Pneumoconiosis is a group of occupational lung diseases caused by the inhalation of mineral dust in the lungs, leading to lung dysfunction. Patients with pneumoconiosis are usually accompanied by weight loss, which suggests a lipid metabolism disorder. Recent progress in lipidomics uncovered detailed lipid profiles that play important roles in respiratory diseases, such as asthma, lung cancer and lung injury. The purpose of this study was to shed light on the different expression of lipidome between pneumoconiosis and healthy, hoping to bring new ideas for the diagnosis and treatment of pneumoconiosis.t-test or one-way ANOVA test) on SPSS.This non-matching case–control study was performed among 96 subjects , data of clinical phenotypes were recorded, and plasma biochemistry (lipidomic profiles) was tested for both pneumoconiosis patients and healthy controls. A total of 426 species in 11 lipid classes were analyzed by high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (HPLC-QqQ-MS) for the cases and controls. We also analyzed the correlation of lipid profiles with clinical phenomes from pneumoconiosis patients by expression quantitative trait locus (eQTL) model to evaluate trans-nodules between lipidomic profiles and clinical phenomes. All visually re-checked data were analyzed using appropriate statistical tools . The majority of those elevated lipid elements were phosphatidylethanolamines (PEs), and the minority were free fatty acids (FFAs), while phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) declined in pneumoconiosis. Clinical trans-omics analyses demonstrated that phenomes in pneumoconiosis connections with multiple lipids, which showed that pH, lung function, mediastinal lymph node calcification, and complication were highly correlated with lipid elements. Furthermore, up-regulated PE was corresponded to pH, smoking history and mediastinal lymph node calcification. PC was corresponded to dust exposure history, BMI and mediastinal lymph node calcification.Compared with healthy people, 26 significantly increased (> 1.5-fold) and 30 decreased lipid elements (< 2/threefold) in patients with pneumoconiosis were identified (We found altered lipid panels between male pneumoconiosis patients and healthy people by qualitatively and quantitatively measured plasma lipidomic profiles. The trans-omic analysis between clinical phenomes and lipidomes might have the potential to uncover the heterogeneity of lipid metabolism of pneumoconiosis patients and to screen out clinically significant phenome-based lipid panels.The online version contains supplementary material available at 10.1186/s41043-023-00400-7. Pneumoconiosis refers to a series of pulmonary diseases caused by the inhalation of mineral dust, usually found in certain occupations . As it iPneumoconiosis patients are usually in poor nutritional status and wasting state, especially those with pneumoconiosis-related complications  , 5. PrevLipids are the fundamental components of biological membranes as well as the metabolites of organisms, which play critical roles in cellular energy storage, structure, and signaling , 9. Lipi1), FEV1/forced vital capacity (FVC), and residual volume/diffusion capacity in smokers with and without COPD, while one CER was associated with diffusion capacity for carbon monoxide. Therefore, the integration of lipidomics with clinical phenomes will provide a novel insight into understanding the molecular mechanisms of diseases [Clinical trans-omics is defined as a new subject to integrate clinical phenomes with multi-omics in multiple dimensions . With thdiseases , 27.We hypothesized that exploration of abnormal lipid metabolism in pneumoconiosis may contribute to understanding the pathogenesis and prevention of pneumoconiosis. This research was to explore and analyze the differences in lipidomic profiles between patients with pneumoconiosis and healthy people using untargeted lipidomics in HPLC-QqQ-MS. In addition, we conducted the clinical trans-omics to reveal the correlation between clinical phenome and specific groups of lipid elements.The study, designed as a retrospective hospital-based non-matching case–control approach including 48 male pneumoconiosis patients and 48 healthy controls, was conducted in Fujian Region of China, between September 2019 to September 2020. Subjects were recruited from the 2nd Affiliated Hospital of Fujian Medical University. The study protocol was approved by the Ethical Evaluation Committee of the 2nd Affiliated Hospital of Fujian Medical University in China . Written informed consent for clinical data collection and general information questionnaires, including demographic information, history of any diseases, and current treatments before starting the study was obtained from all participants, who were assured of the confidentiality of the information provided and their right to withdraw at any time without prejudice.The sample size was determined as a pilot using a 90 percent power and a 0.5 effect size. The sample size was determined to be 27 people. With a 10% dropout rate, the final sample size was calculated to be at least 60 participants (30 in each group) .nd Affiliated Hospital of Fujian Medical University) were diagnosed by dust exposure history and chest imaging or pathology. Other 48 male healthy volunteers were recruited prospective randomly from the medical examination center of the same hospital who met the following criteria: having a BMI ranging from ≥ 18.5 to 27.5, and no history of respiratory or other diseases likely to interfere with the study.We recruited 96 male adults, 48 male patients with pneumoconiosis  . The proMedical history including the history of dust exposure, smoking, and pneumothorax was recorded at the first visit. (1) A clear history of exposure to harmful dusts and exposure time was recorded. (2) Previous and current history of pneumothorax were evaluated by past history and chest imaging. (3) Never-smokers were subjects who had never smoked for 1 year or more, and had a total cigarette exposure of less than 0.5 pack-years while the others were smokers.2 for underweight, 18.5 to 22.9 kg/m2 for normal weight, 23 to 27.49 kg/m2 for overweight, and > 27.5 kg/m2 which indicates obese [Anthropometric measurements: For body weights were measured in light clothing, without shoes to the nearest 0.1 kg (kg) using a digital balance. Heights were measured to the nearest 0.1 cm (cm) using the SECA balance with height attachment. BMI cut-offs for Asians proposed by the International Obesity Task Force (IOTF-2000) were used for identifying overweight and obesity which was; < 18.49 kg/mes obese .2), and arterial oxygen partial pressure (PO2). (3) Lung function analysis  was applied for measuring FEV1, FVC, forced expiratory one-second rate , total lung capacity (TLC).Laboratory measurements and Supplementary Examination: (1) The fasting serum lipid profile  was determined by the enzymatic colorimetric method. (2) The assessment of arterial blood gas (ABG) analysis  was conducted by the laboratory department including the potential of hydrogen (pH), and arterial carbon dioxide partial pressure  Normal spirometry was defined as post-bronchodilator FEV1 ≥ 80%predicted, post-bronchodilator FEV1/FVC > lower limit of normal, and reversibility to 400 µg salbutamol, 10% of the predicted FEV1). Less than 80% of TLC was defined as restrictive ventilation dysfunction. (4) mMRC questionnaire for assessing the severity of dyspnea by symptoms [Others: (1) Mediastinal lymph node calcification was assessed by chest imaging. (2) The diagnostic criteria of respiratory failure were PaOsymptoms . (5) ComBoth the pneumoconiosis patients and the healthy controls were interviewed using a pre-tested semi-structured questionnaire, and then the I.V. blood samples (2 ml per person) were collected in the hospital. Fasting blood was drawn from healthy controls and pneumoconiosis patients on the day of visiting our hospital to harvest plasma. All the medical records, including symptoms, signs, laboratory tests, images, and pathologic information were collected. A total of 15 clinical phenomes were collected for the pneumoconiosis group, it mainly consists of the following parts:The internal standard mix was subscribed from the Internal Standards Kit for Lipidyzer™ Platform . The acetonitrile, water, isopropanol, ammonium acetate and ammonium hydroxide were HPLC grade and obtained from Sigma-Aldrich  .The plasma samples (20 μL each) were precipitated by the addition of isopropanol (400 μL each) which was precooled to 4 °C and then mixed with lipid internal standard mix. Samples were vortex mixed for 1 min. After 10 min of incubation at room temperature, samples were stored overnight at − 20 °C to improve protein precipitation. The next day, the sample was centrifuged at 14 000 g for 15 min. The supernatant was collected (200 μL) in a sample injection bottle and stored at − 80 °C awaiting Mass Spectra (MS) analysis .The mass spectrometry analysis was performed on a Lipidyzer™ Platform, including the Sciex QTRAP®  4500 system. Multiple reaction monitoring (MRM) was used to target and quantitate several hundreds of lipids molecular. All samples were first measured in positive and negative polarity with SelexION separation, followed by measurement without SelexION separation. Lipids were identified based on their retention time, and mass spectral information. We provide this information (filename-identification method.xlsx). All data were acquired and processed automatically using the Lipid Manager Workflow software .www.metaboanalyst.ca) was utilized for conducting multivariate statistical analysis, cluster analysis, dimensionality reduction, and making heat maps.MultiQuant software (AB SCIEX) was used to process data after lipids were identified by mass spectrometry. Further, MetaboAnalyst software 5.0 . The expression quantitative trait locus (eQTL) model was utilized to evaluate trans-nodules between lipidomic profiles and clinical phenomes.Our study made the descriptive clinical phenomes scored by the DESS system  in the pP-value < 0.05. We ranked 15 clinical phenomes of pneumoconiosis patients. Volcano maps showed significantly elevated or declined lipids in pneumoconiosis patients. A VIP plot was further exploited to sort the lipids according to their importance to differentiate groups. To explore the correlation