Global disease burden of and risk factors for acute lower respiratory infections caused by respiratory syncytial virus in preterm infants and young children in 2019: a systematic review and meta-analysis of aggregated and individual participant data.

BACKGROUND: Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation. METHODS: We conducted a systematic review and meta-analysis of aggregated data from studies published between Jan 1, 1995, and Dec 31, 2021, identified from MEDLINE, Embase, and Global Health, and individual participant data shared by the Respiratory Virus Global Epidemiology Network on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children younger than 2 years born prematurely. We conducted two-stage random-effects meta-regression analyses accounting for chronological age groups, gestational age bands (early preterm, <32 weeks gestational age [wGA], and late preterm, 32 to <37 wGA), and changes over 5-year intervals from 2000 to 2019. Using individual participant data, we assessed perinatal, sociodemographic, and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of supplemental oxygen and mechanical ventilation, or intensive care unit admission) by estimating pooled odds ratios (ORs) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis). This study is registered with PROSPERO, CRD42021269742. FINDINGS: We included 47 studies from the literature and 17 studies with individual participant-level data contributed by the participating investigators. We estimated that, in 2019, 1 650 000 (95% uncertainty range [UR] 1 350 000-1 990 000) RSV-associated ALRI episodes, 533 000 (385 000-730 000) RSV-associated hospital admissions, 3050 (1080-8620) RSV-associated in-hospital deaths, and 26 760 (11 190-46 240) RSV-attributable deaths occurred in preterm infants worldwide. Among early preterm infants, the RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than for all infants born at any gestational age. In the second year of life, early preterm infants and young children had a similar incidence rate but still a significantly higher hospitalisation rate (RR 2·26 [95% UR 1·27-3·98]) compared with all infants and young children. Although late preterm infants had RSV-associated ALRI incidence rates similar to that of all infants younger than 1 year, they had higher RSV-associated ALRI hospitalisation rate in the first 6 months (RR 1·93 [1·11-3·26]). Overall, preterm infants accounted for 25% (95% UR 16-37) of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. The factors identified to be associated with RSV-associated ALRI incidence were mainly perinatal and sociodemographic characteristics, and factors associated with severe outcomes from infection were mainly underlying medical conditions including congenital heart disease, tracheostomy, bronchopulmonary dysplasia, chronic lung disease, or Down syndrome (with ORs ranging from 1·40 to 4·23). INTERPRETATION: Preterm infants face a disproportionately high burden of RSV-associated disease, accounting for 25% of RSV hospitalisation burden. Early preterm infants have a substantial RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV can have a substantial public health impact by preventing RSV-associated ALRI and severe outcomes from infection in preterm infants. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe.

Report of the WHO technical consultation on the evaluation of respiratory syncytial virus prevention cost effectiveness in low- and middle-income countries, April 7-8, 2022.

Policymakers often rely on impact and cost-effectiveness evaluations to inform decisions about the introduction of health interventions in low- and middle-income countries (LMICs); however, cost-effectiveness results for the same health intervention can differ by the choice of parameter inputs, modelling assumptions, and geography. Anticipating the near-term availability of new respiratory syncytial virus (RSV) prevention products, WHO convened a two-day virtual consultation in April 2022 with stakeholder groups and global experts in health economics, epidemiology, and vaccine implementation. The objective was to review methods, parameterization, and results of existing cost-effectiveness analyses for RSV prevention in LMICs; identify the most influential inputs and data limitations; and recommend and prioritize future data gathering and research to improve RSV prevention impact estimates in LMICs. Epidemiological parameters identified as both influential and uncertain were those associated with RSV hospitalization and death, specifically setting-specific hospitalization rates and RSV-attributable death rates. Influential economic parameters included product price, delivery costs, willingness-to-pay for health on the part of potential donors, and the cost of RSV-associated hospitalization. Some of the influential parameters identified at this meeting should be more precisely measured by further research. Other influential economic parameters that are highly uncertain may not be resolved, and it is appropriate to use sensitivity analyses to explore these within cost-effectiveness evaluations. This report highlights the presentations and major discussions of the meeting.

Surgery in Nonalcoholic Cirrhosis: Clinical Outcomes, Healthcare Utilization, and Cost Analysis.

