Development Of WHO Guidelines Research Articles

Update of the World Health Organization's Mental Health Gap Action Programme Guideline for Psychoses (Including Schizophrenia).

The World Health Organization's (WHOs) Mental Health Gap Action Programme (mhGAP) aims to improve healthcare for mental, neurological, and substance use disorders in nonspecialized settings, with a focus on low- and middle-income countries (LMICs). mhGAP includes guidelines for the treatment of psychoses (including schizophrenia), which were recently updated in 2023. The complexity of the WHO guideline update process and the updated recommendations on psychoses are presented. The WHO guideline development process is outlined as well as the evidence appraisal and the translation of the evidence into recommendations following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The guideline update process includes a review of the literature, a compilation of systematic reviews, and extracting data related to critical and important outcomes. The updated recommendations and the justifying evidence are discussed. The WHO mhGAP guidelines for psychoses are adapted to LMICs, and consist of 13 recommendations in 2023, whereof 5 were updated, and 1 recommendation was newly developed. Background information on how these recommendations were obtained, and significant changes since the previous guideline update in 2015 are provided. Unlike other guidelines, the WHO must consider various countries, contextual factors, and the WHO Model Lists of Essential Medicines when developing its guidelines. A transformation of the WHO guideline for psychoses into a living guideline would ensure always up-to-date recommendations and facilitate shared decision-making.

COVID-19 self-testing: Countries accelerating policies ahead of WHO guidelines during pandemics, a global consultation.

The widespread use of antigen-detection rapid diagnostic tests (Ag-RDTs) has revolutionized SARS-CoV-2 (COVID-19) testing, particularly through the option of self-testing. The full extent of Ag-RDT utilization for self-testing, however, remains largely unexplored. To inform the development of WHO guidance on COVID-19 self-testing, we conducted a global consultation to gather the views and experiences of policy makers, researchers, and implementers worldwide. The consultation was conducted by disseminating a WHO questionnaire through professional networks via email and social media, encouraging onward sharing. We used a cross-sectional design with both closed and open-ended questions related to policy and program information concerning the regulation, availability, target population, indications, implementation, benefits, and challenges of COVID-19 self-testing (C19ST). We defined self-testing as tests performed and interpreted by an untrained individual, often at home. Descriptive summaries, cross-tabulations, and proportions were used to calculate outcomes at the global level and by WHO region and World Bank income classifications. All information was collated and reported according to WHO guideline development standards and practice for global consultations. Between 01 and 11 February 2022, 844 individuals from 139 countries responded to the survey, with 45% reporting affiliation with governments and 47% operating at the national level. 504 respondents from 101 countries reported policies supporting C19ST for a range of use cases, including symptomatic and asymptomatic populations. More respondents from low-and-middle-income countries (LMICs) than high-income countries (HICs) reported a lack of an C19ST policy (61 vs 11 countries) and low population-level reach of C19ST. Respondents with C19ST experience perceived that the tests were mostly acceptable to target populations, provided significant benefits, and highlighted several key challenges to be addressed for increased success. Reported costs varied widely, ranging from specific programmes enabling free access to certain users and others with high costs via the private sector. Based on this consultation, systems for the regulatory review, policy development and implementation of C19ST appeared to be much more common in HIC when compared to LIC in early 2022, though most respondents indicated self-testing was available to some extent (101 out of 139 countries) in their country. Addressing such global inequities is critical for ensuring access to innovative and impactful interventions in the context of a public health emergency of international concern. The challenges and opportunities highlighted by key stakeholders could be valuable to consider as future testing strategies are being set for outbreak-prone diseases.

Defining Anaemia across the Lifecycle in Healthy Reference Populations: An Analysis for Guideline Development

