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1.
ESMO Open ; 9(5): 103443, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38692082

ABSTRACT

BACKGROUND: The purpose of this study was to evaluate the prognostic value of the multigene EndoPredict test in prospectively collected data of patients screened for the randomized, double-blind, phase III UNIRAD trial, which evaluated the addition of everolimus to adjuvant endocrine therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. PATIENTS AND METHODS: Patients were classified into low or high risk according to the EPclin score, consisting of a 12-gene molecular score combined with tumor size and nodal status. Association of the EPclin score with disease-free survival (DFS) and distant metastasis-free survival (DMFS) was evaluated using Kaplan-Meier estimates. The independent prognostic added value of EPclin score was tested in a multivariate Cox model after adjusting on tumor characteristics. RESULTS: EndoPredict test results were available for 768 patients: 663 patients classified as EPclin high risk (EPCH) and 105 patients as EPclin low risk (EPCL). Median follow-up was 70 months (range 1-172 months). For the 429 EPCH randomized patients, there was no significant difference in DFS between treatment arms. The 60-month relapse rate for patients in the EPCL and EPCH groups was 0% and 7%, respectively. Hazard ratio (HR) supposing continuous EPclin score was 1.87 [95% confidence interval (CI) 1.4-2.5, P < 0.0001]. This prognostic effect remained significant when assessed in a Cox model adjusting on tumor size, number of positive nodes and tumor grade (HR 1.52, 95% CI 1.09-2.13, P = 0.0141). The 60-month DMFS for patients in the EPCL and EPCH groups was 100% and 94%, respectively (adjusted HR 8.10, 95% CI 1.1-59.1, P < 0.0001). CONCLUSIONS: The results confirm the value of EPclin score as an independent prognostic parameter in node-positive, hormone receptor-positive, HER2-negative early breast cancer patients receiving standard adjuvant treatment. EPclin score can be used to identify patients at higher risk of recurrence who may warrant additional systemic treatments.

2.
Environ Sci Atmos ; 19(227): 1-13, 2023 Jul 27.
Article in English | MEDLINE | ID: mdl-37590244

ABSTRACT

Reduced-form modeling approaches are an increasingly popular way to rapidly estimate air quality and human health impacts related to changes in air pollutant emissions. These approaches reduce computation time by making simplifying assumptions about pollutant source characteristics, transport and chemistry. Two reduced form tools used by the Environmental Protection Agency in recent assessments are source apportionment-based benefit per ton (SA BPT) and source apportionment-based air quality surfaces (SABAQS). In this work, we apply these two reduced form tools to predict changes in ambient summer-season ozone, ambient annual PM2.5 component species and monetized health benefits for multiple sector-specific emission control scenarios: on-road mobile, electricity generating units (EGUs), cement kilns, petroleum refineries, and pulp and paper facilities. We then compare results against photochemical grid and standard health model-based estimates. We additionally compare monetized PM2.5 health benefits to values derived from three reduced form tools available in the literature: the Intervention Model for Air Pollution (InMAP), Air Pollution Emission Experiments and Policy Analysis (APEEP) version 2 (AP2) and Estimating Air pollution Social Impact Using Regression (EASIUR). Ozone and PM2.5 changes derived from SABAQS for EGU scenarios were well-correlated with values obtained from photochemical modeling simulations with spatial correlation coefficients between 0.64 and 0.89 for ozone and between 0.75 and 0.94 for PM2.5. SABAQS ambient ozone and PM2.5 bias when compared to photochemical modeling predictions varied by emissions scenario: SABAQS PM2.5 changes were overpredicted by up to 46% in one scenario and underpredicted by up to 19% in another scenario; SABAQS seasonal ozone changes were overpredicted by 34% to 83%. All tools predicted total PM2.5 benefits within a factor of 2 of the full-form predictions consistent with intercomparisons of reduced form tools available in the literature. As reduced form tools evolve, it is important to continue periodic comparison with comprehensive models to identify systematic biases in estimating air pollution impacts and resulting monetized health benefits.

