Combining scores from different patient reported outcome measures in meta-analyses: when is it justified?

BACKGROUND: Combining outcomes and the use of standardized effect measures such as effect size and standardized response mean across instruments allows more comprehensive meta-analyses and should avoid selection bias. However, such analysis ideally requires that the instruments correlate strongly and that the underlying assumption of similar responsiveness is fulfilled. The aim of the study was to assess the correlation between two widely used health-related quality of life instruments for patients with chronic obstructive pulmonary disease and to compare the instruments' responsiveness on a study level. METHODS: We systematically identified all longitudinal studies that used both the Chronic Respiratory Questionnaire (CRQ) and the St. George's Respiratory Questionnaire (SGRQ) through electronic searches of MEDLINE, EMBASE, CENTRAL and PubMed. We assessed the correlation between CRQ (scale 1 – 7) and SGRQ (scale 1 – 100) change scores and compared responsiveness of the two instruments by comparing standardized response means (change scores divided by their standard deviation). RESULTS: We identified 15 studies with 23 patient groups. CRQ change scores ranged from -0.19 to 1.87 (median 0.35, IQR 0.14–0.68) and from -16.00 to 3.00 (median -3.00, IQR -4.73–0.25) for SGRQ change scores. The correlation between CRQ and SGRQ change scores was 0.88. Standardized response means of the CRQ (median 0.51, IQR 0.19–0.98) were significantly higher (p < 0.001) than for the SGRQ (median 0.26, IQR -0.03–0.40). CONCLUSION: Investigators should be cautious about pooling the results from different instruments in meta-analysis even if they appear to measure similar constructs. Despite high correlation in changes scores, responsiveness of instruments may differ substantially and could lead to important between-study heterogeneity and biased meta-analyses

The updating of clinical practice guidelines: insights from an international survey

Contains fulltext : 98466.pdf (publisher's version ) (Open Access)BACKGROUND: Clinical practice guidelines (CPGs) have become increasingly popular, and the methodology to develop guidelines has evolved enormously. However, little attention has been given to the updating process, in contrast to the appraisal of the available literature. We conducted an international survey to identify current practices in CPG updating and explored the need to standardize and improve the methods. METHODS: We developed a questionnaire (28 items) based on a review of the existing literature about guideline updating and expert comments. We carried out the survey between March and July 2009, and it was sent by email to 106 institutions: 69 members of the Guidelines International Network who declared that they developed CPGs; 30 institutions included in the U.S. National Guideline Clearinghouse database that published more than 20 CPGs; and 7 institutions selected by an expert committee. RESULTS: Forty-four institutions answered the questionnaire (42% response rate). In the final analysis, 39 completed questionnaires were included. Thirty-six institutions (92%) reported that they update their guidelines. Thirty-one institutions (86%) have a formal procedure for updating their guidelines, and 19 (53%) have a formal procedure for deciding when a guideline becomes out of date. Institutions describe the process as moderately rigorous (36%) or acknowledge that it could certainly be more rigorous (36%). Twenty-two institutions (61%) alert guideline users on their website when a guideline is older than three to five years or when there is a risk of being outdated. Twenty-five institutions (64%) support the concept of "living guidelines," which are continuously monitored and updated. Eighteen institutions (46%) have plans to design a protocol to improve their guideline-updating process, and 21 (54%) are willing to share resources with other organizations. CONCLUSIONS: Our study is the first to describe the process of updating CPGs among prominent guideline institutions across the world, providing a comprehensive picture of guideline updating. There is an urgent need to develop rigorous international standards for this process and to minimize duplication of effort internationally

Clinical practice guidelines within the Southern African development community: a descriptive study of the quality of guideline development and concordance with best evidence for five priority diseases

<p>Abstract</p> <p>Background</p> <p>Reducing the burden of disease relies on availability of evidence-based clinical practice guidelines (CPGs). There is limited data on availability, quality and content of guidelines within the Southern African Development Community (SADC). This evaluation aims to address this gap in knowledge and provide recommendations for regional guideline development.</p> <p>Methods</p> <p>We prioritised five diseases: HIV in adults, malaria in children and adults, pre-eclampsia, diarrhoea in children and hypertension in primary care. A comprehensive electronic search to locate guidelines was conducted between June and October 2010 and augmented with email contact with SADC Ministries of Health. Independent reviewers used the AGREE II tool to score six quality domains reporting the guideline development process. Alignment of the evidence-base of the guidelines was evaluated by comparing their content with key recommendations from accepted reference guidelines, identified with a content expert, and percentage scores were calculated.</p> <p>Findings</p> <p>We identified 30 guidelines from 13 countries, publication dates ranging from 2003-2010. Overall the '<it>scope and purpose' </it>and '<it>clarity and presentation' </it>domains of the AGREE II instrument scored highest, median 58%(range 19-92) and 83%(range 17-100) respectively. '<it>Stakeholder involvement' </it>followed with median 39%(range 6-75). '<it>Applicability'</it>, '<it>rigour of development' </it>and '<it>editorial independence' </it>scored poorly, all below 25%. Alignment with evidence was variable across member states, the lowest scores occurring in older guidelines or where the guideline being evaluated was part of broader primary healthcare CPG rather than a disease-specific guideline.</p> <p>Conclusion</p> <p>This review identified quality gaps and variable alignment with best evidence in available guidelines within SADC for five priority diseases. Future guideline development processes within SADC should better adhere to global reporting norms requiring broader consultation of stakeholders and transparency of process. A regional guideline support committee could harness local capacity to support context appropriate guideline development.</p

