Alginate-Bentonite-Based Hydrogels Designed to Obtain Controlled-Release Formulations of Dodecyl Acetate.

Dodecyl acetate (DDA), a volatile compound present in insect sex pheromones, was incorporated into alginate-based granules to obtain controlled-release formulations (CRFs). In this research, not only was the effect of adding bentonite to the basic alginate-hydrogel formulation studied, but also that of the encapsulation efficiency on the release rate of DDA in laboratory and field experiments. DDA encapsulation efficiency increased as the alginate/bentonite ratio increased. From the preliminary volatilization experiments, a linear relationship was found between the DDA release percentage and the amount of bentonite present in the alginate CRFs. Laboratory kinetic volatilization experiments showed that the selected alginate-bentonite formulation (DDAB75A10) exhibited a prolonged DDA release profile. The value of the diffusional exponent obtained from the Ritger and Peppas model (n = 0.818) indicated that the release process follows a non-Fickian or anomalous transport mechanism. Field volatilization experiments showed a steady release of DDA over time from the alginate-based hydrogels tested. This result, together with those obtained from the laboratory release experiments, allowed the obtainment of a set of parameters to improve the preparation of alginate-based CRFs for the use of volatile biological molecules, such as DDA, in agricultural biological control programs.

Alginate-based hydrogels modified with olive pomace and lignin to removal organic pollutants from aqueous solutions.

In this study, new hybrid biopolymers based on alginate and low cost materials belong lignocellulose group such as lignin and olive pomace were used to removal organic pollutants. The organic carbon content, granule size, average mass, zero charge point, water uptake and swelling of the resulting alginate-based modified adsorbents were measured. The homogeneity, complexity and encapsulation viability of the novel biopolymers were studied by FT-IR, TGA and SEM. As model of emerging contaminants belong to glucocorticoids group prednisolone drug was selected. 3,4-dichloroaniline (3,4-DCA) was chosen as aniline derivate pollutant. The efficiency of the bioadsorbents to removal 3,4-dichloroaniline and prednisolone was performed by kinetic and equilibrium batch adsorption studies. The experimental data was found well correlated to the pseudo-second order kinetic model. The adsorption of 3,4-DCA and prednisolone was mainly affected by the organic carbon content of the bioadsorbent. A higher adsorption capacity was observed for lignin-alginate based bioadsorbents. The removal efficiency was higher than 90% for 3,4-DCA in all prepared bioadsorbents, reached up to 49% for prednisolone using the bioadsorbent with the higher lignin content. These results suggest the promising potential for the prepared eco-friendly bioadsorbents to removal organic pollutants from water, mainly for aniline derivate such as 3,4-DCA.

Hydatid cyst of the colon: A systematic review of the literature.

BACKGROUND: Primary hydatid disease in the colon is an extremely rare finding. We performed a systematic review of cases of hydatidosis of the colon published to date. AIM: To systematic review the published papers about hydatidosis of the colon. METHODS: Following PRISMA guidelines, we performed an unlimited search for articles on CH in the MEDLINE (PubMed), EMBASE, Cochrane, Latindex and Scielo databases, published in English, Spanish, French, German or Italian between January 1, 1960 and December 15, 2018. The search items were: (Colon) AND [(hydatidosis) OR (hydatid disease) OR (echinococcosis)]. RESULTS: Nine case reports were found [five men, four women, median age 64.55 years (range: 21-81)]. The most frequent clinical manifestation was abdominal pain (8/9) (88.9%). In almost all cases several image studies were carried out, but abdominal computed tomography was the most used (66.7%). Five resections of the colon (62.5%) and three sutures of the fistula between cyst and colon (37.5%) were performed. Four patients did not present post-operative complications, but one died. Postoperative period was recorded for a mean period of 35 months. No recurrences were recorded. CONCLUSION: The most frequent symptom was abdominal pain (evidence level 4). Computed tomography was the most frequently used diagnostic imaging technique (evidence level 4). Colectomy was the most appropriate treatment (evidence level 5). All the diagnostic and therapeutic options for hydatid cysts located in colon have a low level of evidence.

Kinematic study of standing long jump in preadolescents before the occurrence of maximum growth age.

ABSTRACT: The aims of this study were to identify the kinematics characteristics of the standing long jump (SLJ) performance in groups of Mexican girls and boys, with a chronological age such that theoretically, corresponds to the age before the occurrence of the maximum growth. The jump distance is largely dependent on the kinematic values at the time of takeoff. A calculation method was used from video recordings of the sagittal projection of jumps. The location of the body mass center at takeoff was the source for measuring the kinematic values. The Mann-Whitney U non-parametric Test (p < 0.05) and a Z-scores analysis were applied to assess differences between the groups. Almost the 60% of all the participants are within the range that is considered as average BMI and stature, according to the WHO growing standard values. In the sample, boys are bigger, probably stronger and jump longer than girls. Although the statistical tests show there are some similarities, mainly in the older groups, it is not possible to conclude that girls and boys in the sample have an equally performance in the Standing Long Jump.

