Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

Systematic review on efficacy and safety of empirical versus pre-emptive antifungal therapy among children with febrile neutropenia reveals paucity of data.

BACKGROUND: Two approaches are used to manage invasive fungal disease (IFD) in febrile neutropenic patients viz. empirical therapy (without attempting to confirm the diagnosis), or pre-emptive therapy (after screening tests for IFD). OBJECTIVE: This systematic review was undertaken to compare these approaches in children. METHODS: We searched PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, Clinical Trial Registries and grey literature, for randomized controlled trials (RCT) comparing empirical versus pre-emptive antifungal therapy in children with FN suspected to have IFD. We used the Cochrane Risk of bias 2 tool for quality assessment, and evaluated the certainty of evidence using the GRADE approach. RESULTS: We identified 7989 citations. Stepwise screening identified only one relevant RCT that administered empirical (n = 73) or pre-emptive (n = 76) antifungal therapy. There were no significant differences in all-cause mortality (RR 1.56, 95% CI: 0.46, 5.31), IFD mortality (RR 1.04, 95% CI:0.15, 7.20) and other clinically important outcomes such as duration of fever, duration of hospitalization and proportion requiring ICU admission. There were no safety data reported. The number of days of antifungal therapy was significantly lower in the pre-emptive therapy arm. The certainty of evidence for all outcomes was 'moderate'. CONCLUSIONS: This systematic review highlighted the paucity of data, comparing empirical versus pre-emptive antifungal therapy in children with febrile neutropenia having suspected invasive fungal disease. Data from a single included trial suggests that both approaches may be comparable in research settings. Robust trials are warranted to address the gap in existing knowledge about the optimal approach in clinical practice.

A Reporting Tool for Adapted Guidelines in Health Care: The RIGHT-Ad@pt Checklist.

BACKGROUND: Adaptation of existing guidelines can be an efficient way to develop contextualized recommendations. Transparent reporting of the adaptation approach can support the transparency and usability of the adapted guidelines. OBJECTIVE: To develop an extension of the RIGHT (Reporting Items for practice Guidelines in HealThcare) statement for the reporting of adapted guidelines (including recommendations that have been adopted, adapted, or developed de novo), the RIGHT-Ad@pt checklist. DESIGN: A multistep process was followed to develop the checklist: establishing a working group, generating an initial checklist, optimizing the checklist (through an initial assessment of adapted guidelines, semistructured interviews, a Delphi consensus survey, an external review, and a final assessment of adapted guidelines), and approval of the final checklist by the working group. SETTING: International collaboration. PARTICIPANTS: A total of 119 professionals participated in the development process. MEASUREMENTS: Participants' consensus on items in the checklist. RESULTS: The RIGHT-Ad@pt checklist contains 34 items grouped in 7 sections: basic information (7 items); scope (6 items); rigor of development (10 items); recommendations (4 items); external review and quality assurance (2 items); funding, declaration, and management of interest (2 items); and other information (3 items). A user guide with explanations and real-world examples for each item was developed to provide a better user experience. LIMITATION: The RIGHT-Ad@pt checklist requires further validation in real-life use. CONCLUSION: The RIGHT-Ad@pt checklist has been developed to improve the reporting of adapted guidelines, focusing on the standardization, rigor, and transparency of the process and the clarity and explicitness of adapted recommendations. PRIMARY FUNDING SOURCE: None.

Methodology and experiences of rapid advice guideline development for children with COVID-19: responding to the COVID-19 outbreak quickly and efficiently.

BACKGROUND: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. RESULT: The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints. CONCLUSIONS: In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.

Guidelines for the prevention and management of children and adolescents with COVID-19.

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. CONCLUSION: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged. WHAT IS KNOWN: • Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence. WHAT IS NEW: • The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.

Continuous positive airway pressure (CPAP) for acute bronchiolitis in children.