between lipid elements and clinical phenomes, the lipid-quantitative trait loci model modified from eQTL model was applied.Data were presented as mean ± SD. The means of each group were used for calculation and comparison. The research data were subjected to Principal Component Analysis (PCA), Orthogonal signal correction Partial Least Square Discrimination Analysis (OPLS-DA), and Variable Importance in Projection (VIP) with the SIMCA 14.1 software program . Statistical significance of differences between two groups was determined by Student’s t-test. Statistical significance was affirmed when P < 0.05). However, no difference existed in age and smoking status. Of pneumoconiosis patients, there were 50% with complication(s), 56.25% with mediastinal lymph node calcification on chest CT, 60.42% were smokers, 68.75% had a dust exposure time of more than 15 years, 79.17% with abnormal lung function, 37.50% with respiratory failure, 54.16% with BMI ≤ 18.4. The clinical phenomes of pneumoconiosis are BMI, history of dust exposure, smoking and pneumothorax, lung function, FEV1, FEV1%, pH, PCO2, PO2, respiratory failure, restrictive ventilation dysfunction, mediastinal lymph node calcification, complications, and mMRC scores , phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI), and phosphatidylserine (PS). All the identified lipid species were grouped into 11 lipid classes, mainly including 107 PEs, 65 PCs, 12 SMs, 3 cholesterols (CEs), 3 CERs, 2 diacylceramides (DCERs), 5 hexosylceramides (HCERs), 195 tri-acylglycerols (TAGs), 16 lysophosphatidylcholines (LPCs), 1 lysophosphatidylethanolamine (LPE), 17 FFAs , variable important in project (VIP) scores were used to select important lipids. The top 50 lipid elements were defined based on VIP scores mainly distributed in lipids classes of 22 PEs, 10 PCs, 10 LPCs, 2 CERs, 3 HCERs, 1 DCER, and 2 FFAs. Of the top 50 lipids, there were 15 lipid elements significantly elevated (> 1.5 fold) and 18 declined (< 2/threefold) in pneumoconiosis patients compared with healthy control among the top 50 lipid elements , mediastinal lymph node calcification, and pH were highly correlated with lipid elements (VIP > 1). Furthermore, up-regulated PE was correlated to pH, smoking history, and mediastinal lymph node calcification. PC was correlated to dust exposure history, BMI, and mediastinal lymph node calcification  with clinical phenomes were measured by simulating the expression quantitative trait locus (eQTL) model. With the aim to identify disease phenome-specific lipid elements, circulating levels of lipid elements were integrated with clinical phenomes in patients with pneumoconiosis patients. Varied lipid elements and the specific correlated clinical phenotype were displayed in Fig. ion Fig. c.Fig. 3TLipid plays an important role in lung pathology and the physiology of pneumoconiosis. In the present research, lipidomics was used to explore to investigate the differential lipidomics metabolites in pneumoconiosis. Recent researches indicate these lipids were associated with various respiratory diseases.PCs and PEs are the most abundant phospholipids in cell membranes and play essential structural and signaling roles. PCs play significant roles in lung surfactant phospholipid metabolism and are the major phospholipid comprising around 80% of surfactant lipids. Alterations in their composition can cause reduced elasticity, leading to an overall decrease in lung compliance , 36. ShaIn the present study, only one lipid metabolite in the subclass of FFAs, FFA (22:4), was found that significantly higher in pneumoconiosis than in healthy control. Boden et al.  reported1, complication(s), mediastinal lymph node calcification, and pH in pneumoconiosis. Additionally, PE was correlated to smoking history, mediastinal lymph node calcification, and pH, and PC was correlated with BMI, dust exposure history, and mediastinal lymph node calcification separately.Further analysis through the eQTL model and integrated lipidomic and phenomic profiles, clinical phenotypes were discovered to be associated with a variety of altered lipid elements. Lipidomic profiles had strong correlations with FEV2 exposure could result in decreased secretion of 1, 2-Dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC), which was known as a lipid marker of alveolar type 2 epithelial cells, affecting the normal function of alveoli, and lung function potentially [1. The present study indicated that PC was also correlated with BMI. Some studies confirmed that altered lipid metabolism (PCs and lysoPCs) were associated with lean body mass [As to PCs, there are few studies on the relationship between lung function and lipids. Only one study revealed that SiOentially . This prody mass , 45. The1 and lung function [PE was found to correlate with not only lung function, but also smoking history in the study. In a study of COPD patients, PEs were found to be higher in smokers, and altered PEs with a high fold change also showed high correlations with lower FEVfunction . Resultsfunction  found thInterestingly, lipids especially PE and PC were both correlated with mediastinal lymph node calcification. Calcification of mediastinal and hilar lymph nodes was commonly found in pneumoconiosis. However, no research into PCs and PEs has been reported for pneumoconiosis disease. We assume that it might be because of macrophage accumulation and altered lipid metabolism in pneumoconiosis present with similar dystrophic calcification. One of the pathophysiological characteristics of pneumoconiosis was macrophage accumulation. Bargagli et al.  revealedThere were also limitations in the present study. First, the sample size was small. Second, therapeutic factors were not explored, and most correlating groups of patients should be studied in the future to explore the medical influence on lipidomes. Third, it is not clear whether the correlation is positive or negative by the eQTL model for trans-omics.In conclusion, we found altered lipid panels between pneumoconiosis patients and healthy people by qualitatively and quantitatively measuring plasma lipidomic profiles. Levels of PE and FFA elements meaningfully improved while PC and lysoPC were reduced in patients with pneumoconiosis. Clinical trans-omics analyses demonstrated that some phenomes have a strong correlation with lipids, although those needed to be further confirmed by bigger studies including a large population of patients in multicenter. Consequently, our data suggested that trans-omic profiles between clinical phenomes and lipidomes might have the potential value to reveal the heterogeneity of lipid metabolism among pneumoconiosis patients and to identify meaningful phenome-based lipid panels as biomarkers.Additional file 1. Table S1. Clinical phenomes scored and collected in pneumoconiosis patients, including BMI, medical history, Laboratory measurements and Supplementary Examinations and others.


There is a great association between the prevalence of obstructive sleep apnea (OSA) and asthma. Nonetheless, whether OSA impacts lung function, symptoms, and control in asthma and whether asthma increases the respiratory events in OSA are unknown. This meta-analysis aimed to examine the relationship between obstructive sleep apnea and asthma severity and vice versa.Q test and I2 statistics. We also performed subgroup analysis, Meta-regression, and Egger’s test for bias analysis.We carried out a systematic search of PubMed, EMBASE, and Scopus from inception to September 2022. Primary outcomes were lung function, parameters of polysomnography, the risk of OSA in more severe or difficult-to-control asthmatic patients, and the risk of asthma in patients with more severe OSA. Heterogeneity was examined with the 34 studies with 27,912 subjects were totally included. The results showed that the comorbidity of OSA aggravated lung function in asthmatic patients with a consequent decreased forced expiratory volume in one second %predicted (%FEV1) and the effect was particularly evident in children. %FEV1 tended to decrease in adult asthma patients complicated with OSA, but did not reach statistical significance. Interestingly, the risk of asthma seemed to be slightly lower in patients with more severe OSA . Asthma had no significant effect on polysomnography, but increased daytime sleepiness assessed by the Epworth Sleepiness Scale in OSA patients . More severe asthma or difficult-to-control asthma was independently associated with OSA (odds ratio (OR) = 4.36, 95%CI 2.49–7.64).1 in children. The effect of OSA on lung function in adult patients should be further confirmed. Asthma increased daytime sleepiness in OSA patients. More studies are warranted to investigate the effect of asthma on OSA severity and the impact of different OSA severity on the prevalence of asthma. It is strongly recommended that people with moderate-to-severe or difficult-to-control asthma screen for OSA and get the appropriate treatment.OSA was associated with more severe or difficult-to-control asthma with decreased %FEVThe online version contains supplementary material available at 10.1186/s40001-023-01097-4. The prevalence of obstructive sleep apnea (OSA) and asthma is increasing. Nevertheless, OSA and asthma have adverse effects on each other with distinct interactive mechanisms under the upper and lower airway pathologies, in addition to shared comorbidities such as obesity, rhinitis, and gastro-oesophageal reflux . The preA large retrospective cohort study of patients with OSA showed significantly higher rates of all-cause readmission compared with those without OSA  –26. AlthWe conducted a meta-analysis according to PRISMA statement guidelines . The firWe carried out a systematic search through PubMed, Medline, EMBASE, and Scopus, ClinicalTrials . Index terms such as medical subject headings and free text were utilized to capture a broad range of literature. Index terms were limited to those identified in the title, abstract, and keywords. The detailed strategy listing all search terms used and how they were combined is shown in the Additional file Two researchers independently assessed the articles for eligibility for inclusion. Any disagreements were resolved through discussion, and the senior author was available to arbitrate if necessary.1), forced vital capacity % predicted (FVC%), forced expiratory volume in one