Pharmacokinetics and Tolerability of Lorcaserin in Special Populations: Elderly Patients and Patients with Renal or Hepatic Impairment.

PURPOSE: To determine whether dosage adjustment is likely to be necessary for effective and well-tolerated use of a pharmaceutical agent, guidance documents from the US Food and Drug Administration recommend pharmacokinetics studies in patients with impaired renal or impaired hepatic function and in the elderly population. Three studies were conducted to evaluate the pharmacokinetic properties and tolerability of lorcaserin in these populations. METHODS: Lorcaserin was evaluated in single-dose pharmacokinetics studies of 3 overweight/obese populations: (1) elderly (aged >65 years) patients; (2) patients with impaired renal function; and (3) those with impaired hepatic function. FINDINGS: In elderly patients, Cmax was lower (geometric mean ratio [GMR], 0.83; 90% CI, 0.71-0.97), but AUC was unchanged versus adult patients. In patients with renal impairment, Cmax was reduced versus that in patients with normal renal function (GMR: mild impairment, 0.99 [90% CI, 0.76-1.29]; moderate, 0.70 [90% CI, 0.54-0.90]; and severe, 0.69 [90% CI, 0.53-0.89]); no trend in AUC was observed in this group versus renal impairment. In patients with hepatic impairment, Cmax was decreased (GMR: mild impairment, 0.92 [90% CI, 0.76-1.11]; moderate, 0.86 [90% CI, 0.71-1.04]), and AUC was increased versus patients with normal hepatic function. IMPLICATIONS: Based on these findings, no lorcaserin dose adjustments are necessary in elderly patients with normal renal function or in patients with mild/moderate renal or hepatic impairment. ClinicalTrials.gov identifiers: NCT00828581, NCT00828438, and NCT00828932.

Attitude and knowledge about foot health: a spanish view.

OBJECTIVE:: to explore attitudes towards patients' self-reported data about foot health-related beliefs from a behavioural and attitudinal perspective. METHODS:: a sample of 282 participants of a mean age of 39.46 ± 16.026 came to a health centre where self-reported demographic, clinical characteristics and beliefs relating to foot health data were registered, informants' completed all the stages of the research process. RESULTS:: the results of the analysis revealed an 8-factor factorial structure based on (1) podiatric behaviours, (2) the intention to carry out protective behaviour, (3) attitudinal beliefs, (4) normative beliefs, (5) needs, (6) apathy, (7) self-care, and (8) the general perception of foot health. They all explained 62.78% of the variance, and were considered as independent variables in a regression analysis to determine which provided the best explanations for the importance attributed to foot health. CONCLUSIONS:: the participants in the study revealed a positive attitude in relation to foot health care and responsible behaviour. OBJETIVO:: explorar as atitudes em relação aos dados auto-relatados dos pacientes sobre crenças relacionadas à saúde do pé, desde uma perspectiva comportamental e atitudinal. MÉTODOS:: uma amostra de 282 participantes com idade média de 39,46 ± 16,026 chegaram a um centro de saúde onde foram registradas características demográficas, clínicas e crenças auto-relatadas referentes a dados de saúde do pé, os quais completaram todas as fases do processo de pesquisa. RESULTADOS:: os resultados da análise revelaram uma estrutura fatorial de 8 fatores baseada em (1) comportamentos podiátricos, (2) a intenção de realizar comportamentos protetores, (3) crenças atitudinais, (4) crenças normativas, (6) apatia, (7) autocuidado, e (8) a percepção geral da saúde do pé. Todos eles explicaram 62,78% da variância e foram considerados como variáveis ​​independentes em uma análise de regressão para determinar quais forneceram as melhores explicações para a importância atribuída à saúde do pé. CONCLUSÕES:: os participantes do estudo revelaram uma atitude positiva em relação à saúde do pé e comportamento responsável. OBJETIVO:: explorar las actitudes relacionadas con datos autoinformados sobre las creencias de la salud del pie desde una perspectiva actitudinal. MÉTODO:: una muestra de 282 participantes edad media 39.46 ± 16.026 acudieron a un centro de salud donde se registraron datos autoinformados de las características demográficas, características clínicas y creencias relacionadas con la salud del pie, completándose todas las etapas del proceso de investigación. RESULTADOS:: los resultados del análisis revelaron una estructura factorial de 8 factores basado en (1) conductas podológicas, (2) la intención de llevar a cabo una conducta de protección, (3) las creencias actitudinales, (4) las creencias normativas, (5) las necesidades, (6) la apatía, (7) el autocuidado, y (8) la percepción general de salud podal. Todos ellos explicaron un 62,78% de la varianza, y fueron considerados como variables independientes en una ecuación de regresión para determinar cuáles de ellos explicaban mejor la importancia atribuida a la salud del pie. CONCLUSIONES:: los participantes en el estudio revelaron una actitud positiva en relación al cuidado de la salud del pie y al comportamiento responsable.

