID-19 group and the pre-pandemic group. The increased diabetes risk in the COVID-19 group remained in a sensitivity analysis that limited the comparator groups to individuals with an AURI diagnosis. US National Institute of Diabetes and Digestive and Kidney Diseases.

Resurgence of respiratory syncytial virus with dominance of RSV-B during the 2022-2023 season.

Respiratory syncytial virus (RSV) is a common cause of upper and lower respiratory tract infections. This study aimed to explore the prevalence of respiratory syncytial virus (RSV) and other respiratory viruses in Bulgaria, characterize the genetic diversity of RSV strains, and perform amino acid sequence analyses of RSV surface and internal proteins. Clinical and epidemiological data and nasopharyngeal swabs were prospectively collected from patients with acute respiratory infections between October 2020 and May 2023. Real-time PCR for 13 respiratory viruses, whole-genome sequencing, phylogenetic, and amino acid analyses were performed. This study included three epidemic seasons (2020-2021, 2021-2022, and 2022-2023) from week 40 of the previous year to week 20 of the following year. Of the 3,047 patients examined, 1,813 (59.5%) tested positive for at least one viral respiratory pathogen. RSV was the second most detected virus (10.9%) after SARS-CoV-2 (22%). Coinfections between RSV and other respiratory viruses were detected in 68 cases, including 14 with SARS-CoV-2. After two seasons of low circulation, RSV activity increased significantly during the 2022-2023 season. The detection rates of RSV were 3.2, 6.6, and 13.7% in the first, second, and third seasons, respectively. RSV was the most common virus found in children under 5 years old with bronchiolitis (40%) and pneumonia (24.5%). RSV-B drove the 2022-2023 epidemic. Phylogenetic analysis indicated that the sequenced RSV-B strains belonged to the GB5.0.5a and GB5.0.6a genotypes. Amino acid substitutions in the surface and internal proteins, including the F protein antigenic sites were identified compared to the BA prototype strain. This study revealed a strong resurgence of RSV in the autumn of 2022 after the lifting of anti-COVID-19 measures, the leading role of RSV as a causative agent of serious respiratory illnesses in early childhood, and relatively low genetic diversity in circulating RSV strains.

Evaluation of IL-4 and IL-13 Single Nucleotide Polymorphisms and Their Association With Childhood Asthma and Its Severity: A Hospital-Based Case-Control Study.

Asthma is a common, chronic, atopic respiratory disease that is on the rise among children and adults worldwide. Various environmental, genetic, and biological interactions contribute to the surge in susceptibility to this disease. Interleukin (IL) genes, particularly IL-4 and IL-13, have been linked to asthma pathogenesis. The present study aims to investigate the genetic aberrations, specifically single nucleotide polymorphisms (SNPs) of IL-4 and IL-13, and their association with childhood asthma and its severity. An unmatched hospital-based case-control study was conducted in a tertiary care hospital in Assam, India. The sample size was calculated to be 120 (60 cases and 60 controls) using the Epi Info software version 7.2 (Centers for Disease Control and Prevention, Atlanta, GA, USA), assuming a confidence interval of 95%, a power of the study at 80%, a ratio of control to cases as 1, a proportion of controls with exposure at 22%, and a proportion of cases with exposure at 46%. A total of 53 clinically diagnosed cases of childhood asthma in the age range of three to 12 years and 39 healthy controls free from respiratory diseases and having no history of asthma and/or allergy of the same age group attending a tertiary care hospital were included in the study. Children who never had asthma or allergies and who did not suffer from any upper or lower respiratory infections for the previous four weeks were considered controls. Prior informed consent and ethical clearance were obtained. Very seriously ill cases and controls were excluded from the study. The genetic investigation used polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP), to discover SNPs in the IL-4 and IL-13 genes. Sequencing analysis was done for the cases with +2044 G>A of the IL-13 gene in relation to the severity of the disease. The difference in the proportions of specific SNPs between cases and controls was analyzed using the χ2test (a p-value of <0.05 was considered significant). Both the rs2070874 and rs2243250 polymorphisms of IL-4 showed no statistically significant associations. The mutation of the IL-13 gene in 1111C>T was higher among cases than controls. Both genotypic and allelic distributions of the +2044G>A polymorphism of the IL-13 gene revealed a significant association (p<0.05) with the severity of the disease. Genetic aberrations in SNPs of IL-4 and IL-13 are prevalent among the pediatric patients of the study region. The SNP +2044G>A of IL-13 is instrumental in disease manifestation and severity among the pediatric population of the study region.

