In genomics, perceived and personal utility have been proposed as constructs of value that include the subjective meanings and uses of genetic testing. Precisely what constitutes these constructs of utility and how they vary by stakeholder perspective remains unresolved. To advance methods for measuring the value of genetic testing in child health, we conducted a scoping review of the literature to characterize utility from the perspective of parents/caregivers. Peer reviewed literature that included empiric findings from parents/caregivers who received genetic test results for an index child and was written in English from 2016–2020 was included. Identified concepts of utility were coded according to Kohler’s construct of personal utility. Of 2142 abstracts screened, 33 met inclusion criteria. Studies reflected a range of genetic test types; the majority of testing was pursued for children with developmental or neurodevelopmental concerns. Coding resulted in 15 elements of utility that mapped to Kohler’s four domains of personal utility  and one additional medical management domain. An adapted construct of utility for parents/caregivers may enable specific and standardized strategies for researchers to use to generate evidence of the post-test value of genetic testing. In turn, this will contribute to emerging methods for health technology assessment and policy decision making for genomics in child health. Anticipated benefits of existing and emerging genome diagnostics include definitive diagnosis and risk identification, enabling early intervention and a precision medicine approach to management that can potentially reduce morbidity and improve quality of life ,2. In adDefining and measuring the notion of benefit in the context of genome diagnostics requires the inclusion of metrics that extend beyond laboratory-based performance and incorporate patients’ perspectives ,7,8,9. TMost recently, Kohler et al.  conducteparental/caregiver utility associated with receiving genetic test results.What constitutes patient-oriented utility is complex and multi-dimensional. Arguably, how the construct is defined also depends on the clinical context and patient/respondent population to whom it is offered ,13. In tThis study complies with the “Preferred Reporting Items for Systematic reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR)” guidelines . Papers n = 138) was conducted by two independent reviewers and followed the same inclusion criteria as above. Any differences in assessment of eligibility between the two reviewers were resolved by discussion and a third reviewer was consulted where necessary. The percent agreement between raters with regard to eligibility was determined.Search results from all four databases were imported into an EndNote (X7) library. Duplicate articles were identified and removed using the Bramer method . ConfereTwo authors extracted the following characteristics from each study: PubMed ID, authors, publication year, study title, country of data collection, respondent type, International Classification of Diseases (ICD-11) disease category  for indeOrganizing and synthesizing extracted outcomes and themes followed a multi-step process. First, outcomes and themes were extracted from the final eligible pool of studies. These outcomes and themes were assigned to domains of personal utility, as described by Kohler  , whole exome sequencing , multi-gene panel , and karyotype . The 33 studies included a total of 3606 primary sample participants and 93 secondary sample participants. Respondent type included: parents/caregivers of minor patient (73%), prospective parents , caregivers of adult patient (8%), and other (3%). The most common clinical conditions under study were developmental anomalies (61%), behavioural or neurodevelopmental disorders (39%), prenatal or pre-implementation genetic testing (27%), and diseases of the nervous system (21%) (The majority (55%) of the studies were conducted in the United States. The remaining studies were conducted in Europe (18%), Australia (15%), Canada (9%), and New Zealand (3%). Of the 33, 20 (61%) were qualitative, nine (27%) were quantitative, and four (12%) were mixed methods. In decreasing order, the most common genetic tests on which study participants reflected were chromosome microarray (em (21%) . The comWith respect to quality, quantitative studies reviewed scored the highest, with an average score of 82.9%, compared to qualitative (81.0%) and mixed methods (80.8%) studies. Almost all qualitative studies were given a perfect rating for study design; the reflexivity item  scored the lowest. All quantitative studies had clear study objectives and design; the lowest scoring item related to controlling for confounding. Two of the four mixed methods studies did not address inconsistencies between qualitative and quantitative findings well. No studies were excluded based on their quality appraisal score The outcomes and themes identified in 33 studies that were specific to the receipt of results from genetic testing from parents’/caregivers’ perspectives aligned with Kohler’s four domains and 14 elements of utility. The outcomes and themes characterized as element concepts associated with each element of each domain are displayed in While Kohler’s four domains of personal utility were identified in the studies reviewed, our findings extend the definitions of some of Kohler’s domain elements to include aspects of utility that were germane to parents/caregivers. While these aspects may be implicit in the definitions of the existing elements in Kohler’s framework, our review prompted us to explicitly name these aspects as important parts of the construct of utility when thinking about it from parent/caregiver perspectives.In the affective domain, where outcomes of genetic testing refer to an individual’s emotional state,  the studIn the behavioural domain, where outcomes represent practical uses of genomic information, studies reviewed suggest the addition of concepts to each of the three existing elements of utility. Regarding ‘ability for future planning’, studies reviewed include impact on career, finances and lifestyle for parents. Regarding ‘reproductive autonomy’, studies reviewed extend this element to include informing planning of future pregnancies not only for the index case but also for other family members. Regarding ‘communication’, while communication with family members is inclusive of all members, studies reviewed describe communication with the child as a distinct concept. Finally, in the social domain, where outcomes of genetic testing involve changes in social support or status on individual, familial, and societal levels, the only additional concept identified in the studies reviewed related to the ‘concern over discrimination’ element. Similar to Kohler’s systematic review , studiesAdapting the construct of personal utility derived from Kohler’s systematic review  and DelpOur findings map neatly onto four domains and 14 elements of personal utility identified by Kohler ,17. WithA significant difference between Kohler’s characterization of personal utility and that defined by the studies reviewed herein is the addition of the medical management domain. In related literature about genetic test evaluation, medical management implications are more often described as a component of the clinical utility construct. While many have argued that medical management implications constitute health-related outcomes and fit within the construct of clinical utility, others consider medical management as an example of an indirect or intermediate non-health related outcome, since a medical management decision, unto itself, does not comprise a health outcome ,67,68,69Several patient-reported outcome measures have been validated for use in genetics, many of which include elements of the construct of personal utility defined by Kohler et al. ,17 as weWhile findings from this work provide a more detailed characterization of the construct of utility from parents’/caregivers’ perspectives, we acknowledge specific limitations. First, study inclusion criteria were challenging to establish and apply given the absence of an agreed upon definition of the patient-oriented utility in the field of genomics to date. In part, however, the purpose of the review was to contribute to efforts to define this construct for parents/caregivers. Second, we excluded non-English studies, potentially leading to our omission of concepts relevant to utility for parents/caregivers. We also excluded discrete choice experiments, cost effectiveness studies, and outcome measure development or validation studies. While discrete choice experiments provide preference data and use choice sets that are typically derived from the lived experience of the target population, the data generated are technically hypothetical. Cost effectiveness and measurement development/validation studies may reflect patient-oriented utility but the intent of these studies is distinct from our focus on further characterizing the construct of utility from parents’/caregivers’ perspectives. Third, while we view our use of Kohler’s personal utility construct as a strength and as a reference point from which to tailor the construct of utility to parents/caregivers, it may have acted to constrain our thinking about the elements and concepts embedded in this construct, and may have limited the scope of the literature reviewed given that 2016 was our starting point. The exclusion of studies published in 2021 is a further limitation. Finally, we included studies of variable quality, potentially representing a reporting bias.Patient-oriented utility has emerged in the genomics literature as a critical measure of value. While it is generally agreed that personal and perceived utility reflect on the subjective meaning an individual ascribes to genetic testing, consensus has not emerged on the precise definition of these and related constructs. For example, whether or not elements of these constructs are distinct from or overlapping with elements of clinical utility or with elements of psychosocial well-being remains contested ,16,63. IThe field of genomics presents a multitude of challenges for assessing the value of emerging technologies through formal health technology assessment ,67,68,69


