Costs and Clinical Consequences of Compliance with COPD GOLD Recommendations or National Guidelines Compared with Current Clinical Practice in Belgium, Germany, Sweden, and the United States.

Purpose: The objective of this study was to assess the clinical and cost benefits of treating patients with chronic obstructive pulmonary disease (COPD) according to global and national guidelines compared to real-life clinical practice in the United States and three European countries (Belgium, Germany, Sweden). Patients and Methods: A cost-consequence model was developed to compare current prescribing patterns with two alternative scenarios, the first aligned with the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2022) recommendations and the second with national guidelines. Costs and clinical outcomes were modeled for these alternative scenarios over a time horizon of one year, based on real-world evidence and health insurance data. Results: Current clinical practice in each of the countries was inconsistent with published recommendations. A redistribution to prescribing patterns according to global and national recommendations led to a substantial decrease in the use of inhaled corticosteroid (ICS) containing therapies of more than 80% and 44%, respectively. There was a reduced incidence of up to 16% of mild-to-moderate pneumonia and up to 29% of severe pneumonia. Exacerbations decreased across all countries apart from Sweden, where a small increase in the rate of exacerbations was due to the redistribution of some patients currently undergoing inhaled triple therapy to non-ICS-containing therapies. Adapting treatment to recommendations could provide potential cost savings of up to 13% in estimated annual direct costs, resulting predominantly from the reduction in cost of healthcare resource use, including hospitalization associated with treating incident pneumonia, particularly severe pneumonia. Cost savings for prevalent adult patients with COPD on long-acting inhaler therapy ranged from €31 to €675 per patient per year. Conclusion: Redistribution of COPD patients from current clinical practice to treatment according to published recommendations would provide clinical benefits and substantial cost savings.

Hepatitis B surface antigen prevalence and the rates of mother-to-child transmission of hepatitis B virus after the introduction of infant vaccination programs in South East Asia and Western Pacific regions: a systematic review.

OBJECTIVES: Infant vaccination against the hepatitis B virus began in the World Health Organization South East Asia Region and the Western Pacific Region between 1983 and 2016. This systematic review examined the seroprevalence of hepatitis B surface antigen (HBsAg) in children and the rate of mother-to-child transmission (MTCT) in these regions between 1990 and 2020. METHODS: MEDLINE and EMBASE were searched for articles published between January 1990 and September 2020, which reported seroprevalence of HBsAg in children aged 0-15 years and/or the rate of MTCT in the South East Asia Region and Western Pacific Region. A pragmatic review identified supporting information. This review was registered in the International Prospective Register of Systematic Reviews (#CRD42020211707). RESULTS: Of 115 included studies, 77 (24 countries) reported HBsAg prevalence, and 38 (nine countries) reported MTCT. The seroprevalence of HBsAg ranged between 0.0% and 27.4%, with a decreasing trend over time in each country. MTCT rates were 0.0-5.2% in infants of mothers who are hepatitis B e antigen-negative and 2.7-53.0% in infants of mothers who are hepatitis B e antigen-positive. CONCLUSION: After the introduction of infant hepatitis B virus vaccination programs, the countries in South East Asia Region and Western Pacific Region observed a reduction in HBsAg seroprevalence in children. Nevertheless, the risk of MTCT persists, emphasizing the importance of antenatal screening to identify high-risk pregnancies.

Differential Effects of Dietary versus Exercise Intervention on Intrahepatic MAIT Cells and Histological Features of NAFLD.