Attitude and knowledge about foot health: a spanish view / Atitude e conhecimento sobre a saúde do pé: uma visão espanhola / Actitud y conocimiento sobre la salud del pie: una visión Española

ABSTRACT Objective: to explore attitudes towards patients' self-reported data about foot health-related beliefs from a behavioural and attitudinal perspective. Methods: a sample of 282 participants of a mean age of 39.46 ± 16.026 came to a health centre where self-reported demographic, clinical characteristics and beliefs relating to foot health data were registered, informants' completed all the stages of the research process. Results: the results of the analysis revealed an 8-factor factorial structure based on (1) podiatric behaviours, (2) the intention to carry out protective behaviour, (3) attitudinal beliefs, (4) normative beliefs, (5) needs, (6) apathy, (7) self-care, and (8) the general perception of foot health. They all explained 62.78% of the variance, and were considered as independent variables in a regression analysis to determine which provided the best explanations for the importance attributed to foot health. Conclusions: the participants in the study revealed a positive attitude in relation to foot health care and responsible behaviour.

RESUMO Objetivo: explorar as atitudes em relação aos dados auto-relatados dos pacientes sobre crenças relacionadas à saúde do pé, desde uma perspectiva comportamental e atitudinal. Métodos: uma amostra de 282 participantes com idade média de 39,46 ± 16,026 chegaram a um centro de saúde onde foram registradas características demográficas, clínicas e crenças auto-relatadas referentes a dados de saúde do pé, os quais completaram todas as fases do processo de pesquisa. Resultados: os resultados da análise revelaram uma estrutura fatorial de 8 fatores baseada em (1) comportamentos podiátricos, (2) a intenção de realizar comportamentos protetores, (3) crenças atitudinais, (4) crenças normativas, (6) apatia, (7) autocuidado, e (8) a percepção geral da saúde do pé. Todos eles explicaram 62,78% da variância e foram considerados como variáveis ​​independentes em uma análise de regressão para determinar quais forneceram as melhores explicações para a importância atribuída à saúde do pé. Conclusões: os participantes do estudo revelaram uma atitude positiva em relação à saúde do pé e comportamento responsável.

RESUMEN Objetivo: explorar las actitudes relacionadas con datos autoinformados sobre las creencias de la salud del pie desde una perspectiva actitudinal. Método: una muestra de 282 participantes edad media 39.46 ± 16.026 acudieron a un centro de salud donde se registraron datos autoinformados de las características demográficas, características clínicas y creencias relacionadas con la salud del pie, completándose todas las etapas del proceso de investigación. Resultados: los resultados del análisis revelaron una estructura factorial de 8 factores basado en (1) conductas podológicas, (2) la intención de llevar a cabo una conducta de protección, (3) las creencias actitudinales, (4) las creencias normativas, (5) las necesidades, (6) la apatía, (7) el autocuidado, y (8) la percepción general de salud podal. Todos ellos explicaron un 62,78% de la varianza, y fueron considerados como variables independientes en una ecuación de regresión para determinar cuáles de ellos explicaban mejor la importancia atribuida a la salud del pie. Conclusiones: los participantes en el estudio revelaron una actitud positiva en relación al cuidado de la salud del pie y al comportamiento responsable.

Conscientious objection in spanish podiatrists students: a questionnaire survey / Objeción de conciencia en estudiantes españoles de podología: estudio mediante cuestionario / Objeção de consciência em estudantes de podologia na Espanha: um questionário de sondagem

Objective: To explore attitudes towards conscientious objections among podiatrists students in Spain. Methods: Podiatrists students at University of A Coruña, King Rey Juan Carlos University, University of Sevilla and Complutense University of Madrid were emailed a link to complete an anonymous online questionnaire, hosted by an online survey company. A total of 432 podiatrists students responded. Results: Nearly half of the students in this survey stated that they believed in the right of podiatrist to conscientiously object to any procedure. Demand for the right to conscientiously object is greater in Roman Catholic podiatrists students when compared with other groups of religious podiatrists students. Discussion: Examining patients and podiatric treatments continues to be controversy issues among podiatrists students and this may contribute to the looming crisis in podiatry services over next years. This project sheds some light on how future podiatrist view some of their ethical rights and obligations. Using empirical evidence, it reveals that conscientious objection is an issue in the Spain podiatrists student body today. These data could help anticipate problems that may arise when these podiatrists students qualify and practice podiatry in the community. Conclusion: Clearer guidance is needed for podiatrists students about the issue of conscientious objection at podiatry school.