Background Detection of anaemia is critical for clinical medicine and public health in high and low income settings, but anaemia definitions are uncertain, causing discordance across different laboratories and guidelines. Current WHO anaemia definitions, set in 1968 using limited data, reflect the 5th centile of the haemoglobin distribution in apparently healthy populations. WHO is now reviewing these definitions. Haemoglobin concentration is sensitive to iron and other nutrient deficiencies, inflammation, renal impairment, and genetic conditions, and thus conservative criteria to obtain a healthy reference population is crucial in estimating the 5th centile. To support WHO definitions, this study estimated the 5th centile for haemoglobin in healthy reference populations derived from a secondary analysis of large cohorts. Methods We identified data sources from which sufficient clinical and laboratory data were available to identify an apparently healthy reference sample. These comprised the National Health and Nutrition Examination Survey (NHANES, USA, 8 survey years); Health Survey for England (HSE, England, 4 survey years); the Australian Health Survey (AHS), comprising 2 separate surveys: National Health Survey (NHS, Australia) and National Nutrition and Physical Activity Survey (NNPAS, Australia); TARGetKids! (prospective longitudinal cohort of children, Canada); BRISC (trial of oral iron in infants, Bangladesh); Generation R (prospective cohort of pregnant women, Netherlands). Markers or iron status and inflammation were available in all surveys, with exclusions for ferritin<15ug/L (or <12ug/L in children <5 years), or C-Reactive Protein (CRP) >5mg/L. Where possible, exclusions were applied based on renal function, folate, and active B12. Clinical data from all surveys (except Generation R) excluded individuals with pre-existing health conditions, use of medication (other than contraception), recent illness or hospital admission. In the pregnant Generation R group, those with pregnancy complications were excluded. In all groups, current smokers and those who consumed excess alcohol were excluded. Adults with BMI <18.5 or >30kg/m2 were excluded; children were excluded if growth z-scores were <-2 or >+2. In children <24months, those with birth complications or prematurity were excluded. Thresholds were defined in adult men (18-65 years), adult non-pregnant women (18-65 years), pregnant women (18-45 years, by trimester), and children (6-23 months, 24-59 months, 5-11 years, 12-17 years). Discrete 2.5th and 5th centiles were estimated along with two-sided 90% confidence intervals for each data set and estimates were combined across all data sources using a fixed-effect meta-analysis approach. Results In non pregnant adult men and women (total n=57,896 individuals), exclusions resulted in an apparently healthy group of 15-20% of each survey (less where survey years were missing required biochemistry). A broad range of self-reported ethnicities/ancestries were represented. For example in healthy adults: NHANES 17-33% of participants identified as White; HSE >90% identified as White; AHS 50-60% reported European ancestry. 5th centiles of the distribution of haemoglobin values in the derived reference samples were obtained (see Figure 1 for example in non-pregnant women). Pooled estimates for each sample are shown in Table 1. The results generally align with current WHO thresholds, other than adult men, where a 5th centile of 135.1g/L (90% CI 134.4-135.7) is above the WHO threshold of 130g/L, and in children 6-23 months where the 5th centile of 104.5g/L (90% CI 103.6-105.4) is lower than the current value of 110g/L. Our data support the current threshold in non-pregnant adult women of 120g/L. Sensitivity analyses suggest persons of Black race or ethnicity may have 5th centiles lower than values of White persons (predominantly within the US surveys), but presence of haemoglobinopathy as well as other contributing factors cannot be excluded. Conclusion In this analysis using stringent criteria to define healthy reference group at low risk of iron/ other nutrient deficiency, or inflammation, we have estimated statistical thresholds to define anaemia across the lifecycle. These data contribute to WHO guideline development, and provide a platform for harmonisation of thresholds across different laboratories and clinical guidelines. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Using the WHO-INTEGRATE evidence-to-decision framework to develop recommendations for induction of labour

BackgroundIn 2019, WHO prioritized updating recommendations relating to three labour induction topics: labour induction at or beyond term, mechanical methods for labour induction, and outpatient labour induction. As part of this process, we aimed to review the evidence addressing factors beyond clinical effectiveness (values, human rights and sociocultural acceptability, health equity, and economic and feasibility considerations) to inform WHO Guideline Development Group decision-making using the WHO-INTEGRATE evidence-to-decision framework, and to reflect on how methods for identifying, synthesizing and integrating this evidence could be improved.MethodsWe adapted the framework to consider the key criteria and sub-criteria relevant to our intervention. We searched for qualitative and other evidence across a variety of sources and mapped the eligible evidence to country income setting and perspective. Eligibility assessment and quality appraisal of qualitative evidence syntheses was undertaken using a two-step process informed by the ENTREQ statement. We adopted an iterative approach to interpret the evidence and provided both summary and detailed findings to the decision-makers. We also undertook a review to reflect on opportunities to improve the process of applying the framework and identifying the evidence.ResultsUsing the WHO-INTEGRATE framework allowed us to explore health rights and equity in a systematic and transparent way. We identified a lack of qualitative and other evidence from low- and middle-income settings and in populations that are most impacted by structural inequities or traditionally excluded from research. Our process review highlighted opportunities for future improvement, including adopting more systematic evidence mapping methods and working with social science researchers to strengthen theoretical understanding, methods and interpretation of the evidence.ConclusionsUsing the WHO-INTEGRATE evidence-to-decision framework to inform decision-making in a global guideline for induction of labour, we identified both challenges and opportunities relating to the lack of evidence in populations and settings of need and interest; the theoretical approach informing the development and application of WHO-INTEGRATE; and interpretation of the evidence. We hope these insights will be useful for primary researchers as well as the evidence synthesis and health decision-making communities, and ultimately contribute to a reduction in health inequities.

