IntroductionThe Turkey Lakes Watershed (TLW) study (https://www.canada.ca/en/environment-climate-change/services/turkey-lakes-watershed-study.html) was established in 1979 and is one of the longest running watershed-based ecosystem studies in Canada (Foster, Beall & Kreutzweiser, 2005; Jeffries, Kelso & Morrison, 1988; Morrison, Cameron, Foster & Groot, 1999). The watershed drains 10.5 km2 of Eastern Temperate Mixed Forest (Baldwin et al., 2018) or Great Lakes – St. Lawrence forest region (Rowe, 1972) within the Boreal Shield Ecozone (Wiken, 1986), and is located approximately 60 km north of Sault Ste. Marie, Ontario (47°03’N, 84°25’W) (Figure 1). Researchers from several federal government departments (Natural Resources Canada (NRCAN), Environment and Climate Change Canada (ECCC) and Fisheries and Oceans Canada (DFO) established this research watershed to evaluate the impacts of acid rain on terrestrial and aquatic ecosystems (e.g., Foster, Hazlett, Nicolson & Morrison, 1989; Hazlett, Curry & Weldon, 2011; Jeffries, Semkin, Beall & Franklyn, 2002; Kelso 1988). Since its inception, many studies have taken a multi-disciplinary, whole-ecosystem approach to investigate the processes governing terrestrial and aquatic responses to natural and anthropogenic disturbances. This holistic approach has allowed research to expand from its original acidification focus to address a range of other ongoing and emerging environmental issues (e.g. habitat alteration, organic contaminants, forest management, climate change) and to involve numerous academic, government and industrial collaborators.

Background: We studied whether significant differences in care gaps exist between specialists and PCPs. Methods: GOAL Canada enrolled patients with CVD or familial hypercholesterolemia (FH) and LDL-C > 2.0 mmol/L despite maximally tolerated statin therapy. During follow-up, physicians received online reminders of treatment recommendations based on Canadian Guidelines. Results: A total of 177 physicians (58% PCPs) enrolled 2009 patients; approximately half of the patients were enrolled by each physician group. Patients enrolled by specialists were slightly older (mean age 63 years vs. 62), female (45% vs. 40%), Caucasian (77% vs. 65%), and had a slightly higher systolic pressure and lower heart rate. Patients enrolled by specialists had less frequent history of familial hypercholesterolemia, diabetes, hypertension, chronic kidney disease and liver disease but more frequent history of coronary artery disease, atrial fibrillation and premature family history of CVD. There was no significant baseline difference in LDL-C, HDL-C, or non-HDL-c, although total cholesterol and triglycerides were slightly higher in patients managed by PCPs. At baseline, PCPs were more likely to use statins (80% vs.73%, p=0.0002) and other therapies such as niacin or fibrate (10% vs. 6%, p=0.0006) but similar use of ezetimibe (24% vs. 27%, p=0.15). At the end of follow up, specialists used less statins (70% vs. 77%, p=0.0005) and other therapies (6% vs. 10%, p=0.007) but more ezetimibe (45% vs. 38%, p=0.01) and the same frequency of PCSK9i (28% vs. 27%, p=0.65). The proportion of patients achieving the recommended LDL-C level of 2.0 mmol/L or below (primary endpoint) was similar at last available visit between specialists and PCPs (44% vs. 42%, p=0.32). Conclusion: Despite minor differences in the clinical profile of their patients, both PCPs and specialists actively participate in the management of lipid lowering therapy in high risk CVD patients and experience similar challenges and care gaps.

Fast-growing plantations have been expanding in Brazil in the last 50 years, increasing productivity by over 40 m3 / ha in reduced cycles between 5 and 15 years. In the 1990s, environmental warnings about these plantations guided research projects seeking to understand their effects on water and propose forest management actions to minimize them. The assessment of forest management effects on water resources is conducted by long-term experiments in paired catchments. In this study, we present some studies conducted at the hydrological monitoring center of Itatinga Experimental Station, of the University of São Paulo, where hydrological monitoring began in 1987, and currently conduct 4 catchments under different forest management regimes: fast-growing industrial management, long-term forest mosaic management, native forest restoration and long-term coppiced management. Results show that in a site with deep soils and good natural water regulation, main hydrological effects still occur when forest management intensifies, increasing water consumption and making the flow regime vulnerable to intra- and inter-annual seasonality. Regarding water quality, weekly sampling showed little interference of forest management on water chemistry; besides, more intensive management increased the concentration of nutrients in the water. There were no differences in water use in Eucalyptus plantations aged between 10 and 17 years and the use of coppice management had in the first 2 years higher water use than new plantations. The different types of management adopted directly affected the amount of water used, showing that high water demand forest plantations at water deficit regions, water availability is directly controlled by the forest management regime.