50 Why are Black and Mexican American children more vulnerable than White children to upper respiratory viral infection?

OBJECTIVES/GOALS: There is an excess risk of upper respiratory infection (URI) among Black and Mexican-American children in the US. Factors that underpin these disparities are largely unknown. We evaluated the extent to which socioeconomic status (SES), serum cotinine, obesity, and household size explained the association between race/ethnicity and URI. METHODS/STUDY POPULATION: We studied children, 6-17 years of age, who identified as Black, Mexican-American, or White in the National Health and Nutritional Examination Survey (2007-2012). URI was defined as a self-reported cough, cold, phlegm, runny nose, or other respiratory illness (excluding hay fever and allergies) in the past 7 days. The proportion of the association between race/ethnicity and URI explained by SES, serum cotinine, obesity, and household size was estimated as the average causal mediation effect (i.e., the indirect effect of race/ethnicity via the mediator) divided by the total effect of race/ethnicity. The average causal mediation effect was derived from survey weighted logistic regression models adjusted for age and sex. RESULTS/ANTICIPATED RESULTS: Black children were nearly 40% and Mexican American children were ~60% more likely to report a URI than those who identified as White (OR, 1.37; 95% CI, 1.06-1.77 and OR, 1.61; 95% CI, 1.21-2.13, respectively). Lower SES explained ~25% of the association between Black and Mexican American identity and URI (percent mediated 24.7; 95% CI, 23.0-26.6 and 26.1; 95% CI, 24.2-28.2, respectively). Obesity explained ~7% of the association between Black and Mexican-American identity and URI (percent mediated, 7.6; 95% CI, 7.3-8.0 and percent mediated, 6.7; 95% CI, 6.4-6.9, respectively). Nicotine exposure explained 8% of the association between Black identity and URI (percent mediated, 7.9; 95% CI, 5.6-10.1). DISCUSSION/SIGNIFICANCE: Lower SES explained a quarter of the association between race/ethnicity and URI. Low SES is a broad concept that may work through different mechanisms to lead to disparities in URI by race/ethnicity. Future research is needed to better understand these mechanisms and to identify modifiable aspects that can serve as targets for intervention.

Risk Factors for Otitis Media with Effusion in Preschool and School Children in Calabar Municipality.

Predisposing factors for otitis media with effusion are multifactorial, ranging from genetic and anatomical abnormalities to environmental factors and inflammation of the nose and adjacent structures. The study determined the risk factors for otitis media with effusion (OME) among children in Calabar Municipality. This was a descriptive, cross-sectional, community-based study including children aged 1-10 years randomly selected from government and privately owned daycares, nurseries (preschool), and primary schools. The risk factors assessed included upper respiratory tract infection, allergic rhinitis, adenoid enlargement, acute otitis media, recurrent acute otitis media parental educational level, overcrowding (four children sleeping in a room), duration of breastfeeding, cleft palate, and Down's syndrome. Allergic rhinitis was diagnosed when a child had at least two of the rhinological symptoms: nasal congestion, running nose, sneezing, itching of the eye or nose, and at least one of the following: history of allergy, family history of allergy, and positive history of asthma. The questionnaire was the research instrument used to assess the risk factors for OME. OME diagnosis was made with otoscopy and tympanometry. Data were collected and analyzed with IBM SPSS version 25, and a P value <0.05 was considered statistically significant. A total of 24 daycare pupils, 141 nursery pupils, and 155 primary pupils were recruited into the study. The prevalence of otitis media with effusion was more in younger children than in older children and the relationship was statistically significant (P < 0.001). Female children were more statistically affected than male children (P = 0.007). Children with allergic rhinitis accounted for a higher proportion of those with OME than those without allergic rhinitis (26.7% vs. 11.6%), and the difference was statistically significant (P = 0.007). The association between OME and upper respiratory tract infection, acute otitis media, and recurrent acute otitis media was not statistically significant (P > 0.05). Multivariate binary logistic regression was used to identify predictors for the otitis media with effusion. There are many endogenous and exogenous risk factors for OME, but notable risk factors in our study were age 1-2 years, female sex, and allergic rhinitis.

