Fibroblast viability and phenotypic changes within glycated stiffened three-dimensional collagen matrices.

BACKGROUND: There is growing interest in the development of cell culture assays that enable the rigidity of the extracellular matrix to be increased. A promising approach is based on three-dimensional collagen type I matrices that are stiffened by cross-linking through non-enzymatic glycation with reducing sugars. METHODS: The present study evaluated the biomechanical changes in the non-enzymatically glycated type I collagen matrices, including collagen organization, the advanced glycation end products formation and stiffness achievement. Gels were glycated with ribose at different concentrations (0, 5, 15, 30 and 240 mM). The viability and the phenotypic changes of primary human lung fibroblasts cultured within the non-enzymatically glycated gels were also evaluated along three consecutive weeks. Statistical tests used for data analyze were Mann-Whitney U, Kruskal Wallis, Student's t-test, two-way ANOVA, multivariate ANOVA, linear regression test and mixed linear model. RESULTS: Our findings indicated that the process of collagen glycation increases the stiffness of the matrices and generates advanced glycation end products in a ribose concentration-dependent manner. Furthermore, we identified optimal ribose concentrations and media conditions for cell viability and growth within the glycated matrices. The microenvironment of this collagen based three-dimensional culture induces α-smooth muscle actin and tenascin-C fibroblast protein expression. Finally, a progressive contractile phenotype cell differentiation was associated with the contraction of these gels. CONCLUSIONS: The use of non-enzymatic glycation with a low ribose concentration may provide a suitable model with a mechanic and oxidative modified environment with cells embedded in it, which allowed cell proliferation and induced fibroblast phenotypic changes. Such culture model could be appropriate for investigations of the behavior and phenotypic changes in cells that occur during lung fibrosis as well as for testing different antifibrotic therapies in vitro.

[GRADE: Methodology for formulating and grading recommendations in clinical practice]. / Sistema GRADE: metodología para la realización de recomendaciones para la práctica clínica.

Clinical practice guidelines (CPG) provide recommendations on the benefits and harms of different healthcare interventions. Proper CPG development and implementation can potentially reduce variability in clinical practice while improving its quality and safety. The GRADE system is used to assess the quality of evidence and to grade the strength of recommendations in the context of the development of CPGs, systematic reviews or health technology assessments. The aim of this article is to describe the main characteristics of the GRADE system through relevant examples in the context of primary care.

The validity of recommendations from clinical guidelines: a survival analysis.

BACKGROUND: Clinical guidelines should be updated to maintain their validity. Our aim was to estimate the length of time before recommendations become outdated. METHODS: We used a retrospective cohort design and included recommendations from clinical guidelines developed in the Spanish National Health System clinical guideline program since 2008. We performed a descriptive analysis of references, recommendations and resources used, and a survival analysis of recommendations using the Kaplan-Meier method. RESULTS: We included 113 recommendations from 4 clinical guidelines with a median of 4 years since the most recent search (range 3.9-4.4 yr). We retrieved 39 136 references (range 3343-14 787) using an exhaustive literature search, 668 of which were related to the recommendations in our sample. We identified 69 (10.3%) key references, corresponding to 25 (22.1%) recommendations that required updating. Ninety-two percent (95% confidence interval 86.9-97.0) of the recommendations were valid 1 year after their development. This probability decreased at 2 (85.7%), 3 (81.3%) and 4 years (77.8%). INTERPRETATION: Recommendations quickly become outdated, with 1 out of 5 recommendations being out of date after 3 years. Waiting more than 3 years to review a guideline is potentially too long.

The UpPriority tool supported prioritization processes for updating clinical guideline questions.

