scholarly journals Deferiprone Versus Deferoxamine in Thalassemia Intermedia: Results from 5-Year Long-Term Italian Multi-Center Randomized Clinical Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1354-1354 ◽  
Author(s):  
Angela Vitrano ◽  
Giuseppina Calvaruso ◽  
Rosario Di Maggio ◽  
Massimiliano Sacco ◽  
Alessandra Quota ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Serum Ferritin ◽  
Survival Probability ◽  
Mixed Effects ◽  
P Value ◽  
Linear Mixed Effects Model ◽  
Linear Mixed Effects ◽  
Treatment Groups ◽  
Kaplan Meier ◽  
The Mean

Abstract Thalassemia is a group of genetically inherited hemoglobin (Hb) disorders characterized by reduced synthesis of the b-globin chain and a sub-sequent imbalance in the a/b-globin chain ratio that results in chronic hemolytic anemia. The severity of clinical phenotype is used to distinguish this heterogeneous disease in two main subtypes: Thalassemia Major (TM) and Thalassemia Intermedia (TI). Iron overload is mostly due to increased intestinal absorption because of chronic anemia. Transfusions, in contrast with what happens in TM, have a minor role in the development of iron overload. However, although 1-year data from the phase 2, prospective, randomized, double-blind, placebo-controlled trial and 1-year extension results from the THALASSA study assessing the efficacy and safety of deferasirox in TI patients with iron overload have been reported, no data, during randomized trials, have been so far published on Deferiprone (DFP) treatment (Taher et al Blood 2012 and Ann Hematol 2013) Adult patients with TI were randomly assigned in permuted blocks of 10 with a ratio 1:1 to DFP at 75 mg/kg/day for 7 d/week divided into three oral daily doses (DFP-group) or DFO by sc infusion (8–10 h) at 50 mg/kg per day for 5 d/week (DFO-group). The study was designed to detect an improvement in decreasing mean serum ferritin levels in each of the treated-groups from the initiation of therapy to each year (from year 1 to year 5) with a significance level of 5% and 80% power. The planned number of subjects was between 40 and 100 (Rochon Biometrics 1991). The primary endpoint was the treatment efficacy evaluated as change from the baseline value in serum ferritin levels during the 5 years assessed using a linear mixed-effects model (LMM, Laird-Ware Biometrics 1982) where we assumed the patient effect (given by the intercept terms for each patient) as random effect, while the treatment effect (treat), the time effect (time), the treatment-by-time interaction effect (treat×time), and the total transfusions in ml (tot TX) as fixed effects. Secondary endpoints were safety and survival analysis at 5-years evaluated considering the number of advers events and Kaplan-Meir curves respectively. Overall 88 patients, observed at 12 SoSTE centers in Italy between January 2001 and May 2011, were randomized (47 DFP-group and 41 DFO-group). There were no differences observed at baseline between the two randomized groups in clinical and haematological findings. The regression coefficient of time suggested that there was a linear decrease over time in the mean serum ferritin levels in both treatment-groups even if the p-value was very close to the statistical significance (Coeff. -88.4, 95% CI (-182.4; 5.6), p-value =0.065). However, the mean serum ferritin levels did not seem to be significantly different between the two treatment-groups over time (Coeff. -77.4, 95% CI (-231.7; 77.1), p-value=0.326 ). The effect of total blood transfusion on serum ferritin levels was not statistically significant (Coeff. 0.06, 95% CI (-0.01; 0.1), p-value=0.100). The estimated profiles of serum ferritin levels in the two groups were represented in Figure I. Agranulocytosis was reported in 4 case of DFP versus no cases of DFO group, respectively (p-value=0.118). Neutropenia was statistically significant different between the two groups DFP (6 (12.5%) versus no cases in DFO , p-value=0.027). Kaplan-Meier survival probability curves for the two treatment groups are shown in Figure II, and the log-rank test did not show any statistically significant difference in the survival between the two groups (p-value=0.36). In conclusion, these findings suggest as DFP shows same effectiveness and survival probability versus DFO with controlled safety profile. Therefore, these results support the possibility of using this drug in TI patients in which DFO and Deferasiorx is contraindicated. Figure I: Estimated profiles of the mean serum ferritin in the two treatment-groups from the fitted linear mixed-effects model. Figure I:. Estimated profiles of the mean serum ferritin in the two treatment-groups from the fitted linear mixed-effects model. Figure II. Kaplan–Meier survival probability curves in the two treatment groups during multi-center TI clinical trial (DFP: continous line; DFO: dashed line), (p-value=0.36). Figure II. Kaplan–Meier survival probability curves in the two treatment groups during multi-center TI clinical trial (DFP: continous line; DFO: dashed line), (p-value=0.36). Disclosures No relevant conflicts of interest to declare.

