Global disparities in availability of epinephrine auto-injectors.

Background: Anaphylaxis is the most severe clinical presentation of acute systemic allergic reactions and can cause death. Given the prevalence of anaphylaxis within healthcare systems, it is a high priority public health issue. However, management of anaphylaxis - both acute and preventative - varies by region. Methods: The World Allergy Organization (WAO) Anaphylaxis Committee and the WAO Junior Members Steering Group undertook a global online survey to evaluate local practice in the diagnosis and management of anaphylaxis across regions. Results: Responses were received from WAO members in 66 countries. While intramuscular epinephrine (adrenaline) is first-line treatment for anaphylaxis, some countries continue to recommend alternative routes in contrast to guidelines. Epinephrine auto-injector (EAI) devices, prescribed to individuals at ongoing risk of anaphylaxis in the community setting, are only available in 60% of countries surveyed, mainly in high-income countries. Many countries in South America, Africa/Middle-East and Asian-Pacific regions do not have EAI available, or depend on individual importation. In countries where EAIs are commercially available, national policies regarding the availability of EAIs in public settings are limited to few countries (16%). There is no consensus regarding the time patients should be observed following emergency treatment of anaphylaxis. Conclusion: This survey provides a global snapshot view of the current management of anaphylaxis, and highlights key unmet needs including the global availability of epinephrine for self-injection as a key component of anaphylaxis management.

Utility of biomarkers in the diagnosis and monitoring of asthmatic children.

Asthma imposes a heavy morbidity burden during childhood; it affects over 10% of children in Europe and North America and it is estimated to exceed 400 million people worldwide by the year 2025. In clinical practice, diagnosis of asthma in children is mostly based on clinical criteria; nevertheless, assessment of both physiological and pathological processes through biomarkers, support asthma diagnosis, aid monitoring, and further lead to better treatment outcomes and reduced morbidity. Recently, identification and validation of biomarkers in pediatric asthma has emerged as a top priority across leading experts, researchers, and clinicians. Moreover, the implementation of non-invasive biomarkers for the assessment and monitoring of paediatric patients with asthma, has been prioritized; however, only a proportion of them are currently included in the clinical practise. Although, the use of non-invasive biomarkers is highly supported in recent asthma guidelines for documenting diagnosis and supporting monitoring of asthmatic patients, data on the Pediatric population are limited. In the present report, the Pediatric Asthma Committee of the World Allergy Organization (WAO), aims to summarize and discuss available data for the implementation of non-invasive biomarkers in the diagnosis and monitoring in children with asthma. Information on the most studied biomarkers, including spirometry, oscillometry, markers of allergic sensitization, fractional exhaled nitric oxide, and the most recent exhaled breath markers and "omic" approaches, will be reviewed. Practical limitations and considerations based on both experts' opinion and critical review of the literature, on the utility of all "well-known" and newly introduced non-invasive biomarkers will be presented. A critical commentary on biomarkers' use in diagnosing and monitoring asthma during the COVID-19 pandemic, cost and availability of biomarkers in different settings and in developing countries, the differences on the biomarkers use between Primary Practitioners, Pediatricians, and Specialists and their role on the longitudinal aspect of asthma is provided.

Physician's experience on managing asthma in adolescents: results of the International AMADO (Asthma Management in ADOlescents) survey.

BACKGROUND: Worldwide prevalence of asthma seems to be increasing in adolescents, but limited data is available regarding the management of asthma in this age group. OBJECTIVE: Therefore, we conducted an international survey focused on physicians who manage asthma in order to understand how Asthma Management in ADOlescents (AMADO) is currently performed. METHODS: The AMADO survey is a web-based global survey of physician's attitudes towards the management of asthma in adolescents, circulated for 17 weeks. The survey had an anonymous and voluntary standard. The questionnaire consisted in 27 questions covering the training background of respondents, difficulties in diagnosis, and in management of asthma in adolescents. RESULTS: Two hundred forty-four responses were received from 46 countries, from all continents. Most (65%) of participants indicated allergy as being their main specialty. The majority of participants (62%) had more than 5 years of clinical practice, but 62% have no formal training in management of adolescents with asthma. Most of participants (96%) indicated having at least one case of asthma in adolescents per month. 60% of respondents mentioned that the asthmatic adolescents only had the consultation due to the family imposition. All respondents mentioned having difficulties in the management of asthma in adolescents due to patient poor adherence. Overall, 44% of participants have no specific health care resources for adolescents in their departments. Main suggestions from the participants were: optimization of time and personalized communication to these cohort, and standardization of multidisciplinary actions to improve adherence to asthma control treatment. CONCLUSION: Management of asthma in adolescents is still a challenge in clinical practice. The results from this survey helped us to identify the key issues to improve clinical outcomes in the future. This survey is the first step of the international AMADO initiative, which intends to optimize diagnosis and control of asthma and prevent avoidable deaths.

