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For many years it has been clear that melioidosis is endemic in parts of SE Asia and northern Australia, but over the past 25 years, the melioidosis iceberg has been emerging. Within known endemic areas, cases are being recognized with increasing frequency. New endemic areas are also being identified, particularly in Africa and the Americas, but also in Asia. In Laos, for example, the first case of melioidosis was diagnosed as recently as 1999, but since then more than 900 cases of culture-positive melioidosis have been diagnosed in a single laboratory, although this is just the tip of a national iceberg. Worldwide, the disease undoubtedly remains under-diagnosed, especially in the Indian sub-continent. The two main barriers to the diagnosis of the disease, which has its biggest impact on the rural poor, are access to high quality diagnostics, and the lack of awareness and familiarity of clinical and laboratory staff. Clinical diagnosis is difficult due to the protean manifestations of the disease. Where microbiology laboratories exist, the mainstay of diagnosis remains culture. The organism is easy to grow as long as the site of infection can be sampled, but laboratory technicians unfamiliar with the organism may discard it as a contaminant. An important clue is resistance to aminoglycosides and colistin combined with susceptibility to co-amoxiclav, although regional variants have recently been described. Latex agglutination or lateral flow tests are useful for screening suspect isolates, and the latter may be used for rapid diagnosis directly on clinical samples. Molecular tests such as PCR have not yet found a role in routine diagnosis. Available serological tests also lack sensitivity and specificity. Current treatment regimens, comprising an initial parenteral phase with either ceftazidime or a carbapenem followed by a prolonged oral eradication phase with co-trimoxazole or co-amoxiclav, are based on strong evidence from a series of clinical trials conducted in Thailand. Several questions remain unanswered, however, such as the optimal duration of each phase and the role of adjunctive treatment. Even with optimal antibiotic therapy the mortality in developing countries remains disappointingly high. [ABSTRACT FROM AUTHOR]

Background: Burkholderia thailandensis is an environmental bacteria closely related to Burkholderia pseudomallei that rarely causes infection in humans. Some environmental isolates have shown to express a capsular polysaccharide known as B. thailandensis capsular variant (BTCV), but human infection has not previously been reported. Although B. thailandenisis has been identified in environmental samples in Laos before, there have not been any human cases reported., Case: A 44-year-old man presented to a district hospital in Laos with a short history of fever and pain in his left foot. Physical examination identified a deep soft-tissue abscess in his left foot and an elevated white blood count. A deep pus sample was taken and melioidosis was suspected from preliminary laboratory tests. The patient was initially started on cloxacillin, ceftriaxone and metronidazole, and was then changed to ceftazidime treatment following local melioidosis treatment guidelines., Laboratory Methods: A deep pus sample was sent to Mahosot Hospital microbiology laboratory where a mixed infection was identified including Burkholderia sp. Conventional identification tests and API 20NE were inconclusive, and the B. pseudomallei -specific latex agglutination was positive. The isolate then underwent a Burkholderia species specific PCR which identified the isolate as B. thailandensis. The isolate was sent for sequencing on the Illumina NovaSeq 6000 system and multi-locus sequence typing analysis identified the isolate had the same sequence type (ST696) as B. thailandensis E555, a strain which expresses a B. pseudomallei -like capsular polysaccharide., Conclusion: This is the first report of human infection with B. thailandensis in Laos, and the first report of any human infection with the B. thailandensis capsular variant. Due to the potential for laboratory tests to incorrectly identify this bacteria, staff in endemic areas for B. thailandensis and B. pseudomallei should be aware and ensure that appropriate confirmatory methods are used to differentiate between the species., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Vannachone S et al.)