To identify and assess the use of technologies, including mobile health technology, internet of things (IoT) devices and artificial intelligence (AI) in hypertension healthcare in sub-Saharan Africa (SSA).Systematic review.Medline, Embase, Scopus and Web of Science.Studies addressing outcomes related to the use of technologies for hypertension healthcare  in SSA.Databases were searched from inception to 2 August 2021. Screening, data extraction and risk of bias assessment were done in duplicate. Data were extracted on study design, setting, technology(s) employed and outcomes. Blood pressure (BP) reduction due to intervention was extracted from a subset of randomised controlled trials. Methodological quality was assessed using the Mixed Methods Appraisal Tool.1717 hits were retrieved, 1206 deduplicated studies were screened and 67 full texts were assessed for eligibility. 22 studies were included, all reported on clinical investigations. Two studies were observational, and 20 evaluated technology-based interventions. Outcomes included BP reduction/control, treatment adherence, retention in care, awareness/knowledge of hypertension and completeness of medical records. All studies used mobile technology, three linked with IoT devices. Short Message Service (SMS) was the most popular method of targeting patients (n=6). Moderate BP reduction was achieved in three randomised controlled trials. Patients and healthcare providers reported positive perceptions towards the technologies. No studies using AI were identified.There are a range of successful applications of key enabling technologies in SSA, including BP reduction, increased health knowledge and treatment adherence following targeted mobile technology interventions. There is evidence to support use of mobile technology for hypertension management in SSA. However, current application of technologies is highly heterogeneous and key barriers exist, limiting efficacy and uptake in SSA. More research is needed, addressing objective measures such as BP reduction in robust randomised studies.CRD42020223043. This is the first systematic review for use of technologies for hypertension healthcare in sub-Saharan Africa, providing a comprehensive review of the state of the art.Heterogeneity of included studies was too high for meta-analysis; therefore, results are reported narratively.Grey literature was not searched.The search was limited to studies published in English language.et al reports that of those with hypertension in SSA, only 27% were aware of their condition, 18% were receiving treatment and 7% had controlled BP.5Cardiovascular disease (CVD) remains the most common cause of death due to non-communicable disease (NCD) worldwide, with 78% of deaths occurring in low and middle-income countries (LMICs).et al describe uses of AI in resource-poor settings, including expert systems assisting or compensating for a lack of personnel, health monitoring using natural language processing and signal processing for diagnostics.22Low numbers of trained healthcare providers combined with a lack of evidence-based guidance and a high cost in accessing healthcare services for patients in SSA are major challenges.Successful application of the aforementioned technologies for tackling hypertension relies on a strong evidence base in design and implementation. In this way, this work seeks to systematically review the literature regarding the application of mobile phone technologies, AI and the IoT as KETs for healthcare provision for hypertension in SSA. The primary objective is to determine how and which KETs have been used, secondary concerns include study design, setting, quality and findings of outcomes relating to hypertension.The systematic review of KETs for healthcare provision for hypertension in SSA followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines.Search terms covered hypertension , Artificial Intelligence , mobile phones , internet of things , point of healthcare cascade  and countries of SSA . A reference search was conducted on any relevant review articles retrieved. For included studies, data were abstracted to a shared Microsoft Excel document, covering study design, study setting and population , details of KET used, study outcomes, controls/comparators (where applicable), target user (where applicable) and indications of acceptability to user (if provided). For randomised controlled trials, we sought to extract mean baseline and end point BP measurements (in mm Hg), with SD, for the intervention and control groups. If SD was not reported, it was calculated using the CI, as described in the Cochrane Handbook for Systematic Reviews of Interventions.Methodological quality was assessed independently by two review authors (KS and BO) using the 2018 Mixed Methods Appraisal ToolThe funder of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report.Patients and the public were not involved in this research.Searching MEDLINE, Scopus, Embase and Web of Science yielded 1717 titles. After duplicate removal, 1206 titles/abstracts were screened, with 1139 excluded. Of the remaining 67 full texts, 18 studies were found to meet the inclusion criteria . A furthStudy design, participants, location and aims were highly heterogenous . The diset al did not report sufficient information to judge four out of five criteriaet al failed to meet any criteria.49Quality was highest for qualitative and quantitative descriptive methods and relatively low for randomised or non-randomised studies . Eleven All studies employed adult populations, with varying age requirements . Five st31 41 47et al evaluated the general use and perceptions of medical practitioners and patients towards technology, in particular, mobile technology, in dealing with hypertension and HIV. IoT devices employed were automatic BP monitors and their use was also facilitated by mobile phones.SMS messages were mostly targeted to patients, for health knowledge improvement,28 44et al collected survey data using a tablet computer to collect and relay patient information to a central database.et al described use of rubber stamp templates containing checklists of clinical practice guidelines; smartphone cameras were used to take images of these templates, which were then manually synched to a cloud-based database, with plans for further automation.Apps were targeted to healthcare providers, most frequently community health workers. Three studies used apps designed to mediate BP reading collection and dissemination of results for risk assessment and follow-up.et alet al observed significant reduction in both systolic and diastolic BP regardless of whether their tablet-based decision support tool was used by nurses or clinical officers but did not have a control group. Heterogeneity in both outcomes investigated and reported prevented quantitative comparison. Results from three randomised controlled trials which reported baseline and endpoint values for systolic BP are presented in et al and Owolabi et al met all quality criteria, however, Vedanthan et alet al, where greater overall improvements (BP improved or BP at target) in participants with stage 3 hypertension was observed.et al also observed a significant reduction in BP for a subset of subjects with baseline BP >140.90 mm Hg but not an overall significant reduction for all participants.41Concerning outcomes relating either to reduction of BP or improved BP control, the majority of experimental studies reported that their interventions resulted in improvements.et al found no statistical change in overall health knowledge, however, medication adherence was significantly higher due to intervention and self-reported behaviour change improvements.et al reported significant improvements in overall knowledge of healthy living and hypertension following exposure to informative SMS messaging.et al reported positive perceptions