3.
Environ Sci Technol ; 57(29): 10708-10720, 2023 07 25.
Article in English | MEDLINE | ID: mdl-37437161

ABSTRACT

Particulate matter air pollution is a leading cause of global mortality, particularly in Asia and Africa. Addressing the high and wide-ranging air pollution levels requires ambient monitoring, but many low- and middle-income countries (LMICs) remain scarcely monitored. To address these data gaps, recent studies have utilized low-cost sensors. These sensors have varied performance, and little literature exists about sensor intercomparison in Africa. By colocating 2 QuantAQ Modulair-PM, 2 PurpleAir PA-II SD, and 16 Clarity Node-S Generation II monitors with a reference-grade Teledyne monitor in Accra, Ghana, we present the first intercomparisons of different brands of low-cost sensors in Africa, demonstrating that each type of low-cost sensor PM2.5 is strongly correlated with reference PM2.5, but biased high for ambient mixture of sources found in Accra. When compared to a reference monitor, the QuantAQ Modulair-PM has the lowest mean absolute error at 3.04 µg/m3, followed by PurpleAir PA-II (4.54 µg/m3) and Clarity Node-S (13.68 µg/m3). We also compare the usage of 4 statistical or machine learning models (Multiple Linear Regression, Random Forest, Gaussian Mixture Regression, and XGBoost) to correct low-cost sensors data, and find that XGBoost performs the best in testing (R2: 0.97, 0.94, 0.96; mean absolute error: 0.56, 0.80, and 0.68 µg/m3 for PurpleAir PA-II, Clarity Node-S, and Modulair-PM, respectively), but tree-based models do not perform well when correcting data outside the range of the colocation training. Therefore, we used Gaussian Mixture Regression to correct data from the network of 17 Clarity Node-S monitors deployed around Accra, Ghana, from 2018 to 2021. We find that the network daily average PM2.5 concentration in Accra is 23.4 µg/m3, which is 1.6 times the World Health Organization Daily PM2.5 guideline of 15 µg/m3. While this level is lower than those seen in some larger African cities (such as Kinshasa, Democratic Republic of the Congo), mitigation strategies should be developed soon to prevent further impairment to air quality as Accra, and Ghana as a whole, rapidly grow.


Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Ghana , Environmental Monitoring , Democratic Republic of the Congo , Particulate Matter/analysis , Air Pollution/analysis
4.
Ocul Immunol Inflamm ; : 1-5, 2023 May 03.
Article in English | MEDLINE | ID: mdl-37134295

ABSTRACT

PURPOSE: To evaluate the association between ocular trauma and activation of ocular toxoplasmosis. METHODS: Retrospective review of 686 patients with ocular toxoplasmosis and its association with trauma to the eye or the head within 1 week of activation. RESULTS: Ten patients with a history of trauma and activation of ocular toxoplasmosis were detected (10/686; 1.45%). Nine patients showed a primary focus of retinitis without a previous scar and one patient had a recurrent form of ocular toxoplasmosis. From these 10 patients, Toxoplasma IgG was positive in eight of them. The median age of the patients was 35.8 years-old (range 17 to 65). CONCLUSIONS: These cases suggest that trauma can be associated with activation of retinal bradyzoite cysts in ocular toxoplasmosis.