Update of the WHO global air quality guidelines: Systematic reviews – An introduction

This paper aims to serve as an introduction to the Special Issue in Environment International entitled “Update of the WHO Global Air Quality Guidelines: Systematic Reviews”. The article has two main objectives. One is to provide the context to this Special Issue, related to (a) policy context, overall exposure to air pollution, and burden of disease attributable to air pollution, and the other is to describe (b) the WHO guideline development process, with special emphasis on the systematic reviews. In particular, this paper presents the systematic reviews and other supporting evidence that was used and discussed during the process and summarizes important methodological information about the approaches taken to conduct the systematic reviews. These approaches include the definition of population, exposure, comparator, outcomes and study design (PECOS) questions, the assessment of the risk of bias in individual studies and the assessment of the overall certainty of the evidence. In summary, the new WHO global air quality guidelines are informed by the best available scientific evidence covering a vast number of research papers published until September 2018, and appraised by experts and stakeholders in the field of air quality. However, research gaps remain and, therefore, further research is warranted.

Same-day test and treat for infants with HIV infection: finally within reach.

Same-day test and treat for infants with HIV infection: finally within reach.

Integrating planetary health into clinical guidelines to sustainably transform health care

Integrating planetary health into clinical guidelines to sustainably transform health care

Future directions for HIV service delivery research: Research gaps identified through WHO guideline development.

Nathan Ford and co-authors discuss the systematic identification of research gaps in improving HIV service delivery.

Sexual and reproductive health self-care interventions in the Eastern Mediterranean Region: findings from a cross-sectional values and preferences survey to inform WHO normative guidance on self-care interventions

BackgroundSelf-care strategies for sexual and reproductive health (SRH) include practices, tools, and strategies for people to manage their health. Access to SRH services has increased in the Eastern Mediterranean Region (EMR) in the past decade. The objective of this manuscript is to provide a preliminary assessment of self-care SRH interventions focusing on access, knowledge, perceived challenges, and recommendations for the future. We aim to contribute to the evidence base on knowledge and uptake of self-care SRH strategies in the EMR.MethodsWe conducted an online cross-sectional Global Values and Preferences Survey (GVPS) to inform WHO guideline development on self-care interventions for SRH. Recruitment was web-based and included hosting the survey on the WHO Department of Reproductive Health and Research website, and sharing the survey link to diverse SRH websites. Analyses included the subsample of respondents living in EMR countries. We first conducted descriptive statistics of sociodemographic and self-care intervention responses. We then conducted bivariate analyses to examine statistically significant differences in knowledge for each intervention between EMR and non-EMR regions. We extracted open-text responses and applied thematic analysis techniques.ResultsThere were 53 respondents from the EMR spanning 14 countries, including16 health care providers (HCP) and 37 laypersons. Qualitative responses (n = 16) suggest that (a) perceived benefits of self-care SRH strategies include enhanced SRH access, knowledge, and improved SRH outcomes; (b) perceived concerns include misuse and safety; (c) linkage to care following self-care SRH interventions can consider mobile phone apps, hotlines, health care liaisons, and community outreach; (d) HCP want additional training on strengthening therapeutic alliances with patients and practical information on interventions; and (e) future research can focus on reproductive health, condom use, service barriers, and implementation. EMR respondents reported lower knowledge levels than non-EMR respondents on the following strategies: diaphragm/cervical cap, contraceptive patch, web-based SRH information, post-exposure prophylaxis, re-exposure prophylaxis, and HIV treatment.ConclusionsKnowledge of self-care SRH strategies varies by intervention type in the EMR. Future research with larger and more representative samples can inform regional self-care SRH implementation. Knowledge dissemination, stigma reduction, accessibility, and training of health care professionals are key domains for advancing access to self-care SRH strategies in the EMR.