BACKGROUND: Acute bronchiolitis is one of the most frequent causes of emergency department visits and hospitalisation in children up to three years of age. There is no specific treatment for bronchiolitis except for supportive treatment, which includes ensuring adequate hydration and oxygen supplementation. Continuous positive airway pressure (CPAP) aims to widen the lungs' peripheral airways, enabling deflation of overdistended lungs in bronchiolitis. Increased airway pressure also prevents the collapse of poorly supported peripheral small airways during expiration. Observational studies report that CPAP is beneficial for children with acute bronchiolitis. This is an update of a review first published in 2015 and updated in 2019. OBJECTIVES: To assess the efficacy and safety of CPAP compared to no CPAP or sham CPAP in infants and children up to three years of age with acute bronchiolitis. SEARCH METHODS: We conducted searches of CENTRAL (2021, Issue 7), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE (1946 to August 2021), Embase (1974 to August 2021), CINAHL (1981 to August 2021), and LILACS (1982 to August 2021) in August 2021. We also searched the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for completed and ongoing trials on 26 October 2021. SELECTION CRITERIA: We considered randomised controlled trials (RCTs), quasi-RCTs, cross-over RCTs, and cluster-RCTs evaluating the effect of CPAP in children with acute bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data using a structured pro forma, analysed data, and performed meta-analyses. We used the Cochrane risk of bias tool to assess risk of bias in the included studies. We created a summary of the findings table employing GRADEpro GDT software.  MAIN RESULTS: We included three studies with a total of 122 children (62/60 in intervention/control arms) aged up to 12 months investigating nasal CPAP compared with supportive (or 'standard') therapy. We included one new trial (72 children) in the 2019 update that contributed data to the assessment of respiratory rate and the need for mechanical ventilation for this update. We did not identify any new trials for inclusion in the current update. The included studies were single-centre trials conducted in France, the UK, and India. Two studies were parallel-group RCTs, and one study was a cross-over RCT. The evidence provided by the included studies was of low certainty; we made an assessment of high risk of bias for blinding, incomplete outcome data, and selective reporting, and confidence intervals were wide. The effect of CPAP on the need for mechanical ventilation in children with acute bronchiolitis was uncertain due to risk of bias and imprecision around the effect estimate (risk difference -0.01, 95% confidence interval (CI) -0.09 to 0.08; 3 RCTs, 122 children; low certainty evidence). None of the trials measured time to recovery. Limited, low certainty evidence indicated that CPAP decreased respiratory rate (decreased respiratory rate is better) (mean difference (MD) -3.81, 95% CI -5.78 to -1.84; 2 RCTs, 91 children; low certainty evidence). Only one trial measured change in arterial oxygen saturation (increased oxygen saturation is better), and the results were imprecise (MD -1.70%, 95% CI -3.76 to 0.36; 1 RCT, 19 children; low certainty evidence). The effect of CPAP on change in arterial partial carbon dioxide pressure (pCO2) (decrease in pCO2 is better) was imprecise (MD -2.62 mmHg, 95% CI -5.29 to 0.05; 2 RCTs, 50 children; low certainty evidence). Duration of hospital stay was similar in both the CPAP and supportive care groups (MD 0.07 days, 95% CI -0.36 to 0.50; 2 RCTs, 50 children; low certainty evidence). Two studies did not report pneumothorax, but pneumothorax did not occur in one study. No studies reported occurrences of deaths. Several outcomes (change in partial oxygen pressure, hospital admission rate (from the emergency department to hospital), duration of emergency department stay, and need for intensive care unit admission) were not reported in the included studies. AUTHORS' CONCLUSIONS: The use of CPAP did not reduce the need for mechanical ventilation in children with bronchiolitis, although the evidence was of low certainty. Limited, low certainty evidence suggests that breathing improved (a decreased respiratory rate) in children with bronchiolitis who received CPAP; this finding is unchanged from the 2015 review and 2019 update. Due to the limited available evidence, the effect of CPAP in children with acute bronchiolitis is uncertain for our other outcomes. Larger, adequately powered trials are needed to evaluate the effect of CPAP for children with acute bronchiolitis.

Flexible Fibreoptic Bronchoscopy and Bronchoalveolar Lavage for Confirmation of Pulmonary Hydatid Disease in Children: A Case Series.

Hydatid disease of the lungs is common in endemic regions. It can be suspected clinically by non-specific respiratory symptoms in children living in endemic regions, especially when they are close to sheep or dogs. Chest imaging X-ray or computed tomography may show characteristic cysts in some cases, but typical findings are absent in many children. Hydatid serology may contribute to the diagnosis, but does not have sufficient sensitivity for pulmonary cysts. Thus, there is no confirmatory diagnostic test, other than surgical excision and histopathologic examination. Hence, there is a need for more reliable diagnostic tests. We present a series of children, both with and without suspected pulmonary hydatid, wherein flexible fibreoptic bronchoscopy (FFOB) performed under conscious sedation, revealed hydatid membranes in the airways. Bronchoalveolar lavage (BAL) analysis revealed hydatid in most of them. Thus the diagnosis could be confirmed even before surgical excision of cysts was performed. We propose that FFOB with BAL could be useful to confirm the diagnosis of pulmonary hydatid in children. This will be particularly helpful in children without characteristic radiological or serological findings. To the best of our knowledge, this is a completely novel approach to the condition with potential to alter the diagnostic paradigm Lay summary Hydatid disease of the lungs is commonly encountered in endemic regions. However, there is no confirmatory diagnostic test for pulmonary hydatid cyst, other than surgical excision and histopathologic examination. Imaging including chest X-ray and computed tomography may not be typical, especially in complicated cysts and hydatid serology does not have a satisfactory sensitivity for diagnosing lung cysts. Thus, there is a need for more reliable diagnostic tests. We present a series of children, both with and without suspected pulmonary hydatid, wherein flexible fibreoptic bronchoscopy (FFOB) under conscious sedation, revealed hydatid membranes in the airways. Bronchoalveolar lavage (BAL) analysis confirmed hydatid in most of them. We propose FFOB with BAL as a useful diagnostic modality to confirm pulmonary hydatid in children, prior to surgical excision. To the best of our knowledge, this is a completely novel approach to the condition with potential to alter the diagnostic paradigm.

