Upper Respiratory Tract Infection Research Articles

Deucravacitinib, an Oral Selective Tyrosine Kinase 2 (TYK2) Inhibitor, in Patients with Moderate to Severe Scalp Psoriasis: Efficacy and Safety Results of a Phase 3b/4, Multicenter, Randomized, Double-blinded, Placebo-controlled Trial (PSORIATYK SCALP)

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. PSORIATYK SCALP, an ongoing, 52-week, phase 3b/4, multicenter, randomized, double-blinded, placebo-controlled trial, evaluated deucravacitinib efficacy/safety in patients with moderate to severe scalp psoriasis, including those with more limited overall psoriasis. Methods: Adults with moderate to severe scalp psoriasis defined by more focused and objective inclusion criteria (ss-PGA ≥3, scalp surface area involvement ≥20%, and PSSI ≥12 at baseline) and BSA involvement ≥3% were randomized 1:2 to oral placebo or deucravacitinib 6 mg once daily through Week 16. The primary efficacy outcome was ss-PGA 0/1; key secondary outcomes were PSSI 90, change from baseline in scalp-specific itch numeric rating scale (NRS), and sPGA 0/1 at Week 16. Efficacy outcomes were evaluated at Week 16 for the overall population and the subpopulation with global sPGA ≥3. Nonresponder imputation and modified baseline observation carried forward were used for patients who discontinued or had missing data for binary and continuous outcomes, respectively. Results: 154 patients were randomized (placebo, n=51; deucravacitinib, n=103). Baseline characteristics were similar in each group (placebo: mean BSA 10.0%, PASI 9.4, PSSI 32.2; deucravacitinib: mean BSA 10.5%, PASI 10.2, PSSI 33.5). In the overall population, a higher proportion of patients receiving deucravacitinib versus placebo achieved ss-PGA 0/1 at Week 16 (48.5% vs 13.7%; P<0.0001). Deucravacitinib was superior to placebo for PSSI 90 (38.8% vs 2.0%; P<0.0001) and mean change from baseline in scalp-specific itch NRS (−3.2 vs −0.7; P<0.0001). In the subpopulation (sPGA ≥3), a greater proportion achieved sPGA 0/1 with deucravacitinib versus placebo (51.0% vs 4.3%; P<0.0001). The most common adverse events (AEs) in the deucravacitinib group (≥5%) were nasopharyngitis (14.6%), upper respiratory tract infection (11.7%), acne (9.7%), headache (7.8%), COVID-19 (5.8%), and pustular acne (5.8%). Two serious AEs were reported (1/group); neither was considered treatment related or led to discontinuation. Conclusion: Deucravacitinib was efficacious and well tolerated in patients with moderate to severe scalp psoriasis, including those with less extensive overall psoriasis (BSA ≥3%). The overall psoriasis response rate (sPGA 0/1) was consistent with POETYK trial results, despite including patients with more limited BSA involvement. Safety findings were consistent with the known deucravacitinib safety profile.

Skin Clearance, Treatment Response Off-therapy, and Safety of Tapinarof Cream 1% Once Daily: Results from ADORING 3, a 48-week Phase 3 Trial in Adults and Children Down to 2 Years of Age with Atopic Dermatitis

Introduction: In the ADORING 1 and 2 phase 3 trials, tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) once daily (QD) demonstrated significant efficacy and was well tolerated in patients down to age 2 years with atopic dermatitis (AD). We present efficacy, safety, and tolerability outcomes from ADORING 3. Methods: Eligible patients from ADORING 1, ADORING 2, from a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients with mild, or moderate or severe AD, that did not meet eligibility criteria for ADORING 1 or 2, received tapinarof cream 1% QD for up to 48 weeks. Efficacy endpoints included achievement of complete disease clearance (Validated Investigator Global Assessment for Atopic Dermatitis™ [vIGA-AD™] score=0 [clear]), and clear or almost clear skin (vIGA-AD™=0 or 1). Safety and tolerability were assessed. Patients entering with vIGA-AD™≥1 were treated with tapinarof until complete clearance (vIGA-AD™=0 [clear]). Those entering with or achieving complete clearance discontinued tapinarof and were assessed for maintenance of clear or almost clear skin off-treatment (duration of treatment-free interval). Patients whose AD returned to mild (vIGA-AD™≥2) were re-treated until complete clearance was achieved. Results: 728 patients enrolled; 83.0% were pediatric (2–17 years). Overall, 51.9% (378/728) achieved complete disease clearance, and 81.6% achieved clear or almost clear skin at least once in the trial. Mean duration of first treatment-free interval was 79.8 consecutive days (standard deviation: 81.4 days). No tachyphylaxis on either continuous or intermittent therapy was observed for up to 48 weeks. Most frequent adverse events were folliculitis (12.1%), nasopharyngitis (6.9%), and upper respiratory tract infection (6.9%). Follicular events and contact dermatitis were mostly mild or moderate and associated with low discontinuations (1.0% and 0.4%, respectively). Tapinarof was well tolerated locally, even when applied on sensitive skin. Conclusions: Tapinarof cream monotherapy demonstrated a high rate of complete disease clearance in patients down to age 2 years with AD. After discontinuing tapinarof, patients maintained clear or almost clear skin for 79.8 consecutive days. Tapinarof was well tolerated over 48 weeks.