The Development of WHO Guidelines for Burns Care in Mass Casualty Incidents: WHO Emergency Medical Teams Technical Working Group on Burns

The Development of WHO Guidelines for Burns Care in Mass Casualty Incidents: WHO Emergency Medical Teams Technical Working Group on Burns

Dexamethasone and remdesivir: finding method in the COVID-19 madness

Dexamethasone and remdesivir: finding method in the COVID-19 madness

Identifying research questions for HIV, tuberculosis, tuberculosis-HIV, malaria, and neglected tropical diseases through the World Health Organization guideline development process: a retrospective analysis, 2008–2018

ObjectivesWorld Health Organization (WHO) guidelines for health programmes and healthcare delivery are the foundation of its technical leadership in public health and essential to decision-making globally. A key function of guideline development is to identify areas in which further evidence is needed because filling these gaps will lead to future improvements in population health. The objective of this study was to examine the knowledge gaps and research questions for addressing those gaps generated through the WHO guideline development process, with the goal of informing future strategies for improving and strengthening the guideline development process. Study designWe did a systematic, retrospective analysis of research questions identified in the published guidelines. MethodsWe analyzed guidelines published between January 1, 2008, and December 31, 2018, by the Communicable Diseases Cluster in five disease areas: tuberculosis (TB), HIV, malaria, TB-HIV, and neglected tropical diseases (NTDs). Research questions were extracted independently by two researchers. We analyzed the distribution of research questions by disease and by topic category and did a qualitative assessment of optimum practice for research question generation during the guideline development process. ResultsA total of 48 guidelines were included: 26 on HIV, 1 on malaria, 11 on TB, 5 on TB/HIV, and 5 on NTDs. Overall, 36 (75%) guidelines encompassed a total of 360 explicit research questions; the remainder did not contain specific research questions. The number of research questions that focused on TB was 49, TB/HIV was 38, HIV was 250, and NTDs was 23. The number of research questions that focused on diagnosis was 43 (11.9%) of 360, prevention was 62 (17.2%), treatment was 103 (28.6%), good practice was 12 (3.3%), service delivery was 86 (23.8%), and other areas was 54 (15%). Research questions were often not formulated in a specific or actionable way and were hard to identify in the guideline. Examples of good practice identified by the review team involved the generation of specific and narrowly defined research questions, with accompanying recommendations for appropriate study design. ConclusionsThe WHO must strengthen its approach to identifying and presenting research questions during the guideline development process. Ensuring access to research questions is a key next step in adding value to the guideline development process.

WHO Hemoglobin Thresholds to Define Anemia in Clinical Medicine and Public Health: A Scoping Exercise

Abstract Objectives WHO is reviewing the use and interpretation of hemoglobin thresholds for assessing iron status in individuals and populations following established evidence-informed guideline development procedures to culminate in updated guidelines for clinical and public health use. Methods To define priorities and identify key questions a scoping exercise was developed via a two-stage international consultation based on the Child Health and Nutrition Research Initiative method. The first survey allowed respondents to suggest priorities, and the second asked respondents to rank the key questions with established criteria. A transparent approach was used to identify more than 4000 international experts in anemia research based on publication records and ensuring representatives from all WHO regions and low income and middle-income countries. Results The first survey received 123 respondents from 48 countries across all six WHO regions. The 553 proposed questions spanned many themes and were consolidated to a shortlist of 48 questions spanning six subtopics, including physiology of anemia, hemoglobin thresholds for different population groups, definition of anemia across clinical and environmental contexts, approach to development of anemia thresholds, laboratory and diagnostic considerations, and implementation of WHO's hemoglobin threshold guidelines. The second survey received 195 respondents from 64 countries across all six WHO regions. Questions covered diverse themes, including variation in thresholds between individuals of different sex and age, categorisation of anaemia severity and the burden of anaemia, optimal clinical and field laboratory measurements of haemoglobin, and antenatal and infant haemoglobin concentrations associated with adverse developmental outcomes. Conclusions Based on the normative needs identified in this scoping exercise the available evidence will be summarized and presented to a WHO guideline development group after input from an expert panel. This rigorous, inclusive, and transparent approach should enable international harmonization of hemoglobin thresholds used to define anemia in both clinical and public health practice. Funding Sources The World Health Organization The United States Agency for International Development (USAID), USA Centers for Disease Control and Prevention (CDC), USA.

