Effects of C-reactive protein rapid testing and communication skills training on antibiotic prescribing for acute cough. A cluster factorial randomised controlled trial.

This cluster randomised clinical trial carried out in 20 primary care centres in Barcelona was aimed at assessing the effect of a continuous intervention focused on C-reactive protein (CRP) rapid testing and training in enhanced communication skills (ECS) on antibiotic consumption for adults with acute cough due to lower respiratory tract infection (LRTI). The interventions consisted of general practitioners and nurses' use of CRP point-of-care and training in ECS separately and combined, and usual care. The primary outcomes were antibiotic consumption and variation of the quality-adjusted life years during a 6-week follow-up. The difference in the overall antibiotic prescribing between the winter seasons before and after the intervention was calculated. The sample size calculated could not be reached due to the COVID-19 outbreak. A total of 233 patients were recruited. Compared to the usual care group (56.7%) antibiotic consumption among patients assigned to professionals in the ECS group was significantly lower (33.9%, adjusted odds ratio [aOR] 0.38, 95% CI 0.15-0.94, p = 0.037), whereas patients assigned to CRP consumed 43.8% of antibiotics (aOR 0.70, 95% CI 0.29-1.68, p = 0.429) and 38.4% in the combined intervention group (aOR 0.45, 95% CI, 0.17-1.21; p = 0.112). The overall antibiotic prescribing rates in the centres receiving training were lower after the intervention compared to those assigned to usual care, with significant reductions in ß-lactam rates. Patient recovery was similar in all groups. Despite the limited power due to the low number of patients included, we observed that continuous training achieved reductions in antibiotic consumption.

Prevalence of Respiratory Viruses in Children With Acute Respiratory Infections in Shanghai, China, From 2013 to 2022.

BACKGROUND: A variety of viruses can cause acute respiratory infections (ARIs), resulting in a high disease burden worldwide. To explore the dominant viruses and their prevalence characteristics in children with ARIs, comprehensive surveillance was carried out in the Pudong New Area of Shanghai. METHODS: Between January 2013 and December 2022, the basic and clinical information, and respiratory tract specimens of 0-14 years old children with ARIs were collected in five sentinel hospitals in Shanghai Pudong. Each specimen was tested for eight respiratory viruses, and the positive rates of different age groups, case types (inpatient or outpatient) were analyzed. RESULTS: In our study, 30.67% (1294/4219) children with ARIs were positive for at least one virus. Influenza virus (IFV) was the most commonly detected respiratory virus (349/4219, 8.27%), followed by respiratory syncytial virus (RSV) (217/4219, 5.14%), para-influenza virus (PIV) (215/4219, 5.10%), and human coronavirus (HCoV, including 229E, OC43, NL63, and HKU1) (184/4219, 4.36%). IFV was the leading respiratory virus in outpatients aged 5-14 years (201/1673, 12.01%); RSV was the most prevalent respiratory virus in both inpatients (61/238, 25.63%) and outpatients (4/50, 8.00%) for ARI patients aged <6 months old. For PIV, HMPV, HCoV, and HRV, the risk of infection usually was higher among young children. Co-infection with more than two viruses was seen in 3.25% (137/4219). CONCLUSIONS: IFV and RSV played important roles in ARIs among children, but the risk populations were different. There are needs for targeted diagnosis and treatment and necessary immunization and non-pharmaceutical interventions.

Reducing Transmission of Airborne Respiratory Pathogens: A New Beginning as the COVID-19 Emergency Ends.

BACKGROUND: In response to the COVID-19 pandemic, new evidence-based strategies have emerged for reducing transmission of respiratory infections through management of indoor air. OBJECTIVES: This paper reviews critical advances that could reduce the burden of disease from inhaled pathogens and describes challenges in their implementation. DISCUSSION: Proven strategies include assuring sufficient ventilation, air cleaning by filtration, and air disinfection by germicidal ultraviolet (UV) light. Layered intervention strategies are needed to maximize risk reduction. Case studies demonstrate how to implement these tools while also revealing barriers to implementation. Future needs include standards designed with infection resilience and equity in mind, buildings optimized for infection resilience among other drivers, new approaches and technologies to improve ventilation, scientific consensus on the amount of ventilation needed to achieve a desired level of risk, methods for evaluating new air-cleaning technologies, studies of their long-term health effects, workforce training on ventilation systems, easier access to federal funds, demonstration projects in schools, and communication with the public about the importance of indoor air quality and actions people can take to improve it. https://doi.org/10.1289/EHP13878.

Applications of Quantitative Microbial Risk Assessment to Respiratory Pathogens and Implications for Uptake in Policy: A State-of-the-Science Review.