BACKGROUND: Mucosal-associated invariant T (MAIT) cells promote inflammation in obesity and are implicated in the progression of non-alcoholic fatty liver disease (NAFLD). However, as the intrahepatic MAIT cell response to lifestyle intervention in NAFLD has not been investigated, this work aimed to examine circulating and intrahepatic MAIT cell populations in patients with NAFLD, after either 12 weeks of dietary intervention (DI) or aerobic exercise intervention (EI). METHODS: Multicolour flow cytometry was used to immunophenotype circulating and intrahepatic MAIT cells and measure MAIT cell expression (median fluorescence intensity, MFI) of the activation marker CD69 and apoptotic marker CD95. Liver histology, clinical parameters, and MAIT cell populations were assessed at baseline (T0) and following completion (T1) of DI or EI. RESULTS: Forty-five patients completed the study. DI participants showed decreased median (interquartile range) expression of the activation marker CD69 on circulating MAIT cells (T0: 104 (134) versus T1 27 (114) MFI; p = 0.0353) and improvements in histological steatosis grade post-intervention. EI participants showed increased expression of the apoptotic marker CD95, both in circulating (T0: 1549 (888) versus T1: 2563 (1371) MFI; p = 0.0043) and intrahepatic MAIT cells (T0: 2724 (862) versus T1: 3117 (1622) MFI; p = 0.0269). Moreover, the percentage of intrahepatic MAIT cells significantly decreased after EI (T0: 11.1 (14.4) versus T1: 5.3 (9.3)%; p = 0.0029), in conjunction with significant improvements in fibrosis stage and hepatocyte ballooning. CONCLUSIONS: These data demonstrate independent benefits from dietary and exercise intervention and suggest a role for intrahepatic MAIT cells in the observed histological improvements in NAFLD.

Safety and efficacy of supplements in pregnancy.

Pregnancy is a time where expectant mothers often focus on their diet to improve their own health and to preserve the future health of their children. There is much conflicting information in the public domain about the safety and/or efficacy of nutritional supplements during pregnancy. Despite this, the market for supplements is growing. This review discusses the roles of critical nutrients in pregnancy and the available evidence on the use of supplements to reduce risks and improve maternal and fetal outcomes. Recommendations are made for pregnant women, taking into account safety data and tolerable upper intakes set for pregnant women. It is important for dieticians, nutritionists, physicians, and other healthcare providers to be able to offer accurate and evidence-based advice on supplement use in pregnancy. Routine supplementation may not be necessary for all, but individuals at risk are identified.

Development and relative validation of a short food frequency questionnaire for assessing dietary intakes of non-alcoholic fatty liver disease patients.

PURPOSE: This work aimed to design and validate a novel short food frequency questionnaire (SFFQ) to assess habitual intakes of food items related to non-alcoholic fatty liver disease (NAFLD) in a cohort of European patients. METHODS: A 48-item SFFQ was created, with questions from existing FFQs and expert knowledge, emphasizing foods and nutrients implicated in NAFLD pathogenesis. Consenting, fibroscan-diagnosed, NAFLD patients completed the SFFQ during a short interview and were asked to complete a 4-day diet diary (4DDD) at home for return by mail. Nutritional intakes were assessed utilizing the myfood24™ food composition dataset and estimated energy requirements (EER) were calculated using sex-, age- and weight-specific equations. Agreement between the dietary instruments was assessed by Spearman correlations and Bland Altman analysis. RESULTS: Fifty-five patients completed both the SFFQ and the 4DDD within 30 weeks; 42 (76%) were diagnosed with simple steatosis, whereas 13 (24%) had biopsy-proven steatohepatitis; the majority were overweight or obese, with a median (25th; 75th percentile) BMI of 33.2 kg/m2 (29.3; 36.0). Reported energy intakes were well below EER with a median intake of 73% of requirements, suggesting widespread under-reporting. Significant correlations were observed between sugar (r = 0.408, P = 0.002), fat (r = 0.44, P = 0.001), fruits (r = 0.51, P = 0.0001) and vegetables (r = 0.40, P = 0.0024) measurements by the SFFQ and 4DDD. Bland Altman plots with regression analysis demonstrated broad comparability with the 4DDD for intakes of fat (bias - 13.8 g/day) and sugar (bias + 12.9 g/day). CONCLUSIONS: A novel SFFQ designed to be minimally burdensome to participants was effective at assessing dietary intakes in NAFLD patients.

Magnesium in pregnancy.