second/forced vital capacity (FEV1/FVC), forced expiratory flow 25–75% of VC (FEF25-75%), asthma control test (ACT); (4) sufficient data for calculating odds ratio (OR) with 95% confidence interval (CI) of the risk of asthma in OSA with varying severity; (5) English language.The inclusion criteria for Part A were as follows: (1) children or adult patients diagnosed with asthma according to accepted guidelines or criterion; (2) cross-sectional or cohort study including OSA and non-OSA groups in asthmatic patients; (3) at least one of the following outcome measurements included: forced expiratory volume in one second %predicted (%FEV2), oxygen desaturation index (ODI), arousal index (ArI), Epworth Sleepiness Scale, percent sleeping time in which oxygen saturation was below 90% (T90%); (4) sufficient data for calculating odds ratio (OR) with 95% confidence interval (CI) of the risk of OSA in asthma with varying severity; and (5) English language.The inclusion criteria for Part B were: (1) children or adult patients diagnosed with OSA by polysomnography (PSG); (2) cross-sectional or cohort study including asthma and non-asthma groups in OSA patients; (3) at least one of the following outcome measurements included: apnea/hypopnea index (AHI), lowest peripheral oxygen saturation , gender , mean age and body mass index (BMI) of the study population, study design, smoking condition, severity of OSA or asthma, study population, and quality of the study. The definition of OSA severity was based on the American Academy of Sleep Medicine. And the definition of asthma severity was based on Global Initiative for Asthma (GINA), including moderate-to-severe asthma, uncontrolled asthma, and difficult-to-treat asthma. If the original article did not define asthma severity according to GINA, the characteristics of the asthmatic population were recorded. Other specific variables included the number of asthma patients with and without OSA Table , number p < 0.05); otherwise, the fixed-effects model was applied (p ≥ 0.05). We used the I2 index to assess heterogeneity. I2 ≥ 50 was considered moderate-to-high heterogeneity. Subgroup analyses were conducted to determine the sources of heterogeneity when I2 ≥ 50. The pooled weight mean difference (WMD) of each study and 95%CI were used to estimate the following outcomes: %FEV1, FVC%, FEV1/FVC, FEF25–75%, ACT, AHI, LSpO2, ODI, ArI, ESS, and T90%. OR and 95% CI were used to estimate the risk of asthma in OSA with different grades of severity and the risk of OSA in asthma with different degrees of severity. A P-value < 0.05 was considered statistically significant.All analyses were performed using the comprehensive Meta-Analysis Software (Stata 15.0). The random-effects model was conducted if significant heterogeneity was determined   was usedAccording to our research strategy, 1646 articles were retrieved initially and after excluding duplicates, 882 articles remained. After the abstract screening, 752 articles that did not meet the inclusion criterion were excluded. After reading the full text of the remaining 130 articles, a further 99 were excluded: 89 due to a lack of appropriate data, 8 conference abstracts without available data, 1 clinical study protocol, and 1 article that was retracted. 34 eligible studies were included with a total sample size of 27,722 subjects . In Part1 , FVC% , FEV1/FVC , or FEF25–75%  (Table P = 0.05)    that fulfilled the inclusion criterion, OSA was not significantly associated with aggravation of lung function. The initial meta-analysis indicated that OSA had no influence on %FEV1 and FEV1/FVC decreased by 4.33      in patients with AHI ≥ 15/h. Interestingly, FEV1/FVC significantly improved  in patients with AHI ≥ 15/h, but was not significantly affected when OSA complicated with asthma (AHI ≥ 1 or 5/h)  revealed that %FEVP = 0.182, I2 = 81.1%, between-group P value = 0.028) and FEV1/FVC  showed no significant differences in asthmatic patients with AHI  > 5/h  in a large number of subjects . The result suggested that people with more severe OSA are less likely to be complicated with asthma. The characteristics of included OSA patients and the forest plot are shown in Table When exploring the association of asthma with OSA severity, we found that the risk of asthma was lower in patients with more severe OSA with low heterogeneity , LSaO2 , ODI , ArI  and T90% , regardless of subgroup analyses by age (children and adults) or severity of OSA . In addition, our study suggested that comorbidity of asthma may exacerbate daytime sleepiness assessed by ESS   that fulfilled the inclusion criterion revealed that asthma had no significant effect on OSA severity when assessed mainly by parameters of PSG  . Assessment of asthma severity included frequency of severe exacerbations over 12 months, symptoms during the day or night, activity limitation, and frequency of SABA reliever use for symptoms . The met01) Fig. A.Fig. 5A2 for asthmatic patients with mean BMI ≥ 27 dramatically decreased to 0% . Nevertheless, the subgroup of asthmatic patients with mean BMI < 27 still remained a high heterogeneity, presenting a stronger association with OSA  . Moreover, sensitivity analyses of two parts in the meta-analysis confirmed that the result was stable with no statistical significance compared with the estimate  with extremely low heterogeneity.To the best of our knowledge, this is the first meta-analysis to investigate the effect of OSA on lung function in asthmatic patients (Part A) and the effect of asthma on PSG in OSA patients (Part B), with a large amount of subjects. The results of Part A suggested that in asthmatic patients complicated with OSA, lung function may be aggravated with decreased %FEV1, especially in children. Nevertheless, the %FEV1 tended to decrease in adult asthma patients complicated with OSA, but did not reach statistical significance. OSA also had a negative effect on asthma symptoms and airway inflammation, as shown by increased ACT and FeNO. OSA did not affect small airway function assessed by FEFPrevious studies have reported that OSA is one of the most important pathophysiological mechanisms related to the worsening of asthma symptoms and control, in addition to shared risk factors and comorbidities . OSA cau1/FVC are the most common spirometric measurements applied to identify both the presence and degree of airflow obstruction [1/FVC) than those with AHI < 15/h without heterogeneity. Careful analysis of two studies revealed that baseline %FEV1, age, BMI, and gender did not differ between patients with and without OSA. Nonetheless, Oyama and his colleagues showed that 15/20 patients with AHI ≥ 15/h were at asthma treatment stage 4 compared with 4/16 patients with AHI < 15/h [1 in asthmatic patients with severe OSA was higher than that of patients with moderate OSA (77.1 ± 25.3 vs 65.3 ± 24.6), and medication was similar except for leukotriene antagonist (61.8% vs 30.3%) [1 [1 < 60% determines that a patient is at risk of future asthma exacerbations [%FEV1 and FEVtruction . In the truction , 18 shows 30.3%) . When pr0.3%) [1 . Therefo0.3%) [1 , 58. Gui1, FEV1/FVC) in children [Although a significant decline in baseline %FEV1 was observed among children asthmatic patients complicated with OSA, it was not seen in adult patients with high heterogeneity. Some studies indicated that airway hyperresponsiveness is a strong risk factor for low lung function, mainly seen in airway parameters . In the two included studies with the largest population (N = 8400), AHI was slightly lower in asthmatic than in non-asthmatic patients with OSA [P < 0.001; 12.6 vs 11.3 events/h, P < 0.001). In terms of baseline characteristics, those without asthma were more likely to be male and older than those with asthma. Advancing age and male gender will increase the risk and worsen OSA severity [Although more severe OSA aggravated asthma control, the meta-analysis came out that it was not associated with the risk of OSA , and asthma duration was an important predictor of OSA occurrence [The result of Part B in our meta-analysis suggested that more severe asthma or more difficult-to-control asthma was associated with OSA with pooled OR = 4.36. The reasonable explanations may be OSA aggravates asthma, or severe asthma leads to OSA. A large prospective cohort study with 8-year follow-up intervals suggested that patients with asthma experienced a higher risk of OSA than those without asthma  in OSA in our meta-analysis , which is consistent with the previous study. The risk of daytime sleepiness is 50% higher in asthmatic patients compared to those without asthma, and allergic rhinitis, a common comorbidity of asthma, is independently associated with sleepiness [Daytime sleepiness is one of the most important features of OSA evaluated by the ESS score. The results of the meta-analysis indicated that comorbidity with asthma slightly increased ESS in patients with OSA . Table S2. Search Embase via Ovid (up to September 2022). Table S3. Search Scopus (up to September 2022). Table S4. Subgroup meta-analysis of main outcomes in adults patients with asthma in OSA group and non-OSA group. Table S5. Subgroup meta-analysis of main outcomes in adults patients with OSA in asthma group and non-asthma group. Fig S1. The meta-analysis of asthma control trial (ACT) in the relationship between OSA and asthma control status. Fig S2. The meta-analysis of forced expiratory flow (25–75% of VC) (FEF25–75%) in the relationship between OSA and lung function in asthma patients. Fig S3. The meta-analysis of fractional exhaled nitric oxide (FeNO) in asthma patients with or without OSA. Fig S4. The meta-analysis of Epworth Sleepiness Scale (ESS) in OSA patients with or without asthma. Fig S5. The Egger’s test for publication bias. (a): The relationship between OSA and %FEV1 in asthma patients(b): The relationship between asthma and AHI in OSA patients(c): The relationship between OSA and asthma severity in asthma patients(d): The relationship between asthma and OSA severity in asthma patients.Fig S6. The sensitivity analyses for assessing the stability of the results. (a): The relationship between OSA and %FEV1 in asthma patients(b): The relationship between asthma and AHI in OSA patients(c): The relationship between OSA and asthma severity in asthma patients(d): The relationship between asthma and OSA severity in asthma patients.