5.
Anaesthesia ; 77(4): 416-427, 2022 04.
Article in English | MEDLINE | ID: mdl-35167136

ABSTRACT

Mortality and morbidity for high-risk surgical patients are often high, especially in low-resource settings. Enhanced peri-operative care has the potential to reduce preventable deaths but must be designed to meet local needs. This before-and-after cohort study aimed to assess the effectiveness of a postoperative 48-hour enhanced care pathway for high-risk surgical patients ('high-risk surgical bundle') who did not meet the criteria for elective admission to intensive care. The pathway comprised of six elements: risk identification and communication; adoption of a high-risk post-anaesthesia care unit discharge checklist; prompt nursing admission to ward; intensification of vital signs monitoring; troponin measurement; and prompt access to medical support if required. The primary outcome was in-hospital mortality. Data describing 1189 patients from two groups, before and after implementation of the pathway, were compared. The usual care group comprised a retrospective cohort of high-risk surgical patients between September 2015 and December 2016. The intervention group prospectively included high-risk surgical patients from February 2019 to March 2020. Unadjusted mortality rate was 10.5% (78/746) for the usual care and 6.3% (28/443) for the intervention group. After adjustment, the intervention effect remained significant (RR 0.46 (95%CI 0.30-0.72). The high-risk surgical bundle group received more rapid response team calls (24% vs. 12.6%; RR 0.63 [95%CI 0.49-0.80]) and surgical re-interventions (18.9 vs. 7.5%; RR 0.41 [95%CI 0.30-0.59]). These data suggest that a clinical pathway based on enhanced surveillance for high-risk surgical patients in a resource-constrained setting could reduce in-hospital mortality.


Subject(s)
Perioperative Care , Brazil/epidemiology , Cohort Studies , Hospital Mortality , Humans , Retrospective Studies
6.
Environ Entomol ; 49(2): 269-276, 2020 04 14.
Article in English | MEDLINE | ID: mdl-31990325

ABSTRACT

The spotted lanternfly, Lycorma delicatula (White), an invasive, phloem-feeding fulgorid generalist, was recently discovered in the United States. Current trapping methods include placing glue-covered sticky bands around trunks of host trees to exploit the lanternfly's behavior of climbing up tree trunks. These bands are messy and need to be replaced often as they become covered in both target and nontarget insects and debris. Fourth instar nymphs and adults have also shown an ability to escape from traditional tree bands or avoid capture. A promising commercially available tree band (BugBarrier) design that faces inward to the trunk and targets larger developmental stages was tested. A modified pecan weevil trap (circle trunk trap) was also compared with tree bands. This design does not require the use of insect-trapping adhesive. Circle trunk traps caught more third and fourth instar and adult L. delicatula than BugBarrier bands. Flight intercept traps caught fewer adult L. delicatula than trunk-based tree bands. In a separate comparison, more spotted lanternflies were caught on adhesive-coated 'tree mimicking' traps placed along the edges of Ailanthus altissima Swingle (Sapindales: Simaroubaceae) stands than away from hosts in an open field. Circle trunk traps are recommended for their effectiveness at capturing L. delicatula as well as their relative ease-of-use and reusability.


Subject(s)
Ailanthus , Hemiptera , Animals , Insect Control , Insecta , Nymph , Trees , United States
7.
Geohealth ; 3(5): 127-144, 2019.
Article in English | MEDLINE | ID: mdl-31276080

ABSTRACT

The U.S. Southwest is projected to experience increasing aridity due to climate change. We quantify the resulting impacts on ambient dust levels and public health using methods consistent with the Environmental Protection Agency's Climate Change Impacts and Risk Analysis framework. We first demonstrate that U.S. Southwest fine (PM2.5) and coarse (PM2.5-10) dust levels are strongly sensitive to variability in the 2-month Standardized Precipitation-Evapotranspiration Index across southwestern North America. We then estimate potential changes in dust levels through 2099 by applying the observed sensitivities to downscaled meteorological output projected by six climate models following an intermediate (Representative Concentration Pathway 4.5, RCP4.5) and a high (RCP8.5) greenhouse gas concentration scenario. By 2080-2099 under RCP8.5 relative to 1986-2005 in the U.S. Southwest: (1) Fine dust levels could increase by 57%, and fine dust-attributable all-cause mortality and hospitalizations could increase by 230% and 360%, respectively; (2) coarse dust levels could increase by 38%, and coarse dust-attributable cardiovascular mortality and asthma emergency department visits could increase by 210% and 88%, respectively; (3) climate-driven changes in dust concentrations can account for 34-47% of these health impacts, with the rest due to increases in population and baseline incidence rates; and (4) economic damages of the health impacts could total $47 billion per year additional to the 1986-2005 value of $13 billion per year. Compared to national-scale climate impacts projected for other U.S. sectors using the Climate Change Impacts and Risk Analysis framework, dust-related mortality ranks fourth behind extreme temperature-related mortality, labor productivity decline, and coastal property loss.