towards an SMS-based medicine information exchange between patients and pharmacists, patients requested information on adverse medication effects.et al, with a 21% improvement in hypertension documentation scoring.36In terms of health knowledge improvement, in one study, CVD nursers reported that their own hypertension awareness and knowledge increased as well as that of the community, due to the ComHIP project.et al indicated that health providers and policymakers identified major challenges in the use of a cloud-based health records system, which would require heavy reliance on outside resources.47When perceptions towards the proposed technology were gathered, interventions were well received by patientset al’s 2019 narrative literature review of telehealth interventions for hypertension in SSAet al18 50Our systematic review of the literature found broad and diverse applications of KETs for tackling hypertension in SSA. The findings indicated that there is still relatively limited published research, particularly of controlled trials. All studies leveraged mobile phones for purposes of screening for hypertension, improving patient knowledge/treatment adherence or aiding non-physician healthcare workers in providing hypertension care. Other reviews targeted to SSA have focused on assessing either specific technological applications or different NCDs, and all noted a lack of published research.Overall, our identified studies reported success in their outcomes, with overwhelmingly positive responses from participants towards the use of KETs. Consistent with our findings, other reviews comment on overall good acceptance of technologies by health workerset alNo publications using AI were identified in this study. Owoyemi Many studies used KETs to facilitate task redistribution, which is a well-evidenced strategy to improving healthcare provision in areas with low numbers of qualified doctors/specialists, for which the body of evidence relating to hypertension is growing.58A notable finding was that few studies reported statistically significant benefits of KET-based interventions. Authors speculated that small sample sizes,A major limitation of this systematic review was the heterogeneity of the included studies, which did not allow for quantitative synthesis of outcomes/results. Since this study also failed to identify any reports of use of AI, it is possible that extending the search beyond the scientific literature may have found cases where AI was intrinsic as part of manufactured technology already being used for healthcare in SSA. A strength of this study is that it is the first systematic review concerning use of KETs for hypertension healthcare in SSA, and in this way provides a comprehensive overview of the current state of the art and indicates gaps to be addressed in future research.Our study indicates that there is limited research on use of KETs for hypertension in SSA, particularly we did not identify any studies using AI. The study demonstrates that mHealth strategies provided positive impact on BP control, health knowledge and treatment adherence. Furthermore, stakeholder perceptions towards technology for hypertension prevention and management were positive. Therefore, further primary studies should be conducted, with an emphasis on objective measures such as BP reduction or BP control. It remains to be seen whether AI may also prove beneficial, such as through development of further diagnostic aids or boosting signals from cheap easily manufactured sensors.


Preconception care is the provision of biomedical, behavioural, and social health interventions provided to women and couples before conception. However, in Ethiopia, little is known and practised to support preconception care. Therefore, this study aimed to assess women’s knowledge and utilisation of preconception care and its associated factors in Ethiopia using systematic review and meta-analysis.2 tests assessed heterogeneity between the studies. A random-effect model was used to forecast the pooled knowledge and utilisation of preconception care.In the current meta-analysis, variables were searched from different electronic database systems, which included PubMed, Google Scholar, EMBASE, HINAR, Scopus, Web of Sciences, and Grey literature. Data were extracted using a standardised data collection measurement tool. The data were analysed by using STATA 14 statistical software. IThirteen full-text studies were included. The pooled prevalence of knowledge and utilisation of preconception care among women in Ethiopia was 30.95% and 16.27% respectivelly. Secondary education , college and above , and antenatal care  were significantly associated with knowledge level whereas; age  and knowledge on preconception care  were positively associated with utilisation of preconception.Women’s level of knowledge and utilisation of preconception care was significantly low. Educational status and antenatal care follow-up were factors shown to affect knowledge of preconception care. Age and having a sound knowledge of preconception care indicated a significant association towards utilisation of preconception care. Thus, integrating preconception care strategies and policies that can address all the components of preconception care services with other maternal and child health services will be essential when designing effective implementation strategies to improve preconception care uptake. Besides this, advocating for better education for women, awareness creation, and increasing antenatal care services are essential.Prospero registration: CRD42020218062The online version contains supplementary material available at 10.1186/s12978-021-01132-9. Preconception care is an intervention provided to women and couples of a reproductive age irrespective of pregnancy status or desire, before conception, to improve women, newborns, and children's health outcomes.This systematic review and meta-analysis used the following electronic database; PubMed, Google Scholar, EMBASE, HINAR, Scopus, Web of Sciences to search the primary articles. A total of 13 primary studies assessing knowledge and utilisation of preconception care (PCC) were included based on study eligibility criteria. Out of these eleven primary articles were focusing on knowledge of PCC, and six reported on utilisation of PCC.The current systematic review and meta-analysis found that the pooled prevalence of PCC knowledge and utilisation amongst Ethiopian women was 30.95 and 16.27%, respectively. Women’s secondary education status, college and above, and history of antenatal care (ANC) follow-up was significantly associated with PCC knowledge. Whereas, women’s age and an adequate level of knowledge on PCC were found to be factors significantly associated with utilisation of PCC.This systematic review and meta-analysis report that PCC knowledge and its utilisation amongst Ethiopian women were significantly low. Therefore, establishing, PCC strategies and policies that can address all the components of preconception care services with other maternal and child health services will be essential when designing effective implementation strategies to improve knowledge and uptake of preconception care.Preconception care (PCC) comprises biomedical, behavioural, and social health interventions provided to women and couples before the occurrence of conception provision of information around health promotion, disease prevention, and information on treating existing diseases may assist with improving patient’s health status, and reducing behavioural and environmental factors that may contribute to poor maternal and child health outcomes .PCC is essential for improving pregnancy and birth outcomes and the future health outcome of women, newborns, children, and the patient’s family , 3. PCC The Sustainable Development Goal (SDG) number three aims to reduce the global ratio of maternal mortality to less than 70 per 100,000 live births and newborn death to 12 per 1000 live births by the year 2030 . PCC hasEven though governments, policy planners, and stakeholders are given a priority agenda for maternal and child health care services, the reduction of maternal and neonatal morbidity and mortality is not closely the target goal . PreconcBased on the World Health Organization (WHO), a recent report indicated that worldwide four out of ten women had unplanned pregnancies. As a result, 40% of pregnancies lack the necessary health interventions required before the occurrence of conception . To enhaMaternal nutritional status in the preconception period has an essential role in the future life of offspring and lack of adequate nutrition in this critical period creates a transgenerational cycle of poor health outcomes. The balance of macronutrients in the maternal diet influences both birthweight and placental weight. The imbalance of protein and carbohydrate intake before and during pregnancy has been associated with reduced birth weight, gestational age, impaired glucose tolerance, and increased blood pressure in the offspring.Although PCC is a crucial component of maternal and child health care