Candida auris. Eligible participants were ≥18 years, with established candidemia and/or invasive candidiasis caused by C. auris,  and limited treatment options. Participants were treated with FMGX . Switching to oral FMGX 800 mg QD was permitted from Day 4. Primary endpoint was treatment success  at the end of the study treatment (EOST), assessed by an independent data review committee (DRC). Day 30 survival was a secondary endpoint. In vitro susceptibility of Candida isolates was assessed. Nine participants with candidemia  in intensive care units in South Africa were enrolled; all received IV FMGX only. DRC-assessed treatment success at EOST and Day 30 survival were 89% (8/9). No treatment related adverse events or study drug discontinuations were reported. FMGX demonstrated potent in vitro activity against all C. auris isolates , with the lowest MICs compared to other antifungals tested. Thus, the results showed that FMGX was safe, well-tolerated, and efficacious in participants with candidemia caused by C. auris.Fosmanogepix (FMGX), a novel antifungal available in intravenous (IV) and oral formulations, has broad-spectrum activity against pathogenic yeasts and molds, including fungi resistant to standard of care antifungals. This multicenter, open-label, single-arm study evaluated FMGX safety and efficacy for treatment of candidemia and/or invasive candidiasis caused by  Candida auris is a fungal pathogen that was first identified in 2009 and has since emerged as a global threat. C. auris isolates have been implicated in nosocomial outbreaks worldwide, with 5 distinct clades classified by region of independent emergence. Based on current profiling, these clades are referred to as Clade I (South Asian), Clade II (East Asian), Clade III (African), Clade IV (South American), and Clade V (Iranian) with different genetic determinants of resistance and resulting antifungal resistance profiles. Despite the classification of each clade based on the initial geographical region of detection, transmission in other areas has been reported, with multiple clades identified in Canada, Kenya, and the United States . MGX inhibits the conserved fungal glycosylphosphatidylinositol (GPI)-anchored wall transfer protein 1 (Gwt1)  is the first member in the “gepix” class of antifungals, with a unique mechanism of action (MOA). FMGX is a prodrug that is rapidly converted 1 (Gwt1) , 14. In 1 (Gwt1) . Broad-s1 (Gwt1) –18.C. auris isolates, including strains which were multi-drug resistant   . When insed mice . In a st by 24 h . AdditioC. auris .C. auris, with limited antifungal treatment options.In a Phase 2 study in 20 patients with invasive candidiasis, FMGX was safe, well-tolerated, and demonstrated a high treatment success rate of 80% at end of study treatment (EOST) and Day 30 survival of 85% . In the The study enrolled 9 participants from 2 sites in South Africa (15 participants were planned for enrollment). However, the study was terminated early due to the impact of the COVID-19 pandemic on patient enrollment. The intent-to-treat and safety populations each included all 9 enrolled participants with candidemia . Eight participants completed a full course of treatment, and one did not complete treatment due to death. Seven participants completed the study through the 4-week follow-up, with an additional death reported during the follow-up period.C. auris infections  prior to start of FMGX treatment. No other class of antifungal was administered prior to FMGX treatment.Demographics and baseline characteristics for enrolled participants were consistent with the epidemiology of fections . The stu50 target was 100% for total-drug plasma AUC:MIC ratio evaluated on Day 7 and averaged over study treatment. FMGX exposures were minimal, as expected, given the rapid conversion by systemic phosphatases of parent (FMGX) to active moiety (MGX), as observed previously in Phase 1 and Phase 1b studies.The mean (SD) duration of treatment with FMGX was 19 (5.83) days, ranging from 11 to 27 days; most participants (5/9 [55.6%]) received FMGX for >14 days but ≤28 days. All participants received FMGX via IV infusion; none were switched to the oral formulation. PK sampling was sparse and relatively few PK samples were collected, precluding a model-based compartmental analysis. However, a linear, two-compartment population PK model-based on previous phase I studies provided an adequate fit for the MGX concentrations observed. The PK data collected indicated that all participants had systemic exposures to MGX , consistent with prior exposure data from Phase 1 and Phase 1b studies in healthy volunteers and in patients with acute myeloid leukemia. MGX AUC:MIC ratios were also determined . Attainment of the total-drug plasma AUC:MIC ratio ED(i) Primary efficacy endpoint: Treatment success at EOST. DRC-assessed treatment success at EOST was 89% (8/9) in the study population (pulation . One (11Secondary efficacy endpoints. (i) Time to first negative blood culture. All participants had positive C. auris blood cultures during the enrollment period. A positive blood culture was reported for 3 participants on Day 1 before starting FMGX treatment (n = 3). For these participants, the mean (SD) time to first negative blood culture was 8.7 (5.51) days.C. auris bloodstream infection at EOST, 2 were indeterminate due to missing blood cultures, 1 participant had a recurrence 2 days after stopping FMGX (based on a single positive blood culture but was asymptomatic)  participants demonstrated eradication of tomatic) . All sub(ii) Mycology. All screened C. auris isolates recovered from blood cultures had low MIC values to MGX using both CLSI and EUCAST assay methods  Secondary safety endpoints. All participants experienced a treatment-emergent adverse event (TEAE); however, none were considered treatment related  due to a cardiac arrest in a patient with Gram-negative sepsis, and the second occurred after treatment completion (Day 36) in a patient who developed ventilator-associated pneumonia and multi-organ failure.C. auris candidemia and/or invasive candidiasis. The enrolled population was consistent with the disease epidemiology. All participants were in the ICU and were generally younger (median age of 45 years) and with fewer comorbidities than participants evaluated in prior candidemia and invasive candidiasis studies (C. auris study isolates with an MIC range of 0.008 to 0.015 μg/mL (CLSI) and 0.004 to 0.03 μg/mL (EUCAST). This is consistent with previous in vitro studies showing MGX to be the most potent antifungal tested against C. auris isolates , with endemic hospital-associated infections being reported worldwide  have also been detected in other countries, including Canada and the United States  in all dosing cohorts of FMGX in the survival arm of the study , evaluated the safety and efficacy of FMGX for the treatment of candidemia and/or invasive candidiasis caused by C. auris from blood collected <120 h (for participants with candidemia) or from a normally sterile site <168 h (for participants with invasive candidiasis without candidemia) from the time of enrollment, and had limited or no treatment options due to either antifungal resistance, contraindication(s), intolerance, or lack of clinical response to standard of care antifungal therapy, as advocated by the relevant regional/country treatment guidelines  had an established diagnosis of candidemia and/or invasive candidiasis caused by idelines , 37.C. auris , attributable clinical signs  within the permitted 120 h or 168 h enrollment period for candidemia or invasive candidiasis, respectively.Mycological and clinical diagnoses criteria were: ≥ 1 positive culture from blood or other normally sterile site for C. krusei infection, deep-seated Candida-related infections requiring >42 days of treatment; and pregnancy or lactation. Participants with severe or moderate renal impairment were initially excluded, but became eligible later on, based on a protocol amendment.Exclusion criteria included severe or moderate hepatic impairment ; concomitant use of strong CYP inhibitors; investigator-assessed life expectancy <7 days; diagnosis of Candida from the bloodstream (2 consecutive negative blood cultures), and in accordance with clinical judgment as applicable for other infected sites, up to a maximum of 42 days. Participants were monitored for continued safety and efficacy at 2 weeks and 4 weeks after EOST.Participants were treated with FMGX within 12 h of study enrollment . ParticiPlasma samples for pharmacokinetic (PK) analysis of FMGX and MGX levels were collected at baseline (pre-dose), twice weekly during treatment, at EOST/early termination (ET), and 2 weeks after EOST. Adverse events (AEs) were recorded from the date of informed consent through study completion, and coded .C. auris from the blood/infection site with no additional antifungal treatment and survival. Clearance was defined as 2 consecutive blood cultures negative for Candida spp., and/or ≥ 1 negative tissue culture or aspirate/fluid culture for deep-seated infections. For participants with a deep-seated infection involving visceral organs from which a tissue culture was not obtainable, resolution of the attributable clinical signs of infection that were recorded at baseline, and as applicable, radiological improvement associated with the site of infection, were required.The primary efficacy endpoint was the percentage of participants with DRC-assessed treatment success at EOST, defined as clearance of Secondary efficacy parameters included all-cause mortality through Day 30, and time to first negative blood culture. The DRC also assessed treatment success at 2 and 4 weeks after EOST. Investigator-assessed secondary parameters included percentage of participants with successful mycological outcomes, treatment success at EOST and 2 and 4 weeks after EOST, and the number of participants with TEAEs.https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See