Innovations to automate manual ventilation during Covid-19 pandemic and beyond.

Manual ventilation by compressing self-inflating bags is a life-saving option for respiratory support in many resource-limited settings. Previous efforts to automate manual ventilation using mechatronic systems were unsuccessful. The Covid-19 pandemic stimulated re-exploration of automating manual ventilation as an economically viable alternative to address the anticipated shortage of mechanical ventilators. Many devices have been developed and displayed in the lay press and social media platforms. However, most are unsuitable for clinical use for a variety of reasons. These include failure to understand the clinical needs, complex ventilatory requirements in Covid-19 patients, lack of technical specifications to guide innovators, technical challenges in delivering ventilation parameters in a physiological manner, absence of guidelines for bench testing of innovative devices and lack of clinical validation in patients. The insights gained during the design, development, laboratory testing and clinical validation of a novel device designated the 'Artificial Breathing Capability Device' are shared here to assist innovators in developing clinically usable devices. A detailed set of clinical requirements from such devices, technical specifications to meet these requirements and framework for bench testing are presented. In addition, regulatory and certification issues, as well as concerns related to the protection of intellectual property, are highlighted. These insights are designed to foster an innovation ecosystem whereby clinically useful automated manual ventilation devices can be developed and deployed to meet the needs associated with the Covid-19 pandemic and beyond.

Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia.