services, it is not offered in many low-income countries such as Ethiopia. Hence, it has not been widely adopted because the aims and objectives are not widely understood and embraced , 14.Previous studies conducted across Ethiopia, estimate a women’s knowledge and utilisation of PCC –27. ThesPCC is one of the critical elements for reducing child and maternal mortality and achieving other MDG goals. Women’s age, educational status, history of family planning (FP) use, previous adverse birth outcome, and chronic medical diseases have been highly correlated with levels of knowledge and utilisation of PCC in Ethiopia.The rationale for variation in the level of knowledge and utilisation of PCC among Ethiopian women to date has not been reported. Hence, it is essential to provide evidence of the level of knowledge and utilisation and other PCC factors among women to identify existing gaps and provide recommendations around suitable strategies to increase the availability, accessibility, and utilisation of PCC in Ethiopia. This study reports on evidence of knowledge and utilisation and associated factors among women in Ethiopia.This study uses a systemic review and meta-analysis approach of relevant articles on the prevalence rate of knowledge and PCC utilisation among women in Ethiopia. This systematic review was registered with the prospective international register of systematic reviews  and was conducted following the guidelines for the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA).Study participants included those women of reproductive age who resided in Ethiopia. Participants comprised women from diverse socioeconomic backgrounds, all ethnic groups, and those who spoke different dialects. This study included all published and unpublished observational  studies on knowledge and utilisation of PCC and factors affecting knowledge of PCC and service utilisation amongst women of reproductive age in Ethiopia. This review included studies done until October 20, 2020, and was written in the English language.Studies were excluded: (1) if the study was not published in English and we were unable to access a copy translated in the English language; (2) qualitative papers that did not include reproductive data for women of childbearing age to be included in the analysis; (3) cases studies, as most studies lacked robust quality reproductive data to include in the analysis and to reduce the potential for identifying a patient in the review; (4) secondary works .A literature search was performed using PubMed, Google Scholar, EMBASE, HINAR, Scopus, Web of Sciences, and Grey literature. Manuscripts that report on the prevalence of knowledge and utilisation of preconception care and associated factors affecting knowledge and utilisation of PCC in Ethiopia. We also performed hand searched for cross-references to distinguish additional relevant articles.The PECO  search format has used this review to search for pertinent studies.Reproductive age group women.Determinants of knowledge and utilisation of PCC  reproductive related factors , health care, and disease-related factor .The reported reference groups for each determinant factor in each respective study such as, knowledge of PCC among women who have attended secondary education versus those who had no formal education, and utilisation of PCC among women who had adverse pregnancy outcome versus their counterparts.Level of knowledge and utilisation of PCC among women.Studies were searched by three authors  using comprehensive searching strategies. Initially, articles were searched by examining the full titles  and then keywords . Besides this, studies were also searched from all included studies reference lists to find additional studies not included in our search strategies. Furthermore, to find relevant unpublished studies, Ethiopian universities’ digital libraries were searched . The searching periods were from September 20, 2020, to October 20, 2020  screened and assessed articles independently. The studies full text was further assessed based on aims, methodology, participants/population, and critical findings (knowledge and utilisation of PCC and factors affecting knowledge and utilisation of PCC). Any disagreements were resolved through discussion and consensus-based on established criteria or through a fourth investigator (MD) if consensus could not be reached.Each study's scientific strength and quality incorporated original cross-sectional study was assessed by using the Newcastle–Ottawa Scale quality assessment tool adapted for cross-sectional study quality assessments . The tooAfter selecting the suitable studies selecting suitable studies, all necessary data were abstracted by three authors  independently using a pre-tested standardised data extraction form. This form includes primary author, year of publication, study setting, sample size, study design, response rate, the prevalence of knowledge and utilisation of PCC, and specific factors associated with knowledge and utilisation of PCC. For the second objective (factors), the information extraction format was prepared for each specific factor, i.e., women’s age, educational status, ANC visit utilisation of fertility preservation (FP), adverse pregnancy outcome, and chronic medical problem. In this study, variables were selected if two or more studies reported them as a significant factor. During discrepancy in data abstraction between the investigators, it was resolved through consensus and by a fourth investigator.Level of knowledge and utilisation of PCC were the primary outcomes explored in this systematic review and meta-analysis. The second objective of the review was to determine the factors affecting the level of knowledge and utilisation of PCC.2) statistics with its corresponding p-value using the random-effect model.Rigorous searches  have been used to minimise the risk of bias. The authors' cooperative work was also critical in reducing bias, selecting articles based on the clear objectives and eligibility criteria, deciding the studies quality, and extracting and compiling the data. We examine publication bias with a visual inspection of the funnel plot graph qualitatively. Besides, Egger’s correlation tests at a 5% significant level were conducted to assess the presence of publication bias , 31. Fur2 statistics at a p-value of ≤ 0.0542], Sri The current meta-analysis also revealed that knowledge scores increase with the frequency of ANC visits. Women who had at least one or/and more ANC visits presented with good knowledge scores on PCC. Our findings were similar to those conducted in Sudan , and NigIn this meta-analysis women whose age was greater than 30 years of age were 2.4 times more likely to utilise PCC than younger women. Similarly, studies conducted in Brazil , OkhlamaLastly, our study reports that women’s knowledge was positively associated with PCC utilisation.Those women who had good knowledge of PCC services were nearly four times more likely to utilise PCC services than those with inadequate knowledge. Findings from China , Saudi AMoreover, comprehensive knowledge of PCC may provide better insight and awareness, which can positively impact the overall healthy life of women, newborns, and the wider-community.Despite its significant importance, this systematic review and meta-analysis have limitations. First of all, all of the studies included in this review were cross-sectional; hence, the outcome variable might be influenced by other confounding variables such as misconceptions, knowledge, accessibility of the care. Second, some of the studies included in this systematic review and meta-analysis had small sample sizes, which may affect the actual magnitude of knowledge and utilisation at the country level. Third, all Ethiopia regions were not represented in this systematic review and meta-analysis due to a limited number of studies in the country (only four regions and one administrative town were represented in this study).Our findings presented in this study showed that women’s level of knowledge and utilisation of PCC was significantly low. Educational status and ANC follow-up were factors that affect knowledge of PCC and older age and having sound knowledge of PCC had shown significant association towards utilisation of PCC. Thus, integrating PCC strategies and policies that can address all the components of preconception care services with other maternal and child health services will be essential when designing effective implementation strategies to improve preconception care uptake. Besides this, advocating for better education for women, awareness creation, and increasing antenatal care services are essential. Furthermore, we recommend synchronised and cooperated work between the clinical and research teams to change knowledge and utilisation of PCC services.Additional file 1. A searching strategy for knowledge and utilisation of PCC and associated factors among women in Ethiopia.Additional file 2. Newcastle–Ottawa Quality Assessment Scale for cross-sectional studies to assess knowledge and utilisation of PCC among women in Ethiopia.