Orange Peel Lactiplantibacillus plantarum: Development of A Mucoadhesive Nasal Spray with Antimicrobial and Anti-Inflammatory Activity

Background/Objectives: Due to the high frequency and severity of upper respiratory bacterial infections, probiotics could offer a new medical approach. We explored the antibacterial and anti-inflammatory properties of the new strain Lactiplantibacillus plantarum BIA and formulated a nasal spray. Methods: L. plantarum BIA was isolated from orange peel and taxonomically identified through 16S rRNA gene sequencing. Its antibacterial activity was tested against Pseudomonas aeruginosa, Streptococcus pyogenes, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus, while anti-inflammatory potential was evaluated by Griess assay. BIA genome was fully sequenced and analyzed to assess its safety. BIA was formulated in a freeze-dried matrix, containing prebiotics and cryoprotectants, to be reconstituted with a polymer solution. Solutions containing two types of hydroxypropyl methylcellulose (HPMC) and hyaluronic acid were evaluated as resuspending media and compared in terms of pH, viscosity, and mucoadhesion ability. The biological activity of BIA formulated as nasal spray was verified together with the stability of the selected formulations. Results: L. plantarum BIA inhibited human pathogens’ growth and showed anti-inflammatory activity and a safe profile. In the best-performing formulation, the probiotic is lyophilized in 10% fructooligosaccharides, 0.1% ascorbic acid, and 0.5% lactose and reconstituted with HPMC high viscosity 1% w/v. This composition ensured the probiotic’s viability for up to six months in its dried form and one week after reconstitution. It also allowed interaction with the nasal mucosa, preserving its antimicrobial and anti-inflammatory activities. Conclusion: The developed nasal spray could become a promising formulation in the field of nasal infectious and inflammatory diseases.

Antibacterial Mechanisms and Clinical Impact of Sitafloxacin

Sitafloxacin is a 4th generation fluoroquinolone antibiotic with broad activity against a wide range of Gram-negative and Gram-positive bacteria. It is approved in Japan and used to treat pneumonia and urinary tract infections (UTIs) as well as other upper and lower respiratory infections, genitourinary infections, oral infections and otitis media. Compared to other fluoroquinolones, sitafloxacin displays a low minimal inhibitory concentration (MIC) for many bacterial species but also activity against anaerobes, intracellular bacteria, and persisters. Furthermore, it has also shown strong activity against biofilms of P. aeruginosa and S. aureus in vitro, which was recently validated in vivo with murine models of S. aureus implant-associated bone infection. Although limited in scale at present, the published literature supports the further evaluation of sitafloxacin in implant-related infections and other biofilm-related infections. The aim of this review is to summarize the chemical-positioning-based mechanisms, activity, resistance profile, and future clinical potential of sitafloxacin.

Preoperative Challenges for Pediatric Ambulatory Surgery

The demand for ambulatory anesthesia in pediatric surgery has been increasing, reflecting a significant shift over recent decades toward performing a growing number of procedures in an outpatient setting.1 The growing shortage of pediatric anesthesiologists, coupled with an increase in pediatric ambulatory surgery volumes, will require general anesthesiologists to deliver anesthesia care to children. Children with prematurity, hypotonia, upper respiratory tract infections (URTI), obesity, and congenital heart disease (CHD) are frequently encountered in the ambulatory setting and present significant challenges for ambulatory anesthesiologists. In addition, the management of preoperative fasting, pregnancy testing, and perioperative anxiety further complicates the care of a pediatric patient. This review will examine the existing evidence and provide guidance for ambulatory anesthesiologists on preoperative considerations for pediatric patients undergoing ambulatory surgical procedures.

Tackling antibiotic resistance-insights from eHealthResp's educational interventions.

