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Background: Bronchiectasis is a chronic lung disease characterized by permanent bronchial wall dilatation. Although it has been known as an orphan disease, it has recently gained attention because of registry-based studies and drug research. Aims: We aimed to use a multicenter database to analyze and compare data regarding the etiology, associated comorbidities, microbiological characteristics, and preventive strategies of bronchiectasis in Türkiye to those of other countries. Study Design: A multicenter prospective cohort study. Methods: The multicenter, prospective cohort study was conducted between March 2019 and January 2022 using the Turkish Adult Bronchiectasis Database, in which 25 centers in Türkiye participated. Patients aged > 18 years who presented with respiratory symptoms such as cough, sputum, and dyspnea and were diagnosed with non-cystic fibrosis bronchiectasis using computed tomography were included in the study. Demographic information, etiologies, comorbidities, pulmonary functions, and microbiological, radiological, and clinical data were collected from the patients. Results: Of the 1,035 study participants, 518 (50%) were females. The mean age of the patients was 56.1 ± 16.1 years. The underlying etiology was detected in 565 (54.6%) patients. While postinfectious origin was the most common cause of bronchiectasis (39.5%), tuberculosis was identified in 11.3% of the patients. An additional comorbidity was detected in 688 (66.5%) patients. The most common comorbidity was cardiovascular disease, and chronic obstructive pulmonary disease (COPD) and bronchiectasis was identified in 19.5% of the patients. The most commonly detected microbiological agent was Pseudomonas aeruginosa (29.4%). Inhaled corticosteroids (ICS) were used in 70.1% of the patients, and the frequency of exacerbations in the last year was significantly higher in patients using ICS than in nonusers (p < 0.0001). Age [odds ratio (OR): 1.028; 95% confidence interval (CI): 1.005-1.051], cachexia (OR: 4.774; 95% CI: 2,054-11,097), high modified medical research [ABSTRACT FROM AUTHOR]

A 32-year-old woman with no clinically significant medical history presented to the emergency department in the winter with a 10-day history of shortness of breath, fevers, and cough. She also reported sore throat and myalgias but no chest pain. Her symptoms did not abate with a 5-day course of azithromycin. She had no pertinent travel or sick contacts and owned no pets. She took a multivitamin daily but no other medications. She reported no tobacco, alcohol, or illicit substance use. [ABSTRACT FROM AUTHOR]

Background/Objectives: Older patients are subject to a high number of Emergency Department (ED) visits and hospitalizations. Innovative strategies to manage geriatric urgencies in the community are thus needed. Methods: In this prospective observational study, we examined the case mix of a hospital-based domiciliary urgent care service tailored to older patients, called Multidisciplinary Mobile Unit (MMU), from January to September 2023. The service, activated by general practitioners or territorial specialists during workdays, provided domiciliary geriatric assessment, point-of-care diagnostics, including multi-site ultrasound and lab tests, and therapeutical measures, including intravenous treatment and insertion of invasive devices, with the goal of reaching on-site stabilization and avoiding ED referral. We collected data regarding multimorbidity, polypharmacy, and frailty according to the Clinical Frailty Scale (CFS), reasons for MMU activation, and diagnostic and therapeutical services provided. The assessed outcomes were immediate hospitalization after a visit, 30-day admission, and 30-day mortality. Results: Participants (n = 205, 102 M) were mostly aged (median age 83 years old), with multimorbidity and frailty (CFS median 6). The most frequent reasons for MMU activation were dyspnea (49%), cough (34%), and musculoskeletal pain (17%), while the commonest diagnostic test provided was thoracic ultrasound (81%). Only five patients (2.4%) were hospitalized immediately after MMU visit. The 30-day rate of hospitalization was 10.2%, with age, cancer, and abdominal pain as independent predictors on a stepwise binary logistic regression model. 30-day mortality was 4.9%. Conclusions: The MMU model is a feasible strategy to manage geriatric urgencies, especially involving the cardiorespiratory system, is associated with good outcomes and may prevent ED visits. [ABSTRACT FROM AUTHOR]

Mechanical insufflation-exsufflation (MI-E) is essential for secretion clearance, especially in neuromuscular disorders. For the best outcomes, initiation of MI-E should be started at the correct time with regular evaluation to the response to treatment. Typically, cough peak flow has been used to evaluate cough effectiveness with and without MI-E. This review highlights the limitations of this and discussed other tools to evaluate MI-E efficacy in this rapidly developing field. Such tools include the interpretation of parameters (like pressure, flow and volumes) that derive from the MI-E device and external methods to evaluate upper airway closure. In this review we pinpoint the differences between different devices in the market and discuss new tools to better titrate MI-E and detect pathological responses of the upper airway. We discuss the importance of point of care ultrasound (POCUS), transnasal fiberoptic laryngoscopy and wave form analysis in this setting. To improve clinical practice newer generation MI-E devices should allow real-time evaluation of waveforms and standardize some of the derived parameters. [ABSTRACT FROM AUTHOR]

Expiratory central airway collapse (ECAC) comprising excessive central airway collapse (EDAC) and tracheobronchomalacia. Treatment is challenging for severe cases that are not candidates for surgical management. We report a case of severe ECAC successfully managed with continuous positive airway pressure (CPAP) therapy. A 75‐year‐old female patient status post right pneumonectomy, presented with chronic cough. Dynamic bronchoscopy evaluation showed severe EDAC which improved with intraprocedural noninvasive positive pressure (NIPPV) therapy. Due to patients' comorbidities, she was not a candidate to surgical tracheobronchoplasty. Therefore, we attempted pneumatic stenting with long‐term CPAP therapy resulting in improvement of symptoms and functional capacity. The long‐term efficacy of pneumatic stenting has not been clearly established yet. Literature review of management of ECAC with NIPPV consist primarily of case reports and there is only one clinical trial being conducted to assess the efficacy of CPAP therapy in ECAC. While NIPPV arises as a sufficient alternative for management of severe ECAC, larger scale studies are needed to prove the real efficacy of NIPPV in this setting. [ABSTRACT FROM AUTHOR]

Tracheobronchomalacia (TBM) occurs due to the weakening of cartilaginous part of the trachea, resulting in compromised airway function and leading to symptoms such as dyspnea, cough, and inability to clear secretions. Bronchiolitis obliterans syndrome (BOS) is the most prevalent late noninfectious pulmonary complication in patients who underwent allogeneic haematopoietic stem cell transplantation (HSCT). Therefore, patients experiencing progressive dyspnea and chronic cough after allogenic HSCT, with new obstructive pattern on pulmonary function test, are typically diagnosed with post‐transplant BOS. However, it is important to note that TBM can also manifest as an obstructive defect pattern on pulmonary function test. Tracheomalacia has been reported as a rare complication of allogenic stem cell transplantation. We present two patients who developed TBM following allogeneic HSCT and were initially treated for post‐transplant BOS but did not experience symptom improvement. However, after treatment with continuous positive airway pressure, their symptom subsided. [ABSTRACT FROM AUTHOR]

Restrictive cardiomyopathy is one of the rarest forms of cardiomyopathies in paediatric patients characterised by impaired myocardial relaxation or compliance with restricted ventricular filling, leading to a reduced diastolic volume with a preserved systolic function. We report 2 cases—a 5-year-old boy who presented with abdominal distension and palpitation with family history of similar complaints but no definite genetic diagnosis as yet and a 5-year-old girl who presented with chronic cough and shortness of breath. Both cases were diagnosed in a tertiary care hospital in Muscat, Oman, in 2019 and are managed supportively with regular outpatient follow-up. This is the first series of reported cases of paediatric restrictive cardiomyopathy from Oman. [ABSTRACT FROM AUTHOR]

Cough is a common symptom of several respiratory diseases. However, frequent coughing from acute to chronic often causes great pain to patients. It may turn into cough variant asthma, which seriously affects people's quality of life. For cough treatment, it is dominated by over-the-counter antitussive drugs, such as asmeton, but most currently available antitussive drugs have serious side effects. Thus, there is a great need for the development of new drugs with potent cough suppressant. BALB/c mice were used to construct mice model with cough to investigate the pharmacological effects of pectolinarigenin (PEC). Hematoxylin-eosin and Masson staining were used to assess lung injury and airway remodeling, and ELISA was used to assess the level of inflammatory factor release. In addition, inflammatory cell counts were measured to assess airway inflammation. Airway hyperresponsiveness assay was used to assess respiratory resistance in mice. Finally, we used Western blotting to explore the potential mechanisms of PEC. We found that PEC could alleviate lung tissue injury and reduce the release of inflammatory factors, inhibit of cough frequency and airway wall collagen deposition in mice model with cough. Meanwhile, PEC inhibited the Ras/ERK/c-Fos pathway to exhibit antitussive effect. Therefore, PEC may be a potential drug for cough suppression. [ABSTRACT FROM AUTHOR]