BACKGROUND: Respiratory tract infections are major contributors to the global disease burden. Quantitative microbial risk assessment (QMRA) holds potential as a rapidly deployable framework to understand respiratory pathogen transmission and inform policy on infection control. OBJECTIVES: The goal of this paper was to evaluate, motivate, and inform further development of the use of QMRA as a rapid tool to understand the transmission of respiratory pathogens and improve the evidence base for infection control policies. METHODS: We conducted a literature review to identify peer-reviewed studies of complete QMRA frameworks on aerosol inhalation or contact transmission of respiratory pathogens. From each of the identified studies, we extracted and summarized information on the applied exposure model approaches, dose-response models, and parameter values, including risk characterization. Finally, we reviewed linkages between model outcomes and policy. RESULTS: We identified 93 studies conducted in 16 different countries with complete QMRA frameworks for diverse respiratory pathogens, including SARS-CoV-2, Legionella spp., Staphylococcus aureus, influenza, and Bacillus anthracis. Six distinct exposure models were identified across diverse and complex transmission pathways. In 57 studies, exposure model frameworks were informed by their ability to model the efficacy of potential interventions. Among interventions, masking, ventilation, social distancing, and other environmental source controls were commonly assessed. Pathogen concentration, aerosol concentration, and partitioning coefficient were influential exposure parameters as identified by sensitivity analysis. Most (84%, n=78) studies presented policy-relevant content including a) determining disease burden to call for policy intervention, b) determining risk-based threshold values for regulations, c) informing intervention and control strategies, and d) making recommendations and suggestions for QMRA application in policy. CONCLUSIONS: We identified needs to further the development of QMRA frameworks for respiratory pathogens that prioritize appropriate aerosol exposure modeling approaches, consider trade-offs between model validity and complexity, and incorporate research that strengthens confidence in QMRA results. https://doi.org/10.1289/EHP12695.

Monitoring of antimicrobial resistance in respiratory tract pathogens during the COVID-19 pandemic: A retrospective study.

To understand the distribution and antimicrobial resistance (AMR) of pathogens in respiratory samples in Changle District People's Hospital in Fujian Province in recent years, and provide empirical guidance for infection control and clinical treatment in the region. A retrospective analysis was conducted on 5137 isolates of pathogens from respiratory samples collected from 2019 to 2022. The AMR patterns were systematically analyzed. For research purposes, the data was accessed on October 12, 2023. A total of 3517 isolates were included in the study, including 811 (23.06%) gram-positive bacteria and 2706 (76.94%) gram-negative bacteria. The top 3 gram-positive bacteria were Staphylococcus aureus with 455 isolates (12.94%), Streptococcus pneumoniae with 99 isolates (2.81%), and Staphylococcus hemolytic with 99 isolates (2.81%). The top 3 gram-negative bacteria were Klebsiella pneumoniae with 815 isolates (23.17%), Pseudomonas aeruginosa with 589 isolates (16.75%), and Acinetobacter baumannii with 328 isolates (9.33%). The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and K pneumoniae fluctuated between 41.9% and 70.5%, and 18.6% and 20.9%, respectively. The resistance rates of E coli, K pneumoniae, P aeruginosa, and A baumannii to carbapenems were 2.36%, 8.9%, 18.5%, and 19.6%, respectively. The prevalence of methicillin-resistant S aureus (MRSA) was 48.55%, but it decreased to 38.4% by 2022. The resistance rate of Staphylococcus haemolyticus to methicillin was 100%, and 1 case of vancomycin-resistant strain was detected. K pneumoniae, P aeruginosa, A baumannii, and S aureus are the main pathogens in respiratory samples. Although the resistance rates of some multidrug-resistant strains have decreased, ESBL-producing Enterobacteriaceae, carbapenem-resistant bacteria have still increased. Therefore, it is necessary to strengthen the monitoring of pathogen resistance, promote rational use of antibiotics, and promptly report findings.

Hungarian general practice paediatricians' antibiotic prescribing behaviour for suspected respiratory tract infections: a qualitative study.