BACKGROUND: Patients with cirrhosis are at increased risk of complications following surgery due to multiple factors, including portal hypertension and alterations in hemostasis. Improvements in perioperative management as well as risk stratification scores have helped improve outcomes, but gaps remain in our understanding of the cost and morbidity of cirrhotic patients who undergo surgery. METHODS: We conducted a case-control study using the IBM Electronic Health Record (EHR) MarketScan Commercial Claims (MSCC) database from January 1, 2007 to December 31, 2017. Nonalcoholic cirrhotic patients who underwent surgery were identified based on International Classification of Diseases, Ninth Revision (ICD-9)/Tenth Revision (ICD-10) codes for multiple surgical categories and matched with controls with cirrhosis who did not undergo surgery in this time period. A total of 115,512 patients were identified with cirrhosis, of whom 19,542 (16.92%) had surgery. Medical history and comorbidities were compiled, and outcomes in the six-month period following surgery were analyzed between matched groups. A cost analysis was performed based on claims data. RESULTS: Nonalcoholic cirrhotic patients who underwent surgery had a higher comorbidity index at baseline compared with controls (1.34 vs. 0.88, P<0.0001). Mortality was increased in the surgery group (4.68% vs. 2.38%, P<0.001) in the follow-up period. The surgical cohort had higher rates of adverse hepatic outcomes, including hepatic encephalopathy (5.00% vs. 2.50%, P<0.0001), spontaneous bacterial peritonitis (0.64% vs. 0.25%, P<0.001), and higher rates of septic shock (0.66% vs. 0.14%, P<0.001), intracerebral hemorrhage (0.49% vs. 0.04%, P<0.001), and acute hypoxemic respiratory failure (7.02% vs. 2.31%, P<0.001). Healthcare utilization analysis revealed increased total claims per patient in the surgical cohort (38.11 vs. 28.64, P<0.0001), higher inpatient admissions (6.05 vs. 2.35, P<0.0001), more outpatient visits (19.72 vs. 15.23, P<0.0001), and prescription claims per patient (11.76 vs. 10.61, P<0.0001) in the postsurgical period. The likelihood of at least one inpatient stay was higher in the surgical cohort (51.63% vs. 22.32%, P<0.0001), and inpatient stays were longer (4.99 days vs. 2.09 days, P<0.0001). The total cost of health services was significantly increased per patient in the postoperative period for patients undergoing surgery ($58,246 vs. $26,842, P<0.0001), largely due to increased inpatient costs ($34,446 vs. $10,789, P<0.0001). CONCLUSION: Nonalcoholic cirrhotics undergoing surgery experienced worse outcomes with respect to adverse hepatic events and complications, including septic shock and intracerebral hemorrhage. Claims and cost analysis showed a significant increase in health expenditure in the surgical group, largely due to the cost of more frequent and longer inpatient admissions.

Value profile for respiratory syncytial virus vaccines and monoclonal antibodies.

Respiratory syncytial virus (RSV) is the predominant cause of acute lower respiratory infection (ALRI) in young children worldwide, yet no licensed RSV vaccine exists to help prevent the millions of illnesses and hospitalizations and tens of thousands of young lives taken each year. Monoclonal antibody (mAb) prophylaxis exists for prevention of RSV in a small subset of very high-risk infants and young children, but the only currently licensed product is impractical, requiring multiple doses and expensive for the low-income settings where the RSV disease burden is greatest. A robust candidate pipeline exists to one day prevent RSV disease in infant and pediatric populations, and it focuses on two promising passive immunization approaches appropriate for low-income contexts: maternal RSV vaccines and long-acting infant mAbs. Licensure of one or more candidates is feasible over the next one to three years and, depending on final product characteristics, current economic models suggest both approaches are likely to be cost-effective. Strong coordination between maternal and child health programs and the Expanded Program on Immunization will be needed for effective, efficient, and equitable delivery of either intervention. This 'Vaccine Value Profile' (VVP) for RSV is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations, and in collaboration with stakeholders from the WHO headquarters. All contributors have extensive expertise on various elements of the RSV VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

An accurate, efficient, and economical identification technology for black twig borer based on species-specific cytochrome C oxidase subunit I PCR assay.