Objective: The incidence of gastroesophageal reflux disease (GERD) is increasing year by year, the clinical manifestations are complex and diverse, and the adverse effects of long-term use of proton pump inhibitors and gastrointestinal motility drugs have been of great concern in recent years. The effectiveness of tegoprazan in the treatment of GERD is still controversial. This protocol describes a systematic review and meta-analysis to evaluate the efficacy and safety of tegoprazan in the treatment of gastroesophageal reflux disease. Methods: PubMed, Embase, Cochrane Library and Web of Science will be searched from the database inception to 1 March 2023. All randomized controlled trials related to tegoprazan for GERD will be included. Extracted data will include publication details, basic information, demographic data, intervention details and patient outcomes. The primary outcome will be complete resolution of major symptoms, complete resolution of heartburn, proportion of heartburn-free days, chronic cough, hoarseness, and adverse events. Risk of bias will be assessed using the Cochrane Collaboration's tool for assessing risk of bias. Article selection, data extraction and risk of bias assessment will be performed in duplicate by two independent reviewers. If the meta-analysis is precluded, we will conduct a descriptive synthesis using a best-evidence synthesis approach. Discussion: The results of this study will provide reliable evidence to evaluate the efficacy and safety of tegoprazan in the treatment of GERD and help patients, physicians and clinical investigators choose the most appropriate treatment. [ABSTRACT FROM AUTHOR]

Purpose: Sensorimotor cough skill training (CST) has been shown to improve cough strength, as well as facilitate changes during training (i.e., motor performance) and generalization to untrained tasks (i.e., motor learning). However, there is a gap in our understanding of the effects of voluntary CST (without sensory stimuli) on motor performance and learning. Furthermore, the contribution of physiologic factors, such as lung volume, a driver of cough strength in healthy adults, and treatment-specific factors, such as biofeedback, remains unexamined. Method: Twenty individuals with Parkinson’s disease (PD) completed pre- and post-CST single voluntary, sequential voluntary, and reflex cough testing. Participants were randomized to biofeedback or no biofeedback groups. They completed one CST session involving 25 trials of voluntary coughs, with the treatment target set 25% above baseline peak flow. Participants were instructed to “cough hard” to exceed the target. In the biofeedback group, participants received direct visualization of the target line in real time. Results: Cough peak flow showed positive improvements in motor performance (β = .02; 95% credible interval [CI]: 0.01, 0.03) and learning (β = .26; 95% CI: 0.03, 0.47). Changes in lung volume from pre- to post-CST did not predict treatment response. No differences in treatment response were detected between the biofeedback groups. Conclusions: A single session of voluntary CST improved voluntary cough motor performance and learning. Although lung volume increased during CST, changes to lung volume did not predict treatment response. These findings demonstrate the potential of voluntary CST to improve motor performance and motor learning among individuals with PD and cough dysfunction. [ABSTRACT FROM AUTHOR]

Context Vitamin D plays an important role in immune function, and the deficiency thereof has been associated with several infections, most notably respiratory tract infections. However, data from intervention studies investigating the effect of high-dose vitamin D supplementation on infections have been inconclusive. Objective The aim of this study was to evaluate the level of evidence regarding the efficacy of vitamin D supplementation above the standard dose (400 IU) in preventing infections in apparently healthy children < 5 years of age. Data Sources PubMed, Scopus, Science Direct, Web of Science, Google Scholar, CINAHL, and MEDLINE electronic databases were searched between August 2022 and November 2022. Seven studies met the inclusion criteria. Data Extraction Meta-analyses of outcomes in more than one study were performed using Review Manager software. Heterogeneity was evaluated using the I2 statistic. Randomized controlled trials in which vitamin D was supplemented at > 400 IU compared with placebo, no treatment, or standard dose were included. Data Analysis Seven trials that enrolled a total of 5748 children were included. Odds ratios (ORs) with 95%CIs were calculated using random- and fixed-effects models. There was no significant effect of high-dose vitamin D supplementation on the incidence of upper respiratory tract infection (OR, 0.83; 95%CI, 0.62–1.10). There was a 57% (95%CI, 0.30–0.61), 56% (95%CI, 0.27–0.07), and 59% (95%CI, 0.26–0.65) reduction in the odds of influenza/cold, cough, and fever incidence, respectively, with daily supplementation of vitamin D > 1000 IU. No effect was found on bronchitis, otitis media, diarrhea/gastroenteritis, primary care visits for infections, hospitalizations, or mortality. Conclusion High-dose vitamin D supplementation provided no benefit in preventing upper respiratory tract infections (moderate certainty of evidence) but reduced the incidence influenza/cold (moderate certainty of evidence), cough, and fever (low certainty of evidence). These findings are based on a limited number of trials and should be interpreted with caution. Further research is needed. Systematic Review Registration PROSPERO registration number CRD42022355206. [ABSTRACT FROM AUTHOR]

The article focuses on child asthma management in Great Britain. Asthma is the most common chronic condition in British children, with high prevalence and emergency rates, particularly in deprived areas. The Royal College of Physicians (RCP) report, ‘Why asthma still kills: National Review of Asthma Deaths (2014) (NRAD), suggests for a more structured review, training to be given on inhaler technique, and every patient to have a personal asthma action plan.

ENDS use is highly prevalent among U.S. youth, and there is concern about its respiratory health effects. However, evidence from nationally representative longitudinal data is limited. Using youth (aged 12–17 years) data from Waves 1–5 (2013–2019) of the Population Assessment of Tobacco and Health Study, multilevel Poisson regression models were estimated to examine the association between ENDS use; cigarettes; and diagnosed bronchitis, pneumonia, or chronic cough. Current product use was lagged by 1 wave and categorized as (1) never/noncurrent use, (2) exclusive cigarette use, (3) exclusive ENDS use, and (4) dual ENDS/cigarette use. Multivariable models adjusted for age, sex, race and ethnicity; parental education; asthma; BMI; cannabis use; secondhand smoke exposure; and household use of combustible products. Data analysis was conducted in 2022–2023. A total of 7.4% of respondents were diagnosed with bronchitis, pneumonia, or chronic cough at follow-up. In the multivariable model, exclusive cigarette use (incident rate ratio=1.85, 95% CI=1.29, 2.65), exclusive ENDS use (incident rate ratio=1.49, 95% CI=1.06, 2.08), and dual use (incident rate ratio=2.70, 95% CI=1.61, 3.50) were associated with a higher risk of diagnosed bronchitis, pneumonia, or chronic cough than never/noncurrent use. These results suggest that ENDS and cigarettes, used exclusively or jointly, increased the risk of diagnosed bronchitis, pneumonia, or chronic cough among U.S. youth. However, dual use was associated with the highest risk. Targeted policies aimed at continuing to reduce cigarette smoking and ENDS use among youth, especially among those with dual use, are needed. [ABSTRACT FROM AUTHOR]

Background: Chronic cough significantly impairs the quality of life. Although various studies focused on MNBI as assessed in the distal esophagus, scarce data are available on the clinical value of proximal measurements. Aim: To investigate the role of proximal MNBI in the workup of patients with chronic cough and its ability to predict PPI response. Methods: Demographic, clinical, endoscopy findings, impedance‐pH and HRM tracings from consecutive cough patients were evaluated. MNBI was calculated at proximal and distal esophagus. Results: One hundred and sixty four patients were included. In addition to traditional variables, when considering also the PSPW index or MNBI at 3 cm or 15 cm, the proportion of patients with pathological impedance‐pH monitoring significantly increased. 70/164 patients were responders, while 94 (57.3%) were non‐responder to double PPI dose (p < 0.05). Patients with pathologic MNBI at 3 cm and/or 15 cm as well as those with pathologic PSPW index were characterized by a significantly higher proportion of responders than that observed among patients with normal impedance‐pH variables (p < 0.001). The proportion of responders with pathological MNBI at 15 cm was significantly higher than the proportion of responders with pathological MNBI at 3 cm (82.8% vs. 64.3%, p < 0.05). At multivariable model, pathological MNBI at both 3 cm and 15 cm as well as PSPW index were associated with PPI responsiveness. The strongest association with PPI response was observed for MNBI at 15 cm. Conclusions: The assessment of MNBI at proximal esophagus increases the diagnostic yield of impedance‐pH monitoring and may represent a useful predictor of PPI responsiveness in the cumbersome clinical setting of suspected reflux‐related cough. [ABSTRACT FROM AUTHOR]

The article discusses the development of a Holistic Pinniped Welfare Index (HPWI) as a tool to assess the welfare of pinnipeds in managed care. The HPWI incorporates both animal-based and resource-based approaches to welfare assessment, taking into account factors such as hunger and thirst, appropriate housing, absence of illness or injury, and appropriate behaviors and interactions. The index is specifically tailored to address the unique needs and behaviors of furred pinnipeds. The article highlights the importance of considering factors such as fur condition and skin health in assessing pinniped welfare. The text also discusses the use of the Pinniped Welfare Index (HPWI) as a tool for assessing the health and well-being of pinnipeds in managed care facilities. The HPWI includes both physiological and behavioral measures, such as body condition, skin lesions, respiratory effort, and willingness to perform trained behaviors. The index can be used to compare data over time and identify abnormalities that may indicate disease or stress. The text emphasizes the importance of developing specific ethograms for each facility to accurately assess behavioral patterns. The list of references includes various scientific articles related to animal welfare, specifically focusing on topics such as the assessment of welfare in captive dolphins, the use of behavioral indicators to evaluate welfare, and the monitoring of body temperature as a stress response in marine mammals. The articles cover a range of species, including bottlenose dolphins, sea lions, and pinnipeds, and discuss different methods and indicators used [Extracted from the article]