OBJECTIVES: To assess the effects of phosphodiesterase inhibitors (PDEI) compared to placebo and other standard of care drugs i.e alpha blockers (AB) and 5-alpha reductase inhibitors (5-ARI) in men with LUTS consistent with benign prostatic hyperplasia (BPH). METHODS: We conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science, and clinical trials registries of the World Health Organization (WHO) and the National Institutes of Health (NIH) (updated 2 August 2018). Citation tracking and hand-searching of abstracts and conference proceedings was done. We also attempted to contact the study authors in case additional information was needed. Randomised controlled trials (RCT) comparing PDEI versus placebo, AB, or 5-ARI used for at least four weeks in men with BPH-LUTS were included. Three review authors independently screened the literature and extracted data. Primary outcomes were effects on urinary symptoms as assessed by the International Prostate Symptom Score (IPSS-total; score ranging from 0 to 35, with higher values reflecting more symptoms), urinary bother as assessed by the Benign Prostatic Hyperplasia Impact Index (BPHII; score ranging from 0 to 13, with higher values reflecting more bother), and adverse events (AE). We used GRADE to rate the quality of evidence. We considered short-term (up to 12 weeks) and long-term (12 weeks or longer) results separately. RESULTS: We included a total of 16 randomised trials in this review. Primary outcomes: PDEI versus placebo: PDEI may result in a small improvement in IPSS-total score (mean difference (MD) 1.89 lower, 95% confidence interval (CI) 2.27 lower to 1.50 lower; n = 4293; low-quality evidence) compared to placebo, and may reduce the BPHII score slightly (MD 0.52 lower, 95% CI 0.71 lower to 0.33 lower; n = 3646; low-quality evidence). Rates of AEs may be increased (risk ratio (RR) 1.42, 95% CI 1.21 to 1.67; n = 4386; low-quality evidence). This corresponds to 95 more AEs per 1000 participants (95% CI 47 more to 151 more per 1000). Study results were limited to a treatment duration of six to 12 weeks. PDEI versus AB: PDEI and AB probably provide similar improvement in IPSS-total score (MD 0.22 higher, 95% CI 0.49 lower to 0.93 higher; n = 933; moderate-quality evidence) and may have a similar effect on BPHII score (MD 0.03 higher, 95% CI 1.10 lower to 1.16 higher; n = 550; low-quality evidence) and AE (RR 1.35, 95% CI 0.80 to 2.30; n = 936; low-quality evidence). This corresponds to 71 more AEs per 1000 participants (95% CI 41 fewer to 264 more per 1000). Study results were limited to a treatment duration of six to 12 weeks. PDEI and AB versus AB : The combination of PDEI and AB may provide a small improvement in IPSS-total score (MD 2.56 lower, 95% CI 3.92 lower to 1.19 lower; n = 193; low-quality evidence) compared to AB alone. We found no evidence for BPHII scores. AE may be increased (RR 2.81, 95% CI 1.53 to 5.17; n = 194; moderate-quality evidence). This corresponds to 235 more AE per 1000 participants (95% CI 69 more to 542 more per 1000). Study results were limited to treatment duration of four to 12 weeks. PDEI and AB versus PDEI alone: The combination of PDEI and AB may provide a small improvement in IPSS-total (MD 2.4 lower, 95% CI 6.47 lower to 1.67 higher; n = 40; low-quality evidence) compared to PDEI alone. We found no data on BPHII or AE. Study results were limited to a treatment duration of four weeks. PDEI and 5-ARI versus 5-ARI alone: in the short term (up to 12 weeks), the combination of PDEI and 5-ARI probably results in a small improvement in IPSS-total score (MD 1.40 lower, 95% CI 2.24 lower to 0.56 lower; n = 695; moderate-quality evidence) compared to 5-ARI alone. We found no evidence on BPHII scores or AE. In the long term (13 to 26 weeks), the combination of PDEI and 5-ARI likely results in a small reduction in IPSS-total score (MD 1.00 less, 95% CI 1.83 lower to 0.17 lower; n = 695; moderate-quality evidence). We found no evidence about effects on BPHII scores. There may be no difference in rates of AE (RR 1.07, 95% CI 0.84 to 1.36; n = 695; low-quality evidence). This corresponds to 19 more AE per 1000 participants (95% CI 43 fewer to 98 more per 1000). We found no trials comparing other combinations of treatments or comparing different PDEI for BPH-LUTS. CONCLUSIONS: Compared to placebo, PDEI likely leads to a small reduction in IPSS-total and BPHII sores, with a possible increase in AE. There may be no differences between PDEI and AB with regards to improvement in IPSS-total, BPHII, and incidence of AE. There appears to be no added benefit of PDEI combined with AB compared to PDEI or AB or PDEI combined with 5-ARI compared to ARI with regards to urinary symptoms. Most evidence was limited to short-term treatment up to 12 weeks and of moderate or low certainty.

Prospective Comparison of MRI and Contrast-Enhanced MDCT for Evaluation of Pediatric Pulmonary Hydatid Disease: Added Diagnostic Value of MRI.

OBJECTIVE. The objective of our study was to prospectively investigate the diagnostic accuracy and added value of fast MRI for evaluating pulmonary hydatid disease in children by comparing fast MRI findings with MDCT findings. SUBJECTS AND METHODS. Twenty-eight consecutive children (24 boys and four girls; mean age ± SD, 8.93 ± 3.1 years; range, 5-17 years) with clinically suspected pulmonary hydatid disease were enrolled in this prospective research study for the period from October 2012 to July 2018. Fast MRI without contrast material and contrast-enhanced MDCT of the chest were performed within 48 hours of each other in all children. Two pediatric radiologists independently evaluated the lungs for the presence of consolidation, nodule, and mass (solid vs cyst). Cysts were further evaluated for the presence of fluid, air, and an internal membrane. The accuracies of fast MRI and MDCT for detecting pulmonary hydatid disease were obtained and compared. Interobserver agreement was measured with the kappa coefficient. RESULTS. The accuracy of fast MRI and MDCT for detecting pulmonary hydatid cyst was 92.86%. There was no difference between fast MRI and MDCT for accurately detecting pulmonary hydatid cyst (p < 0.001). Internal membranes were detected in 11 of 28 patients (39.28%) with fast MRI and three of 28 patients (10.71%) with MDCT. Almost perfect interobserver agreement was present between the two independent reviewers (κ = 1). CONCLUSION. Fast MRI without contrast material is comparable to contrast-enhanced MDCT for accurately detecting lung cysts in pediatric patients with pulmonary hydatid disease. However, fast MRI provides added diagnostic value by showing internal membranes of cysts, which is specific to pulmonary hydatid disease.

Continuous positive airway pressure (CPAP) for acute bronchiolitis in children.