Antibiotic resistance (AR) poses a significant challenging issue in public health worldwide. This phenomenon led to the emergence of antibiotic-resistant bacterial strains, making the treatment of respiratory infections increasingly difficult. Educational interventions targeting healthcare professionals are important to improve prescription practices and promote responsible antibiotic use. Digital tools, including clinical decision support systems and mobile applications, have proven to effectively enhance educational interventions and clinical decision-making. The eHealthResp project is one such initiative that includes an online course and a mobile app designed to improve antibiotic use for upper respiratory tract infections (URTIs). The online course provides clinical information and case studies, whereas the mobile app acts as a clinical decision support system for URTIs diagnosis. The purpose of this study is to analyse the utilization patterns of eHealthResp digital tools among primary care physicians and community pharmacists. Results showed that both physicians and pharmacists (n = 35) had favorable progress and high grades when completing the online course assessment. The mobile app data indicated a diverse range of searched cases with different respiratory symptoms, with the most common being acute nasal discharge and pain when swallowing. Most observations presented mild symptoms for less than seven days, suggesting the occurrence of acute self-limited infections. Despite limitations, digital tools show promise in enhancing patient care outcomes for managing URTIs. Future efforts should focus on expanding participation among health professionals and enhancing educational interventions to promote responsible antibiotic use.

Assessment of the Communicable Disease Status of Children in Türkiye: A Community-Based Cross-Sectional Study.

Assessment of children's communicable disease status is effective in preventing child morbidity. This study aims to evaluate the infectious disease status of children aged 0-14 in Türkiye. The research is a cross-sectional study conducted using the microdataset of the "Türkiye Health Survey 2022" obtained from the Turkish Statistical Institute. Seven thousand nineteen individuals aged 0-14 were included in the analysis. Data on communicable diseases of children aged 0-14 years in the 6-month period before the survey date was obtained by asking the household head. In our research, the data of 7019 individuals aged 0-14 was evaluated. It was determined that 2.2% of children had a vaccine-preventable infectious disease in the last 6 months. It was observed that the frequency of upper respiratory tract infection, lower respiratory tract infection, urinary tract infection, and diarrhea in children was higher in the 0-6 age group than in the 7-14 age group. Urinary tract infections were more common in girls, whereas respiratory tract infections, communicable diseases, and diarrhea were more common in boys. It was determined that diarrhea and upper respiratory tract infections occur in approximately one out of every three children in the 0-6 age group.

Abstract 4124313: An unusual case of pericardial mass

A 30-year-old male electrician presented with two days of fever and positional left shoulder pain and was found to have elevated inflammatory markers and a large pericardial effusion with echocardiographic evidence of tamponade for which he underwent pericardiocentesis. He was discharged on a course of anti-inflammatory therapy with presumed diagnosis of idiopathic pericarditis based on negative cytology. He returned 6 months later with several weeks of upper respiratory infection symptoms as well as new abdominal discomfort and emesis. On presentation, his vital signs were notable for tachycardia to 113 and cardiac exam was notable for tachycardia, regular rhythm, no rubs or murmurs, nondisplaced precordial impulse, normal jugular venous pressure with Kussmaul sign, and pulsus paradoxus of 6. An electrocardiogram showed sinus tachycardia with diffuse ST segment changes (Figure A). His cardiac biomarkers were unremarkable (troponin 21). His labs revealed normocytic anemia with hemoglobin of 11 and erythrocyte sediment rate above assay. Echocardiogram demonstrated a circumferential complex pericardial effusion with echocardiographic evidence of early tamponade (Figure B, C). A pericardiocentesis was attempted with inability to advance wire within pericardial space. A malignancy workup was initiated. CT demonstrated multi-station thoracic and lower cervical lymphadenopathy, moderate left pleural effusion, and an intrapericardial mass with associated pericardial effusion (Figure D). Cardiac magnetic resonance imaging demonstrated a circumferential intrapericardial non-mobile mass measuring up to 22 mm in thickness posteriorly and the mass was isointense to myocardium indicating low-fat content (Figure E). A supraclavicular lymph node biopsy was obtained with immunohistochemical staining positive for WT1 and calretinin, consistent with metastatic epithelioid mesothelioma of pericardial versus pleural etiology (Figure F). A PET-CT subsequently showed a FDG-avid circumferential anterior pericardial mass and multiple pleural-based lesions concerning for metastatic mesothelioma. He was initiated on pemetrexed/carboplatin systemic chemotherapy. With systemic therapy, his disease has been stable for 6 months. Pericardial mesothelioma is a rare malignancy. This case underscores the diagnostic challenges associated with pericardial mesothelioma and the importance of cancer workup as part of the pericardial effusion workup.