scholarly journals Cerebral and Somatic Oxygen Saturation in Neonates with Congenital Heart Disease before Surgery

2021 ◽  
Vol 10 (11) ◽  
pp. 2455
Author(s):  
Mi Jin Kim ◽  
Jae Suk Baek ◽  
Jung A Kim ◽  
Seul Gi Cha ◽  
Jeong Jin Yu
Keyword(s):  
Time Trends ◽  
Biochemical Parameters ◽  
Near Infrared ◽  
Mixed Effects ◽  
Contributing Factors ◽  
Linear Mixed Effects Model ◽  
Linear Mixed Effects ◽  
Hypoxic Brain Injury ◽  
Hypoxic Brain ◽  
Cardiac Diagnosis

BACKGROUND: We investigated preoperative cerebral (ScO2) and abdominal (StO2) regional oxygen saturations according to cardiac diagnosis in neonates with critical CHD, their time trends, and the clinical and biochemical parameters associated with them. METHODS: Thirty-seven neonates with a prenatal diagnosis of CHD were included. ScO2 and StO2 values were continuously evaluated using near-infrared spectroscopy. Measurements were obtained hourly before surgery. A linear mixed effects model was used to assess the effects of time and cardiac diagnosis on regional oxygenation and to explore the contributing factors. RESULTS: Regional oxygenation differed according to cardiac diagnosis (p < 0.001). ScO2 was lowest in the patients with severe atrioventricular valvar regurgitation (AVVR) (48.1 ± 8.0%). StO2 tended to be lower than ScO2, and both worsened gradually during the period between birth and surgery. There was also a significant interaction between cardiac diagnosis and time. The factors related to ScO2 were hemoglobin and arterial saturation, whereas no factor was associated with StO2. CONCLUSIONS: Preoperative ScO2 and StO2 in critical CHD differed according to cardiac diagnosis. ScO2 in the patients with severe AVVR was very low, which may imply cerebral hypoxia. ScO2 gradually decreased, suggesting that the longer the time to surgery, the higher the risk of hypoxic brain injury.

Cognate similarity and intervocalic /d/ production in Riverense Spanish

2021 ◽  
pp. 136700692199680
Author(s):  
Michael Gradoville ◽  
Mark Waltermire ◽  
Avizia Long
Keyword(s):  
Language Contact ◽  
Mixed Effects ◽  
Frequency Effect ◽  
Acoustic Measurements ◽  
Linear Mixed Effects Model ◽  
Phonetic Variation ◽  
Linear Mixed Effects ◽  
Contact Language ◽  
The Relationship ◽  
Phonetic Realization

Aims and objectives: While previous research has shown that phonetic variation in language contact situations is affected by whether a word has a cognate in the contact language, this paper aims to show that such an effect is not monotonic. According to the usage-based model, items in memory are organized according to similarity, thus we anticipated that formally more similar cognates would show a stronger cognate effect. Methodology: This variationist sociophonetic study investigates the relationship between cognate similarity and phonetic realization. We examined this relationship in the bilingual community of Rivera, Uruguay, in which both Portuguese and Spanish are spoken with regularity. Specifically, we focused on intervocalic /d/, which in monolingual Spanish is realized as an approximant [ð̞] or phonetic zero, but in monolingual Brazilian Portuguese is produced as a stop [d] or, in most varieties, an affricate [ʤ] before [i]. Data and analysis: We analyzed a corpus of sociolinguistic interviews of the Spanish spoken in Rivera. Acoustic measurements were taken from approximately 60 tokens each from 40 different speakers. Using a linear mixed-effects model, we examined the relationship between several predictors and the degree of constriction of intervocalic /d/. Findings/conclusions: While there is an overall frequency effect whereby more frequent words exhibit less constriction of intervocalic /d/, as both frequency and cognate similarity increase, less constriction of intervocalic /d/ obtains. Therefore, frequent cognates in Portuguese that have very similar forms affect the production of intervocalic /d/ more so than other cognates. Originality: No previous study has demonstrated that the cognate effect on phonetic variation in a situation of language contact is regulated by form similarity between cognate pairs. Significance/implications: The data support the usage-based model in that similar cognates have more lexical connections and can therefore show greater influence on phonetic realization than can cognates that share less phonetic material.

scholarly journals Restoration thinning reduces bush encroachment on freehold farmlands in north-central Namibia

2021 ◽  
Author(s):  
Matti T Nghikembua ◽  
Laurie L Marker ◽  
Bruce Brewer ◽  
Arvo Leinonen ◽  
Lauri Mehtätalo ◽  
...  
Keyword(s):  
Wildlife Habitat ◽  
Bush Encroachment ◽  
Mature Trees ◽  
Linear Mixed Effects Model ◽  
North Central ◽  
Linear Mixed Effects ◽  
Height Class ◽  
The Mean ◽  
Generalized Linear Mixed Effects ◽  
Restoration Measures