Background: There is limited number of report related to the direct use of non-centrifuged adipose graft in the literature. This preliminary study aims to present our experience on the efficacy of non-centrifuged autologous fat graft use in the treatment of lower extremity wounds. Methods: 16 wounds treated with non-centrifuged autologous fat grafts were retrospectively analyzed. VAC (vacuum-assisted therapy) or silver-impregnated dressing was used to reduce wound exudation and provide a healthy wound bed before fat grafting. Autologous fat grafts were harvested from abdominal or gluteal regions of the patients and injected into the wound bed and wound environment. Clinical observation and photograph records were used to follow the wounds. Results: 12 wounds needed for covering with skin graft or flap surgery whereas 4 healed without surgery. After debridements, the mean wound surface area was 92.69±62.74 cm2 (125[52-175] cm2 for venous ulcers, 100[25-112] cm2 for diabetic ulcer, and 81[42-120] cm2 for traumatic ulcers). The mean fat injection time was 1.63±0.89, and the mean fat volume was 26.56±15.33 cc. The mean healing time was 32.56±12.03 days. The wounds were uneventful in the average 12 month-following periods. Conclusion: With the results of our study, it can be said that non-centrifuged autologous fat grafts can have beneficial effects on the treatment of chronic challenging wounds when it is present on the wound site during healing.

The aim of this study was to describe the occurrence, angulation and mesialization ratio of the ectopic eruption of the maxillary permanent first molar (PFM) and its correlation with the pathological resorption of maxillary primary second molar (PSM). This retrospective study was performed using the panoramic radiographs of 11.924 child patients aged 6–10 years. Ectopic eruption status is categorized as self-corrected and impacted types. To evaluate the differences between the two groups (self-corrected and impacted), the angulation of PFM, mesialization ratio of PFM, and degree of adjacent PSM root resorption were also assessed. The data were statistically analyzed using ANOVA and chi-square tests. Pearson correlation was used to analyze whether a quantitative relationship exists between PFM mesialization ratio and PSM root resorption. Ectopic eruption frequency was determined as 0.83%. The distribution of ectopic eruption according to gender shows a higher prevalence in males than females. In most of the eruption status of cases with ectopic eruption were impacted. The impacted PFMs showed more negative vertical and positive horizontal angle between the PSM and PFM. There was no significantly difference eruption status and angles. Mesialization ratio of impacted PFMs were significantly higher than self-corrected PFMs. There was significant difference between the PFM mesialization ratio and the degree of PSM root resorption. Early diagnosis and detailed imaging techniques evaluation are important to prevent premature loss of arch size.

We first report a successful transcatheter aortic valve implantation using J-Valve system in an elder patient with high-risk pure aortic regurgitation (PAR) and type III endoleak after thoracic endovascular aortic repair (TEVAR).

Purpose: We aimed to reveal the relationship of uric acid with MHR and other inflammatory markers acne patients before and after isotretinoin treatment. In this way, we can try to shed light on the relationship between isotretinoin treatment and atherosclerosis. Methods: Two hundred twenty-four acne patients who administered isotretinoin (0.5-1 mg/kg/day) were enrolled in the study. In the pre-treatment phase and 3 months after treatment, MHR, SUA, mean platelet volume, plateletcrit, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, monocyte-lymphocyte ratio, serum triglyceride, total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels of the patients were analyzed. Results: Compared to the pre-treatment phase, three months after treatment, there was a statistically decrease in neutrophil count and an increase in lymphocyte count (p: 0.002, p: 0.011; respectively). Accordingly, there was a statistically significant decrease in NLR (p: 0.001). It was noteworthy that MHR and SUA levels increased significantly (p: 0.042, p: 0.010; respectively) and there was a positive correlation between SUA level and MHR (r: 0.212, p: 0.012). Serum total cholesterol, LDL, and triglyceride levels increased and HDL levels decreased significantly after treatment (p: 0,001). Conclusion: This study contributes to the comprehension of the relationship between isotretinoin treatment and atherosclerosis, which has been frequently reported in the literature. It was thought that the isotretinoin-induced uric acid increase might be related to dyslipidemia. Isotretinoin may initiate the atherosclerotic process in vascular endothelial and smooth muscles, with uric acid increase and HDL decrease. An increase in MHR is also an inflammatory marker indicating this process.