OBJECTIVES: Inappropriate antibiotic prescribing is a major cause of antimicrobial resistance (AMR). The aim of this study was to explore paediatric general practitioners' (GP Peds) antibiotic prescription practice in suspected respiratory tract infections (RTIs), using the capability-opportunity-motivation-behaviour framework. DESIGN: The design is a qualitative study based on individual, semistructured telephone or virtual interviews. SETTING: Paediatric general practice in Hungary. We applied stratified maximum variation sampling to cover the categories of age, sex and geographical location of participants. PARTICIPANTS: We interviewed 22 GP Peds. Nine were male and 13 were female: 2 of them were less than 40 years old, 14 were between 40 and 60 years, and 6 were above 60 years. 10 worked in low-antibiotic prescription areas, 5 in areas with medium levels of antibiotic prescription, 3 in high-antibiotic prescription areas, and 4 in and around the capital city. RESULTS: Study participants had varying antibiotic prescription preferences. Personal experience and physical examination play a central role in GP Peds' diagnostic and treatment practice. Participants emphasised the need to treat children in their entirety, taking their personal medical record, social background and sometimes parents' preferences into account, besides the acute clinical manifestation of RTI. Most respondents were confident they apply the most effective therapy even if, in some cases, this meant prescribing medicines with a higher chance of contributing to the development of AMR. Some participants felt antibiotic prescription frequency has decreased in recent years. CONCLUSIONS: Our findings suggest that a more prudent attitude toward antibiotic prescribing may have become more common but also highlight relevant gaps in both physicians' and public knowledge of antibiotics and AMR. To reinforce awareness and close remaining gaps, Hungary should adopt its national AMR National Action Plan and further increase its efforts towards active professional communication and feedback for primary care physicians.

Alert for pharynx-centered gastrointestinal and respiratory cross-infection and cryptic cross-transmission routes of 2019-nCoV.

We proposed that the pharynx, as a common organ of the respiratory and digestive tracts, may be a respiratory and digestive tract cross cryptic transmission pathway for 2019-nCoV infection from the nasal cavities to the pharynx and lung, then to nasal cavities by aerosol (respiratory route) to the pharynx and the gastrointestinal tract, then to the oral cavity by feces (fecal-oral route) and to pharynx, lungs, or gastrointestinal tract.

Common cold viruses circulating in children threaten wild chimpanzees through asymptomatic adult carriers.

Reverse zoonotic respiratory diseases threaten great apes across Sub-Saharan Africa. Studies of wild chimpanzees have identified the causative agents of most respiratory disease outbreaks as "common cold" paediatric human pathogens, but reverse zoonotic transmission pathways have remained unclear. Between May 2019 and August 2021, we conducted a prospective cohort study of 234 children aged 3-11 years in communities bordering Kibale National Park, Uganda, and 30 adults who were forest workers and regularly entered the park. We collected 2047 respiratory symptoms surveys to quantify clinical severity and simultaneously collected 1989 nasopharyngeal swabs approximately monthly for multiplex viral diagnostics. Throughout the course of the study, we also collected 445 faecal samples from 55 wild chimpanzees living nearby in Kibale in social groups that have experienced repeated, and sometimes lethal, epidemics of human-origin respiratory viral disease. We characterized respiratory pathogens in each cohort and examined statistical associations between PCR positivity for detected pathogens and potential risk factors. Children exhibited high incidence rates of respiratory infections, whereas incidence rates in adults were far lower. COVID-19 lockdown in 2020-2021 significantly decreased respiratory disease incidence in both people and chimpanzees. Human respiratory infections peaked in June and September, corresponding to when children returned to school. Rhinovirus, which caused a 2013 outbreak that killed 10% of chimpanzees in a Kibale community, was the most prevalent human pathogen throughout the study and the only pathogen present at each monthly sampling, even during COVID-19 lockdown. Rhinovirus was also most likely to be carried asymptomatically by adults. Although we did not detect human respiratory pathogens in the chimpanzees during the cohort study, we detected human metapneumovirus in two chimpanzees from a February 2023 outbreak that were genetically similar to viruses detected in study participants in 2019. Our data suggest that respiratory pathogens circulate in children and that adults become asymptomatically infected during high-transmission times of year. These asymptomatic adults may then unknowingly carry the pathogens into forest and infect chimpanzees. This conclusion, in turn, implies that intervention strategies based on respiratory symptoms in adults are unlikely to be effective for reducing reverse zoonotic transmission of respiratory viruses to chimpanzees.

Respiratory pathogen and clinical features of hospitalized patients in acute exacerbation of chronic obstructive pulmonary disease after COVID 19 pandemic.

Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and clinical features changed from before to after the coronavirus disease 2019 (COVID-19) outbreak. We reviewed the medical records of patients hospitalized with AECOPD at four university hospitals between January 2017 and December 2018 and between January 2021 and December. We evaluated 1180 patients with AECOPD for whom medication histories were available. After the outbreak, the number of patients hospitalized with AECOPD was almost 44% lower compared with before the outbreak. Patients hospitalized with AECOPD after the outbreak were younger (75 vs. 77 years, p = 0.003) and more often stayed at home (96.6% vs. 88.6%, p < 0.001) than patients of AECOPD before the outbreak. Hospital stay was longer after the outbreak than before the outbreak (10 vs. 8 days. p < 0.001). After the COVID-19 outbreak, the identification rates of S. pneumoniae (15.3 vs. 6.2%, p < 0.001) and Hemophilus influenzae (6.4 vs. 2.4%, p = 0.002) decreased, whereas the identification rates of P. aeruginosa (9.4 vs. 13.7%, p = 0.023), Klebsiella pneumoniae (5.3 vs. 9.8%, p = 0.004), and methicillin-resistant Staphylococcus aureus (1.0 vs. 2.8%, p = 0.023) increased. After the outbreak, the identification rate of influenza A decreased (10.4 vs. 1.0%, p = 0.023). After the outbreak, the number of patients hospitalized with AECOPD was lower and the identification rates of community-transmitted pathogens tended to decrease, whereas the rates of pathogens capable of chronic colonization tended to increase. During the period of large-scale viral outbreaks that require quarantine, patients with AECOPD might be given more consideration for treatment against strains that can colonize chronic respiratory disease rather than community acquired pathogens.