Objetivo: Explorar actitudes hacia la objeción de conciencia entre estudiantes de podología en España. Métodos: Se realizó un cuestionario anónimo online vía email a estudiantes de podología de la Universidad del Rey Juan Carlos de la Coruña, la Universidad de Sevilla y la Universidad Complutense de Madrid, organizado por una empresa de encuestas online. Respondieron un total de 432 estudiantes de podología. Resultados: Casi la mitad de los estudiantes afirmaron en la encuesta que creían en el derecho del podólogo a la objeción de conciencia en cualquier procedimiento. La exigencia del derecho a objeción de conciencia fue mayor en estudiantes de podología católicos que en otros grupos de otras religiones. Discusión: Examinar a pacientes y los tratamientos de podología continúan siendo temas controversiales entre los estudiantes de podología y esto puede que contribuya a la inminente crisis en servicios de pedicura en los próximos años. Este proyecto derrama algo de luz sobre como futuros podólogos ven algunos de sus derechos y obligaciones éticas. Usando evidencia científica, revela que la objeción de conciencia es un tema para los estudiantes de podología en España hoy día. Estos datos pueden ayudar a anticipar problemas que puedan surgir cuando estos estudiantes de podología califiquen y practiquen podología en la comunidad. Conclusión: Se necesitan pautas más claras para estudiantes de podología sobre el tema de objeción de conciencia en la Escuela de Podología.

Objetivo: Explorar atitudes com relação à objeção de consciência entre os estudantes de podologia na Espanha. Método: Aos estudantes de podologia da Universidade Universidade Rei Juan Carlos, de Corunha, da Universidade de Sevilla e da Universidade Complutense de Madri foram enviados por email um link para completar um questionário online anônimo, hospedado por uma empresa de pesquisa on-line. Um total de 432 alunos de podologia responderam. Resultados: Quase metade dos alunos nesta pesquisa afirmaram que acreditavam no direito de podólogo se opor conscientemente a qualquer procedimento. A demanda para o direito de se opor conscientemente é maior em estudantes católicos romanos, quando comparado com outros grupos religiosos de estudantes. Discussão: O exame de pacientes e tratamentos podiátricos continuam a ser problema de controvérsia entre os alunos de podologia e isso pode contribuir para a crise iminente nos serviços de podologia para os próximos anos. Este projeto lança alguma luz sobre a forma de o futuro podólogo conhecer alguns dos seus direitos e obrigações éticas. Usando a evidência empírica, revela que a objeção de consciência é um problema no corpo discente de podologia da Espanha, hoje. Estes dados poderiam ajudar a antecipar problemas que podem surgir quando esses estudantes de podología se qualificarem e praticarem a podologia na comunidade. Conclusão: Orientação mais esclarecida é necessária para alunos de podologia sobre a questão da objeção de consciência no curso de graduação.

Preparation and Characterization of Azadirachtin Alginate-Biosorbent Based Formulations: Water Release Kinetics and Photodegradation Study.

The botanical insecticide azadirachtin was incorporated in alginate-based granules to obtain controlled release formulations (CRFs). The basic formulation [sodium alginate (1.47%) - azadirachtin (0.28%) - water] was modified by the addition of biosorbents, obtaining homogeneous hybrid hydrogels with high azadirachtin entrapment efficiency. The effect on azadirachtin release rate caused by the incorporation of biosorbents such as lignin, humic acid, and olive pomace in alginate formulation was studied by immersion of the granules in water under static conditions. The addition of the biosorbents to the basic alginate formulation reduces the rate of release because the lignin-based formulation produces a slower release. Photodegradation experiments showed the potential of the prepared formulations in protecting azadirachtin against simulated sunlight, thus improving its stability. The results showed that formulation prepared with lignin provided extended protection. Therefore, this study provides a new procedure to encapsulate the botanical insecticide azadirachtin, improving its delivery and photostability.

Echocardiographic assessment of cardiac valvular regurgitation with lorcaserin from analysis of 3 phase 3 clinical trials.