Abstract: Background: Spain is one of the European countries affected by the COVID-19 pandemic with a high number of recorded cases and deaths in Europe. Aim: To describe clinical characteristics and outcome of patients with COVID-19 hospitalized in a regional hospital in Spain. Methods: Clinical characteristics of the first COVID-19 patients hospitalised in the early days of the epidemic were recorded upon admission. A logistic regression multivariate analysis was performed to determine factors independently associated with a composite endpoint (death or ICU admission). Results: We included 100 patients, median age was 75 years and 52% were men. The most common comorbidities were hypertension (63%), diabetes (22%) and cardiovascular diseases (28%). The most common symptoms were fever (80%), cough (69%), fatigue (59%) and dyspnoea (52%) and 64% had respiratory insufficiency. Bilateral interstitial infiltrates (65%) and bilateral vertical “B-kerley” lines (82.6%) were the most common findings in chest radiographs and lung ultrasound. All patients received supplementary oxygen, 69% received medical treatment (hydroxychloroquine plus azithromycin the most common regimen) and 12% glucocorticoids. During hospitalization, 26% died, 10% were transferred to ICU and the remaining 62% were discharged at home. In the multivariate analysis a higher comorbidity burden (OR 1.4; 95% CI: 1.1-1.8) and higher C-reactive protein values on admission (OR 1.2; 95%CI: 1.1-1.4) were independent risk factors for the composite endpoint. Conclusions: Case-fatality rate of patients hospitalized with COVID-19 in the early days of the Spanish epidemic was 26%. A high comorbidity burden is associated to an increased risk of death or ICU admission.

Left ventricular surgical remodeling (LVSR) has been, for long time, the procedure applied for large dyskinetic, or akinetic, areas as a consequence of a myocardial infarction, manly located in the left anterior descending area. Many surgical techniques were developed, aimed to a pure reduction of the volume of the left ventricular cavity or to add to volume reduction a more physiologic conical shape. The expansion of interventional procedures invaded most of the fields before treated only by cardiac surgeons. In this issue, Pillay describes an hybrid technique, involving both interventional cardiologists and cardiac surgeons, aimed to LV volume reduction after an anterior myocardial infarction. A series of internal (right ventricular septum) and external (anterior wall) anchors are implanted to approximate the LV free wall to the anterior septum, consequently excluding the scarred myocardium. Although some limitations of this study, the Authors have to be commended for having revitalized a procedure almost eliminated from the surgical scenario

Lung consolidation is a common clinical pathology may be caused by infection process, infarction, tumor, compressed or obstructive atelectasis or thoracic spine trauma, which is sometimes life threatening. However, acute lung consolidation due to Klebsiella pneumoniae infection is very rare and has been rarely reported in the literature after tricuspid valve replacement. We report a rare case of acute lung consolidation caused by klebsiella pneumoniae after reoperation for isolated rheumatic tricuspid regurgitation. Due to the rapid disappearance of tricuspid regurgitation after valve replacement, pulmonary blood significantly increased compared with that before surgery, which led to pulmonary congestion and exudation, aggravating the probability of infection. This case underscores the risk for isolated tricuspid valve replacement in patient with long-terms severe tricuspid valve regurgitation and right heart dysfunction.

Cor triatriatum is a rare congenital heart malformation with different natural history which depends on the size of the aperture in the partition between the proximal and distal chambers. In classic cor triatriatum all pulmonary veins return to proximal chamber (accessory left atrium, aLA), but this case we reported with left upper pulmonary vein returned to distal chamber (true left atrium, tLA). The partition had one 5mm aperture that allowed this patient grown up to adulthood without any symptoms, but finally resorted to hospital with symptomatic atrial flutter and detected this cor triatriatum accidentally. Atrial flutter may be a long-term complication of cor triatriatum during its natural history, surgical correction of cor triatriatum and radiofrequency ablation for atrial flutter is recommended once diagnosed.