The ability to predict human phenotypes and identify biomarkers of disease from metagenomic data is crucial for the development of therapeutics for microbiome-associated diseases. However, metagenomic data is commonly affected by technical variables unrelated to the phenotype of interest, such as sequencing protocol, which can make it difficult to predict phenotype and find biomarkers of disease. Supervised methods to correct for background noise, originally designed for gene expression and RNA-seq data, are commonly applied to microbiome data but may be limited because they cannot account for unmeasured sources of variation. Unsupervised approaches address this issue, but current methods are limited because they are ill-equipped to deal with the unique aspects of microbiome data, which is compositional, highly skewed, and sparse. We perform a comparative analysis of the ability of different denoising transformations in combination with supervised correction methods as well as an unsupervised principal component correction approach that is presently used in other domains but has not been applied to microbiome data to date. We find that the unsupervised principal component correction approach has comparable ability in reducing false discovery of biomarkers as the supervised approaches, with the added benefit of not needing to know the sources of variation apriori. However, in prediction tasks, it appears to only improve prediction when technical variables contribute to the majority of variance in the data. As new and larger metagenomic datasets become increasingly available, background noise correction will become essential for generating reproducible microbiome analyses. The human gut microbiome is known to play a major role in health and is associated with many diseases including colorectal cancer, obesity, and diabetes. The prediction of host phenotypes and identification of biomarkers of disease is essential for harnessing the therapeutic potential of the microbiome. However, many metagenomic datasets are affected by technical variables that introduce unwanted variation that can confound the ability to predict phenotypes and identify biomarkers. Currently, supervised methods originally designed for gene expression and RNA-seq data are commonly applied to microbiome data for correction of background noise, but they are limited in that they cannot correct for unmeasured sources of variation. Unsupervised approaches address this issue, but current methods are limited because they are ill-equipped to deal with the unique aspects of microbiome data, which is compositional, highly skewed, and sparse. We perform a comparative analysis of the ability of different denoising transformations in combination with supervised correction methods as well as an unsupervised principal component correction approach and find that all correction approaches reduce false positives for biomarker discovery. In the task of predicting phenotypes, different approaches have varying success where the unsupervised correction can improve prediction when technical variables contribute to the majority of variance in the data. As new and larger metagenomic datasets become increasingly available, background noise correction will become essential for generating reproducible microbiome analyses. The human gut microbiome is associated with a number of host phenotypes including colorectal cancer , obesityet al. .The first 15 PCs in the CRC-16S taxonomic abundance joined datasets are correlated with variables measured in each of the studies, including phenotype, sex, age, race, dataset label, sequencing method, library size and several others in  AGP,  CRC-16S. The size and color of the circles in each cell indicate the magnitude of correlation while black asterisks indicate the significance of the Pearson correlation of the PCs with each of the variables. The color bar at right of each plot represents the range of correlations observed across all datasets. .The first 15 PCs before  and after  the CLR-transformation are correlated with variables measured in each of the studies, including dataset label, library size, DNA extraction kit used, country of origin, age, body mass index (BMI), sex, and colorectal cancer status (CRC). The size and color of the circles in each cell indicate the magnitude of correlation while black asterisks indicate the significance of the Pearson correlation of the PCs with each of the variables. The color bar at right of each plot represents the range of correlations observed across all datasets. .The first 15 PCs from data transformed with the (A) EdgeR log counts per million (LogCPM) transformation and (B) (TIF)Click here for additional data file.S7 FigFor each study in CRC-WGS, an equal number of cases and controls were drawn to determine significant taxa associated with CRC. Then, at proportions of 25%, 50% and 100%, control samples were replaced with controls from a second study. This experiment was repeated after applying (A) transformations, (B) corrections, or (C) a combination of both (including unsupervised methods) to compare the extent to which new false positive associations arise with increasing confounding between CRC and study label.(TIF)Click here for additional data file.S8 FigHeatmap showing AUC or Pearson correlation in a cross-validated prediction model using either uncorrected data or data after applying one of the following covariate correction approaches: DCC, ComBat, limma6, BMC62]62], and (TIF)Click here for additional data file.S1 TableShown is the mean number of likely false positive associations with respect to the original study 1 case and controls before adding control samples from study two, across all pairs of studies within CRC-WGS and across all five-fold replicates of titration at each mixing proportion of 0%, 25%, 50%, 75%, and 100% controls from study two.(DOCX)Click here for additional data file.