OBJECTIVE: We aim to 1) use the UpPriority tool to identify which clinical questions (CQs) within the clinical guidelines (CGs) need to be prioritized for updating and 2) assess the implementation of the tool in a real-world set of CGs. STUDY DESIGN AND SETTING: We systematically assessed CQs from a sample of CGs developed in the Spanish National Health System CG program. We applied the UpPriority tool to each CG using a step-by-step process that included: 1) establishment of the UpPriority Implementation Working Group, 2) mapping of the original CG questions and recommendations, 3) development of a survey to prioritize CQs, 4) assessment of CQ's priority according to six items, 5) calculation and ranking of priority scores, 6) decision of prioritized CQs for updating, and 7) development of the priority report. We assessed the tool implementation process (appraisers' experience when using the tool) and the inter-observer reliability of the tool, and we provided suggestions for improvement. RESULTS: We included four CGs with a total of 107 CQs on the following topics: chronic heart failure (10 CQs), inherited retinal dystrophies (39 CQs), menopause (20 CQs), and open-angle glaucoma (38 CQs). We included a total of 30 participants, most of them clinicians that were members of the original CG development groups. CQs were classified in three groups: 1) high priority (CQs prioritized for updating [16/107; 15.0%]), 2) medium priority (CQs that could be prioritized for updating [47/107; 43.9%]), and low priority (CQs that were not prioritized for updating [44/107; 41.1%]). The mean time each appraiser needed to assess the CQs with the tool was 3.8 hours (range 0.5 to 10). Agreement among the appraisers varied among the CGs. Appraisers considered that the tool was useful. We suggest some areas for consideration when using the tool including: 1) identification of key appraisers, 2) customization of training materials, 3) establishment of priority thresholds, and 4) provision of methodological support. CONCLUSION: The UpPriority is a useful tool to identify which CQs within a CG need to be prioritized for update in a real-world scenario. Recruitment and training of topic experts are the main challenges when using the tool.

The UpPriority tool was developed to guide the prioritization of clinical guideline questions for updating.

OBJECTIVE: The objective of the study is to develop a pragmatic tool to prioritize clinical guideline (CG) questions for updating, the UpPriority tool. STUDY DESIGN AND SETTING: The development of this tool consisted of the following: (1) establishment of the working group, (2) generation of the initial version, (3) optimization of the tool (including an initial feasibility test, semistructured interviews, Delphi consensus survey, second feasibility test, external review, and pilot test), and (4) approval of the final version. RESULTS: A total of 87 participants including methodologists, clinicians, and other relevant stakeholders contributed to the development of the UpPriority tool. The tool consists of six items: (1) impact of outdated recommendations on safety, (2) availability of new relevant evidence, (3) context relevance of the clinical question, (4) methodological applicability of the clinical question, (5) user's interest, and (6) impact on access to health care. The UpPriority tool includes detailed guidance for using the tool and rating each item (using a 7-point Likert scale), for calculating and ranking the questions, and for summarizing results. CONCLUSION: The UpPriority tool could be useful for standardizing prioritization processes when updating CGs and for fostering more efficient use of resources in the CG field.

Most guideline organizations lack explicit guidance in how to incorporate cost considerations.

OBJECTIVES: Resource use and cost (RUC) evidence is one of the factors that can be considered when formulating recommendations in clinical practice guidelines (CPGs). However, it is unclear how CPG developers incorporate this information. The purpose of this study was to identify available guidance from guideline organizations on how to incorporate RUC in CPGs. STUDY DESIGN AND SETTING: This is a methodological survey. We searched MEDLINE, the G-I-N library, the Cochrane Methodology Register, and gray literature from inception to 2017. We included the most recent version of guidance documents. We excluded those that only reported methodology for adapting, endorsing, or updating CPGs, and documents reporting methods followed in the development of one or more specific CPGs. RESULTS: We included 77 documents from 67 organizations. Fifty-nine organizations (88.1%) include information regarding RUC during the CPG development process. Fifty-five (82.1%) organizations report taking RUC into account when developing recommendations: 44 (65.7%) do this explicitly, 5 (7.5%) implicitly, and 6 (9.0%) explicitly as optional. Twelve of the 44 organizations that explicitly consider RUC (27.3%) provide guidance to identify, assess and use the RUC evidence when developing recommendations. Twenty-three consider RUC when moving from the evidence to recommendations (52.3%). Seventeen of the 44 (38.6%) recommend making qualitative judgments about whether the desirable effects of interventions were worth the associated costs. CONCLUSION: More explicit guidance is needed alongside tools to help CPGs developers incorporate RUC evidence when formulating recommendations. Our results may be of use for guideline developers to improve this guidance.

Guideline on terminology and definitions of updating clinical guidelines: The Updating Glossary.