Magnesium deficiency is prevalent in women of childbearing age in both developing and developed countries. The need for magnesium increases during pregnancy, and the majority of pregnant women likely do not meet this increased need. Magnesium deficiency or insufficiency during pregnancy may pose a health risk for both the mother and the newborn, with implications that may extend into adulthood of the offspring. The measurement of serum magnesium is the most widely used method for determining magnesium levels, but it has significant limitations that have both hindered the assessment of deficiency and affected the reliability of studies in pregnant women. Thus far, limited studies have suggested links between magnesium inadequacy and certain conditions in pregnancy associated with high mortality and morbidity, such as gestational diabetes, preterm labor, preeclampsia, and small for gestational age or intrauterine growth restriction. This review provides recommendations for further study and improved testing using measurement of red cell magnesium. Pregnant women should be counseled to increase their intake of magnesium-rich foods such as nuts, seeds, beans, and leafy greens and/or to supplement with magnesium at a safe level.

Inhibition of Burkholderia multivorans adhesion to lung epithelial cells by bivalent lactosides.

Burkholderia cepacia complex (Bcc) is an opportunistic pathogen in cystic fibrosis patients which is inherently resistant to antimicrobial agents. The mechanisms of attachment and pathogenesis of Bcc, a group of 17 species, are poorly understood. The most commonly identified Bcc species in newly colonised patients, Burkholderia multivorans, continues to be acquired from the environment. Development of therapies which can prevent or reduce the risk of colonization on exposure to Bcc in the environment would be a better alternative to antimicrobial agents. Previously, it has been shown that Bcc strains bound to many glycolipid receptors on lung epithelia. Using a real-time PCR method to quantify the levels of binding of B. multivorans to the lung epithelial cells, we have examined glycoconjugate derivatives for their potential to inhibit host cell attachment. Bivalent lactosides previously shown to inhibit galectin binding significantly reduced the attachment of B. multivorans to CF lung epithelial cells at micromolar concentrations. This was in contrast to monosaccharides and lactose, which were only effective in the millimolar range. Development of glycoconjugate therapies such as these, which inhibit attachment to lung epithelial cells, represent an alternative means of preventing infection with inherently antimicrobially resistant pathogens such as B. multivorans.

Activation of MMP-9 by human lung epithelial cells in response to the cystic fibrosis-associated pathogen Burkholderia cenocepacia reduced wound healing in vitro.

Burkholderia cepacia complex is a group of bacterial pathogens that cause opportunistic infections in cystic fibrosis (CF). The most virulent of these is Burkholderia cenocepacia. Matrix metalloproteinases (MMPs) are upregulated in CF patients. The aim of this work was to examine the role of MMPs in the pathogenesis of B. cepacia complex, which has not been explored to date. Real-time PCR analysis showed that B. cenocepacia infection upregulated MMP-2 and MMP-9 genes in the CF lung cell line CFBE41o- within 1 h, whereas MMP-2, -7, and -9 genes were upregulated in the non-CF lung cell line 16HBE14o-. Conditioned media from both cell lines showed increased MMP-9 activation following B. cenocepacia infection. Conditioned media from B. cenocepacia-infected cells significantly reduced the rate of wound healing in confluent lung epithelia (P < 0.05), in contrast to conditioned media from Pseudomonas aeruginosa-infected cells, which showed predominant MMP-2 activation. Treatment of control conditioned media from both cell lines with the MMP activator 4-aminophenylmercuric acetate (APMA) also resulted in clear activation of MMP-9 and to a much lesser extent MMP-2. APMA treatment of control media also delayed the repair of wound healing in confluent epithelial cells. Furthermore, specific inhibition of MMP-9 in medium from cells exposed to B. cenocepacia completely reversed the delay in wound repair. These data suggest that MMP-9 plays a role in the reduced epithelial repair observed in response to B. cenocepacia infection and that its activation following B. cenocepacia infection contributes to the pathogenesis of this virulent pathogen.