A multicenter, open-label long-term safety study of rimegepant for the acute treatment of migraine.

The present study evaluated the long-term safety and tolerability of rimegepant, an orally administered small molecule calcitonin gene-related peptide receptor antagonist, in people with migraine. This multicenter, long-term, open-label safety study included adults (≥18 years) with ≥1 year history of migraine who were sequentially enrolled into three groups: participants in the first two groups had either 2-8 or 9-14 moderate to severe migraine attacks per month by history and treated as needed (pro re nata [PRN]) with one rimegepant 75 mg oral tablet up to once per calendar day for 52 weeks (PRN 2-8 and PRN 9-14); a third group, included to collect safety data during higher-frequency dosing, had 4-14 moderate to severe migraine attacks per month by history and who took one rimegepant tablet every other day as scheduled dosing plus PRN dosing of one rimegepant tablet for migraine attacks of any severity on nonscheduled dosing days for 12 weeks (every other day (EOD) + PRN). Overall, 1800 participants self-administered rimegepant (PRN 2-8: n = 1033; PRN 9-14: n = 481; EOD + PRN: n = 286). The most common on-treatment adverse events (AEs) were upper respiratory tract infection (8.8%), nasopharyngitis (6.8%) and sinusitis (5.1%). Most AEs were mild or moderate and considered unrelated to rimegepant. Serious AEs considered possibly (n = 1) or unlikely (n = 9) related to rimegepant were reported in ten (0.6%) participants. No signal of drug-induced liver injury because of rimegepant was identified. Rimegepant 75 mg up to once per day as EOD + PRN for 12 weeks or PRN for up to 52 weeks was safe and well tolerated. No signal of hepatotoxicity, potential drug abuse, or medication-overuse headache was identified.Trial registration: Clinicaltrials.gov: NCT03266588.

The effect of probiotic Bifidobacterium lactis Bl-04 on innate antiviral responses invitro

Consumption of certain probiotic strains may be beneficial for reducing the risk of acute upper respiratory tract infections (URTIs), however, underlying immunological mechanisms are elusive. Bifidobacterium lactis Bl-04™ has been reported in humans to significantly reduce the risk of URTIs, affect the innate immunity in the nasal mucosa, and reduce nasal lavage virus titer after a rhinovirus (RV) challenge. To study the immunological mechanisms, we investigated the effect of Bl-04 on cytokine production and transcriptomes of human monocyte-derived macrophages (Mfs) and dendritic cells (DCs), and further on RV replication and cytokine production in MRC-5 fibroblasts. The results showed that Bl-04 modulates antiviral immune responses and potentiates cytokine production during viral challenge mimic in immune cells. However, effect of Bl-04 on RV replication and cytokine production in fibroblasts was negligible. Overall, the findings suggest that Bl-04 mildly stimulates antiviral immunity in Mfs and DCs, and potentially influences viral replication in fibroblasts that however warrants further investigations.

Value-based comparison of ambulatory children with respiratory diseases in an emergency department and a walk-in clinic: a retrospective cohort study in Québec, Canada

ObjectiveTo compare health outcomes and costs given in the emergency department (ED) and walk-in clinics for ambulatory children presenting with acute respiratory diseases.DesignA retrospective cohort study.SettingThis study was conducted from...

Effects of Active Compounds of Nigella sativa in COVID-19: A Narrative Review.