E-cigarettes and vaping products were first introduced in the United States around 2007, and quickly grew in popularity. By 2014, e-cigarettes had become the most commonly used tobacco product among youth in the United States. An e-cigarette, or vaping, product use--associated lung injury (EVALI) outbreak was identified by the Centers for Disease Control and Prevention (CDC) in 2019, with many cases in the adolescent population. The CDC opened a national database of cases and launched a multistate investigation; reported cases reached a peak in September 2019. The CDC investigation found that a vaping liquid additive, vitamin E acetate, was strongly linked to the EVALI outbreak but determined that the decline in cases was likely multifactorial. Due to decreased cases and the identification of a potential cause of the outbreak, the CDC stopped collecting data on EVALI cases as of February 2020. However, e-cigarettes and vaping products have continued to be the most popular tobacco product among youth, though state and national regulations on these products have increased since 2016. While pediatric case series and studies have shown differences in clinical presentation and medical histories between pediatric and adult EVALI cases, the fact that cases are no longer tracked at a national level limits necessary information for pediatric clinicians and researchers. We describe the available literature on the diagnosis, pathophysiology, treatment, and outcomes of EVALI in the pediatric population, and provide clinical and public health recommendations to facilitate prevention and management of EVALI specific to pediatrics. [ABSTRACT FROM AUTHOR]

Background: Patients with coronavirus 2019 (COVID-19) are at high risk for respiratory dysfunction. The pulse oximetry/fraction of inspired oxygen (SpO2/FiO2) ratio is a non-invasive assessment of respiratory dysfunction substituted for the PaO2:FiO2 ratio in Sequential Organ Failure Assessment scoring. We hypothesized that emergency department (ED) SpO2/FiO2 ratios correlate with requirement for mechanical ventilation in COVID-19 patients. Our objective was to identify COVID-19 patients at greatest risk of requiring mechanical ventilation, using SpO2/FiO2 ratios. Methods: We performed a retrospective review of patients admitted with COVID-19 at two hospitals. Highest and lowest SpO2/FiO2 ratios (percent saturation/fraction of inspired O2) were calculated on admission. We performed chi-square, univariate, and multiple regression analysis to evaluate the relationship of admission SpO2/FiO2 ratios with requirement for mechanical ventilation and intensive care unit (ICU) care. Results: A total of 539 patients (46% female; 84% White), with a mean age 67.6 ± 18.6 years, met inclusion criteria. Patients who required mechanical ventilation during their hospital stay were statistically younger in age (P = 0.001), had a higher body mass index (P < .001), and there was a higher percentage of patients who were obese (P = 0.03) and morbidly obese (P < .001). Shortness of breath, cough, and fever were the most common presenting symptoms with a median temperature of 99°F. Average white blood count was higher in patients who required ventilation (P=<0.001). A highest obtained ED SpO2/FiO2 ratio of ≤300 was associated with a requirement for mechanical ventilation. A lowest obtained ED SpO2/FiO2 ratio of ≤300 was associated with a requirement for intensive care unit care. There was no statistically significant correlation between ED SpO2/FiO2 ratios >300 and mechanical ventilation or intensive care unit (ICU) requirement. Conclusion: The ED SpO2/FiO2 ratios correlated with mechanical ventilation and ICU requirements during hospitalization for COVID-19. These results support ED SpO2/FiO2 as a possible triage tool and predictor of hospital resource requirements for patients admitted with COVID-19. Further investigation is warranted. [ABSTRACT FROM AUTHOR]

Background: Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive genetic disorder with approximately 1000 known cases worldwide, in which calcium phosphate microliths deposit in the alveolar air spaces. As of writing this report, no definitive conventional therapy exists, and many PAM cases may progress to severe respiratory failure and potential death. Bilateral lung transplantation (BLx) seems to be the most optimal solution; however, this procedure is challenging along with limited reports regarding the outcome in PAM. We report a case of PAM successfully treated with BLx for the first time in Iran. Method: We present the case of a 42‐year‐old female with a longstanding history of cough, not responding to conventional antitussive medication, who was diagnosed as a case of PAM following a hospitalization due to coughing, dyspnea on exertion, and hemoptysis. Despite treatment with corticosteroid and medical treatment, no improvement was achieved and she subsequently developed respiratory and right ventricular failure, with oxygen ventilation dependence. Eventually, she was scheduled for BLx. The operation was successful and during her 2‐year follow‐up, no recurrence or significant postoperative complications has been reported. Conclusion: This case presentation and literature review confirm the effectiveness of BLx as a promising treatment for PAM‐diagnosed patients, improving both life expectancy and quality of life. [ABSTRACT FROM AUTHOR]

Background: The management of uncontrolled severe asthma has greatly improved since the advent of novel biologic therapies. Up to August 2022, five biologics have been approved for the type 2 asthma phenotype: anti-IgE (omalizumab), anti-IL5 (mepolizumab, reslizumab, benralizumab), and anti-IL4 (dupilumab) monoclonal antibodies. These drugs are usually well tolerated, although long-term safety information is limited, and some adverse events have not yet been fully characterized. Spontaneous reporting systems represent the cornerstone for the detection of potential signals and evaluation of the real-world safety of all marketed drugs. Objective: The aim of this study was to provide an overview of safety data of biologics for severe asthma using VigiBase, the World Health Organization global pharmacovigilance database. Methods: We selected all de-duplicated individual case safety reports (ICSRs) attributed to five approved biologics for severe asthma in VigiBase, up to 31st August 2022 (omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab). Descriptive frequency analyses of ICSRs were carried out both as a whole class and as individual products. Reporting odds ratios (ROR) with 95% confidence intervals (CIs) were used as the measure of disproportionality for suspected adverse drug reactions (ADRs) associated with the study drugs compared with either all other suspected drugs (Reference Group 1, RG1) or inhaled corticosteroids plus long-acting β-agonists (ICSs/LABAs) (Reference Group 2, RG2) or with oral corticosteroids (OCSs) (Reference Group 3, RG3). Results: Overall, 31,724,381 ICSRs were identified in VigiBase and 167,282 (0.5%) were related to study drugs; the remaining reports were considered as RG1. Stratifying all biologic-related ICSRs by therapeutic indication, around 29.4% (n = 48,440) concerned asthma use; omalizumab was mainly indicated as the suspected drug (n = 20,501), followed by dupilumab, mepolizumab, benralizumab and reslizumab. Most asthma ICSRs concerned adults (57%) and women (64.1%). Asthma biologics showed a higher frequency of serious suspected ADR reporting than RG1 (41.3% vs 32.3%). The most reported suspected ADRs included asthma, dyspnea, product use issue, drug ineffective, cough, headache, fatigue and wheezing. Asthma biologics were disproportionally associated with several unknown or less documented adverse events, such as malignancies, pulmonary embolism and deep vein thrombosis with omalizumab; alopecia and lichen planus with dupilumab; alopecia and herpes infections with mepolizumab; alopecia, herpes zoster and eosinophilic granulomatosis with polyangiitis related to benralizumab; and alopecia with reslizumab. Conclusions: The most frequently reported suspected ADRs of asthma biologics in VigiBase confirmed the presence of well-known adverse effects such as general disorders, injection-site reactions, nasopharyngitis, headache and hypersensitivity, while some others (e.g. asthma reactivation or therapeutic failure) could be ascribed to the indication of use. Moreover, the analysis of signals of disproportionate reporting suggests the presence of malignancies, effects on the cardiovascular system, alopecia and autoimmune conditions, requiring further assessment and investigation. [ABSTRACT FROM AUTHOR]

Introduction: The Laryngeal Mask Airway (LMA) is frequently used for managing paediatric airways for short surgical procedures. While it is easy to insert, it can lead to several complications if not removed at the appropriate plane of anaesthesia. Aim: To establish better timing for the removal of the LMA in deeply anaesthetised and awake paediatric patients by comparing the complications associated with each approach. Materials and Methods: The present randomised clinical study, enrolled 90 American Society of Anaesthesiologists (ASA) I and II paediatric patients aged 1 to 12 years, posted for elective short surgical procedures under general anaesthesia with airway management by Classical LMA. The patients were allocated into two groups: Group D (LMA removal under a deep plane/surgical plane of anaesthesia) and Group A (LMA removal in a fully awake state). At emergence from anaesthesia and during LMA removal, both groups were studied for complications including cough, desaturation (SpO2 < 95%), excessive salivation, vomiting, and laryngospasm. Descriptive statistics were reported using mean±standard deviation or median (range) for continuous variables. Comparison of continuous variables was done using the Student's t-test or Wilcoxon rank sum test. Results: Demographic data like age, weight, duration of surgery, heart rate, and respiratory rate were comparable in both groups. A significantly higher incidence of cough was found in group A compared to group D (p-value=0.001). The incidences of desaturation (p-value=1.000), excessive salivation (p-value=0.361), vomiting (p-value=1.000), and laryngospasm (p-value=0.142) were comparable between the two groups. Cough was the most frequent complication in group A (16 out of 45 patients), while laryngospasm was the most frequent complication in group D (8 out of 45 patients). The total number of complications (p-value=0.043) was significantly higher in group A compared to group D. Conclusion: The removal of the Classical LMA in paediatric patients can be safely carried out in a deeply anaesthetised state. Based on the results of present study, the removal of the LMA in deeply anaesthetised paediatric patients is associated with fewer complications compared to its removal in the awake state. [ABSTRACT FROM AUTHOR]