OBJECTIVE: The Guidelines International Network (G-I-N) Updating Guidelines Working Group launched an initiative to develop a glossary (the Updating Glossary) with domains, terms, definitions, and synonyms related to updating of clinical guidelines (CGs). STUDY DESIGN AND SETTING: The steering committee developed an initial list of domains, terms, definitions, and synonyms through brainstorming and discussion. The panel members participated in three rounds of feedback to discuss, refine, and clarify the proposed terms, definitions, and synonyms. Finally, the panel members were surveyed to assess their level of agreement regarding the glossary. RESULTS: Eighteen terms were identified and defined: (1) continuous updating, (2) decision to update, (3) fixed updating, (4) full updating, (5) impact of the new evidence, (6) partial updating, (7) prioritization process, (8) reporting process, (9) signal for an update, (10) surveillance process, (11) time of validity, (12) timeframe, (13) tools and resources, (14) up to date, (15) update cycle, (16) update unit, (17) updated version, and (18) updating strategy. Consensus was reached for all terms, definitions, and synonyms (median agreement scores ≥ 6); except for one term. CONCLUSIONS: The G-I-N Updating Guidelines Working Group assembled the Updating Glossary to facilitate and improve the knowledge exchange among CGs developers, researchers, and users.

Continuous surveillance of a pregnancy clinical guideline: an early experience.

BACKGROUND: To date there is no consensus about the optimal strategy for keeping clinical guidelines (CGs) up-to-date. The aims of this study were (1) to develop a continuous surveillance and updating strategy for CGs and (2) to test the strategy in a specific CG. METHODS: The main steps were as follows: (1) recruiting members for the CG Updating Working Group, (2) mapping the CG, (3) identifying new evidence from the CG Updating Working Group, (4) designing and running restricted literature searches, (5) reviewing drugs and medical devices alerts, (6) screening and assessing the new evidence, (7) reviewing and, if necessary, modifying clinical questions and recommendations, and (8) updating the CG document. RESULTS: The Pregnancy CG Updating Working Group consisted of 29 members, including clinicians, patients and caregivers, and clinical guideline methodology experts. We selected 69 clinical questions (123 recommendations) from the "Assistance during pregnancy" section. For the first update cycle (32-month duration), 9710 references were identified. Of these, 318 were pertinent, 289 were relevant, and 55 were classified as potential key references. For the second and third update cycles (6-month duration each), 2160 and 2010 references were retrieved, respectively. The continuous surveillance and updating strategy has not yet been completely implemented. CONCLUSIONS: Further resources are needed in updating the CG field, both for implementing updating strategies and for developing methodological research.

Incorporating patients' views in guideline development: a systematic review of guidance documents.

OBJECTIVES: To assess how guidance documents for developing clinical guidelines (CGs) address the incorporation of patients' views in CGs. STUDY DESIGN AND SETTING: Systematic review to identify the methodology provided in guidance documents for incorporating (1) patients or representatives and (2) patients' views in the CG development process. The search was performed in 2017 in five databases. Two authors selected the studies, and data extraction was double-checked. RESULTS: We included guidance documents from 56 institutions. Of those, 40 (71.4%) recommended the inclusion of patients or their representatives, mainly for developing recommendations (14/40, 35.0%); reviewing the final version (13/40, 32.5%); formulating clinical questions (13/40, 32.5%); defining the scope and objectives (10/40, 25.0%); and dissemination and implementation (10/40, 25.0%). Concrete methods on how to incorporate patients were provided by 47.5% (19/40) of institutions. Forty (71.4%) institutions provided additional strategies to incorporate patients' views. The majority (30/40, 75.0%) suggested sources for obtaining these views (consultation with patients [24/40, 60.0%], using panels' judgment [10/40, 25.0%], conducting de novo research [10/40, 25.0%], or a systematic review [9/40, 22.5%]). CONCLUSION: Although most institutions suggest incorporating patients and their views when developing CGs, little detail is provided on how to do this. Institutions should provide more guidance as this could have a positive impact in guideline applicability.

Development of a prioritisation tool for the updating of clinical guideline questions: the UpPriority Tool protocol.