Aims We aim to reveal the effect of the crisis period and normalization process after COVID-19 on dermatology practice, to anticipate future health problems, and demonstrate the necessity of teledermatology as a solution. Results The number of patients in the normalization (32.3%) increased compared to the crisis period (11.5%) but also it was found significantly lower than before the pandemic (56.2%). It was remarkable that the change in the distribution of stress-related diseases, such as idiopathic generalized pruritus, alopecia areata, and zona zoster, stably paralleled each other and the trend of increase and decrease during the crisis period and the normalization process, respectively. The increase in the frequency of contact dermatitis, which was not reflected in the crisis period, became evident in the normalization process (p<0.001). There was no significant change in the rate of scabies but a decrease in the number of patients (p=0.276). Discussion The decrease in stress-related diseases indicates that social stress started to decrease with normalization. Rates and the number of patients give an idea about the problems we may encounter aftermath pandemic. Scabies and venereal diseases, which concern public health, should not be neglected. We predicted that much more significant increases in the frequency of scabies will be recorded aftermath of COVID-19. Conclusion The extraordinary conditions that occur after the pandemic will make the management of some diseases, especially scabies, difficult in the future. The chaos that will occur when the unusually decreasing number of patients returns to normal can be alleviated by teledermatology.

The present work presents a mathematical investigation of a Rabinowitsch suspension fluid through elastic walls with heat transfer under the effect of electroosmotic forces (EOFs). The governing equations contain empirical stress-strain equations of Rabinowitsch fluid model, equations of fluid motion along with heat transfer. It is of interest in this work to study the effects of EOFs, rigid spherical particles which are suspended in the Rabinowitsch fluid, Grashof parameter, heat source and elasticity on the shear stress of Rabinowitsch fluid model and flow quantities. The solutions are achieved by taking long wavelength approximation with creeping flow system. A comparison is set between the effect of pseudoplasticity and dilatation on the behaviour of shear stress, axial velocity and pressure rise. Physical behaviours have been graphically discussed. It was found that the Rabinowitsch and electroosmotic parameters enhance the shear stress while they reduce the pressure gradient. The present analysis is particularly important in biomedicine and physiology.

pH is an important factor affecting the growth and production of microorganisms; especially, it is effective on the efficiency of ethanologenic microorganisms. It can change the ionization state of metabolites via the change in the charge of their functional groups that may lead to metabolic alteration. Here, we estimated the ionization state of metabolites and balanced the charge of reactions in genome-scale metabolic models of Saccharomyces cerevisiae, Escherichia coli, and Zymomonas mobilis at pH levels 5, 6, and 7. The robustness analysis was first implemented to anticipate the effect of proton exchange flux on growth rates for the constructed metabolic models at various pH. In accordance with previous experimental reports, the models predict that Z. mobilis is more sensitive to pH rather than S. cerevisiae and the yeast is more regulated by pH rather than E. coli. Then, a systemic approach was proposed to predict the pH effect on metabolic change and to find effective reactions on ethanol production in S. cerevisiae. The correlated reactions with ethanol production at predicted optimal pH in a range of proton exchange rates determined by robustness analysis were identified using the Pearson correlation coefficient. Then, fluxes of these reactions were applied to cluster the various pHs by principal component analysis and to identify the role of these reactions on metabolic differentiation because of pH change. Finally, 12 reactions were selected for up and down-regulation to improve ethanol production. Enzyme Regulators of the selected reactions were identified using the Brenda database and 11 selected regulators were screened and optimized via Plackett-Burman and 2-level full factorial designs, respectively. The proposed approach has enhanced yields of ethanol from 0.18 to 0.36 mol/mol carbon. Hence, not only a comprehensive approach for understanding the effect of pH on metabolism was proposed in this work, but also it successfully introduced key manipulations for ethanol overproduction.