Olamkicept selectively inhibits the cytokine interleukin‐6 (IL‐6) trans‐signaling pathway without blocking the classic pathway and is a promising immunoregulatory therapy for inflammatory bowel disease (IBD). These first‐in‐human, randomized, placebo‐controlled, single‐ (SAD) and multiple‐ascending dose (MAD) trials evaluated olamkicept safety, tolerability, pharmacokinetic, and pharmacodynamic characteristics. Doses tested in the SAD trial included seven single intravenous doses (0.75, 7.5, 75, 150, 300, 600, and 750 mg) and one subcutaneous (SC) dose (60 mg) given to healthy subjects (N = 64), and three intravenous doses (75 mg, 300 mg, and 750 mg) given to patients with Crohn's disease (CD; N = 24). Doses tested in the MAD trial included multiple intravenous doses (75, 300, and 600 mg once weekly for 4 weeks) given to healthy subjects (N = 24). No severe or serious treatment‐emergent adverse events (TEAEs) were recorded. The most common TEAEs were headache, nasopharyngitis, and myalgia in the SAD trial, and diarrhea, headache, and cough in the MAD trial. Infusion‐related reactions occurred in one and two subjects in the SAD and MAD trial, respectively, leading to treatment discontinuation in the MAD trial. Olamkicept showed dose‐independent pharmacokinetics after single and multiple administrations, and there was no major difference in systemic exposure between healthy subjects and patients with CD. Complete target engagement (inhibition of phosphorylation of signal transducer and activator of transcription‐3) was achieved in blood around or above olamkicept serum concentrations of 1–5 μg/mL. Overall, these results suggest that olamkicept is safe and well‐tolerated in healthy subjects and patients with CD after single intravenous/SC and multiple intravenous administrations. [ABSTRACT FROM AUTHOR]

• The development of 5-combined vaccine and others is of high priority in Japan. • The first vaccination of DPT-IPV should be given concomitantly with the Hib vaccine. • Gobik is the first DPT-IPV-Hib pentavalent vaccine approved in Japan. • Gobik simultaneously provide primary and booster immunizations as a single agent. This study investigated the immunogenicity and safety of a pentavalent vaccine Gobik (DPT-IPV- Haemophilus influenzae type b [Hib]) in healthy Japanese infants aged ≥ 2 and < 43 months using a concomitant vaccination with ActHIB® (Hib) and Tetrabik (DPT-IPV) as a comparator. This study was conducted as a phase 3, multicenter, active controlled, assessor-blinded, randomized, parallel-group study. Participants received a total of 4 subcutaneous doses (3 primary immunization doses and a booster dose) of either the experimental drug (DPT-IPV-Hib) or the active comparator (Hib + DPT-IPV). The primary endpoints were the anti-PRP antibody prevalence rate with ≥ 1 μg/mL, and the antibody prevalence rates against pertussis, diphtheria toxin, tetanus toxin, and attenuated poliovirus after the primary immunization. In 267 randomized participants (133 in the DPT-IPV-Hib group and 134 in the Hib + DPT-IPV group), the antibody prevalence rates after the primary immunization in both groups were 100.0 % and 88.7 % for anti-PRP antibody with ≥ 1 μg/mL, 99.2 % and 98.5 % against diphtheria toxin, and 100.0 % and 99.2 % against tetanus toxin, respectively. The antibody prevalence rates against pertussis and attenuated poliovirus were 100.0 % in both groups. The non-inferiority of the DPT-IPV-Hib group to the Hib + DPT-IPV group was verified for all measured antibodies. In both groups, all the GMTs of antibodies after the primary immunization were higher than those before the first dose, and those after the booster dose were higher than those after the primary immunization. No safety issues were identified. A single-agent Gobik, the first DPT-IPV-Hib pentavalent vaccine approved in Japan, was confirmed to simultaneously provide primary and booster immunizations against Hib infection, pertussis, diphtheria, tetanus, and poliomyelitis and to have a preventive effect and safety comparable to concomitant vaccination with Hib (ActHIB®) and DPT-IPV quadrivalent vaccine (Tetrabik). [ABSTRACT FROM AUTHOR]

Background: Prevotellaheparinolytica is a Gram-negative bacterium that is commonly found in the oral, intestinal, and urinary tracts. It has been extensively studied in lower respiratory tract infections in horses, which has heparinolytic activity and can secrete heparinase and further induces virulence factors in cells and causes disease. However, no such cases have been reported in humans. Case presentation: A 58-year-old male patient from China presented to the respiratory clinic in Suzhou with a productive cough producing white sputum for 20 days and fever for 3 days. Prior to this visit, a chest computed tomography scan was conducted, which revealed multiple patchy nodular opacities in both lungs. On admission, the patient presented with a temperature of 38.1 °C and a pulse rate of 110 beats per minute. Despite routine anti-infective treatment with moxifloxacin, his temperature fluctuated and the treatment was ineffective. The patient was diagnosed with Prevotellaheparinolytica infection through metagenomic next-generation sequencing. Therefore, the antibiotics were switched to piperacillin–tazobactam in combination with ornidazole, which alleviated his symptoms; 1 week after discharge, the patient returned to the clinic for a follow-up chest computed tomography, and the opacities on the lungs continued to be absorbed. Conclusion: Prevotellaheparinolytica is an opportunistic pathogen. However, it has not been reported in human pneumonia. In refractory pneumonia, measures such as metagenomic next-generation sequencing can be used to identify pathogens and help guide antibiotic selection and early support. [ABSTRACT FROM AUTHOR]

Empty large volume parenteral (LVP) bottle has irregular shape and narrow opening, and its detection accuracy of the foreign substances at the bottom is higher than that of ordinary packaging bottles. The current traditional detection method for the bottom of LVP bottles is to directly use manual visual inspection, which involves high labor intensity and is prone to visual fatigue and quality fluctuations, resulting in limited applicability for the detection of the bottom of LVP bottles. A geometric constraint-based detection model (GCBDM) has been proposed, which combines the imaging model and the shape characteristics of the bottle to construct a constraint model of the imaging parameters, according to the detection accuracy and the field of view. Then, the imaging model is designed and optimized for the detection. Further, the generalized GCBDM has been adopted to different bottle bottom detection scenarios, such as cough syrup and capsule medicine bottles by changing the target parameters of the model. The GCBDM, on the one hand, can avoid the information at the bottom being blocked by the narrow opening in the imaging optical path. On the other hand, by calculating the maximum position deviation between the center of visual inspection and the center of the bottom, it can provide the basis for the accuracy design of the transmission mechanism in the inspection, thus further ensuring the stability of the detection. [ABSTRACT FROM AUTHOR]

Background and Objectives. The chest computed tomography (chest CT) has played an important role in the management of COVID-19. Few data on its use in sub-Saharan Africa (SSA) are reported. The objectives of this study conducted in Kinshasa, DR Congo, were to describe the lung lesions on day 1 of hospitalization in patients admitted for suspected COVID-19 and to identify those that were most associated with SARS-CoV-2 infection/RT-PCR and the determinants of chest CT associated with death. Methods. We included all patients with respiratory symptoms (dyspnea, fever, and cough) and/or respiratory failure admitted to the SOS Médecins de nuit SARL hospital, DR Congo, during the 2nd and 3rd waves of the COVID-19 pandemic. The diagnosis of COVID-19 was established based on RT-PCR anti-SARS-CoV-2 tests (G1 (RT-PCR positive) vs. G2 (RT-PCR negative)), and all patients had a chest CT on the day of admission. We retrieved the digital files of patients, precisely the clinical, biological, and chest CT parameters of the day of admission as well as the vital outcome (survival or death). Chest CT were read by a very high-definition console using Advantage Windows software and exported to the hospital network using the RadiAnt DICOM viewer. To determine the threshold for the percentage of lung lesions associated with all-cause mortality, we used ROC curves. Factors associated with death, including chest CT parameters, were investigated using logistic regression analysis. Results. The study included 200 patients (average age 56.2 ± 15.2 years; 19% diabetics and 4.5% obese), and COVID-19 was confirmed among 56% of them (G1). Chest CT showed that ground glass (72.3 vs. 39.8%), crazy paving (69.6 vs. 17.0%), and consolidation (83.9 vs. 22.7%), with bilateral and peripheral locations (68.8 vs. 30.7%), were more frequent in G1 vs. G2 (p < 0.001). No case of pulmonary embolism and fibrosis had been documented. The lung lesions affecting 30% of the parenchyma were informative in predicting death (area under the ROC curve at 0.705, p = 0.017). In multivariate analysis, a percentage of lesions affecting 50% of the lung parenchyma increased the risk of dying by 7.194 (1.656-31.250). Conclusion. The chest CT demonstrated certain characteristic lesions more frequently in patients in whom the diagnosis of COVID-19 was confirmed. The extent of lesions affecting at least half of the lung parenchyma from the first day of admission to hospital increases the risk of death by a factor of 7. [ABSTRACT FROM AUTHOR]