Stroke prevention with oral anticoagulant (OAC) therapy, including non-vitamin K antagonist oral anticoagulants (NOACs), is recommended in patients with atrial fibrillation (AF). This analysis describes the antithrombotic prescription patterns for Chinese patients enrolled post-dabigatran approval during Phase II and III of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) program in China.2DS2-VASc score ≥ 1) were consecutively enrolled in the GLORIA-AF registry. This cross-sectional analysis provides descriptive comparison of Chinese patients in Phase III (2015–2016) with those enrolled in Phase II (2013–2014).Patients aged ≥ 18 years with newly diagnosed (< 3 months before baseline visit) nonvalvular AF at risk of stroke . High bleeding risk (HAS-BLED score ≥ 3) rates were similar . In Phase II, 5.8%, 15.2%, 36.7% and 42.2% of patients were prescribed NOACs, vitamin K antagonists (VKAs), antiplatelet therapies or no antithrombotic treatment, respectively. The corresponding figures were 17.2%, 23.5%, 37.4% and 21.8% for patients in Phase III, with an overall increase in OAC prescriptions (NOACs or VKAs). In patients with high stroke risk, the prescription patterns in Phase II were 5.6%, 14.4%, 41.0% and 38.9% for NOACs, VKAs, antiplatelets or no antithrombotic treatment, respectively. The respective proportions in Phase III were 15.1%, 23.5%, 40.9% and 20.5%.Overall, 1,018 and 1,911 Chinese patients were eligible for analysis in Phase II and III, respectively. Most patients  had high stroke risk (CHASince the availability of dabigatran in China, the overall trend of OAC, including NOAC, prescriptions in Chinese patients with nonvalvular AF has increased over time, albeit with VKAs as the most common antithrombotic treatment. Most patients, including those at high stroke risk, remain undertreated according to best practice guidelines.ClinicalTrials.gov NCT01468701.The online version contains supplementary material available at 10.1186/s12959-023-00527-x. Atrial fibrillation (AF) is increasing in prevalence and incidence, conferring a substantial risk of mortality and morbidity from ischemic stroke , 2, with2DS2-VASc score for AF and stroke risk ≥ 1 in males or ≥ 2 in females); aspirins have been found ineffective [Previously, antithrombotic therapy has been shown to reduce stroke risk by almost two-thirds in patients who have AF . Local affective , 10–13. ffective –16. Howeffective .The Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation  is one of the first, large, international, prospective, observational registries to collect data on patients with newly diagnosed nonvalvular AF, enrolling patients from 38 countries across different geographic regions between 2011 and 2016, including China. The registry was designed to monitor antithrombotic treatment patterns in three phases during this time period in participating regions, collecting data from patients who enrolled before and after NOACs were available , 19.This analysis aims to provide a descriptive comparison of the baseline characteristics and antithrombotic prescribing patterns of stroke prevention in patients from China diagnosed with AF, who were enrolled in the GLORIA-AF Phase II and Phase III program after dabigatran became available (approved by the China Food and Drug Administration in February 2013) and had been established as routine clinical care.The full methodology for GLORIA-AF has been described previously . The pro2DS2-VASc score ≥ 1). Exclusions included placement of any mechanical heart valve, or valve disease expected to require valve replacement intervention; patients who had received more than 60 days of VKA treatment in their lifetime; AF with a generally reversible cause; and medical conditions other than AF that required chronic use of an OAC. Patients were classified into four groups according to their prescribed antithrombotic treatment: NOACs, VKAs, antiplatelet therapies without OACs , and no antithrombotic treatment. Additionally, these treatment groups were separated into two broader subgroups of OACs (NOAC or VKA), or no OACs (antiplatelets or no antithrombotic treatment). Patients were also assessed for stroke and bleeding risks using the CHA2DS2-VASc score and HAS-BLED score for major bleeding risk [GLORIA-AF consecutively enrolled patients aged ≥ 18 years with newly diagnosed (< 3 months before the baseline visit) nonvalvular AF at risk for stroke  for continuous variables, and by frequencies and percentage for categorical variables. Data were also stratified by treatment group , and by subgroup for bleeding and stroke risks. No inferential statistical analyses or statistical hypothesis tests were performed. Standardized differences were used to assess baseline comparability between Phase III and Phase II. All analyses were performed using SAS® software version 9.4 .Between November 2011 and February 2014, 10,871 eligible patients from 736 centers were enrolled in the GLORIA-AF Phase II program , and betAntithrombotic treatment patterns at baseline for eligible patients from China in Phase II and Phase III are shown in Fig. For patients prescribed dabigatran, the majority were on a lower dose of 110 mg twice daily in Phase II (98.2%) and Phase III (94.8%), respectively, while 1.8% and 2.4% of patients were on a standard dose of 150 mg twice daily  and Phase III (37.4%), and the proportion of patients who received no antithrombotic treatment at Phase III decreased by almost twofold from Phase II (from 42.2 to 21.8%).Treatment distribution according to stroke risk in patients eligible for Phase II and III is shown in Fig. Figure Antiplatelet therapy remained unchanged as the highest prescribed therapy among patients with high bleeding risk (> 70.0%) regardless of phase, and the trend was also observed to be stable across both phases for patients with low bleeding risk. One-quarter of patients with low bleeding risk did not receive any antithrombotic treatment at Phase III, although this had decreased from 50.8% at Phase II.This analysis reports the trend of antithrombotic treatment since NOAC therapy was first introduced in China, gradually becoming more widely adopted by physicians. Our observations show a continuously increasing uptake of guideline recommended OAC treatment from Phase II to Phase III among patients with newly diagnosed nonvalvular AF at risk of stroke, including both NOAC and VKA prescriptions, with the latter as the more frequently prescribed OAC therapy overall. This trend was also observed in patients at high risk of stroke, although the proportion of those who received NOACs as first-line therapy for antithrombotic treatment remained relatively low. Furthermore, almost two-thirds of patients with AF remained undertreated at Phase III, either with antiplatelets or no antithrombotic treatment.OACs are recognized as the standard of care (SoC) for stroke prevention in patients with AF, both internationally , 13 and Of the OAC treatments, NOACs are recommended in preference to VKAs in NOAC-eligible patients , 10–13. Of the NOACs prescribed in both the GLORIA-AF Phase II and Phase III China cohorts, the most common was dabigatran, followed by rivaroxaban; this is in line with the trend of oral anticoagulant use for AF from other local studies of a similar period . The indFor patients who received dabigatran, most of the prescriptions in this sub-population analysis is of the lower dose, which is common among Asian patients with AF due to concerns regarding known increased bleeding risk with antithrombotic agents among Asian patients due to smaller body sizes, bleeding tendencies, and lower renal clearance rates . While l2DS2-VASc scale  [Guidelines recommend NOAC use in patients with AF at high risk of stroke, as defined by the CHAore ≥ 3) –13, 48, ore ≥ 3) . Suboptiore ≥ 3) , 51. Whiore ≥ 3) ; Phase Iore ≥ 3) , less thore ≥ 3) . The appore ≥ 3) .Among patients at high risk of bleeding, the proportion who received OAC therapy remained low. Previously, VKAs were the only OAC option, therefore the general reluctance of physicians to prescribe VKAs due to international normalized ratio control challenges could have been overgeneralized to NOACs, though the latter have demonstrated comparatively better safety than VKAs for stroke prevention . High riDespite increased awareness of AF and recognition of the need for anticoagulation, barriers preventing patients from accessing effective treatment remain a challenge. Possible reasons for the suboptimal use of OACs and NOACs in China include access to SoC treatments, and divergence in clinical practices across the country , 27. VKAThe limitations of the GLORIA-AF study design and analysis have been discussed previously ; conside2DS2-VASc score ≥ 1. Stroke prevention is the first step in the Atrial Fibrillation Better Care (ABC) pathway for AF management. GLORIA-AF is essential for monitoring the changes and implementation of updated best practice in clinical care as part of the initiative to enable an integrated approach to AF care [The design of GLORIA-AF aimed to capture the uptake of antithrombotic therapy over time; therefore, patient enrollment was focused on those eligible for stroke prevention, or CHA AF care , and thu AF care , 59.Using prospective, consecutively collected local data from Phase III GLORIA-AF, the study has provided evidence that confirm other local regional studies based on retrospective data to monitor the local antithrombotic over similar periods , 61. TheSince the availability of dabigatran in China, the overall trend of OAC, including NOAC prescriptions, in Chinese patients with nonvalvular AF has increased over time, with VKAs as the most commonly prescribed antithrombotic treatment during the timeframe of the study. The use of antiplatelet use in China remained high despite lack of supporting evidence. Overall, most patients, including those at high stroke risk, remain undertreated. Further efforts are required to encourage clinicians and physicians to follow best practice guidelines, which provide evidence-based recommendations for the treatment of AF in newly diagnosed patients.Below is the link to the electronic supplementary material.Supplementary Material 1


Tooth decay is an infectious disease which, in its initial phase, leads to the formation of cavities in the teeth through decalcification of the enamel and local tissue destruction. In addition to proper oral hygiene, prophylactic sealing of fissures and cavities with a sealant is a method of preventing the development of caries. The aim of this study is to summarise the effectiveness of fissure sealing of permanent teeth with fissure sealants compared to other preventive methods or no intervention.An umbrella review was carried out to achieve the purpose of our study. Searches were performed in Medline (via PubMed), Embase (via OVID), and Cochrane Library databases. Quality assessment of the included studies was performed using the AMSTAR2 tool. In addition, a manual search for recommendations/clinical practice guidelines on dental prophylaxis was performed.204 publications were identified, of which 15 met the inclusion criteria. Based on the results of 3 systematic reviews, there was a statistically significant reduced odds of caries occurrence or development with prophylactic sealing of permanent teeth compared with no intervention – depending on the review and follow-up period odds ratio (OR) ranged from 0.06 [95%CI: (0.01–0.32)] to 0.28 [95%CI: (0.20–0.38)]. In the eight systematic reviews that analysed different sealants, there were no statistically significant differences between the types of materials used for prophylactic tooth sealing. For systematic reviews comparing the efficacy of fissure sealants with fluoride varnish, three reported no statistically significant difference in the efficacy of caries incidence, with only one systematic review based on 1 RCT finding a statistically significant difference in favour of fissure sealants.Compared to the no intervention, dental sealing is an effective method for the prevention of dental caries. However, it is not possible to conclude conclusively which type of sealant and which of the available prophylactic methods is more effective in preventing caries.The online version contains supplementary material available at 10.1186/s12903-023-03499-6. As defined by the International Classification of Diseases 11th Revision (ICD-11: DA08.0), “dental caries is a condition characterised by localised destruction of calcified tissue, initiated on the tooth surface by decalcification of the enamel, followed by the enzymatic lysis of organic structures, resulting in cavity formation” . The DMFS  and DFS (decay filled surfaces) rates were also found to be statistically significantly reduced on the basis of 1 RCT, MD (mean difference) = -0.24  and MD = -0.65 , respectively. In addition, a statistically significant effect of resin-based FS application on the reduced odds of caries was demonstrated at 12, 36, and 48–56 months, with the authors of the publication pointing to a low quality of evidence .The authors of the 2016 Wright meta-analysis indicated that fissure sealing statistically significantly reduced the odds of developing caries over a 2 to 3-year (OR = 0.24 [95%CI: (0.19–0.30)]) and 4 to 7-year follow-up period – OR = 0.21 [95%CI: (0.10–0.44)] .Based on 20 RCTs, the authors of