SARS-CoV-2 infection that led to the COVID-19 pandemic has changed human health and the economy globally. SARS CoV-2 is a type of Coronaviruses that has caused pneumonia and its complications with many deaths over the past two years. The use of hydroxychloroquine and chloroquine, accepted as generally safe for patients with autoimmune diseases or malaria, was attempted in many trials for COVID-19 treatment. Nigella sativa (NS) (black caraway, also known as black cumin, nigella or Kalonji) is an annual flowering plant of the Ranunculaceae family, chemically composed of the main constituent natural Thymoquinone (TQ) (30%- 48%) in forms of thymohydroquinone, dithymoquinone (Nigellone) is a native to wider regions, including parts of eastern Europe, west Asia, North of Africa and east of Myanmar. In this review, we explored the Randomized Controlled Trial, Controlled Trial, and Systematic review studies that support Nigella sativa Thymoquinone-targeted SARS-CoV-2 targeting. Therefore, A literature search was performed for publications published on the electronic databases (PubMed, Embase, Scopus, CNKI, and Google Scholar) for Nigella sativa, black seeds, Kalonji, coronavirus, SARS-CoV -2 and COVID-19. This review aimed to find relevant evidence of Nigella sativa preferences as a natural feasible remedy with no side effects in COVID-19. Studies reported the benefits of NS as beneficial, another appropriate remedy for patients with COVID-19. However, all studies have shown limitations, such as limiting clinical symptom outcomes due to regulations imposed by isolation policies and lack of adequate funding. Therefore, the evidence suggests that the chemical contents of NS are a safe and possible treatment for COVID-19 patients that helps to improve COVID-19 infection in patients with no side effects. Nigella sativa seeds were one of the well-documented herbal products. Three reviewed randomized controlled trials reported that NS reduced covid-19 risk and could improve immune function. It was also helpful in upper respiratory infections such as asthma and bronchitis, with one RCT showing that honey and NS significantly improved symptoms, viral clearance, and mortality of COVID-19 patients. This review concludes that NS has a positive barrier effect on people at risk of acquiring a COVID-19 infection.

Antimicrobial Sensitivity Profile in Psittacine Birds at an Avian Teaching Hospital: A Retrospective Study, 2015-2022.

Veterinary hospitals house patient populations with diverse infectious statuses, microbiota, and histories of prior antibiotic therapy. Choanal swabs are commonly used for assessing the upper respiratory tract of birds for bacterial disease, with the samples submitted for cytologic testing and/or culture and antimicrobial sensitivity testing. The aim of this retrospective study was to identify and quantify bacteria isolated from choanal swabs collected from psittacine patients at a veterinary teaching hospital in Mexico City, Mexico. Data regarding bacterial isolates from choanal swabs were obtained from the medical records of companion psittacines suspected of upper respiratory bacterial disease that presented between November 2015 and December 2022. A total of 47.8% (175 of 366) of the bacterial isolates were from specimens obtained from red-lored Amazons (Amazona autumnalis). Gram-negative bacteria predominated, with 27 different genera identified. Klebsiella, Staphylococcus, and Escherichia were the most frequently isolated genera. A total of 90.4% (331 of 366) of the isolates were resistant to at least 1 antibiotic tested in the sensitivity panel, and a single Klebsiella isolate was resistant to 13 different antibiotics. Gentamicin had a high percentage of efficacy (79.5%; 182 of 229) against the bacterial isolates, whereas isolates tested against sulfonamide-trimethoprim (46.7%, 98 of 210), streptomycin (43.8%; 88 of 201), and clindamycin (12.9%; 15 of 116) had susceptibilities <50%. This is the first study to report common bacterial isolates and their antimicrobial susceptibility patterns from choanal swab samples collected from companion psittacines suspected of upper respiratory disease in Mexico. Clinicians can use the information presented in this study as a guide for therapeutic decision-making when managing upper respiratory bacterial infections in companion psittacine patients.

