Flexible selection of a single treatment incorporating short-term endpoint information in a phase II/III clinical trial

Seamless phase II/III clinical trials in which an experimental treatment is selected at an interim analysis have been the focus of much recent research interest. Many of the methods proposed are based on the group sequential approach. This paper considers designs of this type in which the treatment selection can be based on short-term endpoint information for more patients than have primary endpoint data available. We show that in such a case, the familywise type I error rate may be inflated if previously proposed group sequential methods are used and the treatment selection rule is not specified in advance. A method is proposed to avoid this inflation by considering the treatment selection that maximises the conditional error given the data available at the interim analysis. A simulation study is reported that illustrates the type I error rate inflation and compares the power of the new approach with two other methods: a combination testing approach and a group sequential method that does not use the short-term endpoint data, both of which also strongly control the type I error rate. The new method is also illustrated through application to a study in Alzheimer's disease. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Education and Earnings for Poverty Reduction : Short-Term Evidence of Pro-Poor Growth from the Mexican Oportunidades Program

Education, as an indispensable component of human capital, has been acknowledged to play a critical role in economic growth, which is theoretically elaborated by human capital theory and empirically confirmed by evidence from different parts of the world. The educational impact on growth is especially valuable and meaningful when it is for the sake of poverty reduction and pro-poorness of growth. The paper re-explores the precious link between human capital development and poverty reduction by investigating the causal effect of education accumulation on earnings enhancement for anti-poverty and pro-poor growth. The analysis takes the evidence from a well-known conditional cash transfer (CCT) program — Oportunidades in Mexico. Aiming at alleviating poverty and promoting a better future by investing in human capital for children and youth in poverty, this CCT program has been recognized producing significant outcomes. The study investigates a short-term impact of education on earnings of the economically disadvantaged youth, taking the data of both the program’s treated and untreated youth from urban areas in Mexico from 2002 to 2004. Two econometric techniques, i.e. difference-in-differences and difference-in-differences propensity score matching approach are applied for estimation. The empirical analysis first identifies that youth who under the program’s schooling intervention possess an advantage in educational attainment over their non-intervention peers; with this identification of education discrepancy as a prerequisite, further results then present that earnings of the education advantaged youth increase at a higher rate about 20 percent than earnings of their education disadvantaged peers over the two years. This result indicates a confirmation that education accumulation for the economically disadvantaged young has a positive impact on their earnings enhancement and thus inferring a contribution to poverty reduction and pro-poorness of growth.

Omvårdnadspersonals upplevelser av vård i livets slutskede : En kvalitativ intervjustudie

Syftet: Syftet med studien var att beskriva hur omvårdnadspersonal inom kommunens särskilda boende och korttidsboende upplever att vårda personer i livets slutskede.Metod: Studien bygger på åtta kvalitativa intervjuer med undersköterskor. Datainsamlingsmetoden baserades på Critical Incident Technique och som analysmetod användes kvalitativ innehållsanalys. Resultat: I intervjuerna framkom att samarbetet till de övriga i teamet och närstående hade en stor och avgörande betydelse för hur vården utvecklades. Omvårdnadspersonalen kände ibland att sjuksköterskan saknades i vissa omvårdnadssituationer. Fördelning av personal under dygnet bidrog till kontinuitet i samverkan. De upplevde att olika faktorer i miljön kunde vara både till hjälp eller till hinder i samspelet till den döende och närstående. De intervjuade talade också om vikten av att respektera patientens vilja. Omvårdnadspersonalen gav även stöd till de närstående och de kom familjerna nära. De upplevde att närvaro utan krav och stress var av betydelse för interaktionen till den döende och dess närstående. Det var viktigt att både den döende och de närstående var tillfreds med symtomlindringen. Det var viktigt att få ge ett värdigt omhändertagande efter döden. Slutsats: Det genomgåendet temat visade att interaktion och samverkan med vårdteamet, närstående och patienten var av avgörande betydelseför hur vården i livets slut skulle bli trygg och värdig.