Gestational Diabetes and Risk Assessment of Adverse Perinatal Outcomes and Newborns Early Motoric Development.

Background and Objectives: The aim of this study was to analyze the presence of gestational diabetes mellitus (GDM) on maternal and fetal perinatal parameters, as well to evaluate the influence of GDM on neonatal early motoric development. Materials and Methods: In this prospective study, we evaluated 203 eligible participants that were admitted to obstetrics department for a labor. GDM was assessed by evaluation of maternal parameters, fetal parameters, as well its impact on infants early motoric development (Alberta Infant Motor Scale-AIMS). Results: Presence of GDM was significantly positively associated with: pre-pregnancy weight, obesity degree, weight at delivery, gestational weight gain (GWG), body mass index (BMI) at delivery, GWG and increased pre-pregnancy BMI, glucose levels in mother's venous blood after the delivery, positive family history for cardiovascular disease, pregnancy-related hypertension, congenital thrombophilia, drug use in pregnancy, large for gestational age (LGA), mode of delivery (Cesarean section and instrumental delivery). Likewise, GDM association was detected for tested ultrasound parameters (biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femoral length (FL)), length at birth, birth weight, newborn's head circumference, newborn's chest circumference, AIMS supination and pronation at three months, AIMS supination, pronation, sitting and standing at six months. Only Amniotic Fluid Index and AIMS supination at three months of infant's age remained significantly associated in multivariate regression model. Conclusions: The presence of significant positive association of numerous tested parameters in our study on perinatal outcomes and early motoric development, points to the necessity of establishing appropriate clinical decision-making strategies for all pregnant woman at risk and emphasize the importance of providing adequate glycaemia control options and further regular follow ups during the pregnancy.

The Influence of Increased Prepregnancy Body Mass Index and Excessive Gestational Weight Gain on Pregnancy Course and Fetal and Maternal Perinatal Outcomes.

Background: The aim of our study was to assess the influence of prepregnancy Body Mass Index (BMI) changes as well as excessive gestational weight gain (GWG) on maternal and fetal perinatal parameters. Furthermore, we aimed to analyze the influence of increased prepregnancy BMI values and excessive GWG on neonatal early motoric development. Methods: The 203 eligible female participants were evaluated. Prepregnancy Body Mass Index (BMI) and excessive gestational weight gain (GWG) defined according to Institute of Medicine 2009 guidelines in the USA were assessed with tested maternal and fetal perinatal parameters and infants early motoric development (Alberta Infant Motor Scale-AIMS). Results: Significant predictors of increased prepregnancy BMI in perinatal period include: weight at delivery (p = 0.001), GWG (p = 0.002) and BMI at delivery (p < 0.001), while significant predictors of excessive GWG in perinatal period are: prepregnancy BMI (p = 0.029) and BMI at delivery (p < 0.001). In the group of participants with both increased prepregnancy BMI and excessive GWG versus others, significant predictors were: hypertension (HTA) (p = 0.019), amniotic fluid index (AFI) (p = 0.047), Pronation (AIMS) (p = 0.028) and Supination (AIMS) (p = 0.029). Conclusion: Increased prepregnancy BMI and excessive GWG are significantly associated with numerous perinatal factors that could alter the pregnancy course, pregnancy outcome and early motoric development of newborn. Moreover, increased prepregnancy BMI is shown to be a significant predictor of excessive GWG; thus, early selection of pregnant women for close monitoring of weight gain during pregnancy will have positive effects on reducing the risk of less favorable pregnancy course and early motoric development of newborn.

Allergen specific sublingual immunotherapy in children with asthma and allergic rhinitis.