The use of azithromycin in the treatment of inflammatory diseases of the upper respiratory tract and ear

Despite the extensive accumulated clinical experience, inflammatory diseases of the upper respiratory tract and ear still remain an important problem in the field of otorhinolaryngology, especially pediatric practice, since these diseases are associated with the risk of complications. One of the reasons for the ineffectiveness of conservative treatment is the incorrect initial antibacterial therapy. Errors in antimicrobial therapy are associated with both insufficient knowledge of clinical pharmacology by doctors and incorrect interpretation of anamnestic and clinical data, which leads to incorrect treatment of CCA. The aim of the work is to analyze the use of azithromycin in the treatment of upper respiratory tract and ear infections in children, based on pharmacological characteristics, as well as to consider current methods of antibiotic therapy in pediatric practice. An analysis of the literature and our own observations allows us to conclude that azithromycin is an effective antibacterial drug. Taking into account the low toxicity and good bioavailability, azithromycin continues to be one of the main drugs in the arsenal of doctors for the treatment of various infections, including respiratory diseases and infectious processes of ENT organs in children caused by both typical and atypical bacterial pathogens. The convenient dosage form and simple dosage regimen make this drug a popular choice in outpatient pediatric practice, which confirms the widespread use and trust in this antibacterial drug among both doctors and parents.

Evaluating pediatric antimicrobial dosing of β-lactam antibiotics for upper respiratory tract infections in emergency and primary care settings.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Pediatric prescribing is often weight and indication specific and has been associated with high rates of error. The aim of this study was to evaluate outpatient β-lactam suspension dosing practices for pediatric upper respiratory tract infections (URIs), to characterize the rate of error and to describe common error types. This retrospective cohort study was conducted at a community health system with 2 emergency departments and 20 outpatient family medicine practices. Pediatric patients treated from these settings with oral suspension formulations of amoxicillin, amoxicillin/clavulanate, cefdinir, or cephalexin for streptococcal pharyngitis or otitis media between June 1, 2020, and May 31, 2023, were eligible for inclusion. Doses were evaluated against indication-specific best-practice guidelines and assessed for guideline concordance. Of the 200 patients evaluated, 100 were treated for streptococcal pharyngitis and 100 were treated for otitis media. Of the prescribed β-lactam doses, 32% were discordant with best-practice guideline recommendations. Dosing errors were more common for pharyngitis than for otitis media (47% vs 17%; P < 0.001). Overdosing was the most frequently observed error in pharyngitis prescriptions (93.6% of errors) and most commonly occurred in patients weighing more than the 20-kg weight associated with the dosing maximum (80.9% of overdosing errors). All patients receiving an inappropriate dose for otitis media were underdosed. Outpatient pediatric dosing errors for URI indications are common among both emergency medicine and family medicine prescribers. Patients weighing over the weight corresponding to the dosing maximum are at highest risk for error. Antimicrobial stewardship interventions targeting the point of prescribing are urgently needed to provide safe dosing practices for pediatric patients.

Long-Term Safety and Efficacy of Macitentan in Inoperable Chronic Thromboembolic Pulmonary Hypertension: Results from MERIT and its Open-Label Extension.

Evidence for use of pulmonary arterial hypertension targeted-therapies in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is limited. In MERIT-1, the endothelin receptor antagonist macitentan improved hemodynamic and functional parameters versus placebo in patients with inoperable CTEPH over a 24-week double-blind (DB) period. Its open-label (OL) extension study (MERIT-2) provides long-term safety/efficacy data. MERIT-2 (NCT02060721) was a multicenter, single-arm, OL, phase 2 extension study of MERIT-1. Patients completing MERIT-1 were eligible to receive 10 mg macitentan once-daily in MERIT-2. Safety and efficacy (6-min walk distance [6MWD] and change in World Health Organization functional class [WHO FC]) were assessed in all patients in MERIT-2 regardless of treatment received in DB (All patients MERIT-2 OL macitentan 10mg group) and the subgroup of patients receiving DB macitentan in MERIT-1 (Long-term [DB/OL] macitentan 10mg subgroup). Of the 80 patients randomized in MERIT-1, 76 entered MERIT-2 (All patients MERIT-2 OL macitentan 10mg group): 40 who received DB macitentan (DB-macitentan patients) and 36 DB placebo (DB-placebo patients). Median (interquartile range) macitentan exposure in the All patients MERIT-2 OL macitentan 10mg group was 45.5 (26.0, 66.1) months. During the OL period, treatment-emergent adverse events (AE) were reported in 72 (94.7%) patients; most frequent were worsening of pulmonary hypertension (19.7%), decreased hemoglobin (18.4%) and upper respiratory tract infection (15.8%). Fourteen (18.4%) patients died; none were assessed as macitentan-related. At Month 6 post-OL baseline, mean (standard deviation) change in 6MWD was - 0.4m (43.62) for DB-macitentan patients and 10.7m (45.63) for DB-placebo patients; the majority had unchanged (83.3%) or improved (12.5%) WHO FC. Safety/efficacy analyses were consistent in the Long-term (DB/OL) macitentan 10 mg subgroup. These analyses provide long-term safety/efficacy data in patients with inoperable CTEPH treated with macitentan. No unexpected safety findings occurred; reported AEs were consistent with the known safety profile of macitentan. At 6 months post-OL baseline, DB-placebo patients modestly improved 6MWD; DB-macitentan patients maintained improvements observed in MERIT-1. WHO FC was largely unchanged. ClinicalTrials.gov Identifiers: NCT02021292; NCT02060721.