Xylosandrus compactus (Eichhoff) (Coleoptera: Curculionidae, Scolytinae) is a worldwide invasive species that causes huge economic loss and environmental damage in many countries. Traditional morphological characteristics make it hard to identify scolytines due to their tiny size. Besides, the intercepted insect samples are incomplete, and the limitation of insect (larvae and pupae) morphology makes morphological identification more difficult. The majority of the damage is caused by adults and fungi that serve as nutrition for their larvae. They destroy plant trunks, branches, and twigs, affecting plant transport tissues in both weak and healthy plants. An accurate, efficient, and economical molecular identification technique for X. compactus not restricted by professional taxonomic knowledge is necessary. In the present study, a molecular identification tool based on the mitochondrial DNA gene, cytochrome C oxidase subunit I (COI) was developed. A species-specific COI (SS-COI) PCR assay was designed to identify X. compactus regardless of the developmental stage. Twelve scolytines commonly found in eastern China, namely Xylosandrus compactus, X. crassiusculus, X. discolor, X. germanus, X. borealis, X. amputates, X. eupatorii, X. mancus, Xyleborinus saxesenii, Euwallacea interjectus, E. fornicatus, and Acanthotomicus suncei, were included in the study. Additionally, specimens of X. compactus from 17 different areas in China, as well as a specimen collected from the United Stated, were also analyzed. Results demonstrated the accuracy and high efficiency of the assay, regardless of the developmental stage or the type of specimen. These features provide a good application prospect for fundamental departments and can be used to prevent the harmful consequences of the spread of X. compactus.

Pharmacokinetics of YK-1169 in healthy subjects and pharmacokinetic/pharmacodynamic analysis by Monte Carlo simulation.

OBJECTIVE: This study (NCT05588531) aimed to evaluate the safety and pharmacokinetics of cefepime-avibactam (YK-1169) in healthy Chinese subjects and explore the optimal regimen for treating carbapenem-resistant Klebsiella pneumoniae (CRKP) based on the pharmacokinetic/pharmacodynamic evaluation. METHODS: YK-1169 single-ascending doses (0.5, 1.25, 2.5 or 3.75 g, 2-h infusion) and multiple doses (2.5 or 3.75 g every 8 h [q8h], 2-h infusion) given for 7 days were evaluated in pharmacokinetic studies. Subjects were randomized to receive cefepime (2 g), avibactam (0.5 g) or YK-1169 (2.5 g) to assess drug-drug interactions. The minimum inhibitory concentrations (MICs) of YK-1169 were determined by the broth microdilution method. Monte Carlo simulation was used to evaluate 10 different dose regimens. RESULTS: Cefepime and avibactam both showed a linear pharmacokinetic profile. No accumulation was found after multiple doses. The cefepime Cmax,ss and AUC0-∞,ss were 9.20 and 16.0 µg/mL, 407.2 and 659.45 µg·h/mL in the 2.5 and 3.75 g multiple-dose groups, respectively. The avibactam Cmax,ss and AUC0-∞,ss were 0.545 and 0.837 µg/mL, 53.31 and 79.55 µg·h/mL in the 2.5 and 3.75 g multiple-dose groups, respectively. Cefepime and avibactam did not affect each other's pharmacokinetics. No serious adverse events occurred. All regimens achieved 90% probability of target attainment (PTA) goals when the MIC was ≤8 mg/L. The regimens of 2.5 (q8h, 2-h infusion), 3.75 (q8h, 2-, 3- and 4-h infusions) and 7.5 g (24-h continuous infusion) reached a 90% cumulative fraction of response. CONCLUSION: YK-1169 had good antibacterial activity against CRKP and could be an option for CRKP infections. The regimen of 2.5 g q8h intravenously guttae (ivgtt) 2 h should be considered in future clinical trials.