BACKGROUND: The incidence of asthma and allergic rhinitis (AR) is significantly increased, especially in younger children. Current treatment for children with asthma and allergic rhinitis include allergen avoidance, standard pharmacotherapy, and immunotherapy. Since standard pharmacotherapy is prescribed for symptoms, immunotherapy at present plays an important role in the treatment of allergic diseases. This article presents insights into the up-to-date understanding of immunotherapy in the treatment of children with allergic rhinitis and asthma. DATA SOURCES: PubMed articles published from 1990 to 2014 were reviewed using the MeSH terms "asthma", "allergic rhinitis", "children", and "immune therapy". Additional articles were identified by hand searching of the references in the initial search. RESULTS: Numerous studies have shown that sublingual application of allergen specific immunotherapy (SLIT) is an adequate, safe and efficient substitution to subcutaneous route of allergens administration (SCIT) in the treatment of IgE-mediated respiratory tract allergies in children. According to the literature, better clinical efficacy is connected with the duration of treatment and mono sensitized patients. CONCLUSIONS: At least 3 years of treatment and stable asthma before the immunotherapy are positive predictors of good clinical efficacy and tolerability of SLIT. SLIT reduces the symptoms of allergic diseases and the use of medicaments, and improves the quality of life of children with the diseases.

Economic evaluation of ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic genotype 1 hepatitis c virus infection.

OBJECTIVES: To estimate clinical outcomes and cost-effectiveness of ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin (OMB/PTV/r + DSV ± RBV) compared with treatment regimens including pegylated interferon (PegIFN) for patients with chronic genotype 1 hepatitis C virus (HCV) infection. METHODS: An Excel spreadsheet Markov model tracking progression through stages of liver disease was developed. Costs and patient utilities for liver disease stages were taken from published studies. Rates of disease progression were based on studies of untreated HCV infection and long-term follow-up of those achieving sustained virologic response (SVR) after drug treatment. Impact of OMB/PTV/r + DSV ± RBV and other drug regimens on progression was estimated through SVR rates from clinical trials. Analyses were performed for treatment-naive and treatment-experienced patients. Impact of alternative scenarios and input parameter uncertainty on the results were tested. RESULTS: For genotype 1 treatment-naive HCV patients, for OMB/PTV/r + DSV ± RBV, PegIFN + ribavirin (PegIFN/RBV), sofosbuvir + PegIFN/RBV, telaprevir + PegIFN/RBV, boceprevir + PegIFN/RBV, lifetime risk of decompensated liver disease was 5.6%, 18.9%, 7.4%, 11.7%, and 14.9%; hepatocellular carcinoma was 5.4%, 9.2%, 5.7%, 7.0%, and 7.4%; and death from liver disease was 8.7%, 22.2%, 10.4%, 14.8%, and 17.6%, respectively. Estimates of the cost-effectiveness of OMB/PTV/r + DSV ± RBV for treatment-naive and treatment-experienced patients indicated that it dominated all other regimens except PegIFN/RBV. Compared with PegIFN/RBV, the incremental cost-effectiveness ratios were £13,864 and £10,258 per quality-adjusted life-year (QALY) for treatment-naive and treatment-experienced patients, respectively. The results were similar for alternative scenarios and uncertainty analyses. LIMITATIONS: A mixed-treatment comparison for SVR rates for the different treatment regimens was not feasible, because many regimens did not have comparator arms; instead SVR rates were based on those from recent trials. CONCLUSIONS: OMB/PTV/r + DSV ± RBV is a cost-effective oral treatment regimen for chronic genotype 1 HCV infection compared with standard treatment regimens and is estimated to reduce the lifetime risks of advanced liver disease.

Current issues on sublingual allergen-specific immunotherapy in children with asthma and allergic rhinitis.

In 1993 the European Academy of Allergy and Clinical Immunology was the first official organization to recognize that sublingual administration could be "promising route" for allergic desensitization. A few years later, the World Health Organization recommended this therapy as "a viable alternative to the injection route in adults." The first meta-analysis showed sublingual allergen specific immunotherapy (SLIT) effectiveness for allergic rhinitis and another study showed SLIT can actually help prevent the development of asthma both in adults and in children. The main goal of this review article is to present insight into the most up-to-date understanding of the clinical efficacy and safety of immunotherapy in the treatment of pediatric patients with allergic rhinitis and asthma. A literature review was performed on PubMed from 1990 to 2015 using the terms "asthma," "allergic rhinitis," "children," "allergen specific immune therapy." Evaluating data from double-blind placebo-controlled randomized clinical trials (DB-PC-RCTs), the clinical efficacy (assessed as the reduction of symptom score and the need of rescue medicament) of SLIT for allergic rhinitis and allergic asthma, has been confirmed in various meta-analysis Outcomes such as rhinoconjunctivitis score and medication scores, combined scores, quality of life, days with severe symptoms, immunological endpoints, and safety parameters were all improved in the SLIT-tablet compared with placebo group. SLIT safety has been already proven in many DB-PC-RCTs and real-life settings. In accordance with all of the above mentioned, the goals for future trials and studies are the development of comprehensive guidelines for clinical practice on immunotherapy, embracing all the different potential participants. The importance of allergen immunotherapy is of special relevance in the pediatric age, when the plasticity and modulability of the immune system are maximal, and when preventative effects can be reasonably expected.