Synthesising quantitative evidence in systematic reviews of complex health interventions

Public health and health service interventions are typically complex: they are multifaceted, with impacts at multiple levels and on multiple stakeholders. Systematic reviews evaluating the effects of complex health interventions...

Identifying priorities for HIV-associated tuberculosis research through the WHO guidelines process.

Guidelines developed by the WHO aim to provide recommendations to support best practice in health delivery, with a focus on low-income and middle-income countries. As part of the guideline development process, critical knowledge gaps are identified and one of the core functions of WHO guidelines is to set forth priorities for future research. A review of research priorities identified through the WHO guideline development has recently been promoted as one approach to building an overarching priority research agenda in a given area. This paper outlines priorities for HIV-associated TB research identified in WHO HIV and TB guidelines published since 2015. Nine guidelines were reviewed and 29 priority research questions were identified. Research priorities were identified for prevention of HIV-associated TB (11 questions), screening of latent and active TB in people living with HIV (six questions), treatment of drug sensitive (four questions), and drug-resistant (two questions) TB, and treatment of HIV in people coinfected with TB (three questions). Multiple approaches to defining priority research questions for health research exist. Research priorities that arise from the WHO guideline development process are limited to those areas for which guidelines are developed. One strength of this approach is that it takes as a starting point a desire to make actionable recommendations for policy makers. WHO is working to further refine the formulation of research questions within the guideline development process.

Non-clinical interventions for reducing unnecessary caesarean section.

Background Caesarean section rates are steadily increasing globally. The factors contributing to these observed increases are complex. Non-clinical interventions, those applied independent of patient care in a clinical encounter, may have a role in reducing unnecessary caesarean sections. Objectives To evaluate the effectiveness and safety of non-clinical interventions for reducing unnecessary caesarean sections. Search methods We searched the following electronic databases: the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (29 March 2010), the Cochrane Pregnancy and Childbirth Group Specialised Register (29 March 2010), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 2); MEDLINE (1950 to March 2010); EMBASE (1947 to March 2010) and CINAHL (1982 to March 2010). Selection criteria We included randomised controlled trials (RCTs), quasi-experimental studies, controlled clinical trials (CCTs), controlled before and after studies (CBAs) with at least two intervention and control sites, and interrupted time series analyses (ITS) where the intervention time was clearly defined and there were at least three data points before and three after the intervention. Studies evaluated non-clinical interventions to reduce unnecessary caesarean section rates. Participants included pregnant women and their families, healthcare providers who work with expectant mothers, communities and advocacy groups. Data collection and analysis Three review authors independently assessed the quality and abstracted data of all eligible studies using a standardised data extraction form, modified from the Cochrane EPOC checklists. We contacted study authors for additional information. Main results We included 16 studies in this review. Six studies specifically targeted pregnant women. Two RCTs were shown to be effective in reducing caesarean section rates: a nurse-led relaxation training programme for women with a fear or anxiety of childbirth and birth preparation sessions. However, both RCTs were small in size and targeted younger mothers with their first pregnancies. There is insufficient evidence that prenatal education and support programmes, computer patient decision-aids, decision-aid booklets and intensive group therapy are effective. Ten studies targeted health professionals. Three of these studies were effective in reducing caesarean section rates. A cluster-RCT of guideline implementation with mandatory second opinion resulted in a small, statistically significant reduction in total caesarean section rates (adjusted risk difference (RD) -1.9; 95% confidence interval (CI) -3.8 to -0.1); this reduction was predominately in intrapartum sections. An ITS study of mandatory second opinion and peer review feedback at department meetings found statistically significant results at 48 months for reducing repeat caesarean section rates (change in level was -6.4%; 95% CI -9.7% to -3.1% and change in slope -1.14%; 95% CI -1.9% to -0.3%) but not for total caesarean section rates. A cluster-RCT of guideline implementation with support from local opinion leaders increased the proportion of women with a previous caesarean section being offered a trial of labour (absolute difference 16.8%) and the number who had a vaginal birth (VBAC rates) (absolute difference 13.5%). The P values are, however, not reported due to unit of analysis errors. There was insufficient evidence that audit and feedback, training of public health nurses, insurance reform, external peer review and legislative changes are effective. Authors' conclusions Implementation of guidelines with mandatory second opinion can lead to a small reduction in caesarean section rates, predominately in intrapartum sections. Peer review, including pre-caesarean consultation, mandatory secondary opinion and postcaesarean surveillance can lead to a reduction in repeat caesarean section rates. Guidelines disseminated with endorsement and support from local opinion leaders may increase the proportion of women with previous caesarean sections being offered a trial of labour in certain settings. Nurse-led relaxation classes and birth preparation classes may reduce caesarean section rates in low-risk pregnancies.

