Some recommendations for developing multidimensional computerized adaptive tests for patient-reported outcomes

PURPOSE: Multidimensional item response theory and computerized adaptive testing (CAT) are increasingly used in mental health, quality of life (QoL), and patient-reported outcome measurement. Although multidimensional assessment techniques hold promises, they are more challenging in their application than unidimensional ones. The authors comment on minimal standards when developing multidimensional CATs. METHODS: Prompted by pioneering papers published in QLR, the authors reflect on existing guidance and discussions from different psychometric communities, including guidelines developed for unidimensional CATs in the PROMIS project. RESULTS: The commentary focuses on two key topics: (1) the design, evaluation, and calibration of multidimensional item banks and (2) how to study the efficiency and precision of a multidimensional item bank. The authors suggest that the development of a carefully designed and calibrated item bank encompasses a construction phase and a psychometric phase. With respect to efficiency and precision, item banks should be large enough to provide adequate precision over the full range of the latent constructs. Therefore CAT performance should be studied as a function of the latent constructs and with reference to relevant benchmarks. Solutions are also suggested for simulation studies using real data, which often result in too optimistic evaluations of an item bank's efficiency and precision. DISCUSSION: Multidimensional CAT applications are promising but complex statistical assessment tools which necessitate detailed theoretical frameworks and methodological scrutiny when testing their appropriateness for practical applications. The authors advise researchers to evaluate item banks with a broad set of methods, describe their choices in detail, and substantiate their approach for validation

C2 and CFB Genes in Age-Related Maculopathy and Joint Action with CFH and LOC387715 Genes

BackgroundAge-related maculopathy (ARM) is a common cause of visual impairment in the elderly populations of industrialized countries and significantly affects the quality of life of those suffering from the disease. Variants within two genes, the complement factor H (CFH) and the poorly characterized LOC387715 (ARMS2), are widely recognized as ARM risk factors. CFH is important in regulation of the alternative complement pathway suggesting this pathway is involved in ARM pathogenesis. Two other complement pathway genes, the closely linked complement component receptor (C2) and complement factor B (CFB), were recently shown to harbor variants associated with ARM.Methods/principal findingsWe investigated two SNPs in C2 and two in CFB in independent case-control and family cohorts of white subjects and found rs547154, an intronic SNP in C2, to be significantly associated with ARM in both our case-control (P-value 0.00007) and family data (P-value 0.00001). Logistic regression analysis suggested that accounting for the effect at this locus significantly (P-value 0.002) improves the fit of a genetic risk model of CFH and LOC387715 effects only. Modeling with the generalized multifactor dimensionality reduction method showed that adding C2 to the two-factor model of CFH and LOC387715 increases the sensitivity (from 63% to 73%). However, the balanced accuracy increases only from 71% to 72%, and the specificity decreases from 80% to 72%.Conclusions/significanceC2/CFB significantly influences AMD susceptibility and although accounting for effects at this locus does not dramatically increase the overall accuracy of the genetic risk model, the improvement over the CFH-LOC387715 model is statistically significant

Randomized Controlled Trial of a Computer-Based, Tailored Intervention to Increase Smoking Cessation Counseling by Primary Care Physicians

OBJECTIVE: The primary care visit represents an important venue for intervening with a large population of smokers. However, physician adherence to the Smoking Cessation Clinical Guideline (5As) remains low. We evaluated the effectiveness of a computer-tailored intervention designed to increase smoking cessation counseling by primary care physicians. METHODS: Physicians and their patients were randomized to either intervention or control conditions. In addition to brief smoking cessation training, intervention physicians and patients received a one-page report that characterized the patients’ smoking habit and history and offered tailored recommendations. Physician performance of the 5As was assessed via patient exit interviews. Quit rates and smoking behaviors were assessed 6 months postintervention via patient phone interviews. Intervention effects were tested in a sample of 70 physicians and 518 of their patients. Results were analyzed via generalized and mixed linear modeling controlling for clustering. MEASUREMENTS AND MAIN RESULTS: Intervention physicians exceeded controls on “Assess” (OR 5.06; 95% CI 3.22, 7.95), “Advise” (OR 2.79; 95% CI 1.70, 4.59), “Assist–set goals” (OR 4.31; 95% CI 2.59, 7.16), “Assist–provide written materials” (OR 5.14; 95% CI 2.60, 10.14), “Assist–provide referral” (OR 6.48; 95% CI 3.11, 13.49), “Assist–discuss medication” (OR 4.72;95% CI 2.90, 7.68), and “Arrange” (OR 8.14; 95% CI 3.98, 16.68), all p values being < 0.0001. Intervention patients were 1.77 (CI 0.94, 3.34,p = 0.078) times more likely than controls to be abstinent (12 versus 8%), a difference that approached, but did not reach statistical significance, and surpassed controls on number of days quit (18.4 versus 12.2, p < .05) but not on number of quit attempts. CONCLUSIONS: The use of a brief computer-tailored report improved physicians’ implementation of the 5As and had a modest effect on patients’ smoking behaviors 6 months postintervention