BACKGROUND: Lorcaserin is a selective 5-HT2C agonist evaluated for weight management in clinical trials. Echocardiographic monitoring was conducted to test the hypothesis that selective 5-HT2C agonism would avoid valvular heart disease. METHODS AND RESULTS: Echocardiographic and weight change data from 5249 obese and overweight patients in 3 phase 3 trials were integrated. Treatment duration with 10 mg lorcaserin twice daily or placebo was 52 weeks. The proportions of patients who developed Food and Drug Administration-defined valvulopathy (≥ mild aortic or ≥ moderate mitral regurgitation) and changes in regurgitant grade at each heart valve were evaluated. Possible associations between weight or body mass index change and valvulopathy were explored. New valvulopathy was present in 2.04% of placebo and 2.37% of lorcaserin recipients at 52 weeks (risk difference, 0.33%; 95% confidence interval, -0.46 to 1.13; risk ratio, 1.16 [all patients with sufficient echocardiographic data, last-observation-carried-forward imputation] or 1.03 [patients who completed 52 weeks]). Changes in weight and body mass index were negatively associated with presence of valvulopathy at week 52 (P=0.02 and P=0.04, respectively); a 5% decrease in weight was associated with an odds ratio of 1.15 for Food and Drug Administration-defined valvulopathy. Most changes in regurgitation were ±1 grade in both treatment groups at all heart valves. CONCLUSIONS: In 3 prospective placebo-controlled trials with integrated data for 5249 patients, the rate of echocardiographic valvulopathy was similar with lorcaserin and placebo. Point estimates for risk ratios ranged from 1.03 to 1.16 and may be at least partially influenced by greater weight loss in the lorcaserin group than in the placebo group. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00395135, NCT00603291, NCT00603902.

Views on Emerging Issues Pertaining to Data Monitoring Committees for Adaptive Trials.

In this paper, the authors express their views on a range of topics related to data monitoring committees (DMCs) for adaptive trials that have emerged recently. The topics pertain to DMC roles and responsibilities, membership, training, and communication. DMCs have been monitoring trials using the group sequential design (GSD) for over 30 years. While decisions may be more complicated with novel adaptive designs, the fundamental roles and responsibilities of a DMC will remain the same, namely, to protect patient safety and ensure the scientific integrity of the trial. It will be the DMC's responsibility to recommend changes to the trial within the scope of a prespecified adaptation plan or decision criteria and not to otherwise recommend changes to the study design except for serious safety-related concerns. Nevertheless, compared with traditional data monitoring, some additional considerations are necessary when convening DMCs for novel adaptive designs. They include the need to identify DMC members who are familiar with adaptive design and to consider possible sponsor involvement in unique situations. The need for additional expertise in DMC members has prompted some researchers to propose alternative DMC models or alternative governance model. These various options and authors' views on them are expressed in this article.

Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study.

The BLOOM-DM (Behavioral Modification and Lorcaserin for Obesity and Overweight Management in Diabetes Mellitus) study evaluated efficacy and safety of lorcaserin for weight loss in patients with type 2 diabetes. Secondary objectives included evaluations of glycemic control, lipids, blood pressure, and quality of life. This 1-year, randomized, placebo-controlled trial enrolled 604 patients 1:1:1 to placebo, lorcaserin 10 mg once daily (QD) or lorcaserin 10 mg twice daily (BID). Patients were treated with metformin, a sulfonylurea (SFU) or both; had glycated hemoglobin (HbA(1c)) 7-10%; were 18-65 years old; and had BMI 27-45 kg/m(2). Patients received diet and exercise counseling. Safety monitoring included serial echocardiograms. Mean (± SD) age was 52.7 ± 8.7; 54.2% were women; 60.5% were white, 20.9% were African American, and 13.8% were Hispanic. Mean (± SD) weight was 103.6 ± 17.8 kg; BMI was 36.0 ± 4.5 kg/m(2). Most patients (91.7%) took metformin; 50.2% took a SFU. More patients lost ≥5% body weight with lorcaserin BID (37.5%; P < 0.001) or lorcaserin QD (44.7%; P < 0.001) vs. placebo (16.1%; modified intent to treat (MITT)/last observation carried forward (LOCF)). Least square mean (± SEM) weight change was -4.5 ± 0.35% with lorcaserin BID and -5.0 ± 0.5% with lorcaserin QD vs. -1.5 ± 0.36% with placebo (P < 0.001 for each). HbA(1c) decreased 0.9 ± 0.06 with lorcaserin BID, 1.0 ± 0.09 with lorcaserin QD, and 0.4 ± 0.06 with placebo (P < 0.001 for each); fasting glucose decreased 27.4 ± 2.5 mg/dl, -28.4 ± 3.8 mg/dl, and 11.9 ± 2.5 mg/dl, respectively (P < 0.001 for each). Symptomatic hypoglycemia occurred in 7.4% of patients on lorcaserin BID, 10.5% on lorcaserin QD, and 6.3% on placebo. Common adverse events were headache, back pain, nasopharyngitis, and nausea. Lorcaserin was associated with significant weight loss and improvement in glycemic control in patients with type 2 diabetes.