Spirometry, a gold standard technique for measuring lung functions, has been restricted to a select cohort of patients in current COVID-19 pandemic due to the enhanced risk of disease dissemination. To monitor pulmonary functions in various obstructive (e.g., asthma) and restrictive diseases (e.g., COVID-19 pneumonia) on in- and out-patients serially, there is an urgent requirement of an alternate reliable test. Impulse Oscillometry (IOS) measures lung functions by working at tidal volumes and thus reduces the risk of potential aerosol generation. Feasibility of IOS in smaller children and its ability to detect parenchymal and peripheral airway involvement are other advantages over conventional spirometry. IOS could be a potential solution to periodically monitor lung functions in current pandemic situation to keep a check on diseases affecting lung functionality.

A patient developed necrotizing autoimmune myopathy and myasthenia gravis after statin exposure. Clinicians should be alerted to possible concurrent autoimmune neuromuscular disorders to discontinue the drug and promptly begin appropriate treatment,

The mechanisms of forest seed dispersal and regeneration of various altered forest ecosystems are complemented by the action of carnivores. The objective of this study was to evaluate the role of endozoochoric and diploendozoochoric mammals in the dispersal, scarification, and germination of seeds in two different forest ecosystems: temperate forest (TF) and dry tropical forest (DTF). A direct search and scat collection were carried out to determine dispersing agents and the abundance and richness of seeds in the Protected Natural Area, Sierra Fría, Aguascalientes, Mexico. Viability was evaluated by means of X-rays and a germination test using an optical densitometry. In addition, thickness measurements and observations were made on the surfaces of the testas by a scanning electron microscopy. In the TF, four plant species were dispersed, mainly Arctostaphylos pungens (P < 0.05), by four mammals, where the gray fox dispersed the highest average (66.8 ± 68.2; P < 0.05) and diploendozoochory was detected in bobcat scats associated with rabbit hair (Sylvilagus floridanus). The DTF presented higher abundance and richness of species, where Myrtillocactus geometrizans had the highest abundance (2680 ± 4423) and the coati (P < 0.05) dispersed the highest number of seeds (8639 ± 12203). In both types of forest, endozoochory and diploendozoochory did not affect the viability, the thickness of the testas, or the germination of any species of seeds. These results suggest that dispersing carnivores adapt to the abundance and richness of seeds in the forests they inhabit, thus developing an important ecological function by dispersing, scarifying and promoting the selective germination of seeds with thick testas in TF and thin testas in DTF.

Aim To explore the relationship between postural changes in lung function and polysomnography (PSG) in the assessment of early sleep disordered breathing in children with neuromuscular disorders [NMD]. Methods In this prospective cross-sectional study, children with NMD performed spirometry in sitting (si) and supine (su) positions. A control group of age and gender matched healthy children also underwent postural lung function testing. PSG was performed within 6 months of spirometry. Spirometry was acceptable according to ATS standards and PSGs scored according to AASM guidelines. Results Forty-one children with NMD, aged 12.3 ±3 years (21 males) performed sitting spirometry. Thirty [73%] performed acceptable spirometry in the supine position. Underlying diagnoses were heterogeneous, with the majority having Duchenne Muscular Dystrophy (n=17). Mean FEV1sit and FVCsit were 78% (SD ±22) and 75% (SD±20.4) respectively, with mean% ΔFVC (sit – sup) 9±11% (range 2% to 20%), and was significantly greater than healthy controls (n=30 SD ±3) (p<0.001). PSG data on these 30 children showed total AHI 6.9 ±5.9/hr (0.3 to 29), obstructive AHI 5.2±4.0/hr (0.2 to 10), and REM AHI 14.1+/-5.3/hr (0.1 to 34.7). A moderate correlation was present between supine FVC% and AHI (r=0.62, p=0.001) in those not using non-invasive ventilation [NIV] in sleep [N=22] but not with the rise in CO2 from non-REM to REM sleep (6 ±1.9 mmHg, range 4 to 11). Conclusion Children with NMD and mild restrictive lung disease showed greater postural changes in spirometry than healthy controls, with changes being greatest in children who required nocturnal NIV.