Respiratory allergies in childhood: Recent advances and future challenges.

The burden of allergic airway diseases still represents a major health problem in childhood. Despite many different options are currently available for the diagnostic work-up and management, the overall disease control in terms of impact on quality of life, morbidity and mortality, is not yet satisfactory. The extreme variability of individual risk factors and severity determinants may account for it. On the other side, the knowledge of the multifaceted allergy background could pave the way to primary prevention, early intervention and disease course modification. In fact, most of current research is focusing on the identification of biological and clinical predictive markers of allergy and asthma onset. This review aims at summarizing the latest achievements concerning the complex inter-relation between genetic predisposition and environmental factors, and their impact on prevention strategies and early identification of at risk subjects. An update on the diagnostic and monitoring tools as well as an insight into the newest treatments options is also provided.

Prevalence of Salmonella spp. and Yersinia enterocolitica in/on tonsils and mandibular lymph nodes of slaughtered pigs.

A total of 156 tonsils and 156 mandibular lymph nodes from fattening pigs originating from 13 farms were sampled in Croatian slaughterhouses and examined for Salmonella spp. (n=78 per organ) and Yersinia enterocolitica (n=78 per organ) by cultural methods. Salmonella was isolated from two tonsils only, both originated from animals from the same farm (5.12%), while Y. enterocolitica were recovered from 26 tonsils (33.33%) which could be traced back to 10 farms. Salmonella was absent in mandibular lymph nodes, and Y. enterocolitica was isolated from eight lymph nodes (10.25%) which originated from six farms. Y. enterocolitica was present inside the lymph nodes of two pigs. The high prevalence of Y. enterocolitica in/on pig tonsils could be the result of cross-contamination during splitting the carcasses with head. This procedure may result in higher prevalence of Y. enterocolitica on surface of mandibular lymph nodes than in their depth. Traditional veterinary postmortem examination of pig halves will not necessarily contribute to cross-contamination with Salmonella or Yersinia under conditions of present slaughter practice.

A cost-effectiveness analysis of respiratory syncytial virus (RSV) prophylaxis in infants in the United Kingdom.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of respiratory infection that is highly prevalent in infants. Severe cases of RSV infection require hospitalisation; this is most likely to occur in infant populations at high risk. The study assesses the cost-effectiveness of palivizumab versus no prophylaxis in infants at high risk of hospitalisation with RSV in the United Kingdom (UK). METHODS: A decision tree model was developed to reflect the clinical pathway of infants at high risk of severe RSV infection who receive either prophylaxis with palivizumab or no prophylaxis. The main outcome was the incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to assess the degree of uncertainty surrounding the results. A threshold analysis considered the impact of clinical and environmental risk factors on the cost-effectiveness in the subgroup of preterm infants 33-35 weeks gestational age (wGA). RESULTS: Prophylaxis with palivizumab compared with no prophylaxis is associated with the following ICERs; £33,216 for infants with congenital heart disease; £19,168 for infants with chronic lung disease; £3,845 for preterm infants < 29 wGA; £30,205 for preterm infants 29-32 wGA; and £99,056 for preterm infants 33-35 wGA. One-way sensitivity analysis suggests that these results are highly sensitive to the input data. Threshold analysis in the preterm 33-35 wGA subgroup demonstrates that an adjusted RSV-hospitalisation baseline risk of 17.94% or higher would result in an ICER below the £30,000 per quality-adjusted life-year threshold. DISCUSSION: Palivizumab is cost-effective compared to no prophylaxis in the United Kingdom in many of the subgroups considered, showing that palivizumab would be a cost-effective use of National Health Service resources.

Effects of rutin and hesperidin and their Al(III) and Cu(II) complexes on in vitro plasma coagulation assays.