8.
J Helminthol ; 93(4): 447-452, 2019 Jul.
Article in English | MEDLINE | ID: mdl-29669605

ABSTRACT

Many important studies on resistance reversion, anthelmintic efficacy and, especially, new molecules with antiparasitic effects are performed in laboratories using gerbils (Meriones unguiculatus) as the experimental model. This study aimed to evaluate the use of corticosteroids (dexamethasone and methylprednisolone acetate) in gerbils experimentally infected with different doses of infective larvae (sheathed or exsheathed) of Haemonchus contortus. In the first experiment, 28 gerbils were divided into seven groups infected by 2-6 × 103 larvae, with or without immunosuppression using corticosteroids. In the second experiment, eight gerbils were divided into two groups infected by 2 × 103 sheathed or exsheathed larvae. For the third assay, seven immunosuppressed gerbils were infected with 2 × 103 sheathed larvae and were killed 15 days post infection (PI). The highest number of parasites was recovered from methylprednisolone-immunosuppressed animals. We observed red and white blood cell alterations and biochemical parameters in infected animals that had undergone immunosuppression with methylprednisolone. We highlight that in the first and second experiments a satisfactory number of worms was recovered using sheathed larvae and immunocompetent animals. When exsheathed larvae were used, the number of worms recovered was unsatisfactory. A considerable larval burden was recovered from immunosuppressed gerbils 15 days PI, and body weight did not influence establishment of larvae.


Subject(s)
Gerbillinae/parasitology , Haemonchiasis/parasitology , Haemonchus/pathogenicity , Immunosuppressive Agents/administration & dosage , Adrenal Cortex Hormones/administration & dosage , Animals , Disease Models, Animal , Drug Resistance, Multiple , Female , Haemonchiasis/immunology , Haemonchus/drug effects , Immunosuppression Therapy/methods , Larva/drug effects , Larva/pathogenicity , Male
9.
Periodontol 2000 ; 77(1): 123-149, 2018 06.
Article in English | MEDLINE | ID: mdl-29493018

ABSTRACT

Diverse clinical advancements, together with some relevant technical innovations, have led to an increase in popularity of tunneling flap procedures in plastic periodontal and implant surgery in the recent past. This trend is further promoted by the fact that these techniques have lately been introduced to a considerably expanded range of indications. While originally described for the treatment of gingival recession-type defects, tunneling flap procedures may now be applied successfully in a variety of clinical situations in which augmentation of the soft tissues is indicated in the esthetic zone. Potential clinical scenarios include surgical thickening of thin buccal gingiva or peri-implant mucosa, alveolar ridge/socket preservation and implant second-stage surgery, as well as soft-tissue ridge augmentation or pontic site development. In this way, tunneling flap procedures developed from a technique, originally merely intended for surgical root coverage, into a capacious surgical conception in plastic periodontal and implant surgery. The purpose of this article is to provide a comprehensive overview on tunneling flap procedures, to introduce the successive development of the approach along with underlying ideas on surgical wound healing and to present contemporary clinical scenarios in step-by-step photograph-illustrated sequences, which aim to provide clinicians with guidance to help them integrate tunneling flap procedures into their daily clinical routine.