the Hou 2015 meta-analysis showed a statistically significant reduction in the odds of developing caries with fissure sealing of first permanent molars over a follow-up period of 6 months to 5 years, OR = 0.06 [95%CI: (0.01–0.32)] and OR = 0.28 [95%CI: (0.20–0.38)], respectively .The studies compared the efficacy of fissure sealants to fluoride varnish in preventing caries incidence , 17, 23 2 = 84% [The Kashbour 2020 meta-analysis compared the efficacy of fissure sealants with fluoride varnishes in the prevention of caries in the first permanent teeth. The result of the synthesis of the included studies did not reach statistical significance (OR = 0.67 [95%CI: (0.37–1.19)]). As a result, it is not possible to clearly indicate a more effective of the above-mentioned methods of caries prevention; moreover, the authors of the calculations pointed to the high heterogeneity of the analysed studies, i.e. I2 = 84% . Similar2 = 84% .The authors of the 2016 Wright meta-analysis also calculated the effectiveness of fissure sealants in preventing caries over three observation periods of 2–3 years, 4–7 years, and ≥ 7 years. According to the results of this study, the use of fissure sealants at each follow-up period reduces the odds of caries compared to the use of fluoride varnishes OR = 0.27 [95%CI: (0.11–0.69)], OR = 0.19 [95%CI: (0.07–0.51)], and OR = 0.29 [95%CI: (0.17–0.49)], respectively. However, the authors of the meta-analysis themselves pointed out that the result for the longest follow-up period was supported by low-quality evidence .A meta-analysis by Liang 2018, based on secondary caries prevention, showed that the use of resin-based FS on non-cavitied proximal caries, compared to fluoride varnish, statistically significantly reduces the odds of caries progression at 18–24 months (OR = 0.33 [95%CI: (0.19–0.58)]). However, no statistically significant difference was shown between these materials when analysed in subgroups considering caries progression according to caries depth . In contrast, at shorter follow-up periods (24 to 48 months), there were no statistically significant differences between these materials .The authors of the Yengopal 2010 publication compared RM-GIC with RBS and used the probability of caries absence as an endpoint. On the basis of 1 RCT, a reduced probability of caries absence after 36 months of follow-up by 7% to the detriment of RM-GIC was indicated at the limit of statistical significance – RR = 0.93 [95%CI: (0.88–0.97)] . SimilarThe characteristics and individual results of studies on caries prevention using fissure sealing methods for permanent teeth are presented below Table .Seven publications , 23, 27 In the Kühnisch 2020 meta-analysis, the authors compared pooled retention rate estimates (RREs) of five groups of sealants, i.e. primed, auto-polymerising, light-polymerising, fluoride-releasing and glass-ionomer sealant. According to the results of this publication, the shortest retention is characterised by primed and glass-ionomer sealants with RRE = 14.1% [95%CI: (5.7–22.7)] and RRE = 43.2% [95%CI: (30.5–55.8)] at a 2-year follow-up and RRE = 8.4% [95%CI: (10.2–15.8) and RRE = 33.10% [95%CI: (20.8–45.4)] at a 3-year follow-up, respectively. The longest retention was demonstrated by auto-polymerising and light-polymerising sealants showing RRE = 70.0% [95%CI: (48.0–92.1)] and RRE = 57.8% [95%CI: (38.6–76.9)], respectively, over a 5-year follow-up period .In contrast, the authors of the Bagherian 2018 publication compared the retention rate for conventional flowable composite versus conventional sealants. According to a meta-analysis based on nine RCTs, a statistically significantly higher retention rate was shown for flowable composite compared to conventional sealants – OR = 2.387 [95%CI: (1.047–5.444)] .The authors of the publications Bagheri 2022  and AlsaThe Muller-Bolla 2006 meta-analysis compared the probability of maintaining complete retention when using different subtypes of resin-based sealants . According to the results of the publication, there was no statistically significant difference in the maintenance of complete retention for light-cured RBS compared to auto-polymerised RBS between 6 and 60 months. However, a statistically significant 20% reduced probability of maintaining complete retention was found for fluoride-containing RBS compared to light-cured RBS at 48 (2 RCTs) and 54 (1 RCT) months, respectively – RR = 0.80 [95%CI: (0.72–0.89)] and RR = 0.80 [95%CI: (0.68–0.93)] .In the Alirezaei 2018 publication, the authors compared the retention rate for resin-based FS versus GIC  at 6 months after application. Based on 28 RCTs, there was a statistically significantly higher retention rate for resin-based FS compared to GIC – OR = 6.006 [95%CI: (3.226–11.183)]. Furthermore, when analysed in subgroups against GIC subtypes, higher retention rates were also obtained for resin-based FS compared with high-viscosity GIC (OR = 4.091 [95%CI: (1.680–9.963)]), low-viscosity GIC (OR = 5.093 [95%CI: (2.390–10.852)]) and resin-modified GIC (OR = 16.785 [95%CI: (2.355–119.632)]) ) and a result indicating a higher odds of loss of retention with GI sealant compared to resin-modified GI over a 2-3-year follow-up period OR = 3.21 [95%CI: (1.87–5.51)] .The characteristics and individual results of the study regarding the retention of specific types of permanent tooth fissure sealants are presented below Table .Based on the results of studies found in the systematic review, the effectiveness of fissure sealants in preventing the occurrence or development of caries was assessed. Publications comparing, among other things, sealants with no intervention and other preventive methods were analysed, as well as studies comparing different types of fissure sealants.The results of the studies clearly indicate that, compared to no intervention, sealing permanent teeth reduces the odds of caries occurrence or development , 23, 24.In this regard, it should be emphasised that there are significant differences when comparing RBS with GIC in terms of retention rate. The results of the Alirezaei 2018 meta-analysis show a clearly superior retention rate in favour of RBS. This may be influenced by, among other things, “higher wear resistance and compressive strength of RBSs, as well as their micromechanical bonding to the tooth structure after etching procedures” .Meanwhile, research findings suggest that the caries prevention effect of GIC-based sealant may not be directly related to retention. A 2013 study by Mickenautsch found that the risk of loss of complete retention material increased the risk of caries development with RBS, but not with GIC-based sealant , 28.According to the results of studies comparing fissure sealant with fluoride varnish, it is not possible to determine with certainty which of these methods is more effective. Three studies reported no statistically significant differences between fissure sealant and fluoride varnish in terms of caries incidence , 17 or cThere were no systematic reviews in this umbrella review that met the inclusion criteria in terms of clinical treatment time and patient acceptability (as outcomes).To complete the analysis, databases and websites of scientific societies were manually searched for clinical practice guidelines on tooth sealing. Publications from the last 10 years were searched for. The conclusions of the recommendations are presented below.Found documents clearly indicate that sealants can be used on permanent teeth as a caries prevention method , 29–34. The European Academy of Paediatric Dentistry guidelines emphasise that “pit and fissure sealing prevents new occlusal caries in permanent molars and is able to arrest existing non-cavitated lesions” .The 2014 Scottish Intercollegiate Guidelines Network indicated that ‘resin-based fissure sealants should be applied to the permanent molars of all children as early after eruption as possible’ and ‘glass-ionomer sealants may be considered if the application of a resin-based sealant is not possible’ . The docConsidering the above data, it is worth noting the very small number of available guidelines addressing tooth sealing issues with a global reach  published in the last 10 years. The most recent guidelines comprehensively addressing the topic of tooth sealing were published in 2016. It would therefore seem reasonable to issue an update of the guidelines on the sealing of permanent teeth.The economic factor should also be taken into account when analysing issues related to dental prevention. An Akinlotan 2017 systematic review targeted at the cost-effectiveness analysis of sealants compared to no intervention or other caries prevention was found . It idenIn studies comparing dental sealing with other methods of caries prevention, it was not possible to conclude definitively which method was more cost-effective . Only one study found was comparing the use of resin to glass-ionomer sealants, which indicated that light-emitting diode thermocured glass-ionomer sealants were more costly but also more effective than the composite resin group , 39. HowWhen analyzing other issues related to the effectiveness of sealing of pits and fissures, it should also be borne in mind that elements such as using adhesive systems and preparation of tooth surfaces prior to fissure sealants placement may be important. In a systematic review, one of the assumptions of which was “evaluate fissure sealant retention with and without the use of an adhesive system”, it was shown that the use of adhesive systems beneath fissure sealants can significantly increase retention . ResultsDental sealing is an effective method for the prevention of dental caries. Compared to no intervention, it reduces the risk of caries occurrence/development. On the basis of the systematic reviews found, it is not possible to conclude clearly which type of sealant is most effective in preventing caries. There are data indicating better results in terms of the retention rate of resin-based FS, but this cannot be the basis for concluding an absolute superiority of this type of material. It is also not possible to state conclusively whether dental sealing is more effective than other methods of caries prevention (e.g. fluoride varnish).Further studies  comparing retention over a long follow-up period (more than 5 years) are required, in particular regarding the comparison of resin-based FS retention with GI sealant and the effect of retention on caries risk for individual sealants.Only publications in English were included in the review. The studies found were characterised by high heterogeneity and used varied methods of presenting the analysed data. The results of the systematic reviews are limited due to the small number of high-quality studies . It should also be considered that the populations of children, adolescents and adults were not analysed separately .Below is the link to the electronic supplementary material.Supplementary Material 1