Effects of a probiotic soy product and physical exercise on formation of pre-neoplastic lesions in rat colons in a short-term model of carcinogenic

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Combined Pool/Bilateral Short-Term Hydrothermal Scheduling Model for Day-Ahead Energy Markets

This paper proposes a combined pool/bilateral short term hydrothermal scheduling model (PDC) for the context of the day-ahead energy markets. Some innovative aspects are introduced in the model, such as: i) the hydraulic generation is optimized through the opportunity cost function proposed; ii) there is no decoupling between physical and commercial dispatches, as is the case today in Brazil; iii) interrelationships between pool and bilateral markets are represented through a single optimization problem; iv) risk exposures related to future deficits are intrinsically mitigated; v) the model calculates spot prices in an hourly basis and the results show a coherent correlation between hydrological conditions and calculated prices. The proposed PDC model is solved by a primal-dual interior point method and is evaluated by simulations involving a test system. The results are focused on sensitivity analyses involving the parameters of the model, in such a way to emphasize its main modeling aspects. The results show that the proposed PDC provides a conceptual means for short term price formation for hydrothermal systems.

Ovarian response of Suffolk ewes to estrous synchronization using short-term protocol

The efficacy of estrus synchronization using short-term protocol was evaluated by ultrasound exams in Suffolk ewes during the pre-breeding season. The control Group (n = 12) was synchronized by treatment for 12 days with vaginal sponges impregnated with medroxyprogesterone acetate, and 400 IU eCG at sponge withdrawal. Experimental groups I, II and III kept the sponge in place for 4 days, and 100 µg of PGF2a was administered at sponge withdrawal. Additionally, Group I (n = 12) had 0.1 mg of estradiol benzoate (EB) administered during sponge placement and 50 µg of GnRH 48 hours after sponge removal. Group II (n = 6) had 35 mg of progesterone (P4) injected, and 0.1 mg of EB administered during sponge placement, 400 IU eCG at withdrawal and 48 hours after, 50 µg GnRH were administrated. Group III (n = 12) had 35 mg of P4 and 0.2 mg of EB administered at sponge placement, 400 IU eCG at withdrawal, and 50 µg of GnRH was administrated after 56 hours. Ovaries were monitored through ultrasound scanning. Concerning the first wave, no difference was detected between the control group and the experimental groups. However, the characteristics of ovulatory wave were significantly different between the groups. The duration of the follicular wave was shorter for Group III than for Group II. The follicle in Group I reached its maximum diameter before the Group II. The diameter of the follicle at the sponge withdrawal in the control group was larger than in Group I. After sponge withdrawal, the follicular growth rate was smaller in the control group than in Group III. The maximum diameter of the follicle in Group II was larger than in the other groups. The short-term protocol in which estrogen was used did not synchronize the emergence of the wave of follicular development.

Short-term vs long-term calcium hydroxide therapy after immediate tooth replantation: a histomorphometric study in monkey's teeth

Endodontic treatment is an important step of tooth replantation protocols, but the ideal moment for definitive obturation of replanted teeth has not yet been established. In this study, a histomorphometric analysis was undertaken to evaluate the repair process on immediate replantation of monkeys teeth after calcium hydroxide (CH) therapy for 1 and 6 months followed by root canal filling with a CH-based sealer (Sealapex (R)). The maxillary and mandibular lateral incisors of five female Cebus apella monkeys were extracted, kept in sterile saline for 15 min, replanted and splinted with stainless steel orthodontic wire and composite resin for 10 days. In Group I (control), definitive root canal filling was performed before tooth extraction. In Groups II and III, CH therapy started after removal of splint, and definitive root canal filling was performed 1 and 6 months later, respectively. The animals were euthanized 9 months after replantation, and specimens were processed for histomorphometric analysis. In all groups, epithelial attachment occurred at the cementoenamel junction or very close to this region; the areas of resorption on root surface had small extension and depth and were repaired by newly formed cementum; and the periodontal ligament was organized. Statistical analysis of the scores obtained for the histomorphometric parameters did not show any statistically significant difference (P = 0.1221) among the groups. The results suggests that when endodontic treatment is initiated 10 days after immediate replantation and an antibiotic regimen is associated, definitive root canal filling can be performed after a short-term CH therapy.