Cost-effectiveness of pharmaceutical strategies to prevent respiratory syncytial virus disease in young children: a decision-support model for use in low-income and middle-income countries.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of respiratory disease in young children. A number of mathematical models have been used to assess the cost-effectiveness of RSV prevention strategies, but these have not been designed for ease of use by multidisciplinary teams working in low-income and middle-income countries (LMICs). METHODS: We describe the UNIVAC decision-support model (a proportionate outcomes static cohort model) and its approach to exploring the potential cost-effectiveness of two RSV prevention strategies: a single-dose maternal vaccine and a single-dose long-lasting monoclonal antibody (mAb) for infants. We identified model input parameters for 133 LMICs using evidence from the literature and selected national datasets. We calculated the potential cost-effectiveness of each RSV prevention strategy (compared to nothing and to each other) over the lifetimes of all children born in the year 2025 and compared our results to a separate model published by PATH. We ran sensitivity and scenario analyses to identify the inputs with the largest influence on the cost-effectiveness results. RESULTS: Our illustrative results assuming base case input assumptions for maternal vaccination ($3.50 per dose, 69% efficacy, 6 months protection) and infant mAb ($3.50 per dose, 77% efficacy, 5 months protection) showed that both interventions were cost-saving compared to status quo in around one-third of 133 LMICs, and had a cost per DALY averted below 0.5 times the national GDP per capita in the remaining LMICs. UNIVAC generated similar results to a separate model published by PATH. Cost-effectiveness results were most sensitive to changes in the price, efficacy and duration of protection of each strategy, and the rate (and cost) of RSV hospital admissions. CONCLUSIONS: Forthcoming RSV interventions (maternal vaccines and infant mAbs) are worth serious consideration in LMICs, but there is a good deal of uncertainty around several influential inputs, including intervention price, efficacy, and duration of protection. The UNIVAC decision-support model provides a framework for country teams to build consensus on data inputs, explore scenarios, and strengthen the local ownership and policy-relevance of results.

Outcomes, Mortality, and Cost Burden of Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis.

BACKGROUND AND AIMS: Cirrhosis is associated with an increased risk of acute kidney injury (AKI) and hepatorenal syndrome (HRS). Healthcare utilization and cost burden of AKI and HRS in cirrhosis is unknown. We aimed to analyze the health care use and cost burden associated with AKI and HRS in patients with cirrhosis in the United States by using real-world claims data. METHODS: We conducted a case-control study using the Truven Health MarketScan Commercial Claims databases from 2007-2017. A total of 34,398 patients with cirrhosis with or without AKI and 4,364 patients with cirrhosis with or without HRS were identified using International Classification of Diseases, Ninth or Tenth Revision, codes and matched 1:1 by sociodemographic characteristics and comorbidities using propensity scores. Total and service-specific were quantified for the 12-months following versus the 12-months before the first date of AKI or HRS diagnosis and over 12-months following a randomly selected date for cirrhosis controls to capture entire disease burdens. RESULTS: The AKI and HRS group had a higher number of comorbidities and were associated with higher rates of readmission and mortality. The AKI and HRS groups had a significantly higher prevalence of ascites, spontaneous bacterial peritonitis (SBP), encephalopathy, gastrointestinal bleeding, septic shock, pulmonary edema, and respiratory failure. Compared to patients with cirrhosis only, AKI was associated with higher number of claims per person (AKI vs. cirrhosis only, 60.30 vs. 47.09; p<0.0001) and total annual median health care costs (AKI vs. cirrhosis only, $46,150 vs. $26,340; p<0.0001). Compared to patients with cirrhosis only, the HRS cohort was associated with a higher number of claims per person (HRS vs. cirrhosis only, 44.96 vs. 43.50; p<0.0009) and total annual median health care costs (HRS vs. cirrhosis only, $34,912 vs. $23,354; p<0.0001). Inpatient costs were higher than the control cohort for AKI (AKI vs. cirrhosis only, $72,720 vs. $29,111; p<0.0001) and HRS (HRS vs. cirrhosis only, $ 98,246 vs. $27,503; p<0.0001). Compared to the control cohort, AKI and HRS had a higher rate of inpatient admission, mean number of inpatient admissions, and mean total length of stay. CONCLUSIONS: AKI and HRS are associated with higher health care utilization and cost burden compared to cirrhosis alone, highlighting the importance for improved screening and treatment modalities.

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. METHODS: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). FINDINGS: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). INTERPRETATION: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

Global Disease Burden of Respiratory Syncytial Virus in Preterm Children in 2019: A Systematic Review and Individual Participant Data Meta-Analysis Protocol.