A Case of Metapneumovirus Pneumonia-Related Acute Respiratory Distress Syndrome in a Young Adult Patient

Human metapneumovirus (hMPV) infections commonly present as mild upper respiratory tract infections in healthy adults, although severe respiratory complications have been observed, particularly in elderly and immunocompromised patients. We report a case in whom pneumonia caused by hMPV progressed to acute respiratory distress syndrome (ARDS) in a healthy adult without underlying diseases. A 31-year-old female presented with fever and dyspnea, prompting transfer to our hospital for mechanical ventilation 3 days after symptom onset. Auscultation revealed coarse breath sounds and crackles in both lung fields, and chest X-ray showed non-specific infiltrative nodules with poorly defined borders throughout both lungs. ARDS caused by community-acquired pneumonia was diagnosed. hMPV was identified via rapid testing of respiratory samples for genes that encode pneumonia pathogens and drug resistance markers; we employed reverse transcription polymerase chain reactions to these ends. Six days later, the patient was weaned off the mechanical ventilator, and discharged from the hospital in good clinical condition.

Clinical Study on Immunomodulatory Action of Suvarnprashan on Recurrent Upper Respiratory Tract Infection in Children – A Two-Arm Prospective Randomized Controlled Trial

Clinical Study on Immunomodulatory Action of Suvarnprashan on Recurrent Upper Respiratory Tract Infection in Children – A Two-Arm Prospective Randomized Controlled Trial

Real-World Evidence of the Impact of a Novel Surgical Irrigant on Surgical Site Infections in Primary Total Knee Arthroplasty Performed at an Ambulatory Surgery Center.

Background: Total knee arthroplasty (TKA) is one of the most common inpatient and outpatient surgical procedures performed in the United States and is predicted to increase 401% by 2040. Surgical site infections (SSIs) at an incidence rate of approximately 2% are costly post-operative complications in TKA. Intra-operative surgical irrigants are used to decrease contaminating microbial bioburden within the surgical site to prevent SSI. The primary objective of this retrospective study was to evaluate the impact of a novel surgical irrigant called XPERIENCE® Advanced Surgical Irrigation (XP; Next Science, Jacksonville, FL) on SSI incidence in primary TKA performed at an ambulatory surgery center (ASC). Patients and Methods: Primary TKAs were performed at a free-standing ASC. The novel surgical irrigant was used intra-operatively to rinse away debris and micro-organisms from the surgical site. Retrospective data collation included SSI rates, complication rates, and re-admissions due to SSI within 90 days of index surgery. Results: Among the 524 primary TKA surgeries, one peri-prosthetic joint infection (PJI) was diagnosed within 90 days of index surgery and one superficial incisional SSI was diagnosed within 30 days of index surgery. The PJI was attributed to an exogenously acquired upper respiratory tract infection rather than due to the failure of intra-operative regimes. The 0.19% PJI incidence rate indicated significant efficacy of XP in decreasing PJI. An overall complication rate of 7.82% was noted with none of the complications associated with usage of the novel surgical irrigant. Conclusions: XPERIENCE is a promising intra-operative antimicrobial irrigant that can be easily incorporated into a broader infection prevention strategy.

Mucoadhesive Buccal Tablet Formulation of Azithromycin dihydrate for treatment of Upper Respiratory Tract Infection

The buccal drug delivery system is a versatile delivery system which can be designed for local or systemic effect. The objective of the study was to developed patient complacent tablet which can give sustain release of antibacterial agent for relief of upper respiratory tract infection. Azithromycin dihydrate is a semi-synthetic macrolide antibiotic widely used to prevent bacterial infections in the upper respiratory tract. The mucoadhesive buccal tablets of azithromycin dihydrate were formulated by varying concentrations of polymers (natural and synthetic), glidant and other excipients. The drug-excipient compatibility studies were carried out through DSC and FTIR studies. The selected excipients were found to be compatible. Further the dry blend of drug-excipients was evaluated for pre-compression properties. The prepared tablets were evaluated as per the general monograph for tablets of IP. The studies were also carried out to evaluate sustained release of the drug and mucoadhesivity of the tablets. A 23 level (2 level and 3 factors) factorial design was navigated to study the effect of natural, synthetic polymers and the glidant on mucoadhesive strength and percentage cumulative drug release at 8 hours. The responsive variables were analysed using ANOVA by Design-Expert version 12.0. It was concluded that these excipients significantly affected the response variables. The optimized tablet formulation was found to have an adequate mucoadhesion and a cumulative percentage release. The final product was performed for accelerated stability studies, optimized formulation was found to be stable at room temperature and accelerated temperature for three months.