Subject(s)
Dental Implantation, Endosseous/methods , Esthetics, Dental , Gingivoplasty/methods , Periodontal Diseases/surgery , Surgical Flaps , Humans
10.
Environ Res ; 156: 791-800, 2017 07.
Article in English | MEDLINE | ID: mdl-28501677

ABSTRACT

In this study, we modeled concentrations of fine particulate matter (PM2.5) and ozone (O3) attributable to precursor emissions from individual airports in the United States, developing airport-specific health damage functions (deaths per 1000t of precursor emissions) and physically-interpretable regression models to explain variability in these functions. We applied the Community Multiscale Air Quality model using the Decoupled Direct Method to isolate PM2.5- or O3-related contributions from precursor pollutants emitted by 66 individual airports. We linked airport- and pollutant-specific concentrations with population data and literature-based concentration-response functions to create health damage functions. Deaths per 1000t of primary PM2.5 emissions ranged from 3 to 160 across airports, with variability explained by population patterns within 500km of the airport. Deaths per 1000t of precursors for secondary PM2.5 varied across airports from 0.1 to 2.7 for NOx, 0.06 to 2.9 for SO2, and 0.06 to 11 for VOCs, with variability explained by population patterns and ambient concentrations influencing particle formation. Deaths per 1000t of O3 precursors ranged from -0.004 to 1.0 for NOx and 0.03 to 1.5 for VOCs, with strong seasonality and influence of ambient concentrations. Our findings reinforce the importance of location- and source-specific health damage functions in design of health-maximizing emissions control policies.


Subject(s)
Air Pollution/adverse effects , Airports , Models, Theoretical , Adult , Air Pollutants/analysis , Air Pollutants/toxicity , Air Pollution/analysis , Ammonium Compounds/analysis , Ammonium Compounds/toxicity , Humans , Mortality , Nitrogen Oxides/analysis , Nitrogen Oxides/toxicity , Ozone/analysis , Ozone/toxicity , Particulate Matter/analysis , Particulate Matter/toxicity , Sulfur Dioxide/analysis , Sulfur Dioxide/toxicity , Vehicle Emissions , Volatile Organic Compounds/analysis , Volatile Organic Compounds/toxicity
12.
Environ Health Perspect ; 125(3): 324-332, 2017 03.
Article in English | MEDLINE | ID: mdl-27586513

ABSTRACT

BACKGROUND: Residential combustion (RC) and electricity generating unit (EGU) emissions adversely impact air quality and human health by increasing ambient concentrations of fine particulate matter (PM2.5) and ozone (O3). Studies to date have not isolated contributing emissions by state of origin (source-state), which is necessary for policy makers to determine efficient strategies to decrease health impacts. OBJECTIVES: In this study, we aimed to estimate health impacts (premature mortalities) attributable to PM2.5 and O3 from RC and EGU emissions by precursor species, source sector, and source-state in the continental United States for 2005. METHODS: We used the Community Multiscale Air Quality model employing the decoupled direct method to quantify changes in air quality and epidemiological evidence to determine concentration-response functions to calculate associated health impacts. RESULTS: We estimated 21,000 premature mortalities per year from EGU emissions, driven by sulfur dioxide emissions forming PM2.5. More than half of EGU health impacts are attributable to emissions from eight states with significant coal combustion and large downwind populations. We estimate 10,000 premature mortalities per year from RC emissions, driven by primary PM2.5 emissions. States with large populations and significant residential wood combustion dominate RC health impacts. Annual mortality risk per thousand tons of precursor emissions (health damage functions) varied significantly across source-states for both source sectors and all precursor pollutants. CONCLUSIONS: Our findings reinforce the importance of pollutant-specific, location-specific, and source-specific models of health impacts in design of health-risk minimizing emissions control policies. Citation: Penn SL, Arunachalam S, Woody M, Heiger-Bernays W, Tripodis Y, Levy JI. 2017. Estimating state-specific contributions to PM2.5- and O3-related health burden from residential combustion and electricity generating unit emissions in the United States. Environ Health Perspect 125:324-332; http://dx.doi.org/10.1289/EHP550.