Existing guidelines on respiratory syncytial virus (RSV) prophylaxis differ greatly by gestational age (GA) and other underlying risk factors, highlighting the data gaps in RSV disease burden among preterm infants. We will conduct a systematic review and individual participant data (IPD) meta-analysis of RSV global disease burden among preterm-born children. Three databases, Medline, Embase, and Global Health, will be searched for relevant studies on RSV disease burden for 2019 or before in preterm-born children published between 1 January 1995 and 31 December 2021. IPD will be sought by contacting the investigators identified from published literature and from existing collaboration networks. One-stage and 2-stage random-effects meta-analyses will be used to combine information from IPD and non-IPD studies to produce summary RSV burden estimates of incidence rate, hospital admission rate, and in-hospital case fatality ratio. The framework will be extended to examine subgroup(s) with the most substantial RSV disease burden.

Wilson's Disease: An Analysis of Health Care Use and Cost Burden of Commercially Insured Adults in the United States.

The economic and health care use burdens of Wilson's disease (WD) are unknown. In this study, we aimed to quantify this health care resource use and economic burden. We performed a retrospective case-control analysis of individuals in the Truven Health MarketScan Commercial Claims database (2007-2017). Using propensity scores, 424 WD cases were matched 1:1 to chronic liver disease (CLD) controls without WD. Total and service-specific parameters, expressed in monthly averages, were quantified for the 6-month pre-WD diagnosis versus the 12-month period after diagnosis. Wilcoxon signed-rank tests and McNemar tests were used to examine incremental differences in burden between cases and controls. Adjusted multivariable generalized linear regression models were used to compare health care burdens. Relative to the 6-month pre-WD diagnosis, the 12 months after diagnosis had more claims per patient (2.87 vs. 3.35; P < 0.0001) and increased per patient health care costs (US $2,089 vs. US $3,887; P < 0.0001). WD cases incurred US $1,908 more in total unadjusted costs compared to controls in the 12-month postindex date monthly averages. The increase in claims was primarily due to outpatient visits (1.62 vs. 1.82) and pharmaceutical claims (1.11 vs. 1.37). Cases also had higher health care costs for inpatient admissions (US $559 vs. US $1,264), outpatient visits (US $770 vs. US $1,037), and pharmaceutical claims (US $686 vs. US $1,489). Conclusion: WD is associated with significant health care cost and use burdens driven by increased inpatient admissions, outpatient visits, and pharmaceutical claims.

Preinvasion Assessment of Exotic Bark Beetle-Vectored Fungi to Detect Tree-Killing Pathogens.

Exotic diseases and pests of trees have caused continental-scale disturbances in forest ecosystems and industries, and their invasions are considered largely unpredictable. We tested the concept of preinvasion assessment of not yet invasive organisms, which enables empirical risk assessment of potential invasion and impact. Our example assesses fungi associated with Old World bark and ambrosia beetles and their potential to impact North American trees. We selected 55 Asian and European scolytine beetle species using host use, economic, and regulatory criteria. We isolated 111 of their most consistent fungal associates and tested their effect on four important southeastern American pine and oak species. Our test dataset found no highly virulent pathogens that should be classified as an imminent threat. Twenty-two fungal species were minor pathogens, which may require context-dependent response for their vectors at North American borders, while most of the tested fungi displayed no significant impact. Our results are significant in three ways; they ease the concerns over multiple overseas fungus vectors suspected of heightened potential risk, they provide a basis for the focus on the prevention of introduction and establishment of species that may be of consequence, and they demonstrate that preinvasion assessment, if scaled up, can support practical risk assessment of exotic pathogens.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Assessment of probiotic adhesion and inhibitory effect on Escherichia coli and Salmonella adhesion.

In this study, we screened bacterial strains to identify specific probiotics to treat pig diarrhea caused by Escherichia coli or Salmonella. The potential probiotics were assayed for their survival in gastrointestinal solution, their antimicrobial activity, cell-surface properties, adhesion to Caco-2 cells, and inhibition of pathogen adhesion. Nine out of the 20 strains tested showed high tolerance of a simulated gastrointestinal environment and six strains exerted antagonistic effects against enterohemorrhagic E. coli (EHEC) O157:H7 and Salmonella Typhimurium MQ. Lactobacillus johnsonii pDX1e exhibited a higher potent antibacterial activity. Four strains (pDX1a, pDX1e, pDX3a, and pDX5a) displayed auto-aggregation, hydrophobicity, and adhesion to Caco-2 cells similar to those of the reference strain Lacticaseibacillus rhamnosus GG (LGG). Enterococcus durans pDX5a showed the highest adhesion capacity (13.86%), followed by the reference strain LGG (11.20%). All the tested strains competitively suppressed the attachment of pathogens to Caco-2 cells (by 30.73-55.18%); L. johnsonii pDX1e and Ent. durans pDX5a significantly inhibited the adhesion of pathogens by substitution and exclusion, respectively. Therefore, pDX1e and pDX5a were selected as probiotic strains for further investigation and application.