Structure and Stability of the Spinach Aquaporin SoPIP2;1 in Detergent Micelles and Lipid Membranes

Background: SoPIP2;1 constitutes one of the major integral proteins in spinach leaf plasma membranes and belongs to the aquaporin family. SoPIP2;1 is a highly permeable and selective water channel that has been successfully overexpressed and purified with high yields. In order to optimize reconstitution of the purified protein into biomimetic systems, we have here for the first time characterized the structural stability of SoPIP2;1. Methodology/Principal Finding: We have characterized the protein structural stability after purification and after reconstitution into detergent micelles and proteoliposomes using circular dichroism and fluorescence spectroscopy techniques. The structure of SoPIP2;1 was analyzed either with the protein solubilized with octyl-beta-D-glucopyranoside (OG) or reconstituted into lipid membranes formed by E. coli lipids, diphytanoylphosphatidylcholine (DPhPC), or reconstituted into lipid membranes formed from mixtures of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPE), 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE), 1-palmitoyl-2-oleoyl-phosphatidylserine (POPS), and ergosterol. Generally, SoPIP2;1 secondary structure was found to be predominantly a-helical in accordance with crystallographic data. The protein has a high thermal structural stability in detergent solutions, with an irreversible thermal unfolding occurring at a melting temperature of 58 degrees C. Incorporation of the protein into lipid membranes increases the structural stability as evidenced by an increased melting temperature of up to 70 degrees C. Conclusion/Significance: The results of this study provide insights into SoPIP2;1 stability in various host membranes and suggest suitable choices of detergent and lipid composition for reconstitution of SoPIP2;1 into biomimetic membranes for biotechnological applications

Diretrizes para cessação do tabagismo - 2008

Estas diretrizes constituem uma ferramenta atualizada e abrangente para auxiliar o profissional de saúde na abordagem do tabagista, recomendando atitudes baseadas em evidências clínicas como a melhor forma de conduzir cada caso. De forma reduzida e mais objetiva possível, o texto final foi agrupado em dois grandes itens: Avaliação e Tratamento. Os dois itens apresentam comentários e níveis de recomendação das referências utilizadas, bem como algumas propostas de abordagem, como por exemplo, redução de danos, em situações específicas ainda pouco exploradas, como recaídas, tabagismo passivo, tabagismo na categoria médica e uso de tabaco em ambientes específicos.These guidelines are an up-to-date and comprehensive tool to aid health professionals in treating smokers, recommending measures and strategies for managing each case based on clinical evidence. Written in a simplified and objective manner, the text is divided into two principal sections: Evaluation and Treatment. The sections both present comments on and levels of evidence represented by the references cited, as well as some proposals for the reduction of damage and for intervening in specific and still poorly explored situations, such as relapse, passive smoking, physician smoking, and tobacco use in specific environments

Time to definitive diagnosis of breast cancer in Latina and non-Hispanic white women: the six cities study

Time delay after an abnormal screening mammogram may have a critical impact on tumor size, stage at diagnosis, treatment, prognosis, and survival of subsequent breast cancer. This study was undertaken to evaluate disparities between Latina and non-Hispanic white (NHW) women in time to definitive diagnosis of breast cancer after an abnormal screening mammogram, as well as factors contributing to such disparities. As part of the activities of the National Cancer Institute (NCI)-funded Redes En Acción research network, clinical records of 186 Latinas and 74 NHWs who received abnormal screening mammogram results were reviewed to determine the time to obtain a definitive diagnosis. Data was obtained from participating clinics in six U.S. cities and included demographics, clinical history, and mammogram characteristics. Kaplan-Meier estimates and Cox proportional hazards models were used to test differences in median time to definitive diagnosis by ethnicity after adjusting for clinic site, demographics, and clinical characteristics. Time-to-event analysis showed that Latinas took 2.2 times longer to reach 50% definitively diagnosed with breast cancer relative to NHWs, and three times longer to reach 80% diagnosed (p=0.001). Latinas’ median time to definitive diagnosis was 60 days compared to 27 for NHWs, a 59% gap in diagnosis rates (adjusted Hazard Ratio [aHR] = 1.59, 95% CI = 1.09, 2.31; p=0.015). BI-RADS-4/5 women’s diagnosis rate was more than twice that of BI-RADS-3 (aHR = 2.11, 95% CI = 1.18, 3.78; p=0.011). Disparities in time between receipt of abnormal screening result and definitive diagnosis adversely affect Latinas compared to NHWs, and remain significant after adjusting for demographic and clinical variables. With cancer now the leading cause of mortality among Latinos, a greater need exists for ethnically and culturally appropriate interventions like patient navigation to facilitate Latinas’ successful entry into, and progression through, the cancer care system