The effect of focused lung ultrasonography on antibiotic prescribing in patients with acute lower respiratory tract infections in Danish general practice: study protocol for a pragmatic randomized controlled trial (PLUS-FLUS).

BACKGROUND: The use of antibiotics is a key driver of antimicrobial resistance and is considered a major threat to global health. In Denmark, approximately 75% of antibiotic prescriptions are issued in general practice, with acute lower respiratory tract infections (LRTIs) being one of the most common indications. Adults who present to general practice with symptoms of acute LRTI often suffer from self-limiting viral infections. However, some patients have bacterial community-acquired pneumonia (CAP), a potential life-threatening infection, that requires immediate antibiotic treatment. Importantly, no single symptom or specific point-of-care test can be used to discriminate the various diagnoses, and diagnostic uncertainty often leads to (over)use of antibiotics. At present, general practitioners (GPs) lack tools to better identify those patients who will benefit from antibiotic treatment. The primary aim of the PLUS-FLUS trial is to determine whether adults who present with symptoms of an acute LRTI in general practice and who have FLUS performed in addition to usual care are treated less frequently with antibiotics than those who only receive usual care. METHODS: Adults (≥ 18 years) presenting to general practice with acute cough (< 21 days) and at least one other symptom of acute LRTI, where the GP suspects a bacterial CAP, will be invited to participate in this pragmatic randomized controlled trial. All participants will receive usual care. Subsequently, participants will be randomized to either the control group (usual care) or to an additional focused lung ultrasonography performed by the GP (+ FLUS). The primary outcome is the proportion of participants with antibiotics prescribed at the index consultation (day 0). Secondary outcomes include comparisons of the clinical course for participants in groups. DISCUSSION: We will examine whether adults who present with symptoms of acute LRTI in general practice, who have FLUS performed in addition to usual care, have antibiotics prescribed less frequently than those given usual care alone. It is highly important that a possible reduction in antibiotic prescriptions does not compromise patients' recovery or clinical course, which we will assess closely. TRIAL REGISTRATION: ClinicalTrials.gov NCT06210282. Registered on January 17, 2024.

Prevalence of Parainfluenza Viruses in Seoul, 2021 - 2022.

BACKGROUND: Parainfluenza virus (PIV) is a significant etiological agent of acute lower respiratory tract infections (ALRIs) in infants and young children. The present study has been conducted to investigate the prevalence of recently identified respiratory viruses. METHODS: In total, 543 oropharyngeal or nasopharyngeal swab samples collected from hospitalized patients with acute respiratory symptoms (ARS) between January and December 2021 (5,653 females and 4,950 males) were tested for respiratory viruses using RT-PCR. RESULTS: At least one respiratory virus was detected by RT-PCR in 119 out of 175 samples (68%). The most frequently detected virus was human rhinovirus (HRV) (34, 6.5%), followed by human parainfluenza viruses (HPIVs) (19, 3.6%), human bocavirus (HBoV) (8, 1.5%), human adenovirus (HAdV) (7, 1.3%), and human respiratory syncytial virus (HRSV) (4, 0.8%). HPIV-3 accounted for 3.6% (19/175) of all viral pathogens and was the second most frequently detected viral pathogen in our study. HPIV-3 infections peaked in the fall (November) of 2021. Phylogenetic analysis of the coding region of the viral protein HA revealed that all 35 (100%) of 35 HPIV-infected patients were infected with HPIV-3. CONCLUSIONS: HPIV was an important causative pathogen associated with ALRI in children hospitalized in Korea in the late fall of 2021, as the social distancing rules for COVID-19 were relaxed. These findings highlight the im-portance of HPIV as a cause of ALRI.

Adult vaccination against respiratory infections in Egypt: a review of expert opinions.