The feasibility, acceptability and perceived impact of a theory-based intervention on non-medical prescribing students’ antibiotic prescribing behaviour: an experimental study

Abstract Introduction Acute upper respiratory tract infections (URTI) are one of the most common infections. URTIs usually resolve spontaneously but 60% of all prescriptions issued in UK primary care are for URTIs1 contributing to antimicrobial resistance. Non-medical prescribers are a growing group of prescribers but there are few if any antimicrobial stewardship (AMS) interventions to support their prescribing practices. Introducing AMS interventions when learning to prescribe can play an important role to embed appropriate practice at the start of a prescribers’ journey. Aim To test the feasibility, acceptability and perceived impact of a theory-based electronic learning intervention on the antibiotic prescribing behaviour of non-medical prescribing students. Methods Non-medical prescribing students registered at the study setting (university) were recruited via email and word of mouth. Following consent, participants completed an online pre-intervention questionnaire that explored their perceived prescribing behaviour and confidence in treating patients with URTIs. Participants then completed the intervention, accessible from any internet-enabled device via a weblink. The intervention was previously developed2 using the behaviour change wheel and comprised an animation of a prescriber opting against prescribing antibiotics for an adult with self-limiting URTI using a motivational interviewing approach. The patient felt satisfied and confident about their care. Four questions followed the scenario. Participants then completed an online post-intervention questionnaire that explored the usefulness of the intervention, and the same pre-intervention confidence questions. A one-to-one online audio-recorded semi-structured interview followed, exploring participants’ experiences of using the intervention. Questionnaire and interview questions were informed by the Capability Opportunities Motivation-Behaviour model. Questionnaire data were analysed using descriptive statistics. Interviews were transcribed verbatim and analysed using thematic analysis3. Ethical approval was given by the School Research Ethics Committee where the researchers were based. Results Twelve participants (of 50 approached) consented to take part. Eight completed the pre- and post-intervention questionnaires and the intervention. Seven completed all stages of the study. 87.5% of participants worked in a hospital setting. All were qualified for at least two years. Interviews lasted between 9-15 minutes. Participants’ confidence in treating patients with URTI increased in all statements; gain information on patient expectations, support patients’ comprehension of health information, build rapport, communicate effectively, help patients to see and examine different viewpoints (highest mean increase) and patients understand and are happy with their prescribing decision. These increases aligned with qualitative accounts. Participants agreed that the intervention would be useful to them and would change their practice positively. Participants found the intervention easy to use; access was straightforward and took between 5-20minutes to complete. The addition of a wider range of complex, challenging scenarios to the intervention were suggested. Discussion/conclusions The intervention was feasible to complete and acceptable to the participants. Participants’ confidence in treating patients increased; even though many were familiar with AMS, the intervention gave them further confidence to support a no antibiotic prescribing strategy. Participants suggested including more complex patient scenarios; this will be considered in a future study. Study limitations includes a small sample size and most participants worked in hospital settings but the intervention was set in primary care.

Belimumab safety in adult and paediatric Chinese patients with systemic lupus erythematosus: A Phase 4, multicentre, observational study.

