Test result-based sampling: an efficient design for estimating the accuracy of patient safety indicators.

OBJECTIVE: Accuracy studies of Patient Safety Indicators (PSIs) are critical but limited by the large samples required due to low occurrence of most events. We tested a sampling design based on test results (verification-biased sampling [VBS]) that minimizes the number of subjects to be verified. METHODS: We considered 3 real PSIs, whose rates were calculated using 3 years of discharge data from a university hospital and a hypothetical screen of very rare events. Sample size estimates, based on the expected sensitivity and precision, were compared across 4 study designs: random and VBS, with and without constraints on the size of the population to be screened. RESULTS: Over sensitivities ranging from 0.3 to 0.7 and PSI prevalence levels ranging from 0.02 to 0.2, the optimal VBS strategy makes it possible to reduce sample size by up to 60% in comparison with simple random sampling. For PSI prevalence levels below 1%, the minimal sample size required was still over 5000. CONCLUSIONS: Verification-biased sampling permits substantial savings in the required sample size for PSI validation studies. However, sample sizes still need to be very large for many of the rarer PSIs.

Design, conduct, and analyses of Breast International Group (BIG) 1-98: a randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer.

BACKGROUND: Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. PURPOSE: To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. METHODS: From 1998-2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. RESULTS: The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. LIMITATIONS: Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. CONCLUSIONS: BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years apart, and subject to evolving analytic plans influenced by new data that emerge over time.

Validation of Design Recommendations for Integral Abutment Piles, HR-292, 1989

Since integral abutment bridges decrease the initial and maintenance costs of bridges, they provide an attractive alternative for bridge designers. The objective of this project is to develop rational and experimentally verified design recommendations for these bridges. Field testing consisted of instrumenting two bridges in Iowa to monitor air and bridge temperatures, bridge displacements, and pile strains. Core samples were also collected to determine coefficients of thermal expansion for the two bridges. Design values for the coefficient of thermal expansion of concrete are recommended, as well as revised temperature ranges for the deck and girders of steel and concrete bridges. A girder extension model is developed to predict the longitudinal bridge displacements caused by changing bridge temperatures. Abutment rotations and passive soil pressures behind the abutment were neglected. The model is subdivided into segments that have uniform temperatures, coefficients of expansion, and moduli of elasticity. Weak axis pile strains were predicted using a fixed-head model. The pile is idealized as an equivalent cantilever with a length determined by the surrounding soil conditions and pile properties. Both the girder extension model and the fixed-head model are conservative for design purposes. A longitudinal frame model is developed to account for abutment rotations. The frame model better predicts both the longitudinal displacement and weak axis pile strains than do the simpler models. A lateral frame model is presented to predict the lateral motion of skewed bridges and the associated strong axis pile strains. Full passive soil pressure is assumed on the abutment face. Two alternatives for the pile design are presented. Alternative One is the more conservative and includes thermally induced stresses. Alternative Two neglects thermally induced stresses but allows for the partial formation of plastic hinges (inelastic redistribution of forces). Ductility criteria are presented for this alternative. Both alternatives are illustrated in a design example.

The TREAT-NMD Duchenne Muscular Dystrophy Registries: Conception, Design, and Utilization by Industry and Academia.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease, caused by the absence of the dystrophin protein. Although many novel therapies are under development for DMD, there is currently no cure and affected individuals are often confined to a wheelchair by their teens and die in their twenties/thirties. DMD is a rare disease (prevalence <5/10,000). Even the largest countries do not have enough affected patients to rigorously assess novel therapies, unravel genetic complexities, and determine patient outcomes. TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients. The harmonized implementation of national and ultimately global patient registries has been central to the success of TREAT-NMD. For the DMD registries within TREAT-NMD, individual countries have chosen to collect patient information in the form of standardized patient registries to increase the overall patient population on which clinical outcomes and new technologies can be assessed. The registries comprise more than 13,500 patients from 31 different countries. Here, we describe how the TREAT-NMD national patient registries for DMD were established. We look at their continued growth and assess how successful they have been at fostering collaboration between academia, patient organizations, and industry.

Metric Training for the Transportation Industry Module III - Road and Bridge Design, HR-376

"Metric Training For The Highway Industry", HR-376 was designed to produce training materials for the various divisions of the Iowa DOT, local government and the highway construction industry. The project materials were to be used to introduce the highway industry in Iowa to metric measurements in their daily activities. Five modules were developed and used in training over 1,000 DOT, county, city, consultant and contractor staff in the use of metric measurements. The training modules developed deal with the planning through operation areas of highway transportation. The materials and selection of modules were developed with the aid of an advisory personnel from the highway industry. Each module is design as a four hour block of instruction and a stand along module for specific types of personnel. Each module is subdivided into four chapters with chapter one and four covering general topics common to all subjects. Chapters two and three are aimed at hands on experience for a specific group and subject. This module includes: Module 3 - Road and Bridge Design. This module provides hands on examples of how to use metric measurements in the design of roads and structures.

Design and establishment of a biobank in a multicenter prospective cohort study of elderly patients with venous thromboembolism (SWITCO65+).