INTRODUCTION: Lower respiratory tract infection is one of the leading causes of morbidity and mortality all over the world, with a substantial impact on healthcare costs. In Egypt, local consensus on its burden, diagnosis, and vaccination is scarce. This expert opinion is the first to address the local recommendations for vaccinating adults against respiratory infection. It sheds light on the growing need to understand the barriers and underpublicized concept of adult vaccination in Egypt. AREAS COVERED: A collaborative multidisciplinary panel from Egypt developed an expert opinion-based suggestions/points, including epidemiology, microbiology, and highlights on vaccination in Egypt, as well as challenges and recommendations regarding adult vaccination. EXPERT OPINION: Adult vaccinations against respiratory infections are now recommended for high-risk people by all healthcare regulatory bodies. However, it was acknowledged that there may be hesitancy and concerns among patients; in addition, healthcare professionals' awareness about vaccination guidelines and benefits needs improvement. There are several strategies that could be implemented to enhance vaccine adherence in Egypt. These approaches encompass conducting community education programs, addressing the concerns of patients, and enhancing awareness among healthcare professionals through education, policy changes, and periodical reminders in each healthcare setting.

Zinc for prevention and treatment of the common cold.

BACKGROUND: The common cold is an acute, self-limiting viral respiratory illness. Symptoms include nasal congestion and mucus discharge, sneezing, sore throat, cough, and general malaise. Given the frequency of colds, they are a public health burden and a significant cause of lost work productivity and school absenteeism. There are no established interventions to prevent colds or shorten their duration. However, zinc supplements are commonly recommended and taken for this purpose. OBJECTIVES: To assess the effectiveness and safety of zinc for the prevention and treatment of the common cold. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and LILACS to 22 May 2023, and searched Web of Science Core Collection and two trials registries to 14 June 2023. We also used reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children or adults that tested any form of zinc against placebo to prevent or treat the common cold or upper respiratory infection (URTI). We excluded zinc interventions in which zinc was combined with other minerals, vitamins, or herbs (e.g. a multivitamin, or mineral supplement containing zinc). DATA COLLECTION AND ANALYSIS: We used the Cochrane risk of bias tool to assess risks of bias, and GRADE to assess the certainty of the evidence. We independently extracted data. When necessary, we contacted study authors for additional information. We assessed zinc (type and route) with placebo in the prevention and treatment of the common cold. Primary outcomes included the proportion of participants developing colds (for analyses of prevention trials only), duration of cold (measured in days from start to resolution of the cold), adverse events potentially due to zinc supplements (e.g. unpleasant taste, loss of smell, vomiting, stomach cramps, and diarrhoea), and adverse events considered to be potential complications of the common cold (e.g. respiratory bacterial infections). MAIN RESULTS: We included 34 studies (15 prevention, 19 treatment) involving 8526 participants. Twenty-two studies were conducted on adults and 12 studies were conducted on children. Most trials were conducted in the USA (n = 18), followed by India, Indonesia, Iran, and Turkey (two studies each), and Australia, Burkina Faso, Colombia, Denmark, Finland, Tanzania, Thailand, and the UK (one study each). The 15 prevention studies identified the condition as either common cold (n = 8) or URTI (n = 7). However, almost all therapeutic studies (17/19) focused on the common cold. Most studies (17/34) evaluated the effectiveness of zinc administered as lozenges (3 prevention; 14 treatment) in acetate, gluconate, and orotate forms; gluconate lozenges were the most common (9/17). Zinc gluconate was given at doses between 45 and 276 mg/day for between 4.5 and 21 days. Five (5/17) lozenge studies gave acetate lozenges and two (2/17) gave both acetate and gluconate lozenges. One (1/17) lozenge study administered intranasal (gluconate) and lozenge (orotate) zinc in tandem for cold treatment. Of the 17/34 studies that did not use lozenges, 1/17 gave capsules, 3/17 administered dissolved powders, 5/17 gave tablets, 4/17 used syrups, and 4/17 used intranasal administration. Most studies were at unclear or high risk of bias in at least one domain. There may be little or no reduction in the risk of developing a cold with zinc compared to placebo (risk ratio (RR) 0.93, 95% CI 0.85 to 1.01; I2 = 20%; 9 studies, 1449 participants; low-certainty evidence). There may be little or no reduction in the mean number of colds that occur over five to 18 months of follow-up (mean difference (MD) -0.90, 95% CI -1.93 to 0.12; I2 = 96%; 2 studies, 1284 participants; low-certainty evidence). When colds occur, there is probably little or no difference in the duration of colds in days (MD -0.63, 95% CI -1.29 to 0.04; I² = 77%; 3 studies, 740 participants; moderate-certainty evidence), and there may be little or no difference in global symptom severity (standardised mean difference (SMD) 0.04, 95% CI -0.35 to 0.43; I² = 0%; 2 studies, 101 participants; low-certainty evidence). When zinc is used for cold treatment, there may be a reduction in the mean duration of the cold in days (MD -2.37, 95% CI -4.21 to -0.53; I² = 97%; 8 studies, 972 participants; low-certainty evidence), although it is uncertain whether there is a reduction in the risk of having an ongoing cold at the end of follow-up (RR 0.52, 95% CI 0.21 to 1.27; I² = 65%; 5 studies, 357 participants; very low-certainty evidence), or global symptom severity (SMD -0.03, 95% CI -0.56 to 0.50; I² = 78%; 2 studies, 261 participants; very low-certainty evidence), and there may be little or no difference in the risk of a change in global symptom severity (RR 1.02, 95% CI 0.85 to 1.23; 1 study, 114 participants; low-certainty evidence). Thirty-one studies reported non-serious adverse events (2422 participants). It is uncertain whether there is a difference in the risk of adverse events with zinc used for cold prevention (RR 1.11, 95% CI 0.84 to 1.47; I2 = 0%; 7 studies, 1517 participants; very low-certainty evidence) or an increase in the risk of serious adverse events (RR 1.67, 95% CI 0.78 to 3.57; I2 = 0%; 3 studies, 1563 participants; low-certainty evidence). There is probably an increase in the risk of non-serious adverse events when zinc is used for cold treatment (RR 1.34, 95% CI 1.15 to 1.55; I2 = 44%; 2084 participants, 16 studies; moderate-certainty evidence); no treatment study provided information on serious adverse events. No study provided clear information about adverse events considered to be potential complications of the common cold. AUTHORS' CONCLUSIONS: The findings suggest that zinc supplementation may have little or no effect on the prevention of colds but may reduce the duration of ongoing colds, with an increase in non-serious adverse events. Overall, there was wide variation in interventions (including concomitant therapy) and outcomes across the studies, as well as incomplete reporting of several domains, which should be considered when making conclusions about the efficacy of zinc for the common cold.