Objective: To determine facial contour features, measured on computed tomography (CT), related to upper airway morphology in patients with obstructive sleep apnea (OSA); certain phenotype of facial abnormalities implying restriction of craniofacial skeleton and adipose tissue nimiety has predicted the value of the severity of OSA., Materials and Method: Sixty-four male patients with OSA [apnea-hypopnea index (AHI) ≥10/h] who had upper airway CT were randomly selected to quantitatively measure indicators of facial contour and upper airway structures. Pearson correlation analyses were performed. Partial correlation procedure was used to examine correlations while controlling body mass index (BMI)., Results: Upper airway anatomy can nearly all be reflected in the face, except retroglossal airway. Upper face width can be measured to assess the overall skeletal structures of the airway. Lower face width can be used to represent how much adipose tissue deposited. Hard palate, retropalatal, and hypopharyngeal airways have corresponding face indicators respectively. Midface width is a better predictor of AHI severity and minimum blood oxygen even than neck circumference because it contains the most anatomical information about the airway, including RP airway condition, soft palate length, tongue volume, etc. These correlations persisted even after correction for BMI., Conclusions: All anatomical features of the upper airway except retroglossal airway can be reflected in the face, and midface width is the best predictor of AHI severity and minimum blood oxygen, even better than neck circumference and BMI., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Access to inclusive and qualitative education on an equal basis is a clear right of every child, even from the very beginning in Early Childhood Education and Care (ECEC). However, inclusive education is often not possible without access to appropriate (assistive) technologies. Notwithstanding the opportunities of technology to enhance inclusion of all children, it is still limitedly integrated by educators and teachers into their curriculum. Therefore, the SKATE project aims in gearing innovative technology as resource for inclusive education. This study describes and evaluates the preparation, the design, the implementation, and the effects of technology-based classroom activities in inclusive ECEC. The classroom activities are developed and implemented by school teams of 14 preschools spread over four European (EU) countries. A total of 50 school team members participated in a SKATE Learning Programme. This resulted in more than 20 technology-based inclusive class activities, created by school teams together with technology experts. Across the four countries, approximately 330 pre-schoolers, with and without special educational needs (SEN), participated. At this moment, 13 school team members from four EU countries and 45 parents from two EU countries evaluated the technology-based inclusive classroom activities. Nearly all teachers agreed that the activity promoted the inclusion of all children. Teachers reported that most of the children enjoyed the activity. This was confirmed in the evaluation by the parents. Most parents had the impression that the activity was meaningful, joyful and inclusive for all children.

Purpose: Distinguishing obstructive sleep apnea (OSA) in a high-risk population remains challenging. This study aimed to investigate clinical features to identify children with OSA combined with craniofacial photographic analysis., Methods: One hundred and forty-five children (30 controls, 62 with primary snoring, and 53 with OSA) were included. Differences in general demographic characteristics and surface facial morphology among the groups were compared. Risk factors and prediction models for determining the presence of OSA (obstructive sleep apnea-hypopnea index>1) were developed using logistic regression analysis., Results: The BMI (z-score), tonsil hypertrophy, and lower face width (adjusted age, gender, and BMI z-score) were showed significantly different in children with OSA compared with primary snoring and controls (adjusted p<0.05). The screening model based on clinical features and photography measurements correctly classified 79.3% of the children with 64.2% sensitivity and 89.1% specificity. The area under the curve of the model was 81.0 (95% CI, 73.5-98.4%)., Conclusion: A screening model based on clinical features and photography measurements would be helpful in clinical decision-making for children with highly suspected OSA if polysomnography remains inaccessible in resource-stretched healthcare systems., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Wang et al.)

Backgrounds: The COVID-19 pandemic has caused significant impact on human health. Whether obstructive sleep apnea (OSA) increases the risk of COVID-19 remains unclear. We sought to clarify this issue using two-sample Mendelian randomization (TSMR) analysis in large cohorts., Methods: Bidirectional two-sample Mendelian randomization (MR) was used to evaluate the potential causality between OSA and COVID-19 by selecting single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from genome-wide association studies (GWAS). The inverse-variance weighted (IVW) method was selected as the main approach for data analysis to estimate the possible causal effects. Alternative methods such as MR-Egger, the MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out analysis methods were implemented as sensitivity analysis approaches to ensure the robustness of the results., Results: All forward MR analyses consistently indicated the absence of a causal relationship between OSA and any COVID-19 phenotype. In the reverse MR analysis, the IVW mode demonstrated that severe respiratory confirmed COVID-19 was correlated with a 4.9% higher risk of OSA (OR, 1.049; 95%CI, 1.018-1.081; P = 0.002), consistent in MR-PRESSO (OR = 1.049, 95%CI 1.018-1.081, P = 0.004), weighted median (OR = 1.048, 95%CI 1.003-1.095, P = 0.035), and MR-Egger (OR = 1.083, 95%CI 1.012-1.190, P = 0.041) methods., Conclusions: There is no significant evidence supporting a causal association between OSA and any COVID phenotype, while we identified potential evidence for a causal effect of severe COVID-19 on an increased risk of OSA., Competing Interests: Declaration of competing interest Xiang Gao, Tao Wei, Huijun Wang, Rongcui Sui, Jianhong Liao, Dance Sun and Demin Han have no financial or non-financial conflicts of interest to declare., (Copyright © 2022. Published by Elsevier B.V.)