Subject(s)
Air Pollution/statistics & numerical data , Environmental Exposure/statistics & numerical data , Health Status , Ozone/analysis , Particulate Matter/analysis , Power Plants/statistics & numerical data , Air Pollutants/analysis , Humans , United States
13.
Br J Anaesth ; 117(5): 642-649, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27799179

ABSTRACT

BACKGROUND: Preoperative stress might influence postoperative pain, thereby, it is desirable to assess it more precisely. Thus, we developed and evaluated the psychometric properties of a brief measure of emotional preoperative stress (B-MEPS) index using Item Response Category Characteristic Curves. We validated and assessed whether the B-MEPS can predict moderate to intense acute postoperative pain (MIAPP). METHODS: We included 863 adult patients who underwent elective surgeries (ASA I-III physical status). The B-MEPS was constructed based on items selected from instruments to assess anxiety, depression, future self-perception and minor psychiatric disorders. We identified 24 items with greatest discriminant power to identify patients who should undergo surgery to treat cancer with MIAPP. The reliability was maximized using the Cronbach's alpha indices. Fifteen items remained, which were adjusted by the Generalized Partial Credit Model. The convergent validity was assessed correlating the B-MEPS index with the pain catastrophizing (n = 100). Finally, the B-MEPS was applied in a prospective cohort of patients who underwent an abdominal hysterectomy (n = 150). RESULTS: The Cronbach's alpha for selected items was 0.83. The correlation coefficient between B-MEPS index and catastrophizing was r = 0.37 (P < 0.01). A hierarchical regression model evidenced that the B-MEPS index was a factor independent to predict MIAPP after an abdominal hysterectomy [odds ratio (OR)=1.20, confidence interval (CI) 95% 1.05-1.43). CONCLUSIONS: The B-MEPS index presents satisfactory psychometric evaluations based on its internal consistency, convergent, and discriminant validity. The B-MEPS is a propensity index to MIAPP, which might help the clinician to decide on the best therapeutic approaches for acute postoperative pain.


Subject(s)
Acute Pain/psychology , Pain, Postoperative/psychology , Preoperative Period , Stress, Psychological/diagnosis , Stress, Psychological/psychology , Surveys and Questionnaires , Acute Pain/diagnosis , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Pain, Postoperative/diagnosis , Predictive Value of Tests , Psychometrics , Reproducibility of Results , Young Adult
14.
J Comp Pathol ; 155(1): 1-4, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27262503

ABSTRACT

The aim of this study was to evaluate anaemia, serum iron concentrations and δ-aminolevulinate dehydratase (ALA-D) activity in laying hens infected naturally by Salmonella Gallinarum and having severe hepatic lesions. Liver and serum samples were collected from 27 laying hens (20 infected and seven uninfected). The δ-ALA-D activity, haematocrit and serum iron concentrations were evaluated. There were significant decreases in δ-ALA-D activity, haematocrit and serum iron concentrations (P <0.01) in birds infected by S. Gallinarum when compared with uninfected birds. There was a positive correlation (P <0.001) between serum iron concentration, haematocrit (r(2) = 0.82) and δ-ALA-D activity (r(2) = 0.75). A positive correlation was also observed between δ-ALA-D activity and haematocrit (r(2) = 0.78; P <0.01). Liver samples showed moderate focal coagulative necrosis associated with infiltration of lymphoplasmacytic cells, macrophages and heterophils. The anaemia in the infected hens may be related to reduction in δ-ALA-D activity and serum iron concentrations, since both are important for haemopoiesis.


Subject(s)
Anemia/veterinary , Porphobilinogen Synthase/metabolism , Salmonella Infections, Animal/complications , Anemia/etiology , Animals , Chickens , Female , Iron/blood , Salmonella Infections, Animal/enzymology , Salmonella Infections, Animal/pathology , Salmonella enterica
15.
J Comp Pathol ; 154(2-3): 150-6, 2016.
Article in English | MEDLINE | ID: mdl-26929158

ABSTRACT

The aim of this study was to evaluate the role of butyrylcholinesterase (BChE) (in the serum and pancreas), acetylcholinesterase (AChE) (in the whole blood and pancreas) and nitric oxide (NO) (in the serum and pancreas) in cattle infected naturally by Eurytrema coelomaticum. Fifty-one cattle were studied, including 33 infected by E. coelomaticum and 18 uninfected animals. Significantly greater AChE activity was found in the pancreas of infected animals (P <0.01); however, these cattle had lower AChE activity in whole blood. BChE activity was greater in the sera of infected animals (P = 0.05), but was less in pancreatic samples. NO levels were significantly higher in the sera (P <0.05) and pancreas (P <0.001) of infected cattle compared with uninfected animals. A positive correlation was found between AChE activity in the pancreas and parasite load, but there was negative correlation between pancreatic BChE activity and parasitic load. Expression of AChE, BChE and NO is therefore linked to the inflammation caused by E. coelomaticum in cattle.