Home birth is experienced by people very differently worldwide. These experiences likely differ by the type of stakeholder involved , the experience itself , and by the health system within which home birth occurs . Research evidence of stakeholders’ perspectives of home birth could usefully inform personal and policy decisions about choosing and providing home birth, but the current literature is fragmented and its breadth is not fully understood.We conducted a systematic scoping review to understand how the research literature on stakeholders’ perspectives of home birth is characterized in terms of populations, settings and identified issues, and what potential gaps exist in the research evidence. A range of electronic, web-based and key informant sources of evidence were searched. Located references were assessed, data extracted, and descriptively analyzed using robust methods.Our analysis included 460 full reports. Findings from 210 reports of studies in high-resource countries suggested that research with fathers and same-sex partners, midwives, and vulnerable populations and perspectives of freebirth and transfer to hospital could be synthesized. Gaps in primary research exist with respect to family members, policy makers, and those living in rural and remote locations. A further 250 reports of studies in low- and middle-resource countries suggested evidence for syntheses related to fathers and other family members, policy makers, and other health care providers and examination of issues related to emergency transfer to hospital, rural and remote home birth, and those who birth out of hospital, often at home, despite receiving antenatal care intended to increase healthcare-seeking behavior. Gaps in primary research suggest an examination is needed of perspectives in countries with higher maternal mortality and among first-time mothers and young mothers.Our scoping review identified a considerable body of research evidence on stakeholder perspectives of home birth. These could inform the complex factors influencing personal decisions and health system planning around home birth in both high- and low- and middle-resource countries. Future primary research is warranted on specific stakeholders worldwide and with vulnerable populations in areas of high maternal mortality. Childbirth is an important event for a woman and her family –3. BirthBetween 1 and 16% of childbearing people in high-resource countries (HRCs) choose to give birth at home, where midwifery services are well-integrated into the health system model of care –12. HereWithin this myriad of personal, societal, and health system influences, women decide whether to birth at home, their partners decide whether and how to support them, and practitioners and policy makers plan, deliver, and evaluate home birth services. Evidence from research examining the experiences of key stakeholders, including women, partners, family members, health care practitioners, policy and decision-makers, could usefully inform personal and policy decisions regarding home birth. Different stakeholders’ perspectives can provide an important source of evidence underpinning quality of care in both hospital facilities and planned home births . ListeniA large amount of qualitative research on women’s experiences of home birth exists and may be useful, however, this evidence comes from diverse populations. Several previous systematic reviews have examined the perspectives of women, midwives and nurses. The majority of these focus on women’s views in high-resource countries –39. Of tThe primary research exploring perspectives other than women or practitioners is disparate and may provide conflicting findings in countries where home birth is, and is not, well integrated –49. ThesTo facilitate evidence-informed decision-making among women, their support persons, health care professionals, and those setting clinical and policy standards, there is a need to understand the body of research examining the experiences and perspectives of home birth as voiced by those who are involved in home birth decisions. This involves first understanding the breadth of evidence that has been conducted and the types of participants, settings and contexts in which home birth research has been conducted.By mapping or scoping the breadth of research on people’s perspectives of home birth, our aim is to understand the range of debates on the value and place of home birth in different communities and among different populations. By mapping or scoping the breadth of research on people’s perspectives of home birth, our aim is to understand the range of debates on the value and place of home birth in different communities and among different populations. Collating this research literature will identify the breadth of research on this topic, examining determinants such as ethnicity, socioeconomic status, disability, sexual/gender orientation, migration status, age, geography, and with health system factors which interact with issues of sex or gender and influence birth processes and outcomes , 61. SucHow is the research literature on stakeholder perspectives, opinions, and views of planned home birth characterized in terms of populations, settings, and identified issues?Where are there gaps in the research evidence on stakeholder perspectives of planned home birth?In order to prioritize the populations and topics where home birth research exists and could be synthesized usefully for evidence-informed policy, practice and personal decisions, the research landscape must be understood . A scopiA review protocol was published on the McMaster Midwifery Research Centre’s website in March 2020 .As part of a larger CIHR-funded knowledge planning and dissemination grant (CIHR #162186), we consulted an advisory group comprised of midwifery researchers, obstetric, family practice and midwifery practitioners, and a member of the public with maternity policy expertise. Advisory group members were consulted twice: first to advise on review methods and identify potentially relevant key research and second to consider and interpret emerging findings.Searches were updated from our previous systematic review of home birth , 16 and Were an empirical study ;Concerned women/clients who planned to or did give birth at home;Aimed to elicit views, perspectives, opinions or experiences of any stakeholders ;Were published in English or are translatable; andWere published from 2010 onward.All identified references were screened hierarchically and included in the review if they:We excluded narrative descriptive birth stories that described events or outcomes, but any research including rationales, reasons, motivation, values, perspectives, and decision-making as part of the descriptive were included. As English language is the research team’s primary language, this was the minimum required for adequate eligibility screening. However, studies in other languages were marked for possible future research. To ensure that the included research reflected current professional guidance and stakeholder perspectives on home birth, a date limit of 2010 was used. This reflected either the date since data were collected or when the reference was published. Studies were also excluded that focused solely on hospital birth or alternative birth center settings.Data from included studies were extracted using previously developed modified coding frameworks that were informed by the advisory group , 65. ExtTo establish the breadth of research conducted on home birth, extracted study characteristics were descriptively analyzed and summarized in tabular format. Descriptive frequencies of all study characteristics  were calculated using Excel. Assessing risk of bias or critical appraisal of studies was not undertaken, as this stage is not appropriate for a scoping review where the aims are to understand the nature and breadth of research in an area of inquiry , 67. SimEPPI-Reviewer software was utilized for review processes. The protocol and final report were developed as per PRISMA(-P) reporting guidelines , 71. ForAs a scoping review, registration was not possible in PROSPERO’s systematic review register. Instead, the protocol was made publicly available on McMaster University’s Midwifery Research Centre website . Two altn = 3353), were not focused on home birth (n = 2770), or were not research on people’s perspectives (n = 1728). The flow of studies through the review is provided in Fig. Searching identified 10,196 references. After duplicate removal and screening on title and abstract, a total of 720 references were retrieved for assessment based on the full report. Of these, 460 met the eligibility criteria and were included in the scoping review analysis. Most studies were excluded at title/abstract or full text screening stages because they were not empirical research , followed by Australia (20%), the USA (16%), the Netherlands (11%), and Canada (9%). It should be noted that some studies sampled from more than one country, hence numbers add up to the overall totals for HRCs reported above. Several HRCs were not represented, including Chile and Colombia, South Korea, and several countries within Europe .The experiences of a wide range of clients, support persons, and health care practitioners were sought across high-resource countries, as illustrated in Fig. n = 3) and policy makers (n = 2) regarding home birth were rarely studied.Women’s experiences were most often reported , although the perspectives of fathers (9%) and family members (2%) were also included in some studies. Midwives were the most frequently researched healthcare providers (32%), followed by obstetricians (11%), nurses (5%) and family practitioners (4%). Pediatricians (1%) and other health care providers  were studied less often (3%). The views of service managers (4%) and staff members (2%) were studied