Oral vitamin A supplements to prevent acute upper respiratory tract infections in children up to seven years of age.

BACKGROUND: According to global prevalence analysis studies, acute upper respiratory tract infections (URTIs) are the most common acute infectious disease in children, especially in preschool children. Acute URTIs lead to an economic burden on families and society. Vitamin A refers to the fat-soluble compound all-trans-retinol and also represents retinol and its active metabolites. Vitamin A interacts with both the innate immune system and the adaptive immune system and improves the host's defences against infections. Correlation studies show that serum retinol deficiency was associated with a higher risk of respiratory tract infections. Therefore, vitamin A supplementation may be important in preventing acute URTIs. OBJECTIVES: To assess the effectiveness and safety of vitamin A supplements for preventing acute upper respiratory tract infections in children up to seven years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Chinese Biomedical Literature Database, and two trial registration platforms to 8 June 2023. We also checked the reference lists of all primary studies and reviewed relevant systematic reviews and trials for additional references. We imposed no language or publication restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs), which evaluated the role of vitamin A supplementation in the prevention of acute URTIs in children up to seven years of age. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six studies (27,351 participants). Four studies were RCTs and two were cluster-RCTs. The included studies were all conducted in lower-middle-income countries (two in India, two in South Africa, one in Ecuador, and one in Haiti). Three studies included healthy children who had no vitamin A deficiency, one study included children born to HIV-infected women, one study included low-birthweight neonates, and one study included children in areas with a high local prevalence of malnutrition and xerophthalmia. In two studies, vitamin E was a co-treatment administered in addition to vitamin A. We judged the included studies to be at either a high or unclear risk of bias for random sequence generation, incomplete outcome data, and blinding. Primary outcomes Six studies reported the incidence of acute URTIs during the study period. Five studies reported the number of acute URTIs over a period of time, but there was population heterogeneity and the results were presented in different forms, therefore only three studies were meta-analysed. We are uncertain of the effect of vitamin A supplementation on the number of acute URTIs over two weeks (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.92 to 1.09; I2 = 44%; 3 studies, 22,668 participants; low-certainty evidence). Two studies reported the proportion of participants with an acute URTI. We are uncertain of the effect of vitamin A supplementation on the proportion of participants with an acute URTI (2 studies, 15,535 participants; low-certainty evidence). Only one study (116 participants) reported adverse events. No infant in either the placebo or vitamin A group was found to have feeding difficulties (failure to feed or vomiting), a bulging fontanelle, or neurological signs before or after vitamin A administration (very low-certainty evidence). Secondary outcomes Two studies (296 participants) reported the severity of subjective symptoms, presented by the mean duration of acute URTI. Vitamin A may have little to no effect on the mean duration of acute URTI (very low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for the use of vitamin A supplementation to prevent acute URTI is uncertain, because population, dose and duration of interventions, and outcomes vary between studies. From generally very low- to low-certainty evidence, we found that there may be no benefit in the use of vitamin A supplementation to prevent acute URTI in children up to seven years of age. More RCTs are needed to strengthen the current evidence. Future research should report over longer time frames using validated tools and consistent reporting, and ensure adequate power calculations, to allow for easier synthesis of data. Finally, it is important to assess vitamin A supplementation for preschool children with vitamin A deficiency.