Proteobacteria and Actinobacteriota were found in the rhizosphere soil as the main bacterial phyla, and the main fungal phyla were Ascomycota and Mortierellomycota. The soil bacterial and fungal communities under organic fertilizer were distinct from CK. Furthermore, redundancy analysis (RDA) directed that changes in bacterial communities were related to soil properties like pH, available phosphorus (AP), and total organic carbon (TOC), while pH, AP and TP, were crucial contributors in regulating fungal distribution. The correlation between soil parameters and bacteria or fungi varied with the application of biochar and organic fertilizers, and the interaction between the bacteria and fungi in organic fertilizer treatments formed more connections compared with biochar treatments. Our results indicated that biochar was superior to organic fertilizer under the contents set up in this study, and soil parameters increased with biochar and organic fertilizer application rate. The diversity and structure of soil bacteria and fungi differed with the application of biochar and organic fertilizer. The research provides a reference to rational application of organic fertilizer and biochar improvement in saline-alkali soil.The biochar and organic fertilizer amendment have been used as an effective practice to increase soil fertility. Nevertheless, the mechanisms of microbial community response to organic fertilizer and biochar application on saline-alkali soil have not been clarified. This study investigated the effects at different concentrations of organic fertilizer and biochar on the microbial community of wheat rhizosphere soil under field experiment in the Yellow River Delta , using high-throughput sequencing technology. Biochar and organic fertilizer significantly influenced in most soil parameters ( Restricted by salinity stress and nutrient deficiencies, the vegetation structure in this area is simple and biodiversity is low (The Yellow River Delta (YRD), located in the warm-temperate zone, is gradually being degraded as one of the important deltaic agricultural economic zones in China . The saly is low . Soil miy is low . ConsequOrganic fertilizers are a positive option for regulating soil properties and plant growth in degraded soil . ApplicaBiochar has attracted tremendous attention for its soil ameliorating effects, and it enhances carbon storage, soil fertility and quality, and contaminant immobilization and transformation . BiocharTriticum aestivum) is a leading staple crop and is cultivated all over the world, with approximately 2.1 million km2 under cultivation . It was derived from apple shoots and processed at a temperature of 450°C for 1 day. The biochar had a pH value of 7.52 and an electrical conductivity (EC) of 0.35 ms/cm. And it contained 70.2% carbon, 0.35% nitrogen, 0.13% available phosphorus, and 1.53% available potassium. Organic fertilizer was provided by Yangfeng Agricultural Technology Co., Ltd. , based on maize straw and mushroom residue as the main composting substrate. The pH value of organic fertilizer was 7.94, with an EC of 3.25 ms/cm. The organic fertilizer had a high organic matter content more than 60% and nitrogen, phosphorus, and potassium contents more than 6%.2.2.Triticum aestivum L.) was sown in October 2017and harvested in June 2018.We established six treatments with three replications: no biochar or organic fertilizer (CK); low biochar (BL): 10.0 t/ha; medium biochar (BM): 20.0 t/ha; high biochar (BH): 30.0 t/ha; low organic fertilizer (ML): 7.5 t/ha; medium organic fertilizer (MM): 10.0 t/ha. Test plot was designed in random block design with three replicates, the plot area was 10 m × 15 m with 1 m gaps between plots. Organic fertilizer and biochar were spread on the soil surface and then evenly tilled 0–20 cm before planting the crop. Other field management followed local management practice. At the end of the field trial, wheat rhizosphere soil was obtained from the tilled area (0–20 cm) and collected and processed according to Field experiments were made in the Yellow River Delta Institute of Modern Agriculture, Shandong Academy of Agricultural Sciences, Dongying, China . The primary soil type of the experimental plot was a typical saline-alkali of YRD, the specific texture and type of which are shown in 2.3.3 and measured on a continuous flow analyzer . Soil total phosphorus (TP) was measured by wet digestion with HClO4-H2SO4 and quantified using inductively coupled plasma emission spectrometry . Available potassium (AK) was with CH3COONH4 (pH 7.0) and measured by inductively coupled plasma emission spectrometer . Organic matter in soil was quantified using a potassium dichromate oxidation and carbon analyzer .Soil moisture content (M) was measured by the weight method. pH was measured with a water quality analyzer (Shanghai Lechen LC-MP-41 T). Soil electrical conductivity (EC) was measured at 10 cm soil level with a conductivity meter (SANXIN SX836). Other nutrients were assayed according to our previous study . Alkalin2.4.DNA was extracted from wheat rhizosphere soil samples by FastDNA® Spin Kit for Soil  and the quality of the extraction was checked by NanoDrop 2000 luminometer. The extracted DNA was amplified by polymerase chain reaction (PCR) technique. The 16S gene in the V3-V4 region of the rhizosphere soil samples was sequenced using primers 338F (5′-ACTCCTACGGGAGGCAGCAG-3′) and 806R (5′-GGACTACHVGGGTATCTAAT-3′), while the internal transcribed spacer (ITS) were sequenced using primers ITS1F (5′-CTTGGTCATTTAGAGGAAGTAA-3′) and ITS2R (5′-GCTGCGTTCTTCATCGATGC-3′). All sequencing was performed in triplicate and the results obtained are stored in the NCBI SRA database (PRJNA987399).2.5.All data were calculated using Excel 2023 for mean and standard deviation. Duncan multiple range test and Pearson correlation analysis were conducted with DPS Statistics 18.10. Data related to microorganisms are counted and processed on the Majorbio Cloud Platform3.3.1.p < 0.05), apart from M, pH, TN and TP. Compared to CK, all treatments significantly reduced the EC and increased AK (p < 0.05). The concentration of AN was significantly increased in BH as compared to CK and the BL treatment (p < 0.05), while being no significantly different from the other treatments. In comparison to CK, AP levels were significantly increased under BL, BM, and BH treatments (p < 0.05), however, the AP levels were also significantly decreased by the ML and MM treatments compared with CK (p < 0.05), but the increase was lower than the BL, BM, and BH treatments. The level of TOC was significantly higher in the BL, BM, and BH treatments than in CK (p < 0.05), while in the ML and MM treatments compared to CK no obvious changes were observed. The TC level was significantly higher in the BL, BM, BH and MM treatments as compared to CK and the ML treatment (p < 0.05).The impact of organic fertilizer and biochar application on the soil properties and nutrient profile of saline-alkali soil is shown in 3.2.p > 0.05). Nevertheless, the Shannon index of the bacterial communities was significantly increased in the BM treatment versus with the CK and MM treatment (p < 0.05), and was not significantly affected compared with others. When compared to CK, the OTUs or Shannon and Chao1 indices of the fungal communities under biochar amendment and organic fertilizer treated were no significant differences (p > 0.05).After read-quality filtering, 1,378,473 high-quality bacterial sequences and 1,017,877 high-quality fungal sequences were obtained. Bacterial and fungal sequences in this study were clustered into 2,326 and 309 OTUs, respectively, when grouped at 97% sequence similarity. Bacterial and fungal OTUs sparsity curves inclined towards a saturation plateau, which demonstrated that the data were large enough to detect most of the bacterial and fungal taxa in the rhizosphere soil . As show3.3.After classification analysis, wheat rhizosphere soil was identified for 32 bacterial phyla and 11 fungal phyla. The most abundant bacterial phyla were Proteobacteria, Actinobacteriota, Acidobacteriota, Bacteroidota, and Chloroflexi across the soil samples, which represented more than 80% of the total bacterial population . Of thesSphingomonas, norank_f__Geminicoccaceae, Skermanella and Arthrobacter were the top 4 dominant genera, and their relative abundances together represented approximately 13.4% of all sequences  at the OTU level ,B. CoordAnalysis by LEfSe showed that there were 35 bacterial and 14 fungal taxa enriched  score > 2.0) in the six treatments . The bacThe Redundancy analysis (RDA) was used to explain the impact of soil parameters on microbial populations at the genus level. These soil indicators elucidated 46.09% of the total variation in the soil bacterial community  and TOC (p < 0.05), while Actinobacteriota was significant positively associated with EC (p < 0.01), Acidobacteriota was significant positively associated with the TN (p < 0.01) and TOC (p < 0.05), Chloroflexi was significantly positively associated with the TN (p < 0.01), and Firmicutes was significant positively associated with the M (p < 0.01) (p < 0.05), while Basidiomycota was significant positively associated with TC (p < 0.05), pH (p < 0.05), AP (p < 0.05), and AK (p < 0.01)  . Correla < 0.01) .3.4.The complexity of the interactions within the microbial communities and soil parameter under biochar and organic fertilizer application was conducted by to assess their topological properties. The results showed that there was a difference between the microbial communities based on the addition of biochar and organic fertilizer . For bacTo investigate the potential interactions between bacteria and fungi in wheat soil after the application of biochar and organic fertilizer, we constructed a correlation network of microbial communities . Supplem4.p > 0.05). We found in this research that the EC value of the soil decreases with the addition of biochar and organic fertilizer. Previous study has also showed a similar decrease in soil Ec values when various organic additives were used to remediate the soil  in diversity of soil bacterial community compared to CK under the BM, which were consistent with It was shown that either biochar or fertilizer can change the structure of the soil microbial community and crop performance . Biocharp < 0.05) content, it can also partially explain the significant increase in TOC of biochar application compared to CK. Both Ascomycota (copiotrophic) and Basidiomycota (oligotrophic) play important roles in plant growth by improving nutrition and defense against pests (p < 0.05), pH (p < 0.05), AP (p < 0.05), and AK (p < 0.01), also increased with biochar addition and decreased with organic fertilizer addition without statistically significant. This may be one of the reasons why the TC, AP, AK of biochar, especially BH, is higher than those of organic fertilizers. Effects of biochar application on the composition and structure of soil microbial communities have been frequently reported . In thisst pests . Yao et norank_f__JG30-KF-CM45 increased with the increase of biochar and organic fertilizer concent, and was positively correlated with TP and TOC in biochar and organic fertilizer treatments, respectively, which suggested that norank_f__JG30-KF-CM45 may be beneficial for saline alkali land remediation. This result was consistent with norank_f__JG30-KF-CM45 was beneficial genus that might potentially promote tobacco growth. Nitrosospira. In this study, the addition of biochar had no effect on the abundance of Nitrosospira while the addition of organic fertilizer significantly increased the abundance of Nitrosospira, which was consistent with the result of Bacillus increased with biochar and organic fertilizer application rate, but only organic fertilizer application reached significant level. Bacillus species are commercially marketed as biopesticides, biofertilizers, and soil amendments  can be found in the article/ML contributed to the conception of the study and wrote the manuscript. YG and XG also contributed to the conception of the study. CC, HZ, and JL contributed to field investigation and sample acquisition. ZW, XL, and KY performed the experiments and data analyses. NS contributed to the editing and revising of the manuscript. All authors contributed to the article and approved the submitted version.