Background: Acute chest syndrome (ACS) is the leading cause of death for children with sickle cell disease (SCD). Recurrent ACS has detrimental effects on pulmonary health and healthcare costs. Neighborhood characteristics affect the outcomes of many pediatric chronic diseases, but their role in SCD is not well investigated. In this study, we investigated the effects of area-level socioeconomic deprivation and racial composition on the recurrence of ACS. Study design: We performed a retrospective cross-sectional analysis of clinical data from a large pediatric SCD center. Patients’ residential addresses were geocoded and linked to a composite Area Deprivation Index (ADI) and percent African American population at the level of Census block groups. The association of recurrent ACS with neighborhood characteristics was evaluated using logistic regression analysis. Results: The sample included 709 children with SCD. Residence in a socioeconomically deprived neighborhood was associated with 27% less risk of recurrent ACS, and residence in a predominantly African American neighborhood was associated with 41% less risk of ACS recurrence. The racial composition explained the protective effect of living in a high-deprivation area after adjusting for sociodemographic and clinical covariates. Demographic and clinical factors associated with recurrent ACS included older age, male gender, asthma, hydroxyurea use, and chronic transfusion therapy. Conclusions: This is the first study to report a protective effect of residing in a predominantly African American community for ACS recurrence. Further prospective studies are needed to confirm the association and to understand the mechanisms of such relationship.

To the Editor:Severe asthma (SA) affects less than 5% of the pediatric asthma population but is considered to account for approximately half of total pediatric asthma healthcare costs. Allergic comorbidities, including food allergies (FA) and allergic rhinitis (AR), are frequent in children with SA (1). The presence of FA and AR increases asthma severity (1–6) and medication use (4–6). Treating AR improves asthma symptoms (3). However, the economic burden of allergy in children with SA has been poorly studied. We aimed to determine the economic contribution of allergy for the French national health insurance (NHI) for the treament of children with SA at the individual level.Children with SA, defined as those requiring step 4 or 5 of treatment of the Global Initiative for Asthma (GINA), regularly followed in the Department of Pediatric Pulmonology of Necker Hospital were included as previously described (7). The diagnosis of SA, FA, and AR were made by a physician according to guidelines (8-10). A physician-guided questionnaire was completed with parents to assess individual expenditures related to asthma and allergic comorbidities in the previous six months. Parental claims were confirmed by analysis of the medical records. The methods are detailed elsewhere (7). First, we determinated the direct, indirect, and global costs of SA over a six-month period (7) and then assessed the allergy-related costs. The costs related to allergy included anti-allergic medications (oral antihistamines, steroid nasal sprays, anti-allergic eye drops, adrenaline autoinjectors, and allergen immunotherapy), anti-IgE treatment, scheduled ambulatory or hospital outpatient visits to an allergist, pulmonologist, ophthalmologist, or dermatologist, skin tests, blood tests for allergy-specific IgE, and day care unit (DCU) admissions for oral food challenge (OFC) (7). Finally, we compared the economic burden of allergy between children with SA and those without (NSA) (7). Parents were informed and accepted to participate in the study. The local ethical committee confirmed that Institutional Review Board approval was not required.Forty-eight children with SA and 26 with NSA were included. Their general characteristics are summarized in Table 1. The individual global cost of SA was \euro3,982 (4,422) over the six-month study period (7). For children with allergic SA, the cost attributed to allergy was \euro2,803 (3,709), representing 48.1% (35.2) of the direct SA costs and 45.8% (34.9) of the global SA costs. Overall, the number of allergic comorbidities for children with SA weakly correlated with global (r = 0.33, p = 0.02) and direct SA costs (r = 0.35, p = 0.01). The global and direct costs of SA were higher for children with allergic comorbidities than for those without (\euro4,646 (4,635) vs. \euro1,107 (1,173), p = 0.02; respectively). However, these figures partially reflect the actual economic contribution of allergy in children with allergic SA. For those requiring omalizumab, the economic burden of allergy was \euro5,057 (3,809) representing 74.1% (24.4) of direct SA costs and 71.6% (24.3) of global SA costs. In this group, omalizumab was the main driver of costs, representing 73.6% of direct SA costs and 71.5% of global SA costs. For children with allergic SA not requiring omalizumab, the economic burden of allergy was \euro174.50 (289.7), representing 17.8% (16.1) of direct SA costs and 15.8% (15.9) of global SA costs. Regardless of omalizumab use, the economic burden of allergy was similar among children with allergic SA (\euro153.3 (159.4) vs \euro174.50 (289.7), p = 0.99). However, the burden of allergy expressed as a percentage of direct and global SA costs was lower for children with SA requiring omalizumab than those who did not (3% (4.2) vs. 17.8% (16.1), p < 0.01 and 2.9% (4.2) vs. 15.8% (15.9), p < 0.01, respectively).Global, direct, and indirect costs did not differ between children with NSA, with or without allergic comorbidity (Table 3). For children with allergic NSA, the cost of allergy was \euro134.40 (213.90), representing 40.8% (33.3) of the asthma direct costs and 34.7 % (32.2) of the asthma global costs. Thus, regardless of omalizumab use, the cost of allergy for children with allergic SA and that for those with allergic NSA was similar (\euro163.1 (225.9) vs . \euro134.40 (213.9) (p = 0.19). However, the economic burden of allergy was greater for children with NSA than those with SA: 40.8% vs 9.8% of direct costs and 34.7% vs. 8.9% of global costs, respectively (both p < 0.01). Finally, the economic burden of allergy was similar between children with allergic SA not requiring omalizumab and those with allergic NSA (\euro174.5 (289.7 vs. \euro134.4 (213.9), p = 0.29).This study shows that the costs attributed to allergy for children with SA are substantial and mostly driven by omalizumab, but are minor when omalizumab is not taken into account. The economic burden of allergy was similar between children with allergic SA not requiring omalizumab and those with allergic NSA, suggesting a low cost-effectiveness ratio, at least in the latter group. The global and direct costs of children with allergic SA were higher than those of children with non-allergic SA. This finding confirms that the presence of allergic comorbidities increases the costs of asthma management (11) and supports that allergy is associated with asthma severity. Our study had several limitations. Only a small number of children were included. However, we included children with well-defined doctor-confirmed SA, with and without omalizumab, reflecting the heterogenity of this population. In addition, our study was performed in a tertiary-care center. Thus the children with NSA may not be representative of community children. Our estimation was based on parental declarations, with a potential memory bias and a risk of misestimation of certain expenditures. We limited this risk by analyzing the medical records, which confirmed the parental claims. The best design would have been to obtain the data of children selected by a physician from the NHI. However, this approach is rarelly authorized in France. Moreover, the study covered a short period of time including winter and two months of spring, which may lead to underestimation of costs related to seasonal allergy treatments. In addition, the number of children under allergen immunotherapy was small (1 in the group of children with allergic SA vs. 4 children with allergic NSA (p = 0.03)).In summary, this study is the first to precisely analyse the proportion of costs attributed to allergy in pediatric SA. As expected, allergy-related costs are mainly driven by omalizumab. However, for children with allergic SA who do not require omalizumab, the economic contribution of allergy to SA costs is relatively small, suggesting a low cost-effectiveness ratio.