Backgroud: The facial phenotypes of Asian obstructive sleep apnea (OSA) patients remain unclear., Objectives: (1) To describe the facial features of OSA patients. (2) To develop a model based on facial contour indicators to predict OSA. ( 3) To classify the facial phenotypes of Asian OSA patients., Materials and Methods: 110 patients with OSA (apnea-hypopnea index [AHI] ≥ 10/h) and 50 controls (AHI< 10/h) were selected to measure facial contour indicators. Indicators were compared between OSA patients and the control group. We used multivariable linear regression analysis to predict OSA severity and K-means cluster analysis to classify OSA patients into different phenotypes., Results: We built a model to predict OSA which explained 49.1% of its variance and classified OSA patients into four categories. Cluster 1 (Skeletal type) had the narrowest facial width indicators with narrowing of the retroglossal airway. Cluster 2 (Obese type) had the widest face, and narrowest hard palate, retropalatal, and hypopharyngeal airways. Cluster 3 (Nose type) had the narrowest nasal cavity. Cluster 4 (Long type) had the longest airway length., Conclusions and Significance: Patients with OSA were classified into four categories, each of which identified different anatomic risk factors that can be used to select the treatment.

Burkholderia pseudomallei is the causative agent of melioidosis, a life-threatening disease common in Southeast Asia and northern Australia. Melioidosis often presents with nonspecific symptoms and has a fatality rate of upwards of 70% when left untreated. The gold standard for diagnosis is culturing B. pseudomallei from patient samples. Bacterial culture, however, can take up to 7 days, and its sensitivity is poor, at roughly 60%. The successful administration of appropriate antibiotics is reliant on rapid and accurate diagnosis. Hence, there is a genuine need for new diagnostics for this deadly pathogen. The Active Melioidosis Detect (AMD) lateral flow immunoassay (LFI) detects the capsular polysaccharide (CPS) of B. pseudomallei. The assay is designed for use on various clinical samples, including serum and urine; however, there are limited data to support which clinical matrices are the best candidates for detecting CPS. In this study, concentrations of CPS in paired serum and urine samples from melioidosis patients were determined using a quantitative antigen capture enzyme-linked immunosorbent assay. In parallel, samples were tested with the AMD LFI, and the results of the two immunoassays were compared. Additionally, centrifugal concentration was performed on a subset of urine samples to determine if this method may improve detection when CPS levels are initially low or undetectable. The results indicate that while CPS levels varied within the two matrices, there tended to be higher concentrations in urine. The AMD LFI detected CPS in 40.5% of urine samples, compared to 6.5% of serum samples, suggesting that urine is a preferable matrix for point-of-care diagnostic assays. IMPORTANCE Melioidosis is very challenging to diagnose. There is a clear need for a point-of-care assay for the detection of B. pseudomallei antigen directly from patient samples. The Active Melioidosis Detect lateral flow immunoassay detects the capsular polysaccharide (CPS) of B. pseudomallei and is designed for use on various clinical samples, including serum and urine. However, there are limited data regarding which clinical matrix is preferable for the detection of CPS. This study addresses this question by examining quantitative CPS levels in paired serum and urine samples and relating them to clinical parameters. Additionally, centrifugal concentration was performed on a subset of urine samples to determine whether this might enable the detection of CPS in samples in which it was initially present at low or undetectable levels. These results provide valuable insights into the detection of CPS in patients with melioidosis and suggest potential ways forward in the diagnosis and treatment of this challenging disease.