BACKGROUND: Acute bronchiolitis is one of the most frequent causes of emergency department visits and hospitalisation in children. There is no specific treatment for bronchiolitis except for supportive treatment, which includes ensuring adequate hydration and oxygen supplementation. Continuous positive airway pressure (CPAP) aims to widen the lungs' peripheral airways, enabling deflation of overdistended lungs in bronchiolitis. Increased airway pressure also prevents the collapse of poorly supported peripheral small airways during expiration. Observational studies report that CPAP is beneficial for children with acute bronchiolitis. This is an update of a review first published in 2015. OBJECTIVES: To assess the efficacy and safety of CPAP compared to no CPAP or sham CPAP in infants and children up to three years of age with acute bronchiolitis. SEARCH METHODS: We conducted searches of CENTRAL (2017, Issue 12), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1946 to December, 2017), Embase (1974 to December 2017), CINAHL (1981 to December 2017), and LILACS (1982 to December 2017) in January 2018. SELECTION CRITERIA: We considered randomised controlled trials (RCTs), quasi-RCTs, cross-over RCTs, and cluster-RCTs evaluating the effect of CPAP in children with acute bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data using a structured pro forma, analysed data, and performed meta-analyses. MAIN RESULTS: We included three studies with a total of 122 children (62/60 in intervention/control arms) aged up to 12 months that investigated nasal CPAP compared with supportive (or "standard") therapy. We included one new trial (72 children) that contributed data to the assessment of respiratory rate and need for mechanical ventilation for this update. The included studies were single-centre trials conducted in France, the UK, and India. Two studies were parallel-group RCTs and one was a cross-over RCT. The evidence provided by the included studies was low quality; we assessed high risk of bias for blinding, incomplete outcome data, and selective reporting, and confidence intervals were wide.The effect of CPAP on the need for mechanical ventilation in children with acute bronchiolitis was uncertain due to imprecision around the effect estimate (3 RCTs, 122 children; risk ratio (RR) 0.69, 95% confidence interval (CI) 0.14 to 3.36; low-quality evidence). None of the trials measured time to recovery. Limited, low-quality evidence indicated that CPAP decreased respiratory rate (2 RCTs, 91 children; mean difference (MD) -3.81, 95% CI -5.78 to -1.84). Only one trial measured change in arterial oxygen saturation, and the results were imprecise (19 children; MD -1.70%, 95% CI -3.76 to 0.36). The effect of CPAP on change in arterial partial carbon dioxide pressure (pCO2) was imprecise (2 RCTs, 50 children; MD -2.62 mmHg, 95% CI -5.29 to 0.05; low-quality evidence). Duration of hospital stay was similar in both CPAP and supportive care groups (2 RCTs, 50 children; MD 0.07 days, 95% CI -0.36 to 0.50; low-quality evidence). Two studies did not report about pneumothorax, but pneumothorax did not occur in one study. No studies reported occurrences of deaths. Several outcomes (change in partial oxygen pressure, hospital admission rate (from emergency department to hospital), duration of emergency department stay, and need for intensive care unit admission) were not reported in the included studies. AUTHORS' CONCLUSIONS: Limited, low-quality evidence suggests that breathing improved (a decreased respiratory rate) in children with bronchiolitis who received CPAP; this finding is unchanged from the 2015 review. Further evidence for this outcome was provided by the inclusion of a low-quality study for the 2018 update. Due to the limited available evidence, the effect of CPAP in children with acute bronchiolitis is uncertain for other outcomes. Larger, adequately powered trials are needed to evaluate the effect of CPAP for children with acute bronchiolitis.

Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) refers to non-malignant enlargement of the prostate gland that may cause bothersome lower urinary tract symptoms (LUTS). Alpha-blockers (ABs) and 5-alpha reductase inhibitors (5-ARIs) are the mainstay of medical treatment. Recently, phosphodiesterase inhibitors (PDEIs) that so far have been used mainly to treat erectile dysfunction were introduced to treat male LUTS. OBJECTIVES: To assess the effects of PDEIs compared to placebo and other standard of care drugs (ABs and 5-ARIs) in men with LUTS consistent with BPH. SEARCH METHODS: We conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Web of Science, and clinical trials registries of the World Health Organization (WHO) and the National Institutes of Health (NIH) (updated 2 August 2018). We performed citation tracking and handsearching of abstracts and conference proceedings. We also contacted study authors to ask for additional information. SELECTION CRITERIA: We considered for inclusion in this systematic review randomised controlled trials (RCTs) comparing PDEIs versus placebo, ABs, or 5-ARIs for at least four weeks in men with BPH-LUTS. DATA COLLECTION AND ANALYSIS: Three review authors independently screened the literature and extracted data. Primary outcomes were effects on urinary symptoms as assessed by the International Prostate Symptom Score (IPSS-total; score ranging from 0 to 35, with higher values reflecting more symptoms), urinary bother as assessed by the Benign Prostatic Hyperplasia Impact Index (BPHII; score ranging from 0 to 13, with higher values reflecting more bother), and adverse events (AEs). We used GRADE to rate the quality of evidence. We considered short-term (up to 12 weeks) and long-term (12 weeks or longer) results separately. MAIN RESULTS: We included a total of 16 randomised trials in this review. The results for primary outcomes are as follows.PDEI versus placebo: PDEIs may result in a small improvement in IPSS-total score (mean difference (MD) 1.89 lower, 95% confidence interval (CI) 2.27 lower to 1.50 lower; n = 4293; low-quality evidence) compared to placebo, and may reduce the BPHII score slightly (MD 0.52 lower, 95% CI 0.71 lower to 0.33 lower; n = 3646; low-quality evidence). Rates of AEs may be increased (risk ratio (RR) 1.42, 95% CI 1.21 to 1.67; n = 4386; low-quality evidence). This corresponds to 95 more AEs per 1000 participants (95% CI 47 more to 151 more per 1000). Study results were limited to a treatment duration of six to 12 weeks.PDEI versus AB: PDEIs and ABs probably provide similar improvement in IPSS-total score (MD 0.22 higher, 95% CI 0.49 lower to 0.93 higher; n = 933; moderate-quality evidence) and may have a similar effect on BPHII score (MD 0.03 higher, 95% CI 1.10 lower to 1.16 higher; n = 550; low-quality evidence) and AEs (RR 1.35, 95% CI 0.80 to 2.30; n = 936; low-quality evidence). This corresponds to 71 more AEs per 1000 participants (95% CI 41 fewer to 264 more per 1000). Study results were limited to a treatment duration of six to 12 weeks.PDEI and AB versus AB alone: the combination of PDEI and AB may provide a small improvement in IPSS-total score (MD 2.56 lower, 95% CI 3.92 lower to 1.19 lower; n = 193; low-quality evidence) compared to AB alone. We found no evidence for BPHII scores. AEs may be increased (RR 2.81, 95% CI 1.53 to 5.17; n = 194; moderate-quality evidence). This corresponds to 235 more AEs per 1000 participants (95% CI 69 more to 542 more per 1000). Study results were limited to treatment duration of four to 12 weeks.PDEI and AB versus PDEI alone: the combination of PDEI and AB may provide a small improvement in IPSS-total (MD 2.4 lower, 95% CI 6.47 lower to 1.67 higher; n = 40; low-quality evidence) compared to PDEI alone. We found no data on BPHII or AEs. Study results were limited to a treatment duration of four weeks.PDEI and 5-ARI versus 5-ARI alone: in the short term (up to 12 weeks), the combination of PDEI and 5-ARI probably results in a small improvement in IPSS-total score (MD 1.40 lower, 95% CI 2.24 lower to 0.56 lower; n = 695; moderate-quality evidence) compared to 5-ARI alone. We found no evidence on BPHII scores or AEs. In the long term (13 to 26 weeks), the combination of PDEI and 5-ARI likely results in a small reduction in IPSS-total score (MD 1.00 less, 95% CI 1.83 lower to 0.17 lower; n = 695; moderate-quality evidence). We found no evidence about effects on BPHII scores. There may be no difference in rates of AEs (RR 1.07, 95% CI 0.84 to 1.36; n = 695; low-quality evidence). This corresponds to 19 more AEs per 1000 participants (95% CI 43 fewer to 98 more per 1000).We found no trials comparing other combinations of treatments or comparing different PDEI agents. AUTHORS' CONCLUSIONS: Compared to placebo, PDEI likely leads to a small reduction in IPSS-total and BPHII sores, with a possible increase in AEs. There may be no differences between PDEI and AB with regards to improvement in IPSS-total, BPHII, and incidence of AEs. There appears to be no added benefit of PDEI combined with AB compared to PDEI or AB alone or PDEI combined with 5-ARI compared to ARI alone with regards to urinary symptoms. Most evidence was limited to short-term treatment up to 12 weeks and of moderate or low certainty.

Correlation between fungal sensitisation in childhood persistent asthma and disease severity.