Characteristics of Tonsillitis in Children at Massenrempulu Enrekang Regional Hospital During The Period 2017-2022

Tonsillitis, an inflammation of the tonsils due to viral or bacterial infection, manifests with symptoms such as sore throat, tonsil swelling, difficulty swallowing, and fever. While the World Health Organization (WHO) lacks specific global tonsillitis incidence data, Indonesian Ministry of Health's 2018 statistics rank tonsillitis as the 10th most common ailment among 5-9-year-olds. Objective to characterize tonsillitis among children at Massenrempulu Enrekang Regional General Hospital during 2017-2022. The method used is descriptive research with a univariate design. The total sample size is 93, using total sampling technique, and analyzed with a univariate design. The results obtained showed that the age characteristics were as follows: children aged 6-11 years constitute 41 patients (44.1%), early adolescents aged 12-16 years constitute 31 patients (33.3%), toddlers aged 0-5 years constitute 14 patients (15.1%), and late adolescents aged 17-18 years constitute 7 patients (7.5%). The distribution of gender indicates that female patients are 52 (55.9%), while male patients are 41 (44.1%). Parental education level shows that moderate education level is represented by 52 patients (55.9%), followed by high education level by 37 patients (39.8%), and low education level by 4 patients (4.3%). A history of upper respiratory tract infections was found in 85 patients (91.4%), while only 8 patients (8.6%) had no history of upper respiratory tract infections. Allergy history was present in 68 patients (73.1%), while 25 patients (26.9%) had no history of allergies.

Epidemiological Characterization of Respiratory Pathogens Using the Multiplex PCR FilmArray™ Respiratory Panel.

Various pathogens can cause upper respiratory tract infections, presenting challenges in accurate diagnosis due to similar symptomatology. Therefore, rapid and precise diagnostic tests are crucial for effective treatment planning. Traditional culture-based methods for diagnosis are limited by their reliance on skilled personnel and lengthy processing times. In contrast, multiplex polymerase chain reaction (PCR) techniques offer enhanced accuracy and speed in identifying respiratory pathogens. In this study, we aimed to assess the efficacy of the FilmArray™ Respiratory Panel (RP), a multiplex PCR test capable of simultaneously screening 20 pathogens. This retrospective analysis was conducted at Dankook University Hospital, South Korea, between January 2018 and December 2022. Samples from patients with upper respiratory tract infections were analyzed. Results revealed adenovirus as the most prevalent pathogen (18.9%), followed by influenza virus A (16.5%), among others. Notably, a 22.5% co-infection rate was observed. The FilmArray™ RP method successfully identified 20 pathogens within 2 h, facilitating prompt treatment decisions and mitigating unnecessary antibiotic prescriptions. This study underscores the utility of multiplex PCR in respiratory pathogen identification, offering valuable insights for epidemiological surveillance and diagnosis.

Effects of abrocitinib on pruritus and eczema symptoms and tolerance in patients with moderate‑to‑severe atopic dermatitis in randomized, double‑blind and placebo‑controlled trials: A systematic review and a meta‑analysis.