Short-term evaluation of the pulpo-dentin complex response to a resin-modified glass-ionomer cement and a bonding agent applied in deep cavities

Objectives. To evaluate the response of the pulpo-dentin complex following application of a resin-modified glass-ionomer cement or an adhesive system in deep cavities performed in human teeth.Methods. Deep class V cavities were prepared on the buccal surface of 26 premolars. In Group I the cavity walls (dentin) and enamel were conditioned with 32% phosphoric acid and the dentin adhesive system One Step (Bisco, Inc., Itasca, IL, USA) was applied. In Groups 2 and 3, before total etching and application of bonding agent, the cavity floor was lined with the resin-modified glass-ionomer cement-Vitrebond (3M ESPE Dental Products Division, St. Paul, MN, USA) or the calcium hydroxide cement-Dycal (control group, Dentsply, Mildford, DE, USA), respectively. The cavities were restored using light-cured Z-100 composite resin (3M ESPE). The teeth were extracted between 5 and 30 days and prepared for microscopic assessment. Serial sections were stained with H/E, Masson's trichrome, and Brown and Brenn techniques.Results. In Group 1, the inflammatory response was more evident than in Groups 2 and 3. Diffusion of dental material components across dentinal tubules was observed only in Group 1, in which the intensity of the pulp response increased as the remaining dentin thickness decreased. Bacteria were evidenced in the lateral walls of two samples (Group 2) which exhibited no inflammatory response or tissue disorganization.Conclusions. Based on the experimental conditions, it was concluded total acid etching followed by application of One Step bonding agent cannot be recommended as adequate procedures. In this clinical condition the cavity walls should be lined with a biocompatible dental material, such as Vitrebond or Dycal. 2003 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

The influence of short-term diabetes mellitus and insulin therapy on alveolar bone loss in rats

Background: It is well known that the multiple direct and indirect consequences of hyperglycemia in diabetic individuals have been linked to a number of abnormal host effector mechanisms that could lead to an increased risk of developing periodontal disease.Objective: the aim of this study was to investigate the effect of short-term experimental diabetes and insulin therapy on the severity of alveolar bone loss in rats, and the effect of experimental periodontitis on glycemic control.Methods: Seventy-two male Wistar rats were divided into four groups: group I animals were submitted to dental ligature around lower right first molars (ligated); group II consisted of streptozotocin (STZ)-diabetic, ligated rats; group III represented STZ-diabetic, unligated rats; and group IV consisted of insulin-treated (6 U/day), STZ-diabetic, ligated rats. Blood glucose of all diabetic rats was monitored at regular intervals. Standardized digital radiographs were taken after killing at 7, 15 and 30 days to measure the amount of bone loss about the mesial root surface of the first molar tooth in each rat.Results: No significant (p < 0.05) changes in plasma glucose levels of insulin-treated diabetic rats were found among the different examinations after the beginning of insulin therapy. Rats from group II showed significantly greater increases in mean plasma glucose levels at 15 and 30 days after ligature placement compared with rats from group III (p < 0.05). Furthermore, in spite of the significant alveolar bone loss progression that was observed in groups I, II and IV (p < 0.00001; two-way ANOVA), no significant differences among these groups regarding the severity of bone loss (p = 0.77) and no significant interaction between treatment group and time (p = 0.81) were found.Conclusions: Within the limits of this study, it can be suggested that the severity of periodontal disease was not affected by short-term diabetes, and that experimental periodontitis increased blood glucose levels in uncontrolled diabetic rats.

Short-Term Effects of the Use of Non-Rigid Tools for Postural Control by Adults with Intellectual Disabilities

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of short-term immersion and brushing with different denture cleansers on the roughness, hardness, and color of two types of acrylic resin

Purpose: To investigate the cumulative effects of brushing (B) or immersion (I), using different cleansing agents, on the surface roughness, hardness and color stability of a heat-polymerized denture resin, Lucitone 550 (L), and a hard chairside reline resin, Tokuyama Rebase Fast II (T). Methods: A total of 316 specimens (10 x 2 mm) were fabricated. The specimens (n= 9) were divided into brushing or immersion groups according to the following agents: dentifrice/distilled water (D), 1% sodium hypochlorite (Na0C1), Corega Tabs (Pb), 1% chlorhexidine gluconate (Chx), and 0.2% peracetic acid (Ac). Brushing and immersion were tested independently. Assays were performed after 1, 3, 21, 45 and 90 blushing cycles or immersion of 10 seconds each. Data were evaluated statistically by repeated measures ANOVA. Tukey's honestly significant difference (HSD) post-hoc test was used to determine differences between means (a= 0.05). Results: For L there was no statistically significant difference in roughness, except a significant decrease in roughness by brushing with D. T showed a significant effect on the roughness after 90 immersions with Ac. Hardness values decreased for L when specimens were immersed or brushed in Na0C1 and Pb. The hardness of T decreased with increases in the repetitions (immersion or brushing), regardless of the cleaning method. Values of color stability for L resin showed significant color change after brushing with and immersion in Ac and Pb. Brushing with D exhibited a higher incidence of color change. For T there were no significant differences between cleaning agents and repetitions in immersion. A color change was noted after three brushings with the Ac, Chx, and D. Brushing with dentifrice decreased roughness of L. Immersion in or brushing with Na0C1 and Pb decreased the hardness of L. For T, hardness decreased with increases in immersions or brushing. Color changes after the immersion in or brushing with cleaning agents were clinically acceptable according to National Bureau of Standards parameters for both resins.