Hospital utilization rates for influenza and RSV: a novel approach and critical assessment.

BACKGROUND: Influenza and respiratory syncytial virus (RSV) contribute significantly to the burden of acute lower respiratory infection (ALRI) inpatient care, but heterogeneous coding practices and availability of inpatient data make it difficult to estimate global hospital utilization for either disease based on coded diagnoses alone. METHODS: This study estimates rates of influenza and RSV hospitalization by calculating the proportion of ALRI due to influenza and RSV and applying this proportion to inpatient admissions with ALRI coded as primary diagnosis. Proportions of ALRI attributed to influenza and RSV were extracted from a meta-analysis of 360 total sources describing inpatient hospital admissions which were input to a Bayesian mixed effects model over age with random effects over location. Results of this model were applied to inpatient admission datasets for 44 countries to produce rates of hospital utilization for influenza and RSV respectively, and rates were compared to raw coded admissions for each disease. RESULTS: For most age groups, these methods estimated a higher national admission rate than the rate of directly coded influenza or RSV admissions in the same inpatient sources. In many inpatient sources, International Classification of Disease (ICD) coding detail was insufficient to estimate RSV burden directly. The influenza inpatient burden estimates in older adults appear to be substantially underestimated using this method on primary diagnoses alone. Application of the mixed effects model reduced heterogeneity between countries in influenza and RSV which was biased by coding practices and between-country variation. CONCLUSIONS: This new method presents the opportunity of estimating hospital utilization rates for influenza and RSV using a wide range of clinical databases. Estimates generally seem promising for influenza and RSV associated hospitalization, but influenza estimates from primary diagnosis seem highly underestimated among older adults. Considerable heterogeneity remains between countries in ALRI coding (i.e., primary vs non-primary cause), and in the age profile of proportion positive for influenza and RSV across studies. While this analysis is interesting because of its wide data utilization and applicability in locations without laboratory-confirmed admission data, understanding the sources of variability and data quality will be essential in future applications of these methods.

Research on Optimization of Healthcare Waste Management System Based on Green Governance Principle in the COVID-19 Pandemic.

At present, strategies for controlling the COVID-19 pandemic have made significant and strategic strides; however, and the large quantities of healthcare treatment waste have become another important "battlefield". For example, in Wuhan, the production rate of healthcare waste in hospitals, communities, temporary storage, and other units was much faster than the disposal rate during the COVID-19 pandemic. Improving the efficiency of healthcare waste transfer and treatment has become an important task for government health and environmental protection departments at all levels. Based on the situation of healthcare waste disposal in Wuhan during the critical period of the pandemic, this paper analyzes and studies green governance principles and summarizes the problems that exist in the current healthcare waste management system. Through the establishment of temporary storage facilities along transit routes, digital simulation and bionic experiments were carried out in the Hongshan District of Wuhan to improve the efficiency of healthcare waste transfer. Furthermore, this study discusses the coordination and cooperation of government, hospitals, communities, and other departments in the healthcare waste disposal process and provides guiding suggestions for healthcare waste disposal nationwide in order to deal with potential risks and provide effective references in all regions.

Respiratory syncytial virus seasonality and prevention strategy planning for passive immunisation of infants in low-income and middle-income countries: a modelling study.