Two flavonoids, rutin and hesperidin, were investigated in vitro for anticoagulant activity through coagulation tests: activated partial thromboplastin time (aPTT), prothrombin time (PT) and thrombin time (TT). Only an ethanolic solution of rutin at the concentration of 830 µM prolonged aPTT, while TT and PT were unaffected. In order to evaluate whether the prolongation of aPTT was due to the decrease of coagulation factors, the experiment with deficient plasma was performed, showing the effects on factors VIII and IX. Since pharmacological activity of flavonoids is believed to increase when they are coordinated with metal ions, complexes of these flavonoids with Al(III) and Cu(II) ions were also tested. The results showed that complexes significantly prolonged aPTT and had no effects on PT and TT. Assay with deficient plasma (plasma having the investigated factor at less then 1%) revealed that complexes could bind to the coagulation factors, what may lead to a non-specific inhibition and aPTT prolongation. An effort was made to correlate stability of complexes with their anticoagulant properties.

Quantifying the economic burden of productivity loss in rheumatoid arthritis.

OBJECTIVE: In light of the large number of recent studies and systematic reviews investigating the cost of RA, this article examines the methods used to assess the impact of RA on employment and work productivity, and provides an overview of the issues surrounding work productivity loss in the RA population. METHODS: A review of the published literature was conducted in order to identify relevant articles. These articles were then reviewed and their methodologies compared. The various methods used to calculate economic loss were then explained and discussed. RESULTS: We found that although methods of lost productivity and associated costs varied between studies, all suggest that RA is associated with significant burden of illness. Economic analyses that exclude indirect costs will therefore underestimate the full economic impact of RA. However, the methods used to calculate productivity loss have a significant impact on the results of indirect cost analyses, and should be selected carefully when designing such studies. Several factors relating to the disease, the job and socio-demographics have been found to predict work disability. CONCLUSIONS: Consideration of these factors is vital when measuring the extent of both absenteeism and presenteeism, and will allow for more accurate estimation of the impact of RA on work productivity. This information may also guide interventions aiming to prevent or postpone work disability and job loss.

Capecitabine cardiotoxicity--case reports and literature review.

This study presents 3 case reports of patients who experienced anginous pain during treatment with capecitabine. The interruption of capecitabine and sublingual or intravenous nitroglycerine treatment lead to recovery. Rechallenge of capecitabine with dose reduction of 30% lead to repeated anginous pain in 2 patients. Treatment with capecitabine had been replaced with weekly bolus 5FU-LV, without further cardiotoxicity. The literature contains data from about 50 patients who experienced cardiotoxicity during capecitabine treatment. The most frequent manifestations of capecitabine cardiotoxicity included: anginous pain in 38/53 (71.7%), arrhythmia in 6/53 (11.3%), myocardial infarction in 6/53 (11.3%). Cardiotoxicity of capecitabine lead to death in 6/53 (11.3%) patients. Risk factors for cardiotoxicity are associated with the grade 4 and the fatal outcome of cardiotoxicity (p = 0.035, p = 0.015), but not with the symptom recurrence upon capecitabine rechallenge (p = 0.18). The combination chemotherapy regimens are associated with the grade 4 of cardiotoxicity (p = 0.048), but not with the fatal outcome (p = 0.3). Rechallenge of capecitabine lead to symptoms recurrence in 10/16 patients. Neither the dose reduction of capecitabine (p = 0.18) nor the additional medical prophylaxis (p = 0.37) were important for the outcome of capecitabine rechallenge.

Microbial and physicochemical succession in fermented sausages produced with bacteriocinogenic culture of Lactobacillus sakei and semi-purified bacteriocin mesenterocin Y.

The influence of the bacteriocinogenic culture Lactobacillus sakei (10(5)/g) and semi-purified bacteriocin mesenterocin Y (2560AU/kg) on the safety and quality of traditional Croatian fermented sausages was investigated. The addition of Lb. sakei and/or mesenterocin Y reduced microbial counts (P<0.05) in the final products. After 28 days of ripening, coagulase-negative cocci decreased 1.5-2.0log, yeasts 1.2-1.4log and enterococci 1.7-2.7log. In the case of the addition of Lb. sakei, the lactic acid bacteria count was significantly (P<0.05) higher at day 7 of ripening, and was accompanied by a lower pH and a higher amount of lactic acid (P<0.05). In the final product the amount of acetic acid was significantly lower. More intensive proteolysis and an increase in ammonia content were found at the beginning of fermentation, and in the second phase of ripening in the control samples, respectively. The free fatty acid concentration was significantly lower during the entire ripening process compared to the control (P<0.05). Semi-purified mesenterocin Y did not affect the sensory properties of the sausages, whilst the addition of Lb. sakei enhanced them.