Subject(s)
Acetylcholinesterase/metabolism , Butyrylcholinesterase/metabolism , Cattle Diseases/microbiology , Nitric Oxide/metabolism , Trematode Infections/veterinary , Acetylcholinesterase/analysis , Animals , Butyrylcholinesterase/analysis , Cattle , Cattle Diseases/metabolism , Nitric Oxide/analysis , Trematode Infections/metabolism
16.
Ann Oncol ; 27(6): 1020-1029, 2016 06.
Article in English | MEDLINE | ID: mdl-26916095

ABSTRACT

BACKGROUND: Maintenance strategies beyond response or tumor stabilization with first-line chemotherapy in metastatic breast cancer (MBC) have not been extensively studied. Endocrine therapy combined with continued bevacizumab may be a helpful option for estrogen receptor (ER)-positive MBC. PATIENTS AND METHODS: In this prospective, open-label, phase III study, patients with histologically confirmed ER-positive, HER2-negative MBC and non-progressive disease after 16-24 weeks of taxane plus bevacizumab (T + BEV) were randomized to continuation of T + BEV or maintenance bevacizumab plus exemestane (E + BEV). The primary end point was progression-free survival (PFS) from randomization. To have 80% power to detect an improvement in the 6-month PFS rate (PFS6m) from 50% to 65%, 186 assessable patients were needed for a total of 141 PFS events. An interim analysis was planned after 40% of the required events. RESULTS: The interim analysis with 98 patients showed that the probability of reaching a statistically significant improvement in PFS by the end of the study was only 7%. This led the Independent Data and Monitoring Committee to recommend termination of patient enrollment. After a median of 21-month follow-up of all randomized patients (117 in total), PFS6m from randomization was 67.2% [95% confidence interval (CI) 53.6-77.7] with T + BEV and 55.2% (95% CI 41.5-66.9) with E + BEV [hazard ratio (HR): 1.0, 95% CI 0.7-1.5, P = 0.998]. Median PFS from BEV initiation was 12.5 and 12.3 months in the T + BEV and E + BEV arms, respectively. In the T + BEV arm, taxane was prematurely stopped for the majority of patients (94.9%), mainly due to toxicity (49.2%). Updated data after 35 months' median follow-up showed death rates of 44% and 55% in T + BEV and E + BEV arms, respectively. CONCLUSION: In this trial, maintenance therapy with E + BEV in ER-positive, HER2-negative MBC patients with no evidence of progression after first-line T + BEV did not achieve longer PFS compared with continuation of T + BEV. CLINICALTRIALSGOV: NCT01303679.


Subject(s)
Androstadienes/administration & dosage , Bevacizumab/administration & dosage , Breast Neoplasms/drug therapy , Estrogen Receptor alpha/genetics , Receptor, ErbB-2/genetics , Adult , Aged , Aged, 80 and over , Androstadienes/adverse effects , Bevacizumab/adverse effects , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Disease-Free Survival , Drug-Related Side Effects and Adverse Reactions/genetics , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Humans , Middle Aged , Neoplasm Metastasis
17.
Transl Med UniSa ; 12: 1-3, 2015.
Article in English | MEDLINE | ID: mdl-26535180

ABSTRACT

[This corrects the article on p. 44 in vol. 11, PMID: 25674549.].