Background: Chelidonium majus is a well-known traditional Chinese medicine, and has been reported of the effect in relieving cough and asthma. However, the mechanism of action is still unknown. Methods: Asthmatic SD rats were first sensitized and established through ovalbumin (OVA) motivation. Subsequently, Hematoxylin and eosin (H&E) staining, Masson's trichrome (Masson) staining, Periodic acid-Schiff (PAS) staining and inflammatory cytokines assay of interleukin (IL)-4, IL-6, IL-17 were implemented to evaluate the protective effects of Chelidonium majus on asthma. Then, the effects of Chelidonium majus and their molecular mechanisms of action on asthma were detected based on the integration of transcriptomics and metabolomics analyses. Results: After administration with Chelidonium majus, the histological injuries of inflammation, collagen deposition and mucus secretion in lungs were attenuated and the serum inflammatory cytokines perturbations were also converted. Furthermore, integrated analysis revealed that after Chelidonium majus treatment, 7 different expression genes (DEGs) (Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9) and 9 metabolic biomarkers (ADP, Xanthosine, Hypoxanthine, Inosine, prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), phosphatidylserine, Creatine and LysoPC (10:0)) were discovered to be connected with the enrichment metabolic pathways, including Purine metabolism, Arachidonic acid metabolism, Arginine and proline metabolism and Glycerophospholipid metabolism. The obtained metabolic biomarkers and DEGs were mainly related to energy metabolism and inflammation, and may be potential therapeutic targets. Conclusion: Chelidonium majus relieved OVA-induced asthma in rats by regulating the Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9 genes expression to restore the disorders in energy metabolism and inflammation. [ABSTRACT FROM AUTHOR]

Gefapixant (MK‐7264, RO4926219, AF‐219) is a first‐in‐class P2X3 antagonists being developed to treat refractory or unexplained chronic cough. The initial single‐ and multiple‐dose safety, tolerability, and pharmacokinetics of gefapixant at doses ranging from 7.5 to 1800 mg were assessed in four clinical trials. Following single‐dose administration of 10‐450 mg, the pharmacokinetic (PK) profile of gefapixant in plasma and urine demonstrated low inter‐subject variability and a dose‐proportional exposure. Following administration of multiple doses twice daily, the plasma exposures were dose‐proportional at doses ranging from 7.5 to 50 mg and less than dose‐proportional at doses ranging from 100 to 1800 mg. The time to mean peak drug concentration ranged from 2 to 3 h post‐dose, and steady state was achieved by 7 days after dosing, with an accumulation ratio of approximately 2, comparing data from day 1 to steady state. The mean apparent terminal half‐life ranged from 8.2 to 9.6 h. Gefapixant was primarily excreted unmodified in urine. Gefapixant was well tolerated following single‐dose administration up to 1800 mg and multiple doses up to 1800 mg twice daily; there were no serious adverse events (AEs) reported. The most common AE reported was dysgeusia. The PK profile supports a twice‐daily dosing regimen. [ABSTRACT FROM AUTHOR]

Background and Objective: To explore the efficacy of deep diaphragmatic breathing training (DEP) in patients with gastroesophageal reflux-induced chronic cough (GERC). Methods: A randomized controlled study was conducted involving 60 GERC patients who were divided into the intervention group and the control group (each with 30 patients). Both groups received routine medication treatment for GERC, while the intervention group received DEP training additionally. Both groups were evaluated by cough symptom scores, Hull airway reflux questionnaire (HARQ), gastroesophageal reflux diagnostic questionnaire (GerdQ), generalized anxiety disorder scale-7 (GAD-7), patient health questionnaire-9 (PHQ-9), Pittsburgh sleep quality index (PSQI), the Leicester cough questionnaire (LCQ), as well as capsaicin cough sensitivity testing, B-ultrasound and surface electromyography (sEMG) of the diaphragmatic muscles before and after treatment. The cough resolution rate and changes of the above indictors was compared between the two groups after eight weeks of treatment. Results: After eight weeks of treatment, cough symptoms improved in both groups, but the cough resolution rate in the intervention group of 94% was significantly higher than that in the control group of 77% (χ2 = 6.402, P = 0.041). The intervention group showed significant improvements to the control group in GerdQ (6.13(0.35) VS 6.57(0.77)), GAD-7 (0(0;1) VS 1(0;3)), PSQI (2(1;3) VS 4(3;6)), LCQ (17.19(1.56) VS 15.88(1.92)) and PHQ-9 (0(0;0) VS 0(0;3)) after treatment. Compared to control group, sEMG activity of the diaphragmatic muscle was significantly increased in the intervention group after treatment, measured during DEP (79.00(2.49) VS 74.65 (1.93)) and quiet breathing (72.73 (1.96) VS 67.15 (2.48)). Conclusion: DEP training can improve cough symptoms as an adjunctive treatment in GERC patients. Trial registration: The protocol was registered in February 2, 2022 via the Chinese Clinical Trials Register (http://www.chictr.org.cn/) [ChiCTR2200056246]. [ABSTRACT FROM AUTHOR]

Background and purpose: The COVID-19 pandemic has presented unprecedented public health challenges worldwide. Understanding the factors contributing to COVID-19 mortality is critical for effective management and intervention strategies. This study aims to unlock the predictive power of data collected from personal, clinical, preclinical, and laboratory variables through machine learning (ML) analyses. Methods: A retrospective study was conducted in 2022 in a large hospital in Abadan, Iran. Data were collected and categorized into demographic, clinical, comorbid, treatment, initial vital signs, symptoms, and laboratory test groups. The collected data were subjected to ML analysis to identify predictive factors associated with COVID-19 mortality. Five algorithms were used to analyze the data set and derive the latent predictive power of the variables by the shapely additive explanation values. Results: Results highlight key factors associated with COVID-19 mortality, including age, comorbidities (hypertension, diabetes), specific treatments (antibiotics, remdesivir, favipiravir, vitamin zinc), and clinical indicators (heart rate, respiratory rate, temperature). Notably, specific symptoms (productive cough, dyspnea, delirium) and laboratory values (D-dimer, ESR) also play a critical role in predicting outcomes. This study highlights the importance of feature selection and the impact of data quantity and quality on model performance. Conclusion: This study highlights the potential of ML analysis to improve the accuracy of COVID-19 mortality prediction and emphasizes the need for a comprehensive approach that considers multiple feature categories. It highlights the critical role of data quality and quantity in improving model performance and contributes to our understanding of the multifaceted factors that influence COVID-19 outcomes. [ABSTRACT FROM AUTHOR]

Background: Opioids such as sufentanil are used as anaesthetics due to their rapid action and superior analgesic effect. However, sufentanil induces a huge cough in paediatric patients. In contrast, intravenous (IV) lidocaine suppresses opioid-induced cough in children, but its use is limited due to anaesthetists' concern about its toxicity. Therefore, this study aimed to evaluate the effect of dose-dependent IV lidocaine on sufentanil-induced cough (SIC) in paediatric patients. Methods: A total of 188 patients aged 3–12 years scheduled for elective tonsillectomy with or without adenoidectomy were enrolled and divided into four groups depending on different dose of lidocaine: A (0 mg.kg-1), B (1 mg.kg-1), C (1.5 mg.kg-1), and D (2 mg.kg-1). The primary outcome was the SIC grade observed during the induction of general anaesthesia. The secondary outcomes were the incidence of SIC, mean arterial pressure, and heart rate at T0, T1, T2, T3, T4, and T5. Results: The SIC grade was significantly different between groups A and D (P = 0.04) and between groups B and D (P = 0.03). Moreover, the incidence of SIC in groups A, B, C, and D was 81%, 87%, 68%, and 64%, respectively, and the difference between groups B and C (P = 0.03) and between groups B and D (P = 0.0083) was statistically significant. No statistical differences were observed in the hemodynamic parameters between the groups. The incidence of severe cough was statistically different between group D and group A (P < 0.0001), between group D and group B (P < 0.0001), and between group D and group C (P < 0.0001) respectively. Conclusions: Lidocaine suppresses SIC in a dose-dependent manner without severe adverse events. IV lidocaine can be used in paediatric patients safely and efficiently, and the median effective dose was 1.75 mg/kg. Trial registration: This study was approved by the Institutional Review Board of Yichang Central People's Hospital (HEC-KYJJ-2020-038-02), The trial was registered at www.chictr.org.cn (ChiCTR2100053006). [ABSTRACT FROM AUTHOR]

Introduction: Vaccination during pregnancy protects both the mother and the foetus from vaccine-preventable diseases. However, uptake of the recommended vaccines (influenza, pertussis, COVID-19) by pregnant women remains low in Europe and the USA. Understanding the reasons for this is crucial to inform strategies to increase vaccination rates in pregnant women. This qualitative systematic review aimed to identify the barriers and facilitators to vaccination against influenza, pertussis/whooping cough and COVID-19 during pregnancy and identify possible strategies to increase vaccination rates. Methods: We conducted a comprehensive search of electronic databases, including Medline, PsycINFO, CINAHL, Web of Science, WHO database, Embase and grey literature to identify qualitative studies that explored barriers and facilitators to vaccine uptake among pregnant women (PROSPERO CRD42023399488). The search was limited to studies published between 2012 and 2022 conducted in high-income countries with established vaccination programmes during pregnancy. Studies were thematically analysed and underwent quality assessment using the Joanna Briggs Institute validated critical appraisal tool for qualitative research. Results: Out of 2681 articles screened, 28 studies (n = 1573 participants) were eligible for inclusion. Five overarching themes emerged relating to personal, provider and systemic factors. Barriers to vaccine uptake included concerns about vaccine safety and efficacy, lack of knowledge about vaccines' benefits and necessity, fear of adverse effects on the foetus or mother and low perception of disease severity. Facilitators included recommendations from trusted healthcare providers, easy access to vaccination, clear communication on the benefits and safety of vaccination, and positive social influences from family and friends. Strategies for increasing vaccination uptake included strong and proactive vaccine recommendations by trusted healthcare professionals, provision of vaccines during routine antenatal care, and clear and consistent communication about vaccines addressing pregnant women's concerns. Conclusion: This review highlights the need for interventions that address the identified barriers to vaccine uptake among pregnant women. Recommendation from a healthcare provider can play a significant role in promoting vaccine uptake, as can clear risk/benefit communication and convenient access to vaccination. Addressing concerns about vaccine safety and providing accurate information about vaccines is also important. [ABSTRACT FROM AUTHOR]