INTRODUCTION: Due to a continuous emergence of new evidence, clinical guidelines (CGs) require regular surveillance of evidence to maintain their trustworthiness. The updating of CGs is resource intensive and time consuming; therefore, updating may include a prioritisation process to efficiently ensure recommendations remain up to date. The objective of our project is to develop a pragmatic tool to prioritise clinical questions for updating within a CG. METHODS AND ANALYSIS: To develop the tool, we will use the results and conclusions of a systematic review of methodological research on prioritisation processes for updating and will adopt a methodological approach we have successfully implemented in a previous experience.We will perform a multistep process including (1) generation of an initial version of the tool, (2) optimisation of the tool (feasibility test of the tool, semistructured interviews, Delphi consensus survey, external review by CG methodologists and users and pilot test of the tool) and (3) approval of the final version of the tool.At each step of the process, we will (1) calculate absolute frequencies and proportions (quantitative data), (2) use content analysis to summarise and draw conclusions (qualitative data) and (3) draft a final report, discuss results and refine the previous versions of the tool. Finally, we will calculate intraclass coefficients with 95% CIs for each item and overall as indicators of agreement among reviewers. ETHICS AND DISSEMINATION: We have obtained a waiver of approval from the Clinical Research Ethics Committee at the Hospital de la Santa Creu i Sant Pau (Barcelona). The results of the study will be published in peer-reviewed journal and communicated to interested stakeholders.The tool could support the standardisation of prioritisation processes for updating CGs and therefore have important implications for a more efficient use of resources in the CG field.

Methodological systematic review identifies major limitations in prioritization processes for updating.

OBJECTIVES: The aim of the study was to identify and describe strategies to prioritize the updating of systematic reviews (SRs), health technology assessments (HTAs), or clinical guidelines (CGs). STUDY DESIGN AND SETTING: We conducted an SR of studies describing one or more methods to prioritize SRs, HTAs, or CGs for updating. We searched MEDLINE (PubMed, from 1966 to August 2016) and The Cochrane Methodology Register (The Cochrane Library, Issue 8 2016). We hand searched abstract books, reviewed reference lists, and contacted experts. Two reviewers independently screened the references and extracted data. RESULTS: We included 14 studies. Six studies were classified as descriptive (6 of 14, 42.9%) and eight as implementation studies (8 of 14, 57.1%). Six studies reported an updating strategy (6 of 14, 42.9%), six a prioritization process (6 of 14, 42.9%), and two a prioritization criterion (2 of 14, 14.2%). Eight studies focused on SRs (8 of 14, 57.1%), six studies focused on CGs (6 of 14, 42.9%), and none were about HTAs. We identified 76 prioritization criteria that can be applied when prioritizing documents for updating. The most frequently cited criteria were as follows: available evidence (19 of 76, 25.0%), clinical relevance (10 of 76; 13.2%), and users' interest (10 of 76; 13.2%). CONCLUSION: There is wide variability and suboptimal reporting of the methods used to develop and implement processes to prioritize updating of SRs, HTAs, and CGs.

Barriers to making recommendations about medical tests: a qualitative study of European guideline developers.

OBJECTIVES: Development of medical test guidelines differs from intervention guideline development. These differences can pose unique challenges in building evidence-based recommendations to guide clinical practice. The aim of our study was to better understand these challenges, explore reasons behind them and identify possible solutions. SETTING AND PARTICIPANTS: In this qualitative study, we conducted in-depth interviews between February 2012 and April 2013 of a convenience sample of 17 European guideline developers experienced in medical test guideline development. OUTCOMES MEASURED: We used framework analysis with deductive and inductive approaches to generate the themes from the interviews. We kept interpretation grounded in the data. RESULTS: Guideline developers acknowledged that inclusion of patient important outcomes in their guideline development was necessary but lacking. This and other challenges raised fell into 3 broad and overlapping domains: methodological issues, resource limitations and a lack of awareness on the need for evidence that links testing to patient outcomes. Education was mentioned as a key solution to increase awareness and address the resources limitations mentioned. CONCLUSIONS: Challenges guideline developers face were interlinked across the domains of methodological issues, resource limitations and a lack of awareness. Solutions that addressed these challenges in parallel are needed. Raising awareness, education and training of relevant stakeholders such as medical doctors, funders and regulators to look beyond test accuracy is key to having a long-term resolution to the issues faced in medical test guideline development.

Systematic reviews experience major limitations in reporting absolute effects.