Lack of viral suppression (VS) among pregnant and breastfeeding women living with HIV poses challenges for maternal and infant health, and viral load (VL) monitoring via centralized laboratory systems faces many barriers. We aimed to determine the impact of point‐of‐care (POC) VL and targeted drug resistance mutation (DRM) testing in improving VS among pregnant and postpartum women on antiretroviral therapy.We conducted a pre/post‐intervention prospective cohort study among 820 pregnant women accessing HIV care at five public‐sector facilities in western Kenya from 2019 to 2022. The pre‐intervention or “control” group consisted of standard‐of‐care (SOC) centralized VL testing every 6 months and the post‐intervention or “intervention” group consisted of a combined strategy of POC VL every 3 months, targeted DRM testing, and clinical management support. The primary outcome was VS (VL ≤1000 copies/ml) at 6 months postpartum; secondary outcomes included uptake and turnaround times for VL testing and sustained VS.At 6 months postpartum, 321/328 (98%) of participants in the intervention group and 339/347 (98%) in the control group achieved VS . When assessing VS using a threshold of <40 copies/ml, VS proportions were lower overall (90−91%) but remained similar between groups. Among women with viraemia (VL>1000 copies/ml) who underwent successful DRM testing in the intervention group, all  had some DRMs and 20 (43%) had major DRMs (of which 80% were nucleos(t)ide reverse transcriptase inhibitor mutations). POC VL testing uptake was high (>89%) throughout pregnancy, delivery, and postpartum periods, with a median turnaround time of 1 day  for POC VL in the intervention group and 7 days  for SOC VL in the control group. Sustained VS throughout follow‐up was similar between groups with either POC or SOC VL testing .Our combined strategy markedly decreased turnaround time but did not increase VS rates, which were already very high, or sustained VS among pregnant and postpartum women living with HIV. Further research on how best to utilize POC VL and DRM testing is needed to optimize sustained VS among this population. MaternaRoutine VL monitoring while on ART is recommended in low‐ and middle‐income countries (LMICs) , but impWhile improved HIV VL monitoring would enhance the detection of viraemia (VL>1000 copies/ml), a variety of underlying causes exist for the lack of VS among pregnant and postpartum women, including HIV drug resistance mutations (DRMs) . AccordiWe conducted the Opt4Mamas study to evaluate if a combined strategy of higher frequency POC VL with targeted DRM testing and clinical decision support could improve VS rates among pregnant and postpartum women on ART in Kenya. We hypothesized that our combined strategy would facilitate earlier and more appropriate clinical decision‐making, resulting in improved treatment outcomes.22.1We conducted an open‐label, pre/post‐intervention (or intervention/control) prospective cohort study, enrolling pregnant women living with HIV during their ANC care and followed them through 6 months postpartum in five public‐sector HIV treatment facilities in Kenya from February 2019 to November 2022  adult (>17 years of age) pregnant female either already known or newly diagnosed with HIV; (2) at 32 weeks or less of gestational age; (3) with first ANC visit; (4) planning to return to the same facility for the remainder of her pregnancy and postpartum care; and (5) on ART or planning to initiate ART within 1 week. Women on third or salvage ART regimens  or receiving ANC or HIV care at another facility were excluded.2.4Our primary outcome was VS  by POC VL testing at 6 months postpartum . If a POC VL test was not available at 6 months postpartum, any available SOC test in the same window was used. Our secondary outcomes included VS defined by lower VL cutoffs and a set of process outcomes, such as uptake and turnaround time of VL testing results. We define major, minor, and accessory classifications for HIV drug resistance according to the Stanford HIV Resistance Database . We defiThe primary exposure was control versus intervention group. Participant clinical and socio‐demographic information as well as household characteristics (e.g. household commodities and food insecurity) were collected from all participants at enrolment. Other information, such as psychosocial and behavioural data (e.g. self‐reported adherence), were collected at every study visit.2.5Power for the study was for comparing the proportion of women with VS 6 months postpartum in the control versus intervention groups. Based on historical facility data, we expected approximately 75% VS in the control group. We estimated that 270 women per group would provide 80% power to detect an increase of 10% post‐intervention VS (i.e. 75% vs. 85%) using a chi‐squared test with α = 0.05. We aimed to screen 350 women in each group to account for an anticipated 25% of available women not enrolling, transferring out to other facilities, experiencing pregnancy loss or lost to follow‐up at 6 months postpartum. In February 2020, we generated additional power calculations given higher‐than‐expected baseline VS. We estimated that with 410 women per group and 90.5% VS in the control group, we would have approximately 80% power to detect a 50% decrease in the proportion unsuppressed (i.e. 9.5% vs. 4.7% unsuppressed).t‐tests for continuous variables. We describe VS by group at enrolment (any blood draw 0–90 days prior to enrolment), 3 and 6 months after enrolment, delivery, and 3 and 6 months postpartum . The primary analysis compared the observed proportion of women with VS at 6 months postpartum (primary outcome) in the control versus intervention groups using a modified Poisson regression model with robust standard error estimation, adjusting for facility, to obtain the adjusted relative risk (aRR) [a priori sensitivity analysis defined VS as VL<40 copies/ml and a post hoc analysis as VL<400 copies/ml. Further post hoc sensitivity analyses included: (a) adjusting for enrolment characteristics differing (α<0.05) by group, in case of confounding; and (b) using inverse probability weighting, to address missing outcomes. We also conducted a post hoc secondary analysis evaluating the effect of the intervention on SVS.We compared descriptive statistics for participant baseline characteristics by group using chi‐squared tests for categorical and sk (aRR) . An a pr33.1A total of 1105 women were assessed for study eligibility, of which 285 (26%) were excluded , gestational age was 19 weeks , gravida was 3 , parity was 2 , 423 (52%) had achieved a secondary education and 696 (85%) were married (Table p<0.001) and reported no food insecurity . Facility characteristics, ART regimen changes, VS during the course of the study and delivery outcomes can be found in Tables More women in the intervention group versus control group were on INSTI‐containing ART  by POC VL testing, and 256/269 (95%) in the control group by SOC VL testing  of participants in the intervention group and 339/347 (98%) in the control group achieved VS by POC VL testing . Our Clinical Management Committee recommended that 6 (12%) of the 48 women undergo an ART change, of which all six (100%) had an ART change documented by 6 months postpartum. In contrast, we recorded 37 episodes of VL>1000 copies/ml, among 29 (7%) control participants with no DRM tests requested in this group.In the intervention group, from enrolment up until 6 months postpartum, we identified 54 episodes of VL>1000 copies/ml, among 48 (11.7%) participants Table . In the 3.4Of the participants attending each study visit in the intervention group, 100%, 51%, 43%, 90%, 75% and 94% had a POC VL conducted at 0, 3 and 6 months after enrolment, delivery, 3 and 6 months postpartum, respectively  in intervention group and 332/366 (90.7%) in control group  , and major DRMs among these women may be important. POC VL and DRM testing was highly feasible in this setting, with rapid turnaround times, and resulted in a larger proportion of women undergoing these testing during pregnancy and postpartum periods.We did not observe any associations between our combined intervention and VS among pregnant and postpartum women. Our failure to demonstrate efficacy may be due to biased sampling of women better engaged in care, inability to implement POC VL testing with optimal fidelity, overall improvements in VS among the women over time and/or the increased use of dolutegravir‐containing ART which is equally or more potent than efavirenz‐containing ART −39. NoneThe evidence base regarding the utility of POC VL testing in improving clinical outcomes is mixed. We saw no efficacy on VS in our parallel, randomized controlled trial in children . A SouthAmong women with viraemia in our study who underwent successful DRM testing, all had some DRMs and 43% had major DRMs (with NNRTI K103N and NRTI M184V being the most common). A study conducted in Sierra Leone showed K103N as the most frequent DRM, occurring in 20% of pregnant women, with M184V in 11% . Among K4.1Ours is the first study to combine VL with DRM testing in optimizing VS among pregnant and postpartum women; however, it has limitations. First, Opt4Mamas could not be pursued as a randomized clinical trial as a limitation of its funding source, but we believed a contemporaneous intervention/control study, which had overlapping cohorts in time, was the next best robust study design to pursue. Second, our combined strategy of multiple interventions precludes the determination of the success or failure of any one component of the strategy. Additionally, layering on POC VL testing on top of routine care, where providers were not prevented from ordering routine SOC VL testing, further limits the interpretation of our findings. Third, some spillover effects from intervention to control participants may have occurred. Though our intervention package was only offered to intervention group participants, it was the same providers caring for control group participants. We observed greater fidelity in conducting SOC VL tests in the control group than expected and, anecdotally, increased confidence in facility staff over time in managing women with viraemia. Our randomized trial in children faced this same issue . Alterna5In a prospective cohort study with an intervention/control study design with the intervention consisting of a combined strategy of POC with higher frequency VL testing, targeted DRM testing and clinical decision‐making support versus SOC, we observed high rates of VS at 6 months postpartum in both groups and no difference between the intervention and control groups during pregnancy, at delivery or postpartum. Nonetheless, a sizeable number of women experienced viraemia, when considering SVS throughout pregnancy and postpartum periods, many of whom had major DRMs. POC VL uptake was high and DRM testing was feasible. Ultimately, it remains unclear what interventions pregnant/postpartum women with viraemia need to optimize VS, their health outcomes and help prevent vertical transmission.The authors declare no competing interests.Conceptualization—RCP, LLA, PO, IM and KKT.Data curation—NY and KKT.Access and verified data—NY, GWB and KKT.Formal analysis—GWB, NY, KKT, RCP, LLA and PO.Funding acquisition—RCP.Investigation—RCP, LLA, PO, IM, KKT, JW, LK and EK.Methodology—RCP, LLA, PO and KKT.Project administration—EB, PO, KKT, SAH, BO, LK, EK, NY, RCP and LLA.Resources—PO, KKT, JW, EK, FO, FO, BO, LK, EK, NY, LO, RCP and LLA.Software—GWB, NY, KKT, BO and LK.Supervision—EB, PO, KKT, JW, EK, FO, FO, BO, LK, EK, NY, LO, RCP, LLA and GCJ‐S.Validation—N/A.Visualization—GWB, NY, KKT and SAH.Writing, original draft—RCP, LLA, PO, KKT, GWB and SAH.Writing, review and editing—all coauthors.Decision to submit manuscript—RCP, LLA, PO and KKT.This work was supported by the National Institutes of Allergy and Infectious Diseases of the U.S. National Institutes of Health . Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Washington Institute of Translational Health Sciences and supported by the National Center for Advancing Translational Sciences of the NIH (UL1 TR002319).The funding sources or study sponsors had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.Ethical approval for this study has been obtained from the African Medical and Research Foundation (AMREF) and Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) Institutional Review Boards (IRBs) in Kenya, as well as the University of Washington and the University of Colorado Denver IRBs in the United States.  All study procedures were performed in accordance with the Declaration of Helsinki.Supplementary TextClick here for additional data file.Supplemental Figure 1Click here for additional data file.Supplemental TablesClick here for additional data file.