Although belimumab has been widely used in patients with systemic lupus erythematosus (SLE) globally, real-world safety data among Chinese patients are limited, particularly for children. This study assessed the safety and tolerability of belimumab in adult and paediatric patients with SLE in China in real-world clinical practice. This Phase 4, multicentre, prospective, observational study enrolled patients prescribed intravenous belimumab by their physicians in tertiary hospitals, independent of a clinical study, during routine clinical visits between May 2021 and May 2022. Patients could have been receiving belimumab prior to enrolment. The primary objective was to describe the incidence of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs) and AEs of special interest (AESIs) over the 24-week follow-up period. Data were collected at enrolment and approximately 4, 12 and 24weeks post-enrolment, during routine clinical visits. AEs, ADRs and SAEs were collected as independent events. The safety population comprised patients who received ≥1 dose of belimumab and completed ≥1 follow-up visit. Overall, 417 patients were included in the analysis (safety population); 89.2% were female and mean (standard deviation) age was 35.5 (11.9) years. AEs were reported in 158 patients (37.9%) and were mostly mild (79.1%). The most common AEs were upper respiratory tract infections (n = 19, 4.6%) and hypokalaemia (n = 18, 4.3%; all mild). Among 22 patients (5.3%) with SAEs, four patients (1.0%) had drug-related SAEs (pneumonia, respiratory tract infection, gingivitis and decreased white blood cell and neutrophil count). ADRs were experienced by 25 patients (6.0%), most commonly urinary tract infections (n = 5, 1.2%). There were no fatal SAEs. AESIs occurred in 14 patients (3.4%), including infections of interest (n = 5, 1.2% all herpes zoster), serious selected psychiatric events (n = 3, 0.7%) and infusion-related systemic and anaphylactic reactions (n = 7, 1.7%). Of 14 paediatric patients enrolled, six experienced AEs, zero ADRs, two SAEs and one AESI. Belimumab was generally well tolerated in adult and paediatric patients with SLE in this real-world setting in China, with no new safety signals identified. Future assessment of long-term belimumab safety in China beyond 24weeks will extend this current body of evidence.

Landscape of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirusgenus of the Pneumoviridae family in the order Mononegavirales. RSV can cause acute upper and lower respiratory tract infections, sometimes with extrapulmonary complications. The disease burden of RSV infection is enormous, mainly affecting infants and older adults aged 75 years or above. Currently, treatment options for RSV are largely supportive. Prevention strategies remain a critical focus, with efforts centered on vaccine development and the use of prophylactic monoclonal antibodies. To date, three RSV vaccines have been approved for active immunization among individuals aged 60 and above. For children who are not eligible for these vaccines, passive immunization is recommended. A newly approved prophylactic monoclonal antibody, Nirsevimab, which offers enhanced neutralizing activity and an extended half-life, provides exceptional protection for high-risk infants and young children. This review provides a comprehensive and detailed exploration of RSV's virology, immunology, pathogenesis, epidemiology, clinical manifestations, treatment options, and prevention strategies.

Adverse effects of monoclonal antibodies in the treatment of moderate-to-severe asthma: a narrative review

Introduction and purpose: Over the past two decades, the management of severe asthma shifted from high doses of inhaled and oral corticosteroids to targeted biologic agents. Adverse effects of treatment with monoclonal antibodies are not yet fully characterised. The aim of this paper is to provide a comprehensive review of the adverse effects of the FDA-approved monoclonal antibodies in the treatment of moderate-to-severe asthma, including omalizumab, benralizumab, dupilumab, mepolizumab, reslizumab, tezepelumab. Material and methods of research: A thorough literature review was performed using PubMed Web of Science and Embase, employing key words related to monoclonal antibodies, asthma and adverse effects. Description of the state of knowledge: Omalizumab and mepolizumab have black box warning on the risk of anaphylaxis. Due to scarcity of data, no causal association between the use of monoclonal antibodies and risk of malignancy can be established. The most common adverse effects of biologic agents in severe asthma include upper respiratory tract infections, nasopharyngitis and asthma worsening. Conclusions: Overall, monoclonal antibodies have a favourable safety profile, with certain risk of side effects remains present, and is variable for the different molecules. More studies of asthmatic patients treated with monoclonal antibodies are needed to spot rare adverse events and those developing over longer time.

A large cohort from an immunology reference center and an algorithm for the follow-up of chronic neutropenia.