AbstractIntroductionCase StudyResultsConclusionSpontaneous pneumomediastinum with pneumopericardium is an uncommon clinical entity.Here, we report the case of a 23-year-old male with asthma who presented with acute chest pain and shortness of breath after an episode of coughing and sneezing. CT scans of the chest and neck revealed pneumomediastinum and pneumopericardium with extensive subcutaneous emphysema extending into the axilla and neck.The patient was admitted for observation and analgesia. No other interventions were administered. Interval scans performed on day five of the admission demonstrated an interval reduction in the degree of air within the mediastinum, pericardium and subcutaneous tissues, and the patient was subsequently discharged home.This case outlines the presentation, diagnosis, and management of concurrent spontaneous pneumomediastinum and pneumopericardium. [ABSTRACT FROM AUTHOR]

Introduction: Fever and cough in under-five children are common and predominately self-limiting illnesses. Inappropriate prescribing of antibiotics in sub-Saharan Africa is a significant public health concern. However, prescription sources and use among children with fever or cough have not been explored. Therefore, we explored the factors associated with the use of antibiotics obtained from prescription and non-prescription sources for children with illnesses associated with fever and cough. Methods: A secondary data analysis was conducted based on the Demographic and Health Survey (DHS) data from 37 sub-Saharan African countries. A total weighted sample of 18,866 under-five children who had a fever/cough and took antibiotics were considered for this study. Given the hierarchical nature of DHS data and the use of antibiotics prescribed from the formal healthcare setting (> 10%), a multilevel modified poisson regression model was fitted. Deviance was used for model comparison and the model with the lowest deviance value was chosen as the best-fitted model. Variables with p ≤ 0.2 in the bivariable analysis were considered for the multivariable modified poisson regression model. In the multivariable multilevel modified poisson regression model, the Adjusted Prevalence Odds Ratio (APOR) with a 95% Confidence Interval (CI) and p-value < 0.05 were reported to declare a significant association with taking antibiotics for fever/cough prescribed from formal healthcare setting. Results: In sub-Saharan Africa, the proportion of use of antibiotics from informal healthcare setting for fever and cough among under-five children was 67.19% (95% CI: 66.51%, 67.85%). In the multilevel modified poisson regression analysis; residing in a rural area (APOR = 1.08, 95% CI: 1.04, 1.12), a child aged 36–47 months (APOR = 0.94, 95% CI: 0.90, 0.98), a child aged 48–59 months (APOR = 0.89, 95% CI: 0.84, 0.94), maternal primary education (APOR = 0.96, 95% CI: 0.93, 0.99), maternal secondary education (APOR = 0.95, 95% CI: 0.92, 0.99), belonged the middle household wealth status (APOR = 1.07, 95% CI: 1.02, 1.11), maternal exposure to news/electronic media (APR = 1.06, 95% CI: 1.02, 1.10), being from a household with 2 under-five children (APR = 0.94, 95% CI: 0.91, 0.97), being from a household with 3 under-five children (APR = 0.89, 95% CI: 0.85, 0.93), being from a household with 4 under-five children (APR = 0.90, 95% CI: 0.83, 0.98), and children of caregivers who were not involved in decision-making for their child health issues were significantly associated with taking antibiotics prescribed from formal healthcare setting for fever/cough among under-five children. Conclusion: Only two-thirds of the antibiotics used for children under five who had fever and cough were prescribed from formal healthcare setting. Our findings underscore the significance of addressing healthcare disparities, improving access to qualified healthcare providers, promoting maternal education, and empowering mothers in healthcare decision-making to ensure appropriate antibiotic use in this vulnerable population. Further research and interventions targeted at these factors are warranted to optimize antibiotic prescribing practices and promote responsible antibiotic use in the management of fever and cough in under-five children. [ABSTRACT FROM AUTHOR]

Maternal pertussis vaccination during the third trimester of pregnancy was implemented in 2015 in Spain, reaching a national coverage of 84% in 2019. In this ecological study, we investigated whether there was a change in the disease severity for pertussis in infants upon introduction of prenatal pertussis vaccination. We performed a time-trend analysis of infant pertussis hospitalizations during 2005–2019 in Spain using national register data. Annual hospitalization rates per 100,000 population and the mean length of hospitalization were calculated for infants < 3 months of age (target group benefiting from the prenatal vaccination) and a reference group aged 3–11 months. We compared overall rates and annual percent changes of the above variables in both groups for the time period before (2005–2014) and after vaccination introduction (2015–2019), using segmented Poisson regression. During the pre-vaccination period, infants aged 0–2 months had a 5-times higher rate of pertussis hospitalization and spent on average 50 % longer in hospital than the reference group. After the maternal vaccination introduction, the hospitalization rate decreased more rapidly in infants aged 0–2 months than in infants aged 3–11 months: annual reduction of 34 % (95 % CI: 31–38) versus 26 % (95 % CI: 21–31) in the hospitalization rate and 13 % (95 % CI: 11–15) versus 6 % (95 % CI: 2–9) in the mean hospital stay, respectively. In 2019, the mean hospital stay for pertussis was about 4.5 days in both groups. Maternal pertussis vaccination in Spain led to a reduction in disease severity in the target group as compared to older infants, highlighting the need for increased efforts on educating healthcare professionals on the importance of maternal vaccinations. [ABSTRACT FROM AUTHOR]

The complex nature of chronic bronchitis (CB) and changing definitions have contributed to challenges in understanding its aetiology and burden. In children, CB is characterised by persistent airway inflammation often linked to bacterial infections and is therefore termed "protracted bacterial bronchitis" (PBB). Longitudinal studies suggest that CB in childhood persists into adulthood in a subgroup. It can also be associated with future chronic respiratory diseases including asthma, bronchiectasis, and chronic obstructive pulmonary disease (COPD). Adult CB is traditionally associated with smoking, occupational exposures, and lower socioeconomic status. The interplay between risk factors, childhood CB, adult CB, and other chronic respiratory diseases is intricate, requiring comprehensive longitudinal studies for a clearer understanding of the natural history of CB across the lifespan. Such longitudinal studies have been scarce to date given the logistic challenges of maintaining them over time. In this review, we summarise current evidence on the evolution of the definitions, pathophysiology, risk factors, and consequences of childhood and adulthood chronic bronchitis. [ABSTRACT FROM AUTHOR]

Background: Post Acute COVID Syndrome (PACS), a complex and poorly understood condition characterised by persistent symptoms following the acute phase of COVID-19 infection, has emerged as a significant global health concern. Healthcare workers who had been at the forefront of the pandemic response are at heightened risk of contracting the virus and subsequently developing PACS. Therefore, we aim to determine the prevalence and risk factors for PACS among healthcare workers infected with COVID-19. Methods: A cross-sectional study was conducted between October 2022 and August 2023 using an online REDCap electronic data capture tool questionnaire. PACS was defined as new or persistent symptoms lasting more than 28 days after a positive SARS-CoV-2 polymerase chain reaction or rapid test kit antigen test. Multivariable logistic regression was performed to determine predictors associated with PACS. Results: Among 609 infected healthcare workers, they were predominantly female (71.8%), Malays (84.6%), and aged 18–39 years (70.1%). 50.7% of infected healthcare workers experienced PACS. The most common PACS symptoms experienced were fatigue (27.9%), cough (25.1%), decreased physical strength (20.5%), and musculoskeletal pain (19.2%). Those who are more likely to develop PACS were females, underlying asthma, and COVID-19 severity category 3. On the other hand, those who received booster vaccinations were less likely to develop PACS. Conclusion: PACS is prevalent among healthcare workers with COVID-19 at the University Malaya Medical Centre. These findings emphasise the critical need for those with higher risk to receive regular health monitoring and checkups to detect any early signs of PACS. It underscores the need for continuous support and healthcare interventions to mitigate the impacts of PACS and ensure the physical and mental well-being of healthcare workers. [ABSTRACT FROM AUTHOR]

Low-dose computed tomography screening for lung cancer is currently targeted at heavy smokers or those with a family history of lung cancer. This study aimed to identify risk factors for lung cancer in individuals who do not meet the current lung cancer screening criteria as stipulated by the Taiwan Health Promotion Agency's low-dose computed tomography (LDCT) screening policy. A cohort analysis was conducted on 12,542 asymptomatic healthy subjects aged 20–80 years old who voluntarily underwent LDCT scans from January 2016 to December 2021. Logistic regression demonstrated that several factors, including age over 55 years, female gender, a body mass index (BMI) less than 23, a previous history of respiratory diseases such as tuberculosis or obstructive respiratory diseases (chronic obstructive pulmonary disease [COPD], asthma), and previous respiratory symptoms such as cough or dyspnea, were associated with high-risk lung radiology scores according to LDCT scans. These findings indicate that risk-based assessments using primary data and questionnaires to identify risk factors other than heavy smoking and a family history of lung cancer may improve the efficiency of lung cancer screening. [ABSTRACT FROM AUTHOR]