In the field of thrombosis and haemostasis, many preanalytical variables influence the results of coagulation assays and measures to limit potential results variations should be taken. To our knowledge, no paper describing the development and maintenance of a haemostasis biobank has been previously published. Our description of the biobank of the Swiss cohort of elderly patients with venous thromboembolism (SWITCO65+) is intended to facilitate the set-up of other biobanks in the field of thrombosis and haemostasis. SWITCO65+ is a multicentre cohort that prospectively enrolled consecutive patients aged ≥65 years with venous thromboembolism at nine Swiss hospitals from 09/2009 to 03/2012. Patients will be followed up until December 2013. The cohort includes a biobank with biological material from each participant taken at baseline and after 12 months of follow-up. Whole blood from all participants is assayed with a standard haematology panel, for which fresh samples are required. Two buffy coat vials, one PAXgene Blood RNA System tube and one EDTA-whole blood sample are also collected at baseline for RNA/DNA extraction. Blood samples are processed and vialed within 1 h of collection and transported in batches to a central laboratory where they are stored in ultra-low temperature archives. All analyses of the same type are performed in the same laboratory in batches. Using multiple core laboratories increased the speed of sample analyses and reduced storage time. After recruiting, processing and analyzing the blood of more than 1,000 patients, we determined that the adopted methods and technologies were fit-for-purpose and robust.

Design Manual for Strengthening of Continuous-Span Composite Bridges, HR-333, 1993

The need for upgrading a large number of understrength bridges in the United States has been well documented in the literature. This manual presents two methods for strengthening continuous-span composite bridges: post-tensioning of the positive moment regions of the bridge stringers and the addition of superimposed trusses at the piers. The use of these two systems is an efficient method of reducing flexural overstresses in undercapacity bridges. Before strengthening a given bridge however, other deficiencies (inadequate shear connection, fatigue problems, extensive corrosion) should be addressed. Since continuous-span composite bridges are indeterminant structures, there is longitudinal and transverse distribution of the strengthening axial forces and moments. This manual basically provides the engineer with a procedure for determining the distribution of strengthening forces and moments throughout the bridge. As a result of the longitudinal and transverse force distribution, the design methodology presented in this manual for continuous-span composite bridges is extremely complex. To simplify the procedure, a spreadsheet has been developed for use by practicing engineers. This design aid greatly simplifies the design of a strengthening system for a given bridge in that it eliminates numerous tedious hand calculations, computes the required force and moment fractions, and performs the necessary iterations for determining the required strengthening forces. The force and moment distribution fraction formulas developed in this manual are primarily for the Iowa DOT V12 and V14 three-span four-stringer bridges. These formulas may be used on other bridges if they are within the limits stated in this manual. Use of the distribution fraction formulas for bridges not within the stated limits is not recommended.

Efficacy of an adjunctive brief psychodynamic psychotherapy to usual inpatient treatment of depression: rationale and design of a randomized controlled trial.

BACKGROUND: A few recent studies have found indications of the effectiveness of inpatient psychotherapy for depression, usually of an extended duration. However, there is a lack of controlled studies in this area and to date no study of adequate quality on brief psychodynamic psychotherapy for depression during short inpatient stay exists. The present article describes the protocol of a study that will examine the relative efficacy, the cost-effectiveness and the cost-utility of adding an Inpatient Brief Psychodynamic Psychotherapy to pharmacotherapy and treatment-as-usual for inpatients with unipolar depression. METHODS/DESIGN: The study is a one-month randomized controlled trial with a two parallel group design and a 12-month naturalistic follow-up. A sample of 130 consecutive adult inpatients with unipolar depression and Montgomery-Asberg Depression Rating Scale score over 18 will be recruited. The study is carried out in the university hospital section for mood disorders in Lausanne, Switzerland. Patients are assessed upon admission, and at 1-, 3- and 12- month follow-ups. Inpatient therapy is a manualized brief intervention, combining the virtues of inpatient setting and of time-limited dynamic therapies (focal orientation, fixed duration, resource-oriented interventions). Treatment-as-usual represents the best level of practice for a minimal treatment condition usually proposed to inpatients. Final analyses will follow an intention-to-treat strategy. Depressive symptomatology is the primary outcome and secondary outcome includes measures of psychiatric symptomatology, psychosocial role functioning, and psychodynamic-emotional functioning. The mediating role of the therapeutic alliance is also examined. Allocation to treatment groups uses a stratified block randomization method with permuted block. To guarantee allocation concealment, randomization is done by an independent researcher. DISCUSSION: Despite the large number of studies on treatment of depression, there is a clear lack of controlled research in inpatient psychotherapy during the acute phase of a major depressive episode. Research on brief therapy is important to take into account current short lengths of stay in psychiatry. The current study has the potential to scientifically inform appropriate inpatient treatment. This study is the first to address the issue of the economic evaluation of inpatient psychotherapy. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ACTRN12612000909820).

Desempenho de uma semeadora-adubadora para plantio direto, em dois solos com diferentes tipos de cobertura vegetal

O desempenho operacional de uma semeadora-adubadora de plantio direto, versão soja e milho, foi avaliado em um Podzólico Vermelho-Amarelo câmbico, fase terraço, e um Latossolo Vermelho-Amarelo, da Zona da Mata de Minas Gerais. A máquina foi testada em três tipos de cobertura do solo e em duas velocidades de trabalho. Por ocasião do plantio, foram avaliados a patinagem do trator e da semeadora-adubadora, o consumo de combustível e a potência exigida, a distribuição de fertilizante e o nível de danos às sementes. Depois do plantio, foram avaliados o número de sementes distribuídas, o estande final, a profundidade de plantio e a distribuição longitudinal da semente. A uniformidade de distribuição longitudinal foi avaliada pela porcentagem de espaçamentos aceitáveis, distribuição dupla e falhas na distribuição, e pelo coeficiente de variação dos espaçamentos entre sementes. A demanda de potência foi maior no Podzólico, por sua maior densidade e resistência à penetração. Independentemente do tratamento, o número de sementes distribuídas e o estande final não apresentaram diferenças significativas. As sementes distribuídas não tiveram sua qualidade afetada pelos dosadores da máquina. A análise de variância não indicou diferença significativa entre os porcentuais de espaçamentos aceitáveis, a distribuição dupla e as falhas.