A candidate short-term toxicity test using Ampelisca brevicornis to assess sublethal responses to pharmaceuticals bound to marine sediments

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Short-term low-intensity blood flow restricted interval training improves both aerobic fitness and muscle strength

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of Er:YAG and Er,Cr:YSGG lasers on dentine hypersensitivity. Short-term clinical evaluation

Dentine hypersensitivity (DH) is a painful condition and is a clinical challenge due to the different treatment strategies available. High-intensity lasers have been studied as a possible option. The aim of this randomized, controlled, double-blind clinical study was to evaluate the effects of Er:YAG and Er,Cr:YSGG lasers on DH. The study group comprised 28 subjects who met the inclusion criteria. A visual analogue scale was used to quantify sensitivity before treatment as baseline, immediately before and immediately after treatment, and 1 week and 1 month after treatment. Teeth were assigned to four groups: group 1 control (no treatment), group 2 Er:YAG laser treatment (2 Hz/32.4 mJ/5.9 J/cm(2)), group 3 Er,Cr:YSGG laser treatment (0.25 W/4.4 J/cm(2)), and group 4 Er,Cr:YSGG laser treatment (0.50 W/ 8.9 J/cm(2)). Data were collected and submitted to statistical analysis for both evaporative (air) and mechanical (probe) stimulation. For both the air and probe stimulation no differences were observed between the pretreatment sensitivities. With the evaporative stimulus, the pain level immediately after treatment was reduced; however, after this the values remained stable. Irradiation with the Er:YAG laser was associated with the lowest level of pain. With the mechanical stimulus, group 4 showed the most pronounced decrease in pain immediately after treatment; however, by the end of the study, pain levels had increased. Groups 1, 2 and 3 showed a reduction in pain that was significantly different from that in group 4 after the 4 weeks of clinical follow up. Based on the results and within the limits of this study, it can be concluded that none of the laser treatments studied was capable of completely eliminating pain, but the Er:YAG and Er,Cr:YSGG lasers are suitable for the treatment of DH.

Behavioural changes and occlusal splints are effective in the management of masticatory myofascial pain: a short-term evaluation

The aim of this research was to test the hypothesis that treatment with intra-oral appliances with different occlusal designs was beneficial in the management of pain of masticatory muscles compared with a control group. A total of 51 patients were analysed according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) to obtain the diagnosis of masticatory myofascial pain (MMP). The sample was then randomly divided into three groups: group I (n = 21) wore a full coverage acrylic stabilisation occlusal splint; group II (n = 16) wore an anterior device nociceptive trigeminal inhibitory (NTI) system; and group III (n = 14) only received counselling for behavioural changes and self-care (the control group). The first two groups also received counselling. Follow-ups were performed after 2 and 6 weeks and 3 months. In these sessions, patients were evaluated by means of a visual analogue scale (VAS) and pressure pain threshold (PPT) of the masticatory muscles. Possible adverse effects were also recorded, such as discomfort while using the appliance and occlusal changes. The results were analysed with KruskalWallis, anova, Tukeys and Friedman tests, with a significance level of 5%. Group I showed improvement in the reported pain at the first follow-up (2 weeks), whereas for groups II and III, this progress was detected only after 6 weeks and 3 months, respectively. The PPT values did not change significantly. It was concluded that behavioural changes are effective in the management of pain in MMP patients. However, the simultaneous use of occlusal devices appears to produce an earlier improvement.