Background: To investigate the severity of hypoxemia and prevalence of pulmonary hypertension (PHTN) in patients with the overlap syndrome (OS) of restrictive ventilatory defect (RVD) and sleep apnea (SA)., Methods: Patients referred for both sleep test and spirometry for suspected SA and ventilatory disorders were recruited prospectively from January 2019 to January 2020. SA was determined by an apnea-hypopnea index ≥ 5/h; average oxygen saturation during sleep (meanSaO 2 ) and percentage of total sleep time with saturation < 90% (T90) were calculated. RVD was diagnosed in the presence of forced expiratory volume in the first second/forced vital capacity (FVC) > 0.7 and FVC < 80% predicted value. PHTN was defined by tricuspid regurgitation peak velocity ≥ 3.4 m/s, documented by noninvasive transthoracic echocardiography., Results: Patients with OS had significantly lower meanSaO 2 but higher T90 than subjects with isolated SA and isolated RVD. Patients with OS vs. those with isolated SA had higher odds of PHTN in multivariable analysis with age, sex, and body mass index adjusted for (OR 2.96, 95%CI 1.05-8.91, p = 0.040). Patients with meanSaO 2 < 92% vs. meanSaO 2 ≥ 92% had significantly higher odds of being diagnosed with PHTN (OR 5.40, 95%CI 2.01-15.7, p < 0.001). Similarly, T90 (≥ 4.5% versus < 4.5%) was also independently associated with the prevalence of PHTN (OR 7.21, 95%CI 2.54-23.67, p < 0.001)., Conclusion: Patients with OS of RVD and SA had severe hypoxemia, which is associated with the prevalence of PHTN. Further investigation is needed to discern whether therapeutic strategies toward OS might mitigate PHTN in this cohort., Trial Registration: Clinical Trial Registration No. ChiCTR1900027294 on 1 October 2019.

Background: Despite the efficacy of adaptive servo-ventilation (ASV) in suppressing central sleep apnea (CSA), its impact on long-term outcomes is debatable. We aim to identify subjects with specific features who might benefit from ASV therapy., Methods: Randomized clinical trials and comparative observational studies investigating the effects of ASV on cardiovascular (CV) and all-cause mortality and major adverse cardiovascular events (MACEs) in CSA patients were searched from PubMed, EMBASE, Cochrane library and Web of Science. Eligible studies were identified with relative risks (RR) of death and MACEs compared between patients treated by ASV and usual care., Results: A total of eight studies (three randomized controlled trials and five observational studies) including 2208 participants were selected for analysis. All-cause and CV mortality were not significantly reduced by ASV. Patients with nadir nocturnal saturation ≤ 80% (mean value) had lower risk of MACEs by ASV treatment compared with by usual care (RR, 0.18; p < 0.001). Patients with severe heart failure (HF), defined as left ventricular ejection fraction (LVEF) ≤ 33% (mean value), or HF of New York Heart Association (NYHA) classification of III/IV, did not have reduced risk of MACEs post ASV therapy. However, subjects with LVEF > 33% (RR, 0.35; p < 0.001) or NYHA Ⅰ/Ⅱ (RR, 0.35; p < 0.001) had significantly lower risk of MACEs by using ASV than by usual care., Conclusions: Although ASV appears to not reduce CV and all-cause death for HF patients with extremely low LVEF, those with profound CSA associated hypoxemia or less severe HF still benefit from ASV therapy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Xie has served as a consultant for ResMed and Philips. He has spoken at meetings sponsored by Philips and ResMed. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To assess risk factors for oronasal fistula, including 2-stage palate repair., Design: Retrospective analysis., Setting: Tertiary children's hospital., Patients: Patients with non-submucosal cleft palate whose entire cleft repair was completed at the study hospital between 2005 and 2013 with postsurgical follow-up., Interventions: Hierarchical binary logistic regression assessed predictive value of variables for fistula. Variables tested for inclusion were 2 stage repair, Veau classification, sex, age at surgery 1, age at surgery 2, surgeon volume, surgeon, insurance status, socioeconomic status, and syndrome. Variables were added to the model in order of significance and retained if significant at a .05 level., Main Outcome Measure: Postoperative fistula., Results: Of 584 palate repairs, 505 (87%) had follow-up, with an overall fistula rate of 10.1% (n = 51). Among single-stage repairs (n = 211), the fistula rate was 6.7%; it was 12.6% in 2-stage repairs (n = 294, P = .03). In the final model utilizing both single-stage and 2-stage patient data, significant predictors of fistula were 2-stage repair (odds ratio [OR]: 2.5, P = .012), surgeon volume, and surgeon. When examining only single-stage patients, higher surgeon volume was protective against fistula. In the model examining 2-stage patients, surgeon and age at hard palate repair were significant; older age at hard palate closure was protective for fistula, with an OR of 0.82 ( P = .046) for each additional 6 months in age at repair., Conclusions: Two-stage surgery, surgeon, and surgeon volume were significant predictors of fistula occurrence in all children, and older age at hard palate repair was protective in those with 2-stage repair.