Chronic neutropenia causes involve nutritional deficiencies and inborn errors of immunity(IEI), such as severe congenital neutropenia. To classify common chronic neutropenia causes in a pediatric immunology unit. We enrolled 109 chronic neutropenia patients admitted to a pediatric immunology department between 2002-2022. We recorded clinical/laboratory features and genetic characteristics. The male/female ratio was 63/46. Fifty-eight patients had parental consanguinity(57.4%). 26.6% (n = 29) patients had at least one individual in their family with neutropenia. Common symtpoms at presentation were upper respiratory tract infections(URTI)(31.1%), oral aphthae(23.6%), skin infections(23.6%), pneumonia(20.8%), and recurrent abscesses(12.3%). Common infections during follow-up were URTI(56.8%), pneumonia(33%), skin infections(25.6%), gastroenteritis(18.3%), and recurrent abscesses(14,6%). Common long-term complications were dental problems(n = 51), osteoporosis(n = 22), growth retardation(n = 14), malignancy(n = 16)[myelodysplastic syndrome(n = 10), large granulocytic leukemia(n = 1), acute lymphoblastic leukemia(n = 1), Hodgkin lymphoma(n = 1), EBV-related lymphoma(n = 1), leiomyosarcoma(n = 1), and thyroid neoplasm(n = 1)]. We performed a genetic study in 86 patients, and 69(71%) got a genetic diagnosis. Common gene defects were HAX-1(n = 26), ELA-2 (ELANE)(n = 10), AP3B1(n = 4), and ADA-2(n = 4) gene defects. The IEI ratio(70.6%) was high. GCSF treatment(93.4%), immunoglobulin replacement therapy(18.7%), and HSCT(15.9%) were the treatment options. The mortality rate was 12.9%(n = 14). The most common long term complications were dental problems that is three times more common in patients with known genetic mutations. We prepared an algorithm for chronic neutropenia depending on the present cohort. An important rate of inborn errors of immunity, especially combined immunodeficiency(11.9%) was presented in addition to congenital phagocytic cell defects. Early diagnosis will allow us tailor the disease-specific treatment options sooner, preventing irreversible consequences.

Retrospective Analysis of RSV Infection in Pediatric Patients: Epidemiology, Comorbidities, Treatment, and Costs in Dubai (2014-2023)

Background: Infections attributable to respiratory syncytial virus (RSV) are a major cause of hospitalization among young children worldwide. Despite substantial clinical and economic burden, real-world data associated with RSV infections in the United Arab Emirates (UAE) are limited. Objectives: This study aimed to assess among children (&lt;18 years) diagnosed with RSV the epidemiology, seasonality, comorbidities, treatment patterns, length of hospital stay, healthcare resource utilization (HCRU), and costs associated with pediatric infection in Dubai, UAE. Methods: This 10-year retrospective cohort study (Jan. 1, 2014–Sept. 30, 2023) utilized Dubai Real-World Database, a private insurance claims database. Patients aged &lt;18 years with a first-episode diagnosis claim (primary or secondary, or a hospital admission) for RSV any time during the index period (Jan. 1, 2014–June 30, 2023) were included. Outcomes were analyzed during a 3-month follow-up. Patients were stratified into 3 cohorts: Cohort 1 (&lt;2 years), Cohort 2 (2 to &lt;6 years), and Cohort 3 (6 to &lt;18 years). Results: Of 28 011 patients identified, 25 729 were aged &lt;18 years with RSV infection. An increasing trend in reported cases was observed from 2014 to 2022, with an average annual increase of 55%. Half of study patients (49.3%) belonged to Cohort 1, with a mean age of 0.6 years, while less than 2% had known risk factors and 22% of the patients in cohort 1 were hospitalized. In Cohort 1, 32.0% had upper respiratory tract infections, 39.4% had lower respiratory tract infections, and 44.4% of patients had an “other respiratory disease.” The average length of hospitalization was about 4 days across all cohorts. The total hospitalization cost was highest in patients &lt;2 years, amounting to US $9 798 174 (median, US $2241.30). Conclusion: Among the RSV patients, 49.3% were &lt;2 years of age and few had recognized risk factors. Among patients &lt;2 years, 22% were hospitalized, with an average hospital stay of 4 days; the cost of hospitalization totaled US $9 798 174. These findings can inform healthcare stakeholders about future policy measures and the need for effective preventive strategies.

Retrospective Analysis of RSV Infection in Pediatric Patients: Epidemiology, Comorbidities, Treatment, and Costs in Dubai (2014-2023)

Background: Infections attributable to respiratory syncytial virus (RSV) are a major cause of hospitalization among young children worldwide. Despite substantial clinical and economic burden, real-world data associated with RSV infections in the United Arab Emirates (UAE) are limited. Objectives: This study aimed to assess among children (&lt;18 years) diagnosed with RSV the epidemiology, seasonality, comorbidities, treatment patterns, length of hospital stay, healthcare resource utilization (HCRU), and costs associated with pediatric infection in Dubai, UAE. Methods: This 10-year retrospective cohort study (Jan. 1, 2014–Sept. 30, 2023) utilized Dubai Real-World Database, a private insurance claims database. Patients aged &lt;18 years with a first-episode diagnosis claim (primary or secondary, or a hospital admission) for RSV any time during the index period (Jan. 1, 2014–June 30, 2023) were included. Outcomes were analyzed during a 3-month follow-up. Patients were stratified into 3 cohorts: Cohort 1 (&lt;2 years), Cohort 2 (2 to &lt;6 years), and Cohort 3 (6 to &lt;18 years). Results: Of 28 011 patients identified, 25 729 were aged &lt;18 years with RSV infection. An increasing trend in reported cases was observed from 2014 to 2022, with an average annual increase of 55%. Half of study patients (49.3%) belonged to Cohort 1, with a mean age of 0.6 years, while less than 2% had known risk factors and 22% of the patients in cohort 1 were hospitalized. In Cohort 1, 32.0% had upper respiratory tract infections, 39.4% had lower respiratory tract infections, and 44.4% of patients had an “other respiratory disease.” The average length of hospitalization was about 4 days across all cohorts. The total hospitalization cost was highest in patients &lt;2 years, amounting to US $9 798 174 (median, US $2241.30). Conclusion: Among the RSV patients, 49.3% were &lt;2 years of age and few had recognized risk factors. Among patients &lt;2 years, 22% were hospitalized, with an average hospital stay of 4 days; the cost of hospitalization totaled US $9 798 174. These findings can inform healthcare stakeholders about future policy measures and the need for effective preventive strategies.