infrequently. The perspectives of community leaders . Another 67 studies (32%) focused on understanding home birth from the perspectives of those providing home birth services.The perspectives of different types of clients were also the main focus of a group of studies. Perspectives of home birth among women experiencing their first pregnancy were reported in 23 studies within HRCs (11%), with only 5% asking multiparous women. The experiences of rural and remote participants (3%), Indigenous groups (3%), and immigrants (one study) were less often reported.Some studies also explored purposely the views of partners and family members: the perspectives of fathers or partners were the specific focus in nine studies (4%). Only one study sought the experiences of children/siblings who were present during home births.Perspectives on risk in home birth were also a focus. A total of 11 studies (5%) considered the experiences of those who chose to freebirth. The experiences of home birth for those with high-risk pregnancy were reported in eleven studies (5%) and of women who had a previous hospital delivery in eight studies (4%). The perspectives of those who experienced transfer from home to hospital during birth were reported in 15 of the included HRC studies (7%).A slightly higher proportion of the included studies took place in low- and middle-resource countries (LMRCs): a total of 250 studies eliciting the views of stakeholders about home birth across 48 countries. This is shown in Fig. Studies of stakeholder perspectives of home birth were conducted in multiple LMRCs, as illustrated in Fig. The largest body of research in this group has been conducted in Ethiopia . A modest number of studies have been conducted in other countries with high rates of maternal mortality including Brazil (9%), Nigeria (7%), India (6%), Tanzania and Kenya (5%), and Zambia, Nepal, Ghana, and Bangladesh (4% each). Countries with the highest maternal mortality rates  as defined by the WHO, UNICEF, the UN Population Fund, and the World Bank  were parAs in studies conducted in HRCs, the perspectives of women experiencing home birth in LMRCs were most often sought . This is shown in Fig. Many other types of stakeholders participated in home birth research studies across LMRCs. Fathers perspectives were explored in 45 studies (18%), as were family members (8%). A diversity of healthcare providers perspectives were also studied, including outreach workers, health extension workers, and unspecified health workers (17%). The experiences of traditional birth attendants were reported in similar proportions (17%), followed by midwives (8%), nurses (7%), and skilled birth attendants (2%). The experiences of service managers (5%) and staff members and obstetricians (2% each), family practitioners (three studies), and pediatricians (one study) were less often reported.A modest number of studies within LMRCs included the perspectives or community leaders (10%), followed by community members (9%), and policy makers (4%). Perspectives of academics or social service personnel (two studies each) and religious leaders (one study) were less often stated.A wide range of topics were studied across LMRCs, as shown in Fig. Within LMRCs, participants’ perspectives shaped by geographic and economic determinants were evidenced, with studies of those experiencing rural or remote home birth , in poorly resourced areas (20%), nomadic or pastoralist communities (5%) studied.Almost one third of the studies in LMRCs sought to understand home birth from the perspective of those people experiencing home birth . The focus of those providing home birth services was examined in 32 studies (9%).Many of the studies conducted in LMRCs sought to understand why home birth took place despite an emphasis on promoting health facility delivery (26%). Other related studies examined perspectives of women who experienced home birth despite receiving antenatal care (6%), or not utilizing antenatal care (2%). The views of those women experiencing previous hospital delivery were reported in four studies (2%). Another six studies (2%) examined the views of those experiencing transfer from home to hospital.Specific populations at risk of poor outcomes were less often studied, including first time mothers, multiparas, and Indigenous groups (four studies each), refugees and migrants, and those with high-risk pregnancies (three studies each). Studies originating in LMRCs with a specific focus on the perspectives of fathers only were rarely reported (one study).It has long been considered important that health policy and practice decisions should be informed by the perspectives of those who plan, provide and are affected by them . The resIn HRCs, a body of research was located on fathers’ and same-sex partners’ experiences of home birth. A synthesis of the existing literature on these partners’ perspectives of home birth in high resource countries is an important area of need, as this appears to be a new area of birth research. In LMRCs, it has been suggested that fathers and other family members influence women’s health care decisions, including place of birth –82. Our A substantial number of studies examining LMRC community members’ views of home birth were also located. This could further supplement existing evidence syntheses of community interventions to prevent maternal and newborn mortality , 86. In Health professionals’ perspectives of home birth also hold the potential to inform maternity policy and practice; however, only one previous systematic review was located which examined midwives’ discussions of place of birth options with women in HRCs . This scSeveral topics or issues of interest also emerged from the analysis of HRC research on stakeholder views of home birth. This included new primary research on people’s perspectives of freebirth or unassisted birth, where women choose to birth without a trained professional present, even where there is access to medical facilities. Previous syntheses of this research suggest that women make this choice, for reasons of autonomy, choice, and control over their own bodies, due to midwives and current maternity services , 87. ThiSimilarly, our scoping review identified multiple research studies of stakeholder perspectives on home birth in high-risk pregnancy, in those who had a previous hospital delivery and among women experiencing transfer from home to hospital. Integration of this body of research conducted in high-resource settings could broaden our understanding of home birth with reference to safety and risk. For example, this could update an existing evidence synthesis examining perspectives of transfer from home to hospital . This foSeveral studies originating in LMRCs also examined stakeholder perspectives of home birth where the population is rural, remote, or has poor access to health services. It has been noted that poor geographic access to hospital facilities in LMRCs impedes health care utilization . StakehoThis scoping review of stakeholder research about home birth also identified several gaps in primary research. For example, in high-resource countries, very little research was identified which sought the views of same-sex childbearing partners, or other family members, such as grandparents. Given the influence of family members on women’s birth decisions , 81, 82,The views of specific populations concerning home birth also bear further examination. These include the perspectives of stakeholders in countries of higher maternal mortality, including countries in sub-Saharan Africa and Southeast Asia .Research on the perspectives of first-time mothers and multiparas, whose experiences may differ from one another, could also suggest different avenues of health system support.In addition, primary research seeking young mothers’ perspectives of home birth was rarely located. Given that the highest rate of maternal mortality in LMRCs occurs in women aged 10 to 14 years, this is an important area of future research .Finally, primary stakeholder research on home birth among specific and potentially more vulnerable populations is also lacking in both HRCs and LMRCs, including Indigenous populations, immigrants, refugees, and migrants. Displaced populations are at higher risk of maternal mortality due to the associated conflict and humanitarian crises . This suThe main strength of this systematic scoping review lies in its broad search for relevant literature and consistent methods of screening, coding and analysis. To our knowledge, this is the first representation of the landscape of qualitative literature worldwide focused specifically on stakeholders’ experience and perspectives of home birth. As such, it provides a valuable resource for researchers, members of the public and decision-makers for informing personal and policy decisions related to home birth and identifies areas for future research.The results of this review are limited by the depth of analysis possible using scoping review methods, a challenge noted by others , 96. TheOur systematic scoping review identified a large body of research literature that privileged the experiences and perspectives of a wide range of key stakeholders about home birth in both high and low and middle income countries.Groups of primary research focused on different topics and populations within HRCs and LMRCs could be usefully synthesized to inform personal practice and policy decisions. However, these research syntheses would be best informed by collaboration between researchers and childbearing women and their support people, clinicians, professional organizations, research funders, and clinical and policy decision-makers. These stakeholders can better inform personal and policy decisions by working together to collectively identify emerging issues, priorities, and the associated research questions , 97, 98.