Preparation and characterization of imidacloprid lignin-polyethylene glycol matrices coated with ethylcellulose.

Imidacloprid, a systemic insecticide that has a water solubility of 610 mg L(-1), has been formulated in lignin-polyethylene glycol matrices by a melting process. This formulation was coated in a Wurster type fluidized-bed equipment using ethylcellulose and dibutyl sebacate. Imidacloprid has been entrapped, with an entrapment efficiency higher than 87% in all cases. Thermogravimetric analysis, differential scanning calorimetry, and Fourier transformed infrared spectroscopy studies indicate the stability and compatibility of polymers and imidacloprid. Scanning electron microscopy images show a homogeneous film of ethylcellulose in coated formulations. From T(50) values (the time taken for 50% of the active ingredient to be released into water), the release rate of imidacloprid is controlled by changing the thickness of the coating film and modifying its surface properties by adding a plasticizer. T(50) values, ranging from 3.02 to 168.6 h, allow supplying the appropriate amount of imidacloprid in each specific agronomic practice to increase the efficiency of this bioactive material and minimize the risk of environmental pollution.

Effect of an induction period of pegylated interferon-α2a and ribavirin on early virological response in HIV-HCV-coinfected patients: results from the CORAL-2 study.

BACKGROUND: It is uncertain whether a 4-week induction period of pegylated interferon and ribavirin increases early virological response (EVR) in HIV-HCV-coinfected patients. METHODS: HIV and HCV genotype 1- and 4-coinfected subjects were randomized to receive pegylated interferon-α2a 270 µg/week plus ribavirin 1,600 mg daily and epoetin-ß for 4 weeks, followed by pegylated interferon-α2a at standard dosages plus weight-based ribavirin (WBR) dosage for 8 weeks (induction arm [IA]), or pegylated interferon-α2a plus WBR for 12 weeks (standard therapy arm [SA]). HCV RNA was determined at weeks 0, 1, 2, 3, 4, 8 and 12. Ribavirin plasma trough concentrations were determined at weeks 4 (RBV-C(4)) and 12 (RBV-C(12)). RESULTS: A total of 67 patients were included; 33 in the SA and 34 in the IA. Overall, 25% received nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens. More patients achieved an HCV RNA decrease ≥1 log(10) at week 4 in the IA than in the SA (62% versus 38%; P=0.017), but EVR rates were similar in the two groups (74% versus 59% in the IA and SA, respectively; P=0.15). Independent predictors of faster HCV RNA decrease at 12 weeks were higher RBV-C(4) and younger age. RBV-C(4) were higher in patients allocated in the IA and in those receiving NRTIs (P=0.039). CONCLUSIONS: A 4-week induction with pegylated interferon-α2a plus ribavirin was associated with a greater decrease in HCV RNA at week 4; however, this did not translate into higher EVR rates. Higher RBV doses and avoidance of NRTI-sparing antiretroviral regimens might improve HCV treatment efficacy.

A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial.

CONTEXT: Lorcaserin is a novel selective agonist of the serotonin 2C receptor. OBJECTIVE: Our objective was to evaluate the effects of lorcaserin on body weight, cardiovascular risk factors, and safety in obese and overweight patients. DESIGN AND SETTING: This randomized, placebo-controlled, double-blind, parallel arm trial took place at 97 U.S. research centers. PATIENTS: Patients included 4008 patients, aged 18-65 yr, with a body mass index between 30 and 45 kg/m(2) or between 27 and 29.9 kg/m(2) with an obesity-related comorbid condition. INTERVENTIONS: Patients were randomly assigned in a 2:1:2 ratio to receive lorcaserin 10 mg twice daily (BID), lorcaserin 10 mg once daily (QD), or placebo. All patients received diet and exercise counseling. MAIN OUTCOME MEASURES: The ordered primary endpoints were proportion of patients achieving at least 5% reduction in body weight, mean change in body weight, and proportion of patients achieving at least 10% reduction in body weight at 1 yr. Serial echocardiograms monitored heart valve function. RESULTS: Significantly more patients treated with lorcaserin 10 mg BID and QD lost at least 5% of baseline body weight (47.2 and 40.2%, respectively) as compared with placebo (25.0%, P < 0.001 vs. lorcaserin BID). Least squares mean (95% confidence interval) weight loss with lorcaserin BID and QD was 5.8% (5.5-6.2%) and 4.7% (4.3-5.2%), respectively, compared with 2.8% (2.5-3.2%) with placebo (P < 0.001 vs. lorcaserin BID; least squares mean difference, 3.0%). Weight loss of at least 10% was achieved by 22.6 and 17.4% of patients receiving lorcaserin 10 mg BID and QD, respectively, and 9.7% of patients in the placebo group (P < 0.001 vs. lorcaserin BID). Headache, nausea, and dizziness were the most common lorcaserin-related adverse events. U.S. Food and Drug Administration-defined echocardiographic valvulopathy occurred in 2.0% of patients on placebo and 2.0% on lorcaserin 10 mg BID. CONCLUSIONS: Lorcaserin administered in conjunction with a lifestyle modification program was associated with dose-dependent weight loss that was significantly greater than with placebo.