Fungal sensitisation in adults is associated with severe asthma but prevalence and clinical significance of fungal sensitisation remains unclear in paediatric population. The aim of this study was to study the association of fungal sensitisation with disease severity in children with persistent asthma. One hundred children with persistent asthma in age group 7-15 years, symptom duration >2 years and forced expiratory volume in first second >50% of expected were enrolled. Skin prick test (SPT) to 8 fungal antigens and total serum immunoglobulin E (IgE) were done. Fungal sensitisation was described as positive SPT (wheel diameter more than 3 mm larger than the negative control) to any of the fungal antigens and total serum IgE >200 ng/mL. Seventeen patients showed evidence of fungal sensitisation, of which, 6 demonstrated sensitisation to multiple fungi. 17.6% patients with fungal sensitisation had severe asthma as compared to 2.4% patients without fungal sensitisation (P value .032). Significant increase in family history of allergic comorbidities was noted among patients with fungal sensitisation (47.1% vs 21.7%, P value .03). The most common implicated organism in fungal sensitised patients was Aspergillus flavus (47.1%). The results of this study, a first among Indian children with asthma, suggest that children with fungal sensitisation have more severe asthma as compared to children without fungal sensitisation.

Intrapleural streptokinase is effective and safe for children with multi-loculated empyema regardless of the time from disease onset.

AIM: This study compared the efficacy of administering intrapleural streptokinase to children with multi-loculated empyema within 14 days or at any time after disease onset. METHODS: We studied children under 12 years with multi-loculated empyema who were admitted to a teaching hospital in Chandigarh, India, from July 2013 to June 2017. They received antibiotics, pleural drainage and intrapleural streptokinase. The first group received three doses within 14 days of disease onset, the second received three doses regardless of time after onset and the third group received four to six doses regardless of time after onset. The three phases lasted 18, 18 and 12 months, respectively. RESULTS: Of 195 children, 133 (68%) received streptokinase within 14 days, 46 (24%) beyond 14 days and 16 (8%) did not receive it. There was no difference in surgical decortication (14/133 versus 7/46, p > 0.05) and median hospitalisation duration (15 versus 14 days, p > 0.05) between administration before versus after 14 days. Median hospitalisation was shorter with four to six doses than three doses (11 versus 16 days, p < 0.01). CONCLUSION: Intrapleural streptokinase was effective for multi-loculated empyema even when it was administered more than 14 days after disease onset and four to six doses were superior to three doses.

Continuous positive airway pressure (CPAP) for acute bronchiolitis in children.

BACKGROUND: Acute bronchiolitis is one of the most frequent causes of emergency department visits and hospitalisation in infants. There is no specific treatment for bronchiolitis except for supportive therapy. Continuous positive airway pressure (CPAP) is supposed to widen the peripheral airways of the lung, allowing deflation of over-distended lungs in bronchiolitis. The increase in airway pressure also prevents the collapse of poorly supported peripheral small airways during expiration. In observational studies, CPAP is found to be beneficial in acute bronchiolitis. OBJECTIVES: To assess the efficacy and safety of CPAP compared to no CPAP or sham CPAP in infants and children up to three years of age with acute bronchiolitis. SEARCH METHODS: We searched CENTRAL (2014, Issue 3), MEDLINE (1946 to April week 2, 2014), EMBASE (1974 to April 2014), CINAHL (1981 to April 2014) and LILACS (1982 to April 2014). SELECTION CRITERIA: We considered randomised controlled trials (RCTs), quasi-RCTS, cross-over RCTs and cluster-RCTs evaluating the effect of CPAP in children with acute bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data using a structured proforma, analysed the data and performed meta-analyses. MAIN RESULTS: We included two studies with a total of 50 participants under 12 months of age. In one study there was a high risk of bias for incomplete outcome data and selective reporting, and both studies had an unclear risk of bias for several domains including random sequence generation. The effect of CPAP on the need for mechanical ventilation in children with acute bronchiolitis was uncertain due to imprecision around the effect estimate (two RCTs, 50 participants; risk ratio (RR) 0.19, 95% CI 0.01 to 3.63; low quality evidence). Neither trial measured our other primary outcome of time to recovery. One trial found that CPAP significantly improved respiratory rate compared with no CPAP (one RCT, 19 participants; mean difference (MD) -5.70 breaths per minute, 95% CI -9.30 to -2.10), although the other study reported no difference between groups with no numerical data to pool. Change in arterial oxygen saturation was measured in only one trial and the results were imprecise (one RCT, 19 participants; MD -1.70%, 95% CI -3.76 to 0.36). The effect of CPAP on the change in partial pressure of carbon dioxide (pCO2) was also imprecise (two RCTs, 50 participants; MD -2.62 mmHg, 95% CI -5.29 to 0.05; low quality evidence). Duration of hospital stay was similar in both of the groups (two RCTs, 50 participants; MD 0.07 days, 95% CI -0.36 to 0.50; low quality evidence). Both trials reported no cases of pneumothorax and there were no deaths in either study. Change in partial pressure of oxygen (pO2), hospital admission rate (from emergency department to hospital), duration of emergency department stay, need for intensive care unit admission, local nasal effects and shock were not measured in either study. AUTHORS' CONCLUSIONS: The effect of CPAP in children with acute bronchiolitis is uncertain due to the limited evidence available. Larger trials with adequate power are needed to evaluate the effect of CPAP in children with acute bronchiolitis.