Abstract Bush encroachment affects ~45 million ha of Namibia and, without appropriate restoration measures, it negatively affects rangeland productivity and biodiversity. Thinning is a common method to counteract bush encroachment. The thinning strategy applied in north-central Namibia was assessed to examine how effective it has been in reducing bush encroachment. Trees/shrubs were selectively thinned manually, targeting all height classes, except individuals with stem diameters ≥18 cm. We investigated the effects on the vegetation and soil properties using surveys on three freehold farms (in 2016 and 2017) in bush-encroached and previously thinned habitats. Our results revealed significant differences in the mean total nitrogen (TN) content between the treatments; thinned areas had higher TN content which would be beneficial for fast-growing grasses. In the thinned plots, the occurrence probability of red umbrella thorn (Vachellia reficiens Warwa) was significantly reduced, indicating that it was the most harvested species; and umbrella thorn (Vachellia tortilis (Burch.) Brenan spp. heteracantha) was increased, indicating that it favoured reduced densities of dominant species. Natural regeneration was rapid; the tree/shrub abundance in the 0–1-m height class in the thinned area surpassed those in the non-thinned by 34 per cent, ~7.2 years since thinning. Thinning significantly reduced tree/shrub abundances of the 1–3- and &gt;3-m height classes, which was still evident 7.2 years since thinning. Based upon the generalized linear mixed-effects model, tree/shrub counts between treatments may equalize in ~14 and 15 years for the 1–3- and &gt;3-m height classes, respectively. Thinning was effective in reducing tree/shrub abundances and can be used to restore wildlife habitat on the Namibian farmland: however, post-thinning management is required to maintain an open savannah vegetation structure as the 0–1-m height class cohort will eventually grow into mature trees/shrubs.

scholarly journals Respiratory function declines in children with asthma associated with chemical species of fine particulate matter (PM2.5) in Nagasaki, Japan

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yoonhee Kim ◽  
Eun Ha Park ◽  
Chris Fook Sheng Ng ◽  
Yeonseung Chung ◽  
Kunio Hashimoto ◽  
...  
Keyword(s):  
Air Pollution ◽  
Lung Function ◽  
Urban Areas ◽  
Chemical Species ◽  
Mixed Effects ◽  
Linear Mixed Effects Model ◽  
Linear Mixed Effects ◽  
Asthmatic Children ◽  
Transboundary Air Pollution ◽  
Children With Asthma

Abstract Background The differential effects of PM2.5 fractions on children’s lung function remain inconclusive. This study aimed to examine whether lung function in asthmatic children was associated with increased PM2.5 fractions in urban areas in Nagasaki prefecture, Japan, where the air pollution level is relatively low but influenced by transboundary air pollution. Methods We conducted a multiyear panel study of 73 asthmatic children (boys, 60.3%; mean age, 8.2 years) spanning spring 2014–2016 in two cities. We collected self-measured peak expiratory flow (PEF) twice a day and daily time-series data for PM2.5 total mass and its chemical species. We fitted a linear mixed effects model to examine short-term associations between PEF and PM2.5, adjusting for individual and time-varying confounders. A generalized linear mixed effects model was also used to estimate the association for worsening asthma defined by severe PEF decline. Back-trajectory and cluster analyses were used to investigate the long-range transboundary PM2.5 in the study areas. Results We found that morning PEFs were adversely associated with higher levels of sulfate (− 1.61 L/min; 95% CI: − 3.07, − 0.15) in Nagasaki city and organic carbon (OC) (− 1.02 L/min; 95% CI: − 1.94, − 0.09) in Isahaya city, per interquartile range (IQR) increase at lag1. In addition, we observed consistent findings for worsening asthma, with higher odds of severe PEF decline in the morning for sulfate (odds ratio (OR) = 2.31; 95% CI: 1.12, 4.77) and ammonium (OR = 1.73; 95% CI: 1.06, 2.84) in Nagasaki city and OC (OR = 1.51; 95% CI: 1.06, 2.15) in Isahaya city, per IQR increase at lag1. The significant chemical species were higher on days that could be largely attributed to the path of Northeast China origin (for sulfate and ammonium) or both the same path and local sources (for OC) than by other clusters. Conclusions This study provides evidence of the differential effects of PM2.5 fractions on lung function among asthmatic children in urban areas, where the Japanese national standards of air quality have been nearly met. Continuous efforts to promote mitigation actions and public awareness of hazardous transboundary air pollution are needed to protect susceptible children with asthma.

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