OBJECTIVES: Expressing treatment effects in relative terms yields larger numbers than expressions in absolute terms, affecting the judgment of the clinicians and patients regarding the treatment options. It is uncertain how authors of systematic reviews (SRs) absolute effect estimates are reported in. We therefore undertook a systematic survey to identify and describe the reporting and methods for calculating absolute effect estimates in SRs. STUDY DESIGN AND SETTING: Two reviewers independently screened title, abstract, and full text and extracted data from a sample of Cochrane and non-Cochrane SRs. We used regression analyses to examine the association between study characteristics and the reporting of absolute estimates for the most patient-important outcome. RESULTS: We included 202 SRs (98 Cochrane and 104 non-Cochrane), most of which (92.1%) included standard meta-analyses including relative estimates of effect. Of the 202 SRs, 73 (36.1%) reported absolute effect estimates for the most patient-important outcome. SRs with statistically significant effects were more likely to report absolute estimates (odds ratio, 2.26; 95% confidence interval: 1.08, 4.74). The most commonly reported absolute estimates were: for each intervention, risk of adverse outcomes expressed as a percentage (41.1%); number needed to treat (26.0%); and risk for each intervention expressed as natural units or natural frequencies (24.7%). In 12.3% of the SRs that reported absolute effect estimates for both benefit and harm outcomes, harm outcomes were reported exclusively as absolute estimates. Exclusively reporting of beneficial outcomes as absolute estimates occurred in 6.8% of the SRs. CONCLUSIONS: Most SRs do not report absolute effects. Those that do often report them inadequately, thus requiring users of SRs to generate their own estimates of absolute effects. For any apparently effective or harmful intervention, SR authors should report both absolute and relative estimates to optimize the interpretation of their findings.

Reporting, handling and assessing the risk of bias associated with missing participant data in systematic reviews: a methodological survey.

OBJECTIVES: To describe how systematic reviewers are reporting missing data for dichotomous outcomes, handling them in the analysis and assessing the risk of associated bias. METHODS: We searched MEDLINE and the Cochrane Database of Systematic Reviews for systematic reviews of randomised trials published in 2010, and reporting a meta-analysis of a dichotomous outcome. We randomly selected 98 Cochrane and 104 non-Cochrane systematic reviews. Teams of 2 reviewers selected eligible studies and abstracted data independently and in duplicate using standardised, piloted forms with accompanying instructions. We conducted regression analyses to explore factors associated with using complete case analysis and with judging the risk of bias associated with missing participant data. RESULTS: Of Cochrane and non-Cochrane reviews, 47% and 7% (p<0.0001), respectively, reported on the number of participants with missing data, and 41% and 9% reported a plan for handling missing categorical data. The 2 most reported approaches for handling missing data were complete case analysis (8.5%, out of the 202 reviews) and assuming no participants with missing data had the event (4%). The use of complete case analysis was associated only with Cochrane reviews (relative to non-Cochrane: OR=7.25; 95% CI 1.58 to 33.3, p=0.01). 65% of reviews assessed risk of bias associated with missing data; this was associated with Cochrane reviews (relative to non-Cochrane: OR=6.63; 95% CI 2.50 to 17.57, p=0.0001), and the use of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology (OR=5.02; 95% CI 1.02 to 24.75, p=0.047). CONCLUSIONS: Though Cochrane reviews are somewhat less problematic, most Cochrane and non-Cochrane systematic reviews fail to adequately report and handle missing data, potentially resulting in misleading judgements regarding risk of bias.

Guidance for updating clinical practice guidelines: a systematic review of methodological handbooks.

BACKGROUND: Updating clinical practice guidelines (CPGs) is a crucial process for maintaining the validity of recommendations. Methodological handbooks should provide guidance on both developing and updating CPGs. However, little is known about the updating guidance provided by these handbooks. METHODS: We conducted a systematic review to identify and describe the updating guidance provided by CPG methodological handbooks and included handbooks that provide updating guidance for CPGs. We searched in the Guidelines International Network library, US National Guidelines Clearinghouse and MEDLINE (PubMed) from 1966 to September 2013. Two authors independently selected the handbooks and extracted the data. We used descriptive statistics to analyze the extracted data and conducted a narrative synthesis. RESULTS: We included 35 handbooks. Most handbooks (97.1%) focus mainly on developing CPGs, including variable degrees of information about updating. Guidance on identifying new evidence and the methodology of assessing the need for an update is described in 11 (31.4%) and eight handbooks (22.8%), respectively. The period of time between two updates is described in 25 handbooks (71.4%), two to three years being the most frequent (40.0%). The majority of handbooks do not provide guidance for the literature search, evidence selection, assessment, synthesis, and external review of the updating process. CONCLUSIONS: Guidance for updating CPGs is poorly described in methodological handbooks. This guidance should be more rigorous and explicit. This could lead to a more optimal updating process, and, ultimately to valid trustworthy guidelines.