Simple Summary: We studied the feasibility and safety of using bronchoscopically implanted electromagnetic transponders to monitor deep inspiration breath hold (DIBH) for thoracic radiation therapy (RT) of primary lung cancers or lung metastases. Three transponders were implanted near the tumor, followed by CT simulation. The initial gating window was ±5 mm; in a second cohort, the window was incrementally reduced to determine the smallest feasible gating window: this was identified to be ±3 mm. Among the 48 patients enrolled, transponder-guided DIBH was feasible in all but two patients (96% feasible), where it failed because the distance between the transponders and the antenna was >19 cm. Toxicities at least possibly related to transponders or the implantation procedure were grade 2 in six patients, grade 3 in three patients, and grade 4 in one patient. Toxicities at least possibly related to RT were grade 2 in 18 patients and grade 3 in four patients. Transponder-guided DIBH is a feasible and safe approach for delivering thoracic RT. Background: Electromagnetic transponders bronchoscopically implanted near the tumor can be used to monitor deep inspiration breath hold (DIBH) for thoracic radiation therapy (RT). The feasibility and safety of this approach require further study. Methods: We enrolled patients with primary lung cancer or lung metastases. Three transponders were implanted near the tumor, followed by simulation with DIBH, free breathing, and 4D-CT as backup. The initial gating window for treatment was ±5 mm; in a second cohort, the window was incrementally reduced to determine the smallest feasible gating window. The primary endpoint was feasibility, defined as completion of RT using transponder-guided DIBH. Patients were followed for assessment of transponder- and RT-related toxicity. Results: We enrolled 48 patients (35 with primary lung cancer and 13 with lung metastases). The median distance of transponders to tumor was 1.6 cm (IQR 0.6–2.8 cm). RT delivery ranged from 3 to 35 fractions. Transponder-guided DIBH was feasible in all but two patients (96% feasible), where it failed because the distance between the transponders and the antenna was >19 cm. Among the remaining 46 patients, 6 were treated prone to keep the transponders within 19 cm of the antenna, and 40 were treated supine. The smallest feasible gating window was identified as ±3 mm. Thirty-nine (85%) patients completed one year of follow-up. Toxicities at least possibly related to transponders or the implantation procedure were grade 2 in six patients (six incidences, cough and hemoptysis), grade 3 in three patients (five incidences, cough, dyspnea, pneumonia, and supraventricular tachycardia), and grade 4 pneumonia in one patient (occurring a few days after implantation but recovered fully and completed RT). Toxicities at least possibly related to RT were grade 2 in 18 patients (41 incidences, most commonly cough, fatigue, and pneumonitis) and grade 3 in four patients (seven incidences, most commonly pneumonia), and no patients had grade 4 or higher toxicity. Conclusions: Bronchoscopically implanted electromagnetic transponder–guided DIBH lung RT is feasible and safe, allowing for precise tumor targeting and reduced normal tissue exposure. Transponder–antenna distance was the most common challenge due to a limited antenna range, which could sometimes be circumvented by prone positioning. [ABSTRACT FROM AUTHOR]

Background and Purpose: The P2X3 receptor, a trimeric ionotropic purinergic receptor, has emerged as a potential therapeutic target for refractory chronic cough (RCC). Nevertheless, gefapixant/AF‐219, the only marketed P2X3 receptor antagonist, might lead taste disorders by modulating the human P2X2/3 (hP2X2/3) heterotrimer. Hence, in RCC drug development, compounds exhibiting strong affinity for the hP2X3 homotrimer and a weak affinity for the hP2X2/3 heterotrimer hold promise. An example of such a molecule is sivopixant/S‐600918, a clinical Phase II RCC candidate with a reduced incidence of taste disturbance compared to gefapixant. Sivopixant and its analogue, (3‐(4‐([3‐chloro‐4‐isopropoxyphenyl]amino)‐3‐(4‐methylbenzyl)‐2,6‐dioxo‐3,6‐dihydro‐1,3,5‐triazin‐1(2H)‐yl)propanoic acid (DDTPA), exhibit both high affinity and high selectivity for hP2X3 homotrimers, compared with hP2X2/3 heterotrimers. The mechanism underlying the druggable site and its high selectivity remains unclear. Experimental Approach: To analyse mechanisms that distinguish this drug candidate from other inhibitors of the P2X3 receptors we used a combination of chimera construction, site covalent occupation, metadynamics, mutagenesis and whole‐cell recording. Key Results: The high affinity and selectivity of sivopixant/DDTPA for hP2X3 receptors was determined by the tri‐symmetric site located close to the upper vestibule. Substitution of only four amino acids inside the upper body domain of hP2X2 with those of hP2X3, enabled the hP2X2/3 heterotrimer to exhibit a similar level of apparent affinity for sivopixant/DDTPA as the hP2X3 homotrimer. Conclusion and Implications: From the receptor‐ligand recognition perspective, we have elucidated the molecular basis of novel RCC clinical candidates' cough‐suppressing properties and reduced side effects, offering a promising approach to the discovery of novel drugs that specifically target P2X3 receptors. [ABSTRACT FROM AUTHOR]

Background: We recently adopted a guideline for chronic cough in children in the Egyptian health system. Adapting clinical practice guidelines (CPGs) to the local healthcare setting is a valid alternative to de-novo development that can improve their uptake and implementation without demanding a substantial drain on resources. The objective of this study was to adapt evidence-based recommendations from global high-quality CPGs for children with a chronic cough to suit the Egyptian healthcare context. Methods: We followed the Adapted ADAPTE methodological framework for guideline adaptation. This process includes three phases: set-up, adaptation, and finalization. A guideline adaptation group (GAG) and an external review group including clinical content experts and methodologists conducted the process. Results: The GAG adapted 10 sections of recommendations from three original CPG(s) including (i) the American College of Chest Physicians (ACCP) 2006–2020, (ii) the European Respiratory Society (ERS) 2019, (iii) the Korean Academy of Asthma, Allergy and Clinical Immunology (KAAACI) 2018. A set of CPG implementation tools was added to enhance implementability including an algorithm, a slide presentation for clinical diagnosis, investigations and treatment of chronic cough, patient education, and online resources. Conclusion: The adapted CPG provides pediatricians and related healthcare workers with applicable evidence-based recommendations for chronic cough in children in Egypt. The project also highlighted the utility of Adapted ADAPTE and the invaluable collaboration between the clinical and methodological experts for the adaptation of pediatric national guidelines. [ABSTRACT FROM AUTHOR]

In 2021, an estimated 10.6 million people fell ill with tuberculosis (TB) globally and 11.3% were children. About 40% of children aged five to fourteen years with TB are missed annually. In Uganda, 44% of adolescents with chronic cough of more than two weeks do not seek care from health facilities. Therefore, strategies to promote health care-seeking behaviour among adolescents were urgently needed to resolve the gap. In regard to this, the research project utilized a before and after design, in which the number of adolescents (10-19years) enrolled in the project health facilities were compared before and after the intervention. The intervention package that comprised of tuberculosis awareness and screening information was developed together with adolescents, thus; a human-centred approach was used. The package consisted of TB screening cards, poster messages and a local song. The song was broadcasted in the community radios. Poster messages were deployed in the community by the village health teams (VHTS). The TB screening cards were given to TB positive and presumptive adults to screen adolescents at home. Adolescents that were found with TB symptoms were referred to the project health facilities. Socio-demographic and clinical characteristics of eligible adolescents were collected in a period of six months from Kawolo, Iganga, Gombe and Kiwoko health facilities. To determine the effectiveness of the package, before and after intervention data were equally collected. A total of 394 adolescents were enrolled, majority (76%) were school going. The intervention improved adolescent TB care seeking in the four project health facilities. The average number of adolescents screened increased from 159 to 309 (incidence rate ratio (IRR) = 1.9, P<0.001, 95% CI [1.9, 2.0]). Those presumed to have TB increased from 13 to 29(IRR = 2.2, P<0.001, 95% CI [1.9, 2.5]). The ones tested with GeneXpert increased in average from 8 to 28(IRR = 3.3, P<0.001, 95% CI [2.8, 3.8]). There was a minimal increase in the average monthly number of adolescents with a positive result of 0.8, from 1.6 to 2.4(p = 0.170) and linkage to TB care services of 1.1, from 2 to 3.1(p = 0.154). The project improved uptake of TB services among adolescents along the TB care cascade. We recommend a robust and fully powered randomized controlled trial to evaluate the effectiveness of the Package. [ABSTRACT FROM AUTHOR]