Background: The purpose of this single-centre study was to analyse the outcomes of extracranial germ cell tumors (GCTs) in children treated on a multi-modality regimen at a single-centre. Methods: Retrospective study of children (<18 years) with a histopathologically confirmed diagnosis of extracranial GCT over a period of 10 years (January’09-December’18) treated on a uniform institution-based protocol. All completely excised teratomas and stage I gonadal tumors received no further therapy (low risk); Stage IV Ovarian, Stage III-IV extragonadal GCTs received 6 cycles of chemotherapy (high risk) and the remaining received 4 cycles of chemotherapy (intermediate risk). Results: A total of 336 kids were treated of which the analysable cohort comprised of 297with a boy-girl ratio of 1.72:1 and median age of 4 years. Gonadal GCTs(n-180) were commoner than extragonadal GCTs(n-117) with ovary as primary site in 128 children(43%) and sacrococcygeal site being the commonest extragonadal location(n-41;14%). LR, IR and HR disease were noted in 60(20.2%) patients, 125(42%)patients and 112(37.8%)patients respectively. Forty-one patients relapsed and 43 children expired (disease related-33; toxic deaths-9; unknown-1). The 5-year EFS/OS was 79.3%/84.4% respectively with gonadal site, low-risk and non-metastatic disease associated with statistically better EFS (median follow-up:52.1±37.3 months). Conclusion(s): Both cisplatin and carboplatin based regimens had comparable outcomes. The low and intermediate GCTs had an excellent outcome, thus warranting a gradual shift in the approach to these tumors by reducing therapy and decreasing late effects of therapy. In high risk GCTs however, intensifying therapies to improve outcomes must be balanced against the risk of cumulative toxicity.