Updated recommendations: an assessment of NICE clinical guidelines.

BACKGROUND: Updating is important to ensure clinical guideline (CG) recommendations remain valid. However, little research has been undertaken in this field. We assessed CGs produced by the National Institute for Health and Care Excellence (NICE) to identify and describe updated recommendations and to investigate potential factors associated with updating. Also, we evaluated the reporting and presentation of recommendation changes. METHODS: We performed a descriptive analysis of original and updated CGs and recommendations, and an assessment of presentation formats and methods for recording information. We conducted a case-control study, defining cases as original recommendations that were updated ('new-replaced' recommendations), and controls as original recommendations that were considered to remain valid ('not changed' recommendations). We performed a comparison of main characteristics between cases and controls, and we planned a multiple regression analysis to identify potential predictive factors for updating. RESULTS: We included nine updated CGs (1,306 recommendations) and their corresponding original versions (1,106 recommendations). Updated CGs included 812 (62%) recommendations 'not reviewed', 368 (28.1%) 'new' recommendations, 104 (7.9%) 'amended' recommendations, and 25 (1.9%) recommendations reviewed but unchanged. The presentation formats used to indicate the changes in recommendations varied widely across CGs. Changes in 'amended', 'deleted', and 'new-replaced' recommendations (n = 296) were reported infrequently, mostly in appendices. These changes were recorded in 167 (56.4%) recommendations; and were explained in 81 (27.4%) recommendations. We retrieved a total of 7.1% (n = 78) case recommendations ('new-replaced') and 2.4% (n = 27) control recommendations ('not changed') in original CGs. The updates were mainly from 'Fertility CG', about 'gynaecology, pregnancy and birth' topic, and 'treatment' or 'prevention' purposes. We did not perform the multiple regression analysis as originally planned due to the small sample of recommendations retrieved. CONCLUSION: Our study is the first to describe and assess updated CGs and recommendations from a national guideline program. Our results highlight the pressing need to standardise the reporting and presentation of updated recommendations and the research gap about the optimal way to present updates to guideline users. Furthermore, there is a need to investigate updating predictive factors.

Strategies to assess the validity of recommendations: a study protocol.

BACKGROUND: Clinical practice guidelines (CPGs) become quickly outdated and require a periodic reassessment of evidence research to maintain their validity. However, there is little research about this topic. Our project will provide evidence for some of the most pressing questions in this field: 1) what is the average time for recommendations to become out of date?; 2) what is the comparative performance of two restricted search strategies to evaluate the need to update recommendations?; and 3) what is the feasibility of a more regular monitoring and updating strategy compared to usual practice?. In this protocol we will focus on questions one and two. METHODS: The CPG Development Programme of the Spanish Ministry of Health developed 14 CPGs between 2008 and 2009. We will stratify guidelines by topic and by publication year, and include one CPG by strata.We will develop a strategy to assess the validity of CPG recommendations, which includes a baseline survey of clinical experts, an update of the original exhaustive literature searches, the identification of key references (reference that trigger a potential recommendation update), and the assessment of the potential changes in each recommendation.We will run two alternative search strategies to efficiently identify important new evidence: 1) PLUS search based in McMaster Premium LiteratUre Service (PLUS) database; and 2) a Restrictive Search (ReSe) based on the least number of MeSH terms and free text words needed to locate all the references of each original recommendation.We will perform a survival analysis of recommendations using the Kaplan-Meier method and we will use the log-rank test to analyse differences between survival curves according to the topic, the purpose, the strength of recommendations and the turnover. We will retrieve key references from the exhaustive search and evaluate their presence in the PLUS and ReSe search results. DISCUSSION: Our project, using a highly structured and transparent methodology, will provide guidance of when recommendations are likely to be at risk of being out of date. We will also assess two novel restrictive search strategies which could reduce the workload without compromising rigour when CPGs developers check for the need of updating.