Process of Development of WHO Guidelines

A WHO guideline is any document containing recommendations about health interventions, whether these are clinical, public health or policy recommendations. A recommendation provides information about what policy-makers, health-care providers or patients should do. It implies a choice between different interventions that have an impact on health and that have implications for the use of resources. The purpose of WHO guidelines is to improve the health and well-being of individuals and populations

Tackling antimicrobial resistance in food-producing animals

Tackling antimicrobial resistance in food-producing animals

Restricting the use of antibiotics in food-producing animals and its associations with antibiotic resistance in food-producing animals and human beings: a systematic review and meta-analysis

SummaryBackgroundAntibiotic use in human medicine, veterinary medicine, and agriculture has been linked to the rise of antibiotic resistance globally. We did a systematic review and meta-analysis to summarise the effect that interventions to reduce antibiotic use in food-producing animals have on the presence of antibiotic-resistant bacteria in animals and in humans.MethodsOn July 14, 2016, we searched electronic databases (Agricola, AGRIS, BIOSIS Previews, CAB s, MEDLINE, Embase, Global Index Medicus, ProQuest Dissertations, Science Citation Index) and the grey literature. The search was updated on Jan 27, 2017. Inclusion criteria were original studies that reported on interventions to reduce antibiotic use in food-producing animals and compared presence of antibiotic-resistant bacteria between intervention and comparator groups in animals or in human beings. We extracted data from included studies and did meta-analyses using random effects models. The main outcome assessed was the risk difference in the proportion of antibiotic-resistant bacteria.FindingsA total of 181 studies met inclusion criteria. Of these, 179 (99%) described antibiotic resistance outcomes in animals, and 81 (45%) of these studies were included in the meta-analysis. 21 studies described antibiotic resistance outcomes in humans, and 13 (62%) of these studies were included in the meta-analysis. The pooled absolute risk reduction of the prevalence of antibiotic resistance in animals with interventions that restricted antibiotic use commonly ranged between 10 and 15% (total range 0–39), depending on the antibiotic class, sample type, and bacteria under assessment. Similarly, in the human studies, the pooled prevalence of antibiotic resistance reported was 24% lower in the intervention groups compared with control groups, with a stronger association seen for humans with direct contact with food-producing animals.InterpretationInterventions that restrict antibiotic use in food-producing animals are associated with a reduction in the presence of antibiotic-resistant bacteria in these animals. A smaller body of evidence suggests a similar association in the studied human populations, particularly those with direct exposure to food-producing animals. The implications for the general human population are less clear, given the low number of studies. The overall findings have directly informed the development of WHO guidelines on the use of antibiotics in food-producing animals.FundingWorld Health Organization.

The First Meeting of the WHO Guideline Development Group for the Revision of the WHO 1999 Guidelines for Iodine Thyroid Blocking.

The meeting held in May 2014 in Würzburg, Germany, discussed the scope of the revision of the 1999 WHO guidelines for iodine thyroid blocking (ITB) by following the WHO handbook for guideline development. This article describes the process and methods of developing the revised, evidence-based WHO guidelines for ITB following nuclear and radiological accidents, the results of the kick-off meeting as well as further steps taken to complete the revision.