Assessment of effectiveness and impact of universal prophylaxis with nirsevimab for prevention of hospitalizations due to respiratory syncytial virus in infants. The NIRSE-GAL study protocol.

Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children's wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6-24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023-377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.

Effectiveness of cocoon strategy vaccination on prevention of influenza-like illness in young infants.

During the initial half-year of their existence, infants cannot receive the influenza vaccine, yet they face the greatest susceptibility to severe influenza complications. In this study, we seek to determine whether influenza vaccination of maternal and household contacts is associated with a reduced risk of influenza-like illness (ILI) and severe acute respiratory infection (SARI) in infants. This work was prospectively conducted during the influenza season. A total of 206 infants were included in this study. The percentage of infants with only the mother vaccinated is 12.6% (n:26), and the percent of infants with all household contacts vaccinated is 16% (n:33). Among the infants with only the mother vaccinated, the effectiveness of influenza vaccine is estimated as 35.3% for ILI and 41.3% for SARI. Among infants with all household contacts vaccinated, the effectiveness is estimated as 48.9% for ILI and 76.9% for SARI. Based on the results of multivariate logistic regression analysis, all-household vaccination is a protective factor against SARI (OR: 0.07 95% CI [0.01-0.56]), household size (OR: 1.75, 95% CI [1.24-2.48]) and presence of secondhand smoke (OR: 2.2, 95% CI [1.12-4.45]) significant risk factors for SARI in infants. The mother alone being vaccinated is not a statistically significant protective factor against ILI (OR: 0.46, 95% CI [0.19-1.18]) or SARI (OR: 0.3, 95% CI [0.11-1.21]). Along with the obtained results and analysis, this study provides clear evidence that influenza vaccination of all household contacts of infants aged 0-6 months is significantly associated with protecting infants from both ILI and SARI.

Assessing the change in the epidemiology of seasonal respiratory viruses with the onset of the COVID-19 pandemic.

Background. Respiratory tract infections are among the most important causes of mortality and morbidity in children worldwide. The COVID-19 pandemic has affected the distribution of seasonal respiratory viruses as in all areas of life. In this study, we have aimed to evaluate the changes in the rates of seasonal respiratory viruses with the onset of the pandemic.Methods. This study included patients who were admitted to the Pediatrics Clinic of Eskisehir Osmangazi University Faculty of Medicine Hospital between December 2018 and February 2022 with respiratory tract infections and in whom pathogens were detected from nasopharyngeal swab samples analysed by multiplex PCR method.Results. A total of 833 respiratory tract pathogens were detected in 684 cases consisting of male (55.3 %), and female (44.7 %), patients with a total mean age of 42 months. Single pathogen was revealed in 550, and multiple pathogens in 134 cases. Intensive care was needed in 14 % of the cases. Most frequently influenza A/B, rhinovirus and respiratory syncytial virus (RSV) were detected during the pre-pandemic period, while rhinovirus, RSV, and adenovirus were observed during the lockdown period. In the post-lockdown period, the incidence rates of rhinovirus, RSV, human bocavirus (HboV) (12 %), influenza virus infections increased, and patients with RSV and bocavirus infections required intensive care hospitalization.Conclusion. It is thought that the COVID-9 pandemic lockdown measures may have an impact on the distribution of seasonal respiratory viruses, especially RSV and influenza. Current, prospective and large case series regarding the mechanism of action and dynamics are needed.

Managing children with frequent respiratory infections and associated wheezing: a preliminary randomized study with a new multicomponent nasal spray.

BACKGROUND: Preschoolers frequently have respiratory infections (RIs), which may cause wheezing in some subjects. Type 2 polarization may favor increased susceptibility to RIs and associated wheezing. Non-pharmacological remedies are garnering increasing interest as possible add-on therapies. The present preliminary study investigated the efficacy and safety of a new multi-component nasal spray in preschoolers with frequent RIs and associated wheezing. METHODS: Some preschoolers with these characteristics randomly took this product, containing lactoferrin, dipotassium glycyrrhizinate, carboxymethyl-beta-glucan, and vitamins C and D3 (Saflovir), two sprays per nostril twice daily for 3 months. Other children were randomly treated only with standard therapy. Outcomes included the number of RIs and wheezing episodes, use of medications, and severity of clinical manifestations. RESULTS: Preschoolers treated add-on with this multicomponent product experienced fewer RIs and used fewer beta-2 agonists than untreated children (P = 0.01 and 0.029, respectively). CONCLUSIONS: This preliminary study demonstrated that a multicomponent product, administered add-on as a nasal spray, could reduce the incidence of RIs and use of symptomatic drugs for relieving wheezing in children.