18.
Sci Total Environ ; 527-528: 47-55, 2015 Sep 15.
Article in English | MEDLINE | ID: mdl-25956147

ABSTRACT

Aircraft activity and airport operations can increase combustion-related air pollutant concentrations, but it is difficult to distinguish aviation emissions from traffic and other local sources. Emission inventories are uncertain and dispersion models may not capture aircraft plume complexity; ambient monitoring data require detailed statistical analyses to extract aviation signals. The goal of this study is to compare two modeling approaches including monitoring-based regression models and the EDMS/AERMOD dispersion model, informing improvements and allowing quantitation of aviation impacts on air quality through multi-pollutant sensitivity and multi-monitor fate/transport analyses. Aggregate concentration comparisons are similar, though diurnal patterns show potential weaknesses in near-field dispersion, treatment of overnight conditions, and emission inventory accuracy.


Subject(s)
Air Pollutants/analysis , Airports , Environmental Monitoring/methods , Models, Chemical , Nitrogen Oxides/analysis , Particulate Matter/analysis , Air Pollution/statistics & numerical data , Los Angeles , Soot/analysis
19.
Trop Biomed ; 32(1): 160-6, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25801266

ABSTRACT

This study aimed to evaluate the repellent effect of tea tree (Melaleuca alternifolia) and andiroba (Carapa guianensis) essential oils on two species of flies (Haemotobia irritans and Chrysomya megacephala). For the in vitro studies, free-living adult flies were captured and reared in the laboratory. To verify the repellency effect, an apparatus was constructed where H. irritans and C. megacephala were exposed to andiroba and tea tree oils (5.0%), as well as to a known repellent (citronella, 5.0%) to validate the test. The study demonstrated that all three oils used showed in vitro repellent effect against both species of flies. It is possible to conclude that the essential oils (tea tree and andiroba) have repellent effect on these species of flies used in this study.


Subject(s)
Diptera/drug effects , Insect Repellents/pharmacology , Melaleuca/chemistry , Meliaceae/chemistry , Plant Oils/pharmacology , Animals , Insect Repellents/isolation & purification , Plant Oils/isolation & purification
20.
Parasitology ; 142(3): 439-48, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25137643

ABSTRACT

This study aimed to evaluate in vitro and in vivo trypanocidal activity of free and nanoencapsulated curcumin against Trypanosoma evansi. In vitro efficacy of free curcumin (CURC) and curcumin-loaded in lipid-core nanocapsules (C-LNCs) was evaluated to verify their lethal effect on T. evansi. To perform the in vivo tests, T. evansi-infected animals were treated with CURC (10 and 100 mg kg(-1), intraperitoneally [i.p.]) and C-LNCs (10 mg kg(-1), i.p.) during 6 days, with the results showing that these treatments significantly attenuated the parasitaemia. Infected untreated rats showed protein peroxidation and an increase of nitrites/nitrates, whereas animals treated with curcumin showed a reduction on these variables. As a result, the activity of antioxidant enzymes (superoxide dismutase and catalase) differs between groups (P<0.05). Infected animals and treated with CURC exhibited a reduction in the levels of alanine aminotransferase and creatinine, when compared with the positive control group. The use of curcumin in vitro resulted in a better parasitaemia control, an antioxidant activity and a protective effect on liver and kidney functions of T. evansi-infected adult male Wistar rats.


Subject(s)
Curcumin/pharmacology , Trypanocidal Agents/pharmacology , Trypanosoma/drug effects , Trypanosomiasis/drug therapy , Advanced Oxidation Protein Products/blood , Alanine Transaminase/metabolism , Alkaline Phosphatase/metabolism , Animals , Aspartate Aminotransferases/metabolism , Catalase/blood , Creatinine/metabolism , Curcumin/administration & dosage , Dogs , Hydrogen-Ion Concentration , Kidney/parasitology , Kidney/pathology , Kidney/physiopathology , Liver/enzymology , Liver/parasitology , Liver/pathology , Male , Nanocapsules , Nitrates/blood , Nitrites/blood , Parasitemia/drug therapy , Parasitemia/parasitology , Rats , Rats, Wistar , Superoxide Dismutase/blood , Trypanocidal Agents/administration & dosage , Trypanosomiasis/pathology
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