Early versus late removal of the laryngeal mask airway (LMA) for general anaesthesia.

BACKGROUND: The laryngeal mask airway (LMA) is a safe and effective modality to maintain the airway for general anaesthesia during surgical procedures. The LMA is removed at the end of surgery and anaesthesia, when the patient maintains an adequate respiratory rate and depth. This removal of the LMA can be done either when the patient is deep under anaesthesia (early removal) or only after the patient has regained consciousness (late removal). It is not clear which of these techniques is superior. OBJECTIVES: The objective of this review was to compare the safety of LMA removal in the deep plane of anaesthesia (early removal) versus removal in the awake state (late removal) for participants undergoing general anaesthesia. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 8); MEDLINE (1966 to August 2014); EMBASE (1980 to August 2014); LILACS (1982 to August 2014); CINAHL (WebSPIRS; 1984 to August 2014); and ISI Web of Science (1984 to August 2014). We searched for ongoing trials through various trial registration websites. In addition, we searched conference proceedings and reference lists of relevant articles. SELECTION CRITERIA: We included randomized controlled trials (RCTs) on adults and children undergoing elective general anaesthesia using the LMA, that compared early removal of the LMA (defined as removal of the LMA in the deep plane of anaesthesia) versus late removal of the LMA (defined as removal of the LMA after the patient is awake). DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We used a random-effects model to generate forest plots from the data. MAIN RESULTS: We identified a total of 9188 citations and included 15 RCTs conducted on 2242 participants in this review. All trials used the LMA Classic in American Society of Anesthesiologists (ASA) physical status I or II for patients undergoing elective general anaesthesia. Children were enrolled in 11 trials and adults in five trials. None of the trials were of high methodological quality. Eight of the 15 studies had adequate generation of random sequence, whereas only one trial had adequate concealment of random sequence. Three trials had blinded the outcome assessor. Thus, the majority of the studies appeared to have a high risk of bias in the study design.Using the GRADE approach, we found low quality evidence that the risk of laryngospasm was similar with early removal of the LMA (3.3%) versus late removal (2.7%): risk ratio (RR) 1.23, 95% confidence interval (CI) 0.74 to 2.03; 11 trials, 1615 participants. The quality of evidence was very low that the risk of coughing was less after early removal (13.9%) than late removal (19.4%): RR 0.52, 95% CI 0.29 to 0.94; 11 trials, 1430 participants. The quality of evidence for the risk of desaturation was also very low; there was no difference between early removal (7.9%) and late removal (10.1%): RR 0.68, 95% CI 0.4 to 1.16; 13 trials, 2037 participants. We found low quality evidence that the risk of airway obstruction was higher with early removal (15.6%) compared to late removal of the LMA (4.6%): RR 2.69, 95% CI 1.32 to 5.5; eight trials, 1313 participants. AUTHORS' CONCLUSIONS: This systematic review suggests that current best evidence comparing early versus late removal of the LMA in participants undergoing general anaesthesia does not demonstrate superiority of either intervention. However, the quality of evidence available is either low or very low. There is a paucity of well designed RCTs and a need for large scale RCTs to demonstrate whether early removal or late removal of the LMA is better after general anaesthesia.

Sleeping too close together: obesity and obstructive sleep apnea in childhood and adolescence.

To review the current available literature exploring the prevalence, severity, consequences and treatments for obesity related OSA in children and adolescents. The published literature was searched through EMBASE and Pubmed using a pre-defined search strategy. There is evidence showing that OSA occurs more frequently and may be more severe in children and adolescents who are overweight or obese compared with lean children. Obesity and OSA are independently associated with adverse cardiovascular, metabolic, and neuropsychological consequences. The magnitude of these abnormalities when obesity and OSA co-exist is not well established. Treatment options for obesity related OSA includes adenotonsillectomy, but it does not cure OSA in over 50% of obese children. Positive airway pressure (PAP) therapy delivered through continuous or bi-level modes is successful, but limited by generally poor compliance. There is increasing experience with bariatric surgical techniques which are effective for the treatment of obesity and its related complications. As obesity related OSA is highly prevalent, more research is needed to understand the interaction of these two conditions with regards to pathophysiology, adverse consequences and optimal management strategies.