Bronchoscopy-guided antimicrobial therapy for cystic fibrosis.

BACKGROUND: Early diagnosis and treatment of lower respiratory tract infections is the mainstay of management of lung disease in cystic fibrosis (CF). When sputum samples are unavailable, diagnosis relies mainly on cultures from oropharyngeal specimens; however, there are concerns about whether this approach is sensitive enough to identify lower respiratory organisms. Bronchoscopy and related procedures such as bronchoalveolar lavage (BAL) are invasive but allow the collection of lower respiratory specimens from non-sputum producers. Cultures of bronchoscopic specimens provide a higher yield of organisms compared to those from oropharyngeal specimens. Regular use of bronchoscopy and related procedures may increase the accuracy of diagnosis of lower respiratory tract infections and improve the selection of antimicrobials, which may lead to clinical benefits. This is an update of a previous review that was first published in 2013 and was updated in 2016 and in 2018. OBJECTIVES: To evaluate the use of bronchoscopy-guided (also known as bronchoscopy-directed) antimicrobial therapy in the management of lung infection in adults and children with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched three registries of ongoing studies and the reference lists of relevant articles and reviews. The date of the most recent searches was 1 November 2023. SELECTION CRITERIA: We included randomised controlled studies involving people of any age with CF that compared the outcomes of antimicrobial therapies guided by the results of bronchoscopy (and related procedures) versus those guided by any other type of sampling (e.g. cultures from sputum, throat swab and cough swab). DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed their risk of bias and extracted data. We contacted study investigators for further information when required. We assessed the certainty of the evidence using the GRADE criteria. MAIN RESULTS: We included two studies in this updated review. One study enrolled 170 infants under six months of age who had been diagnosed with CF through newborn screening. Participants were followed until they were five years old, and data were available for 157 children. The study compared outcomes for pulmonary exacerbations following treatment directed by BAL versus standard treatment based on clinical features and oropharyngeal cultures. The second study enrolled 30 children with CF aged between five and 18 years and randomised participants to receive treatment based on microbiological results of BAL triggered by an increase in lung clearance index (LCI) of at least one unit above baseline or to receive standard treatment based on microbiological results of oropharyngeal samples collected when participants were symptomatic. We judged both studies to have a low risk of bias across most domains, although the risk of bias for allocation concealment and selective reporting was unclear in the smaller study. In the larger study, the statistical power to detect a significant difference in the prevalence of Pseudomonas aeruginosa was low because Pseudomonas aeruginosa isolation in BAL samples at five years of age in both groups were much lower than the expected rate that was used for the power calculation. We graded the certainty of evidence for the key outcomes as low, other than for high-resolution computed tomography scoring and cost-of-care analysis, which we graded as moderate certainty. Both studies reported similar outcomes, but meta-analysis was not possible due to different ways of measuring the outcomes and different indications for the use of BAL. Whether antimicrobial therapy is directed by the use of BAL or standard care may make little or no difference in lung function z scores after two years (n = 29) as measured by the change from baseline in LCI and forced expiratory volume in one second (FEV1) (low-certainty evidence). At five years, the larger study found little or no difference between groups in absolute FEV1 z score or forced vital capacity (FVC) (low-certainty evidence). BAL-directed therapy probably makes little or no difference to any measure of chest scores assessed by computed tomography (CT) scan at either two or five years (different measures used in the two studies; moderate-certainty evidence). BAL-directed therapy may make little or no difference in nutritional parameters or in the number of positive isolates of P aeruginosa per participant per year, but may lead to more hospitalisations per year (1 study, 157 participants; low-certainty evidence). There is probably no difference in average cost of care per participant (either for hospitalisations or total costs) at five years between BAL-directed therapy and standard care (1 study, 157 participants; moderate-certainty evidence). We found no difference in health-related quality of life between BAL-directed therapy and standard care at either two or five years, and the larger study found no difference in the number of isolates of Pseudomonas aeruginosa per child per year. The eradication rate following one or two courses of eradication treatment and the number of pulmonary exacerbations were comparable in the two groups. Mild adverse events, when reported, were generally well tolerated. The most common adverse event reported was transient worsening of cough after 29% of procedures. Significant clinical deterioration was documented during or within 24 hours of BAL in 4.8% of procedures. AUTHORS' CONCLUSIONS: This review, limited to two well-designed randomised controlled studies, shows no evidence to support the routine use of BAL for the diagnosis and management of pulmonary infection in preschool children with CF compared to the standard practice of providing treatment based on results of oropharyngeal culture and clinical symptoms. No evidence is available for adults.