Background/Aim: London Protocol (LP) and Classification allied to high-resolution manometry (HRM) technological evolution has updated and enhanced the diagnostic armamentarium in anorectal disorders. This study aims to evaluate LP reproducibility under water-perfused HRM, provide normal data and new parameters based on 3D and healthy comparison studies under perfusional HRM. Methods: Fifty healthy (25 F) underwent water-perfused 36 channel HRM based on LP at resting, squeeze, cough, push, and rectal sensory. Additional 3D manometric parameters were: pressure-volume (PV) 104mmHg2.cm (resting, short and long squeeze, cough); highest and lowest pressure asymmetry (resting, short squeeze, and cough). Complementary parameters (CP) were: resting (mean pressure, functional anal canal length); short squeeze (mean and maximum absolute squeeze pressure), endurance (fatigue rate, fatigue rate index, capacity to sustain); cough (anorectal gradient pressure); push (rectum-anal gradient pressure, anal canal relaxation percent); recto-anal inhibitory reflex (anal canal relaxation percent). Results: No difference to genders: resting (LP, CP, and 3D); short squeeze (highest pressure asymmetry); endurance (CP); cough (CP, highest and lowest pressure asymmetry); push (gradient pressure); rectal sensory. Higher pressure in men: short squeeze (maximum incremental, absolute, and mean pressure, PV, lowest pressure asymmetry); long squeeze (PV); cough (anal canal and rectum maximum pressure, anal canal PV); push (anal canal and rectum maximum pressure). Anal canal relaxation was higher in women (push). Conclusions: LP reproducibility is feasible under water-perfused HRM, and comparative studies could bring similarity to dataset expansion. Novel 3D parameters need further studies with healthy and larger data to be validated and for disease comparisons. Key points: • London Protocol and Classification allied with the technological evolution of HRM (software and probes) has refined the diagnostic armamentarium in anorectal disorders. • Novel 3D and deepening the analysis of manometric parameters before the London Classification as a contributory diagnostic tool. • Comparison of healthy volunteers according to the London Protocol under a perfusional high-resolution system could establish equivalence points. [ABSTRACT FROM AUTHOR]

Background: In 2019, the first cases of an acute respiratory infectious disease were announced in the city of Wuhan, China. In places where the speed of transmission and the resulting high prevalence and death from this virus is high, it is important to find things that help prevent and reduce the symptoms and complications of the disease, one of these things. Things are serum levels of vitamin D. As a result of this study, serum levels of vitamin D were measured in patients with Covid-19. Methods: From December to March of 1400, 100 samples of people hospitalized in Khurshid laboratory were examined to identify the RNA of the Covid-19 virus by Real Time PCR method and at the same time to check the serum levels of vitamin D. The data was statistically analyzed using SPSS software. Results: The average age of the patients was between 12.45 and 40.8 years. Comparison the two Covid-19 positive and negative groups in terms of symptoms, it was found that the patients with RH positive had more positive PCR percentage and a significant difference was reported between RH positive and Covid-19 (p=0.006). In comparing the relationship between disease symptoms and the rate of PCR positive reports of gastrointestinal symptoms, history of significant disease, cough, fever, a significant difference was reported (p<0.001). Also, 50% of the samples were PCR positive. Based on the t-test, a significant difference was reported between the serum levels of vitamin D and Covid-19 (p<0.001). Conclusion: The results showed that the vitamin D is an acceptable protective factor against Covid19 infection and its deficiency increases the probability of infection. [ABSTRACT FROM AUTHOR]

A 62-year-old man attended ophthalmology for a simple ptosis repair. He had a chronic cough, a Horner's syndrome with post-gustatory hyperhidrosis. He was referred to the respiratory and neurology teams. MR scan of his head and neck found evidence of multifocal disease at the skull base and carotid canal, and further tests identified additional deposits in the hilar lymph nodes, heart and sacrum. A transbronchial biopsy confirmed the diagnosis of sarcoidosis. His symptoms and imaging responded well to corticosteroids, but he still undergoes regular imaging. We discuss the features of Horner's syndrome, and the autonomic associations of a chronic cough. [ABSTRACT FROM AUTHOR]

Black pepper (Piper nigrum) has been used as an antidote for cough, cold, dyspnoea, throat illnesses, intermittent fever, dysentery, stomach ache, worms, and piles in traditional medicine. It is also used as an anti-inflammatory, antipyretic, and to treat epilepsy and snakebite. Black pepper is a common spice in Asian cuisine, and it has applications in traditional medicine, perfumes, preservatives, and pesticides. Piperine, an alkaloid, increases the therapeutic efficacy of a variety of medications, vaccines, and nutrients by increasing bioavailability by blocking several digestive enzymes. Piperine also promotes digestion by increasing pancreatic and intestinal enzymes, as well as improving cognitive abilities and fertility. Rheumatism, cold, weariness, muscle aches, and infection can all be helped by black pepper essential oil, which makes up about 0.4–7% of the dry weight of berries. It was also utilised to improve blood circulation as a nerve stimulant. Piperine was found in 2–7% of both white and black pepper. Piperamides and nerolidol, two volatile oil constituents, have insecticidal properties. [ABSTRACT FROM AUTHOR]

Orbital infarction syndrome (OIS) is a disease of rare occurrence owing to the rich orbital vascular anastomotic network. We describe a case of a middle-aged female who presented with an acute left middle cerebral artery (MCA) territory infarct with left terminal internal carotid artery and MCA occlusion, underwent emergency mechanical thrombectomy, and developed painful loss of vision shortly after diagnosed as OIS based on clinical and radiological findings. The rarity and severity of OIS, especially in the setting of mechanical thrombectomy, warrant radiologists to be aware of this entity to ensure preventive measures or aid in prompt diagnosis to institute timely treatment. [ABSTRACT FROM AUTHOR]

Background: A voice problem known as dysphonia has been identified as a potential adverse effect of COVID-19 infection. Objective: This study aimed to assess the prevalence of dysphonia in COVID-19 patients and the impact of his/her voice disorder upon daily activities using the Voice Handicap Index (VHI-30). Patients and methods: This prospective study was conducted on a cohort of 231 COVID-19 patients selected from the Otorhinolaryngology Department, Benha University Hospital. Patient evaluation included comprehensive history taking, physical and local examinations, laboratory investigation, voice assessments using (VHI-30), auditory perceptual analysis and local laryngeal examination by indirect rigid laryngoscopy. Results: Among the enrolled patients, 46.8% were males and 53.2% were females, with a mean age of 48.73 ± 11.58 years. The most prevalent symptoms reported were fever (93.5%), exhaustion (83.1%), and cough (76.2%). Dysphonia was found in 37.6% of the patients, with 58.6% experiencing mild dysphonia, 28.7% moderate dysphonia, and 12.6% severe dysphonia. The Voice Handicap Index (VHI) scores, which mean that physical VHI was 18.82 ± 4.69, mean functional VHI was 17.42 ± 3.73, and mean emotional VHI was 14.97 ± 4.67. While mean total VHI was 36.02 ± 13.62 and the result explained the positive relation between total mean VHI score and grade of dysphonia. The mild grade was total mean 25.49 ± 5.11, moderate grade was total mean 42.56 ± 5.3 and severe grade was total mean 61.54 ± 8.16. Our findings showed that the more severe the COVID-19 infection, the higher the scores of total VHI-30. Laryngoscope findings revealed laryngeal mucosa congestion and edema as the most common finding (35.5%), followed by early starting nodules (20.8%), vocal fold immobility (1%), Vocal fold polyp (haemorrhagic polyp) (1%) and normal laryngeal mucosa (42%). The most prevalent cause of dysphonia is organic lesion (22.8%) followed by nonorganic (functional) (15.5%). Conclusion: Our study revealed a considerable prevalence of dysphonia among COVID-19 patients in Benha University Hospitals. The VHI scores indicated the negative impact of dysphonia on physical, functional, and emotional aspects of patients' lives. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Following the loss of consciousness during the Valsalva maneuver and cough induction test, real‐time arterial pressure measurement could clarify the significant blood pressure decrease in a patient with cough syncope. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Tuberculosis (TB) pericarditis, while uncommon, should be considered in patients with pericardial masses and effusion. Timely recognition and treatment with anti‐TB medications are crucial for a successful outcome. TB pericarditis presenting as a pericardial mass is an unusual and rare manifestation of this disease. We report a 59‐year‐old South Asian male who presented with a 1‐week history of dyspnea and cough. He was found to have a hemorrhagic pericardial mass with a massive pericardial effusion. Pleural fluid analysis was positive for TB. The patient was successfully treated with anti‐TB medications. Although rare, tuberculous pericardial involvement should be suspected in patients presenting with symptoms of pericardial masses and effusion. [ABSTRACT FROM AUTHOR]

Background: Hyperosmolar aerosols appear to promote or suppress upper airway dysfunction caused by dehydration in a composition-dependent manner. We sought to explore this composition dependence experimentally, in an interventional human clinical study, and theoretically, by numerical analysis of upper airway ion and water transport. Methods: In a double-blinded, placebo-controlled clinical study, phonation threshold pressure (PTP) was measured prenasal and postnasal inhalation of hypertonic aerosols of NaCl, KCl, CaCl2, and MgCl2 in seven human subjects. Numerical analysis of water and solute exchanges in the upper airways following deposition of these same aerosols was performed using a mathematical model previously described in the literature. Results: PTP decreased by 9%–22% relative to baseline (p < 0.05) for all salts within the first 30 minutes postadministration, indicating effective laryngeal hydration. Only MgCl2 reduced PTP beyond 90 minutes (21% below baseline at 2 hours postadministration). By numerical analysis, we determined that, while airway water volume up to 15 minutes postdeposition is dictated by osmolarity, after 30 minutes, divalent cation salts, such as MgCl2, better retain airway surface liquid (ASL) volume by slow paracellular clearance of the divalent cation. Fall of CFTR chloride flux with rise in ASL height, a promoter of airway acidification, appears to be a signature of permeating cation (NaCl) and nonpermeating anion (mannitol) aerosol deposition. For hypertonic aerosols that lack permeating cation and include permeating anion (CaCl2 and MgCl2), this acid-trigger signature does not exist. Conclusions: Nonpermeating cation and permeating anion hypertonic aerosols appear to hydrate upper airways longer and, rather than provoke, may reduce laryngeal dysfunction such as cough and bronchoconstriction. [ABSTRACT FROM AUTHOR]