Diabetes-Specific Nutrition Algorithm: A Transcultural Program to Optimize Diabetes and Prediabetes Care

Type 2 diabetes (T2D) and prediabetes have a major global impact through high disease prevalence, significant downstream pathophysiologic effects, and enormous financial liabilities. To mitigate this disease burden, interventions of proven effectiveness must be used. Evidence shows that nutrition therapy improves glycemic control and reduces the risks of diabetes and its complications. Accordingly, diabetes-specific nutrition therapy should be incorporated into comprehensive patient management programs. Evidence-based recommendations for healthy lifestyles that include healthy eating can be found in clinical practice guidelines (CPGs) from professional medical organizations. To enable broad implementation of these guidelines, recommendations must be reconstructed to account for cultural differences in lifestyle, food availability, and genetic factors. To begin, published CPGs and relevant medical literature were reviewed and evidence ratings applied according to established protocols for guidelines. From this information, an algorithm for the nutritional management of people with T2D and prediabetes was created. Subsequently, algorithm nodes were populated with transcultural attributes to guide decisions. The resultant transcultural diabetes-specific nutrition algorithm (tDNA) was simplified and optimized for global implementation and validation according to current standards for CPG development and cultural adaptation. Thus, the tDNA is a tool to facilitate the delivery of nutrition therapy to patients with T2D and prediabetes in a variety of cultures and geographic locations. It is anticipated that this novel approach can reduce the burden of diabetes, improve quality of life, and save lives. The specific Southeast Asian and Asian Indian tDNA versions can be found in companion articles in this issue of Current Diabetes Reports

Linking Proteomic and Transcriptional Data through the Interactome and Epigenome Reveals a Map of Oncogene-induced Signaling

Cellular signal transduction generally involves cascades of post-translational protein modifications that rapidly catalyze changes in protein-DNA interactions and gene expression. High-throughput measurements are improving our ability to study each of these stages individually, but do not capture the connections between them. Here we present an approach for building a network of physical links among these data that can be used to prioritize targets for pharmacological intervention. Our method recovers the critical missing links between proteomic and transcriptional data by relating changes in chromatin accessibility to changes in expression and then uses these links to connect proteomic and transcriptome data. We applied our approach to integrate epigenomic, phosphoproteomic and transcriptome changes induced by the variant III mutation of the epidermal growth factor receptor (EGFRvIII) in a cell line model of glioblastoma multiforme (GBM). To test the relevance of the network, we used small molecules to target highly connected nodes implicated by the network model that were not detected by the experimental data in isolation and we found that a large fraction of these agents alter cell viability. Among these are two compounds, ICG-001, targeting CREB binding protein (CREBBP), and PKF118–310, targeting β-catenin (CTNNB1), which have not been tested previously for effectiveness against GBM. At the level of transcriptional regulation, we used chromatin immunoprecipitation sequencing (ChIP-Seq) to experimentally determine the genome-wide binding locations of p300, a transcriptional co-regulator highly connected in the network. Analysis of p300 target genes suggested its role in tumorigenesis. We propose that this general method, in which experimental measurements are used as constraints for building regulatory networks from the interactome while taking into account noise and missing data, should be applicable to a wide range of high-throughput datasets.National Science Foundation (U.S.) (DB1-0821391)National Institutes of Health (U.S.) (Grant U54-CA112967)National Institutes of Health (U.S.) (Grant R01-GM089903)National Institutes of Health (U.S.) (P30-ES002109

Micronutrient fortification of food and its impact on woman and child health: A systematic review

Background: Vitamins and minerals are essential for growth and metabolism. The World Health Organization estimates that more than 2 billion people are deficient in key vitamins and minerals. Groups most vulnerable to these micronutrient deficiencies are pregnant and lactating women and young children, given their increased demands. Food fortification is one of the strategies that has been used safely and effectively to prevent vitamin and mineral deficiencies.Methods: A comprehensive search was done to identify all available evidence for the impact of fortification interventions. Studies were included if food was fortified with a single, dual or multiple micronutrients and impact of fortification was analyzed on the health outcomes and relevant biochemical indicators of women and children. We performed a meta-analysis of outcomes using Review Manager Software version 5.1.Results: Our systematic review identified 201 studies that we reviewed for outcomes of relevance. Fortification for children showed significant impacts on increasing serum micronutrient concentrations. Hematologic markers also improved, including hemoglobin concentrations, which showed a significant rise when food was fortified with vitamin A, iron and multiple micronutrients. Fortification with zinc had no significant adverse impact on hemoglobin levels. Multiple micronutrient fortification showed non-significant impacts on height for age, weight for age and weight for height Z-scores, although they showed positive trends. The results for fortification in women showed that calcium and vitamin D fortification had significant impacts in the post-menopausal age group. Iron fortification led to a significant increase in serum ferritin and hemoglobin levels in women of reproductive age and pregnant women. Folate fortification significantly reduced the incidence of congenital abnormalities like neural tube defects without increasing the incidence of twinning. The number of studies pooled for zinc and multiple micronutrients for women were few, though the evidence suggested benefit. There was a dearth of evidence for the impact of fortification strategies on morbidity and mortality outcomes in women and children.Conclusion: Fortification is potentially an effective strategy but evidence from the developing world is scarce. Programs need to assess the direct impact of fortification on morbidity and mortality