BACKGROUND: Respiratory syncytial virus (RSV) represents a substantial burden of disease in young infants in low-income and middle-income countries (LMICs). Because RSV passive immunisations, including maternal vaccination and monoclonal antibodies, can only grant a temporary period of protection, their effectiveness and efficiency will be determined by the timing of the immunisation relative to the underlying RSV seasonality. We aimed to assess the potential effect of different approaches for passive RSV immunisation of infants in LMICs. METHODS: We included 52 LMICs in this study on the basis of the availability of RSV seasonality data and developed a mathematical model to compare the effect of different RSV passive immunisation approaches (seasonal approaches vs a year-round approach). For each candidate approach, we calculated the expected annual proportion of RSV incidence among infants younger than 6 months averted (effectiveness) and the ratio of per-dose cases averted between that approach and the year-round approach (relative efficiency). FINDINGS: 39 (75%) of 52 LMICs included in the study had clear RSV seasonality, defined as having more than 75% of annual RSV cases occurring in 5 or fewer months. In these countries with clear RSV seasonality, the seasonal approach in which monoclonal antibody administration began 3 months before RSV season onset was only a median of 16% (IQR 13-18) less effective in averting RSV-associated acute lower respiratory infection (ALRI) hospital admissions than a year-round approach, but was a median of 70% (50-97) more efficient in reducing RSV-associated hospital admissions per dose. The seasonal approach that delivered maternal vaccination 1 month before the season onset was a median of 27% (25-33) less effective in averting hospital admissions associated with RSV-ALRI than a year-round approach, but was a median of 126% (87-177) more efficient at averting these hospital admissions per dose. INTERPRETATION: In LMICs with clear RSV seasonality, seasonal approaches to monoclonal antibody and maternal vaccine administration might optimise disease prevention by dose given compared with year-round administration. More data are needed to clarify if seasonal administration of RSV monoclonal antibodies or maternal immunisation is programmatically suitable and cost effective in LMICs. FUNDING: The Bill & Melinda Gates Foundation, World Health Organization.

Estimating Potential Distribution of Sweetgum Pest Acanthotomicus suncei and Potential Economic Losses in Nursery Stock and Urban Areas in China.

American sweetgum Liquidambar styraciflua (Altingiaceae) was first introduced to China over 60 years ago. It is an important tree species for increasing landscape value and promoting afforestation in urbanized areas of eastern China in the past 20 years. Sweetgum inscriber Acanthotomicus suncei (Coleoptera: Curculionidae) is a local bark beetle pest and lethal to the introduced American sweetgum. To provide preliminary estimates of the potential economic losses caused by the sweetgum inscriber, a field investigation was conducted to survey the beetles' natural distribution in China. Based on field collections, potential distribution was predicted using Maxent. All nurseries stocking American sweetgum were in the high and very high suitability area of sweetgum inscriber. Additionally, we employed a model of direct loss incorporating tree and removal cost. A questionnaire was sent to maintenance companies, growers, and gardener associations for tree removal prices. We estimated the removal cost of each tree. In addition, the market price and inventory were also gained from telephone interview. Our economic analysis indicates that if sweetgum inscriber were to become established in the main American sweetgum business, the potential losses of nursery stock and urban area could range from USD 12.81 to 14.41 million.

Healthcare Utilization and Cost Burden of Porphyria in Commercially Insured Adults in the United States.

OBJECTIVES: The healthcare burden associated with porphyria remains unevaluated despite the associated increased risks of morbidity and mortality. We aimed to assess the healthcare utilization and cost burdens of porphyria in the United States (US) using real-world claims data. METHODS: We performed a case-control analysis of adults in the Truven Health MarketScan® Commercial Claims database (2010-2015). Using propensity scores, 2788 porphyria cases were matched 1:1 to porphyria-free controls with chronic liver disease. Total and service-specific parameters were quantified for the 12 months before porphyria diagnosis versus the 12 months after diagnosis and over the 12 months following a randomly selected date for controls. Wilcoxon signed rank tests and McNemar tests were used to examine incremental differences in burden between cases and controls. Adjusted multivariable generalized linear regression models were used to compare healthcare burdens for cases versus controls. RESULTS: Relative to the 12 months before porphyria diagnosis, the following 12 months had more claims per patient (35.94 vs 39.67; p < 0.0001) and increased per-patient healthcare costs (US$21,308 vs US$27,270; p < 0.0001). Porphyria cases incurred US$7839 more in total unadjusted costs compared with controls in the 12 months after index date. Compared with controls, cases also had more claims (39.67 vs 34.81), primarily due to inpatient admissions (1.80 vs 0.78) and outpatient visits (21.41 vs 17.98). Cases also had higher healthcare costs for inpatient admissions (US$8882 vs US$4674) and outpatient visits (US$12,378 vs US$9801). CONCLUSION: Porphyria is associated with significant healthcare costs and utilization burdens driven by increased inpatient admissions, outpatient visits, and pharmaceutical claims.