BackgroundWheezing is a continuous musical sound that can be produced by oscillation of opposing walls of an airway that is narrowed almost to the point of closure 1; it affects approximately one-third of children at least once by the age of nine and is a significant cause of morbidity and mortality in young children worldwide2,3. While wheezing is only transient for most children, around 40% are still diagnosed with recurrent wheezing or asthma after the age of six years2,4. Wheezing is often induced by various respiratory tract infections, which include respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (HMPV), influenza viruses, parainfluenza viruses (PIV), and coronavirus 2. While RSV is the leading cause of hospitalization for lower respiratory tract infection (LRTI) and first wheezing episode in infants3,5, recent improvements in virus detection through methods such as real-time reverse transcriptase polymerase chain reaction (qRT-PCR) have allowed investigators to better elucidate the important role of HRV in LRTIs, wheezing and asthma development. HRV is now known to be the most common virus associated with wheezing at ages 6-12 months and is the second most common virus detected among wheezing infants during the first six months of life, after RSV6,7.Developments in molecular diagnostics have also contributed to the discovery of HMPV and its role in respiratory illnesses8. Because studies show that virus-associated wheezing and LRTI during infancy are associated with the subsequent development of childhood asthma, it is important to determine which viruses are most strongly associated with wheezing and to assess other risk factors that contribute to wheezing, in order to develop interventions when possible6. Few viral epidemiological studies in the Middle East focus on the association between wheezing and respiratory viruses9,10. Our study aimed to determine the association of wheezing with respiratory viruses, demographic and clinical characteristics in young children.

Objective: To investigate the drug clinical trials in pregnant women in China to provide data on the quantity, properties, source of funding and geographical distribution for the registration and post-marketing studies. Methods: We collected data of 10865 clinical trials from the Drug Clinical Trial Registration and Information Disclosure Platform and 33649 clinical trials from Chinese Clinical Trial Registry (ChiCTR) performed on pregnant women between January 2013 and June 2020. Retained trials were analyzed based on several key variables (e.g., study endpoints, sources of funding, area of interest). Results: The percentage of trials regarding pregnancy registered to be carried out in China was 0.26%, where the percentage of trials for new drug applications was 0.27%. Most trials focused on anesthesia/analgesia, infections, and endocrine disorders. In the analyzed trials, most (72.6%,85/117) were designed using randomized parallel or cross-over grouping, and 59.8% (70/117) of which put the health of the mother or fetal as the primary endpoint. There were no pre-planned pharmacokinetic studies in pregnant women. Only 5 new investigational drugs were developed for delivery and postpartum related treatments. The geographic distribution of the study sites was obviously uneven, with higher number of sites being distributed in the southeast of China (50 [41%]). Conclusion: This survey showed that in China, there is a significant shortage in the development, evaluation and safety trial of pregnant drugs. Modifying or adding legislation and financial incentives may encourage the pharmaceutical companies to carry out clinical trials in pregnant women.

Routinely collected data has been increasingly used to evaluate and monitor long-term opioid therapy (LTOT) patterns, with very little guidance on how to measure LTOT from these data sources. We conducted a systematic review of studies published between Jan 2000 and Jul 2019 to catalogue LTOT definitions, the rationale for definitions, and LTOT rates in observational research using routinely collected data in non-surgical settings. We screened 4,056 abstracts, 209 full-text manuscripts and included 126 studies; mostly from the US (82%) and published between 2015 and 2019 (68%). We identified 78 definitions of LTOT, commonly operationalised as 90 days of use within a year (21%). Studies often used multiple criteria to derive definitions (63%), mostly based on measures of duration, such as supply days/days of use (67%), episode length (21%), or prescription fills within specified time periods (9%). Definitions were based on previous publications (63%), clinical judgment (17%), or empirical data (3%); 10% of studies applied more than one definition. LTOT definition was not provided with enough details for replication in 14 studies and 37 studies did not specify the opioids evaluated. Rates of LTOT ranged from 0.2% to 57% according to study design, population and definition used. We observed a substantial rise in studies evaluating LTOT with large variability in the definitions used and poor reporting of the rationale and implementation of the definitions. This variation impacts on research reproducibility, comparability of findings and the development of strategies aiming to curb therapy that is not guideline-recommended.