Lorcaserin, a 5-HT(2C) receptor agonist, reduces body weight by decreasing energy intake without influencing energy expenditure.

CONTEXT: Lorcaserin, a selective 5-hydroxytryptamine (5-HT)(2C) receptor agonist, reduces body weight. It is unclear whether weight loss is due to reduced energy intake (EI) or also to enhanced energy expenditure (EE). OBJECTIVE: This study tested the effect of lorcaserin on EI and EE. DESIGN, PARTICIPANTS, AND INTERVENTION: In a double-blind, randomized, placebo-controlled trial, 57 (39 women) overweight and obese (body mass index, 27-45 kg/m(2)) adults were randomized to placebo (n = 28) or 10 mg twice daily lorcaserin (n = 29) for 56 d. Weight maintenance was imposed during d 1-7. Beginning on d 8, participants followed a diet and exercise plan targeting a 600 kcal/d deficit. OUTCOMES: At baseline and after 7 and 56 d of treatment, we measured body weight, body composition (dual x-ray absorptiometry), blood pressure, heart rate, EI at lunch and dinner, subjective appetite ratings, and 24-h EE and 24-h-respiratory quotient (RQ), measured by indirect calorimetry in a respiratory chamber. RESULTS: After 7 d of weight maintenance, EI was significantly (P < 0.01) reduced with lorcaserin but not placebo (mean ± sem for lorcaserin, -286 ± 86 kcal; placebo, -147 ± 89 kcal). After 56 d, lorcaserin resulted in significantly larger reductions in body weight (lorcaserin, -3.8 ± 0.4 kg; placebo, -2.2 ± 0.5 kg; P < 0.01), EI (lorcaserin, -470 ± 87 kcal; placebo, -205 ± 91 kcal; P < .05), and appetite ratings than in placebo. Changes in 24-h EE and 24-h RQ did not differ between groups, even after 24-h EE was adjusted for body weight and composition. Compared with placebo, lorcaserin had no effect on systolic or diastolic blood pressure or heart rate after 56 d. CONCLUSIONS: Lorcaserin reduces body weight through reduced EI, not altered EE or RQ.

Multicenter, placebo-controlled trial of lorcaserin for weight management.

BACKGROUND: Lorcaserin is a selective serotonin 2C receptor agonist that could be useful in reducing body weight. METHODS: In this double-blind clinical trial, we randomly assigned 3182 obese or overweight adults (mean body-mass index [the weight in kilograms divided by the square of the height in meters] of 36.2) to receive lorcaserin at a dose of 10 mg, or placebo, twice daily for 52 weeks. All patients also underwent diet and exercise counseling. At week 52, patients in the placebo group continued to receive placebo but patients in the lorcaserin group were randomly reassigned to receive either placebo or lorcaserin. Primary outcomes were weight loss at 1 year and maintenance of weight loss at 2 years. Serial echocardiography was used to identify patients in whom valvulopathy (as defined by the Food and Drug Administration) developed. RESULTS: At 1 year, 55.4% of patients (883 of 1595) receiving lorcaserin and 45.1% of patients (716 of 1587) receiving placebo remained in the trial; 1553 patients continued into year 2. At 1 year, 47.5% of patients in the lorcaserin group and 20.3% in the placebo group had lost 5% or more of their body weight (P<0.001), corresponding to an average loss of 5.8+/-0.2 kg with lorcaserin and 2.2+/-0.1 kg with placebo during year 1 (P<0.001). Among the patients who received lorcaserin during year 1 and who had lost 5% or more of their baseline weight at 1 year, the loss was maintained in more patients who continued to receive lorcaserin during year 2 (67.9%) than in patients who received placebo during year 2 (50.3%, P<0.001). Among 2472 patients evaluated at 1 year and 1127 evaluated at 2 years, the rate of cardiac valvulopathy was not increased with the use of lorcaserin. Among the most frequent adverse events reported with lorcaserin were headache, dizziness, and nausea. The rates of serious adverse events in the two groups were similar. CONCLUSIONS: In conjunction with behavioral modification, lorcaserin was associated with significant weight loss and improved maintenance of weight loss, as compared with placebo. (Funded by Arena Pharmaceuticals; ClinicalTrials.gov number, NCT00395135.)