Abrocitinib is a highly selective Janus kinase 1 (JAK1) inhibitor that can block a multitude of inflammatory signaling pathways that underlie atopic dermatitis (AD). In addition, abrocitinib inhibits JAK1 signaling in sensory neurons to alleviate acute and chronic pruritus during AD. However, substantial variations in efficacy and safety risks remain due to variations in doses applied in clinical use. Therefore for the present study, differences in the efficacy and tolerability of 100 and 200 mg abrocitinib for treating pruritus and eczema symptoms in patients with moderate-to-severe AD were evaluated compared with placebo. Specifically, randomized controlled trials (RCTs) of abrocitinib compared with placebo for the treatment of moderate-to-severe AD were searched on Pubmed, E.B. Stephens Company, China National Knowledge Infrastructure, Wanfang Medical network, Web of Science and related Clinical Trials Registry up to November 2023. In total, two researchers evaluated the quality of the included literature according to the Cochrane Handbook of Systematic Reviews. RevMan 5.3 software was used to conduct a meta-analysis of the efficacy and safety indicators in a cross-comparison of the effects exerted by placebo and 100 and 200 mg abrocitinib. A total of 1,825 patients with moderate-to-severe AD were included across five double-blind, placebo RCTs. Compared with the placebo group, during the double-blind trial period, significant improvements were observed in the investigator's global assessment score, response rate of eczema area and severity index (EASI)-50, EASI-75, EASI-90 and pruritus numerical rating scale (P-NRS) in the 100 and 200 mg abrocitinib groups (P<0.05). However, pairwise control analysis of the 100 and 200 mg group yielded significant differences (P<0.05) in all of the aforementioned therapeutic indicators except for the P-NRS score. In terms of safety, compared with the placebo group, there were significantly higher incidence of nausea, upper respiratory tract viral infection, infections and infestations in the 100 mg abrocitinib group (P<0.05). In addition, there were significantly higher incidence of nausea, gastrointestinal disorder, headache and dizziness in the 200 mg group (P<0.05). There were also significant differences in the incidence of nausea, gastrointestinal disorder and dizziness between the 100 and 200 mg groups (P<0.05). For patients with moderate-to-severe AD, oral administration of 100 or 200 mg abrocitinib once/day was concluded to ameliorate skin pruritus and eczema symptoms to varying degrees, with the efficacy significantly superior at the 200 mg dose. However, the risk of a number of adverse reactions, such as headache, dizziness, nausea and gastrointestinal dysfunction, is also significantly increased. Therefore, patients should be made aware of the risk of adverse drug effects prior to the administration of long-term high abrocitinib doses. Furthermore, large-scale, multi-center, rigorous clinical trials remain necessary to validate the findings from the present study.

Surge for narrow-spectrum antibiotics in times of the MDR crisis: Systematic literature review to establish the role of amoxicillin in tonsillopharyngitis

Background: Group A Streptococcus (GAS) is the predominant pathogen accountable for tonsillitis, making it the most prevalent and frequently encountered bacterial cause of upper respiratory infections. Although amoxicillin is a frequently prescribed antibiotic for the treatment of tonsillopharyngitis, alternate agents like macrolides are regularly recommended. The objective of this study was to evaluate and compare the effectiveness of amoxicillin, its side effects, and the associated risk ratio with alternative antibiotic treatments for respiratory tract infections and tonsillopharyngitis in both children and adults. Material and Methods: An initial search was performed via five basic databases PubMed, Medline, Embase, clinicaltrial.gov and the Cochrane Central Register of Controlled Trials, to identify studies meeting the inclusion criteria spanning from July 2012 to June 2023. The primary search of studies resulted in 6260 from four databases during the study period. Results: After the initial scan of titles and abstracts, 06 studies were included in the review, which reported clinical cure rates. Four out of six studies reported adverse events. Conclusion: Our analysis infers that given their narrow spectrum of activity, low incidence of side effects, comparable efficacy and cost-effectiveness, penicillin or amoxicillin can be considered as preferable choice for the management of tonsillopharyngitis and broad-spectrum antibiotics offer no added advantage in disease management. Keywords: Amoxicillin, Tonsillopharyngitis, Tonsillitis, Acute respiratory infection, Streptococcal infection, GAS, SLR, Systematic literature Review, Antibiotics

The Causal Relationship between Plasma Myeloperoxidase Levels and Respiratory Tract Infections: A Bidirectional Mendelian Randomization Study.