Predictors and Profile of Severe Infectious Complications in Multiple Myeloma Patients Treated with Daratumumab-Based Regimens: A Machine Learning Model for Pneumonia Risk.

Daratumumab (Dara) is the first monoclonal antibody introduced into clinical practice to treat multiple myeloma (MM). It currently forms the backbone of therapy regimens in both newly diagnosed (ND) and relapsed/refractory (RR) patients. However, previous reports indicated an increased risk of infectious complications (ICs) during Dara-based treatment. In this study, we aimed to determine the profile of ICs in MM patients treated with Dara-based regimens and establish predictors of their occurrence. This retrospective, real-life study included MM patients treated with Dara-based regimens between July 2019 and March 2024 at our institution. Infectious events were evaluated using the Terminology Criteria for Adverse Events (CTCAE) version 5.0. The study group consisted of a total of 139 patients, including 49 NDMM and 90 RRMM. In the RR setting, the majority (60.0%) of patients received the Dara, bortezomib, and dexamethasone (DVd) regimen, whereas ND patients were predominantly (98%) treated with the Dara, bortezomib, thalidomide, and dexamethasone (DVTd) regimen. Overall, 55 patients (39.6%) experienced ICs. The most common IC was pneumonia (37.5%), followed by upper respiratory tract infections (26.8%). Finally, twenty-five patients had severe ICs (grade ≥ 3) and required hospitalization, and eight patients died due to ICs. In the final multivariable model adjusted for setting (ND/RR) and age, hemoglobin level (OR 0.77, 95% CI: 0.61-0.96, p = 0.0037), and Eastern Cooperative Oncology Group (ECOG) >1 (OR 4.46, 95% CI: 1.63-12.26, p = 0.0037) were significant factors influencing severe IC occurrence. Additionally, we developed predictive models using the J48 decision tree, gradient boosting, and random forest algorithms. After conducting 10-fold cross-validation, these models demonstrated strong performance in predicting the occurrence of pneumonia during treatment with daratumumab-based regimens. Simple clinical and laboratory assessments, including hemoglobin level and ECOG scale, can be valuable in identifying patients vulnerable to infections during Dara-based regimens, facilitating personalized prophylactic strategies.

Costs of treating serious adverse effects of drugs used for treatment of obesity: comparison of selected European countries

Drugs for the treatment of obesity show significant effectiveness, but the adverse effects (ADRs) of these drugs are numerous and varied, and some of them are highly cost-generating. Our research aimed to define the health care utilization pattern in treating ADRs of antiobesity therapy, to compare the costs of treating these ADRs among selected European countries, and to identify the key cost drivers. A comparative analysis of the costs of treating the ADRs of antiobesity drugs in 10 European countries (seven EU members and three from the Western Balkans) was conducted, and the impact of parameters of global health expenditures on them was assessed. There are considerable differences in costs of treating adverse antiobesity drug reactions among European countries: costs of treating gastroesophageal reflux disease varied almost 20 times between North Macedonia (12.6 EUR) and Estonia (202.9 EUR). The Gross Domestic Product per capita was an important cost driver in treating the majority of the ADRs studied (p < .001), except for retinopathy, anaphylaxis, and respiratory disorders. The Domestic Private Health Expenditure increased the costs of treating depression (p = .012), upper respiratory tract infection (p = .008), melanocytic naevus (p = .027), and drug-induced hepatitis (p = .023). Investment in pharmaceuticals, medical goods, and preventive care tended to reduce the costs of treating several ADRs, which are seemingly unrelated to the body site or mechanism. Healthcare utilization and costs of treating ADRs to antiobesity drugs vary significantly among European countries. These differences should be considered when creating inputs for cost-effectiveness and budget impact models to decrease their uncertainty.