Prevention of chloridazon and metribuzin pollution using lignin-based formulations.

The herbicides chloridazon and metribuzin, identified as groundwater pollutants, were incorporated in lignin-based granules with different sizes to obtain controlled release formulations (CRFs) and reduce water pollution risk. Kinetics release tests in water and soil showed that the release rate of both from CRFs diminished in comparison to technical products. A linear correlation was obtained between the time taken for 50% of the active ingredient to be released (T(50)) into water and granule size of the CRFs. Besides, a linear correlation was reached between T(50) values in water and soil. Mobility experiments carried out in calcareous soil show that the use of lignin-based CRFs reduces the presence of both herbicides in the leachate compared to the technical grade products. The set of experiments developed in this research can be useful to design, prepare and evaluate formulations with CR properties which can reduce the pollution derived from the use of herbicides.

Use of ethylcellulose to control chlorsulfuron leaching in a calcareous soil.

Controlled release formulations (CRFs) have been researched to reduce the water-polluting risk derived from the use of conventional formulations of chlorsulfuron. Coated chlorsulfuron granules were produced in a Wuster-type fluidized-bed equipment using two different amounts of ethylcellulose. The highest one was modified by the addition of a plasticizer such as dibutyl sebacate. The encapsulation efficiency and morphological properties of coated granules having been studied, the chlorsulfuron kinetic release in water was studied. In addition, the mobility of chlorsulfuron in a calcareous soil was finally carried out. High encapsulation efficiency was obtained, being nearly 100% in all cases. SEM pictures show a homogeneous film in coated CRFs; thickness oscillates between 23.32 microm for the system prepared with a 10% of ethylcellulose and 32.61 microm for the system prepared with a 20% ethylcellulose plus plasticizer. The rate of chlorsulfuron release from coated CRFs is diminished in all cases in relation to chlorsulfuron commercial formulation, the latter being completely dissolved in <1 h, but it took at least 50 days to release 90% of chlorsulfuron from the formulation coated with a 20% ethylcellulose plus plasticizer. Using a generic equation, the time taken for 50% of the active ingredient to be released into water (t(50)) was calculated. From the analysis of the t(50) values, it can be deduced that the release rate of chlorsulfuron can be mainly controlled by changing the thickness of the coating film, by modifying the surface properties of the coating film, and by adding a plasticizer. Mobility experiments carried out in calcareous soil show that the use of coated CRFs reduces the presence of chlorsulfuron in the leachate compared to commercial formulation.

APD125, a selective serotonin 5-HT(2A) receptor inverse agonist, significantly improves sleep maintenance in primary insomnia.

INTRODUCTION: Insomnia is a condition affecting 10% to 15% of the adult population and is characterized by difficulty falling asleep, difficulty staying asleep, or nonrestorative sleep, accompanied by daytime impairment or distress. This study evaluates APD125, a selective inverse agonist of the 5-HT(2A) receptor, for treatment of chronic insomnia, with particular emphasis on sleep maintenance. In phase 1 studies, APD125 improved sleep maintenance and was well tolerated. METHODOLOGY: Adult subjects (n=173) with DSM-IV defined primary insomnia were randomized into a multicenter, double-blind, placebo-controlled, 3-way crossover study to compare 2 doses of APD125 (10 mg and 40 mg) with placebo. Each treatment period was 7 days with a 7- to 9-day washout period between treatments. Polysomnographic recordings were performed at the initial 2 screening nights and at nights (N) 1/2 and N 6/7 of each treatment period. RESULTS: APD125 was associated with significant improvements in key sleep maintenance parameters measured by PSG. Wake time after sleep onset decreased (SEM) by 52.5 (3.2) min (10 mg) and 53.5 (3.5) min (40 mg) from baseline to N 1/2 vs. 37.8 (3.4) min for placebo, (P < 0.0001 for both doses vs. placebo), and by 51.7 (3.4) min (P = 0.01) and 48.0 (3.6) min (P = 0.2) at N 6/7 vs. 44.0 (3.8) min for placebo. Significant APD125 effects on wake time during sleep were also seen (P < 0.0001 N 1/2, P < 0.001 N 6/7). The number of arousals and number of awakenings decreased significantly with APD125 treatment compared to placebo. Slow wave sleep showed a statistically significant dose-dependent increase. There was no significant decrease in latency to persistent sleep. No serious adverse events were reported, and no meaningful differences in adverse event profiles were observed between either dose of APD125 and placebo. APD125 was not associated with next-day psychomotor impairment as measured by Digit Span, Digit Symbol Copy, and Digit Symbol Coding Tests. CONCLUSIONS: APD125 produced statistically significant improvements in objective parameters of sleep maintenance and sleep consolidation and was well tolerated in adults with primary chronic insomnia.