Observational researches reported the underlying correlation of plasma myeloperoxidase (MPO) concentration with respiratory tract infections (RTIs), but their causality remained unclear. Here, we examined the cause-effect relation between plasma MPO levels and RTIs. Datasets of plasma MPO levels were from the Folkersen et al. study (n = 21,758) and INTERVAL study (n = 3,301). Summarized data for upper respiratory tract infection (URTI) (2,795 cases and 483,689 controls) and lower respiratory tract infection (LRTI) in the intensive care unit (ICU) (585 cases and 430,780 controls) were from the UK Biobank database. The primary method for Mendelian randomization (MR) analysis was the inverse variance weighted approach, with MR-Egger and weighted median methods as supplements. Cochrane's Q test, MR-Egger intercept test, MR pleiotropy residual sum and outliers global test, funnel plots, and leave-one-out analysis were used for sensitivity analysis. We found that plasma MPO levels were positively associated with URTI (odds ratio (OR) = 1.135; 95% confidence interval (CI) = 1.011-1.274; P=0.032) and LRTI (ICU) (OR = 1.323; 95% CI = 1.006-1.739; P=0.045). The consistent impact direction is shown when additional plasma MPO level genome-wide association study datasets are used (URTI: OR = 1.158; 95% CI = 1.072-1.251; P < 0.001; LRTI (ICU): OR = 1.216; 95% CI = 1.020-1.450; P=0.030). There was no evidence of a causal effect of URTI and LRTI (ICU) on plasma MPO concentration in the reverse analysis (P > 0.050). The sensitivity analysis revealed no violations of MR presumptions. Plasma MPO levels may causally affect the risks of URTI and LRTI (ICU). In contrast, the causal role of URTI and LRTI (ICU) on plasma MPO concentration was not supported in our MR analysis. Further studies are needed to identify the relationship between RTIs and plasma MPO levels.

Evolocumab Treatment in Pediatric Patients With Homozygous Familial Hypercholesterolemia: Pooled Data From Three Open-Label Studies.

Pediatric patients with homozygous familial hypercholesterolemia (HoFH) have an increased risk of atherosclerotic cardiovascular disease and difficulty meeting low-density lipoprotein cholesterol (LDL-C) goals. In this post hoc analysis, we evaluated pooled safety and efficacy data from 3 studies in pediatric patients with HoFH treated with the PCSK9 (proprotein convertase subtilisin/kexin type 9) monoclonal antibody inhibitor evolocumab. Patients with HoFH aged 10 to 17 years received treatment with open-label evolocumab 420 mg subcutaneously monthly or biweekly in the TAUSSIG, RAMAN, or HAUSER-OLE clinical studies. All patients received background statins with or without ezetimibe. Study duration ranged from 12 to 260 weeks. The primary end point was treatment-emergent adverse events per 100 patient-years. Efficacy end points were changes from baseline to week 12 in lipids and PCSK9. Of the 39 patients in the pooled analysis, 69.2% were males, median age was 13.0 years, and 79.5% (31/39) had genotyped HoFH with LDLR pathogenic variants. Overall, median exposure to evolocumab was 18.2 (Q1, Q3: 3.0, 18.5) months. Treatment-emergent adverse events with an exposure-adjusted patient incidence rate of ≥5% were upper respiratory tract infection (6.6%), influenza (5.2%), and acne (5.0%) per 100 patient-years. Exposure-adjusted patient incidence of serious treatment-emergent adverse events was 13.3% per 100 patient-years. Excluding 4 patients receiving lipoprotein apheresis, week 12 median percentage change from baseline in LDL-C was -2.9% (Q1, Q3: -21.7, 1.5); however, 42.9% (15/35) of patients achieved ≥15% reduction in LDL-C from baseline. Residual LDLR (LDL receptor) activity was not associated with a reduction in LDL-C. In this pooled data analysis from 3 studies in pediatric patients with HoFH, evolocumab was well tolerated, with no new safety signals reported. These safety findings are consistent with findings from previous studies of evolocumab. Patients showed marked variability in LDL-C reduction. Results from this pooled analysis support guidelines suggesting a trial of PCSK9 inhibitor therapy regardless of estimated residual LDLR function. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01624142, NCT03403374, and NCT02624869.