To summarise the evidentiary basis related to causes of inequities in chronic kidney disease among Indigenous Peoples.We conducted a Kaupapa Māori meta-synthesis evaluating the epidemiology of chronic kidney diseases in Indigenous Peoples. Systematic searching of MEDLINE, Google Scholar, OVID Nursing, CENTRAL and Embase was conducted to 31 December 2019. Eligible studies were quantitative analyses  including the following Indigenous Peoples: Māori, Aboriginal and Torres Strait Islander, Métis, First Nations Peoples of Canada, First Nations Peoples of the United States of America, Native Hawaiian and Indigenous Peoples of Taiwan. In the first cycle of coding, a descriptive synthesis of the study research aims, methods and outcomes was used to categorise findings inductively based on similarity in meaning using the David R Williams framework headings and subheadings. In the second cycle of analysis, the numbers of studies contributing to each category were summarised by frequency analysis.Completeness of reporting related to health research involving Indigenous Peoples was evaluated using the CONSIDER checklist.Four thousand three hundred seventy-two unique study reports were screened and 180 studies proved eligible. The key finding was that epidemiological investigators most frequently reported biological processes of chronic kidney disease, particularly type 2 diabetes and cardiovascular disease as the principal causes of inequities in the burden of chronic kidney disease for colonised Indigenous Peoples. Social and basic causes of unequal health including the influences of economic, political and legal structures on chronic kidney disease burden were infrequently reported or absent in existing literature.In this systematic review with meta-synthesis, a Kaupapa Māori methodology and the David R Williams framework was used to evaluate reported causes of health differences in chronic kidney disease in Indigenous Peoples. Current epidemiological practice is focussed on biological processes and surface causes of inequity, with limited reporting of the basic and social causes of disparities such as racism, economic and political/legal structures and socioeconomic status as sources of inequities. The United Nations Declaration of the Rights of Indigenous Peoples asserts that Indigenous Peoples have an equal right to the highest attainable standard of physical and mental health . DespiteWhile a substantial literature exists to evaluate the determinants of unequal health outcomes of Indigenous Peoples and minority populations, inequities have often been explained via individual “biological risk factors”, as opposed to identifying structural and systemic perpetrators of health inequities, including racism and coloniality –8. A widWe conducted a systematic review with quantitative analysis with the aim to summarise the reported basis related to causes of inequities in chronic kidney disease among Indigenous Peoples.The investigators employed a Kaupapa Māori approach to undertake this systematic review and meta-synthesis of quantitative studies evaluating chronic kidney diseases including Indigenous Peoples . The KauElectronic searches of MEDLINE, Google Scholar, OVID Nursing, CENTRAL and Embase, were conducted from database inception to 31 Dec 2019 using the keywords “Indigenous”, “chronic kidney disease”, “end-stage renal disease” and “end-stage kidney disease.” After removing duplicate reports, the titles and abstracts of retrieved citations were screened according to the inclusion criteria independently by two investigators (TH and NM). TH and NM discussed abstracts requiring a consensus decision. Any differences that arose were resolved by discussion or with a third investigator (SCP or SGP). The full text of records meeting the criteria were then examined by TH.Studies were eligible if they were an observational study design  in which the epidemiology of chronic kidney disease was evaluated in the following Indigenous Peoples who continue to experience colonisation: Māori, Aboriginal and Torres Strait Islander, Métis, First Nations Peoples of Canada, First Nations Peoples of the United States of America, Native Hawaiian and the Indigenous Peoples of Taiwan. Studies were limited to publications in the English language and studies of adults aged 18 years or older. A systematic review protocol was not registered.Data were extracted from each study into a purpose-built database by a single investigator (TH). The extracted variables were study characteristics, including populations, settings, exposures, study methods and outcomes.culture, biology/geographical origins, racism, economic structures, political/legal), social status , surface causes , biological processes  and health status  [Two cycles of analysis of extracted data were conducted aligned with a Kaupapa Māori methodology, to support the critique of systemic barriers and colonial norms that maintain health inequities. A Kaupapa Māori approach requires a Māori researcher to lead the study development and research process. The review was conducted utilising the David R Williams framework for studying racial differences in health to analyse reported sources of Indigenous inequities in chronic kidney disease . The Dav health) . In the A sub-group analysis explored frequencies occurring in two distinct time periods (1994–2005 and 2006–2019), and in studies with or without reporting an Indigenous methodology for study conduct.The Consolidated Criteria for strengthening reporting of health research involving Indigenous Peoples (CONSIDER) were used to evaluate the completeness of reporting. The CONSIDER statement is a checklist for reporting of research methodologies based on ethical guidance for research involving Indigenous Peoples .The search screened 4372 records Fig. . Of thesThe analyses were conducted within an existing database or registry (60 studies (33%)), community-based research (34 studies (19%)), primary care or rural clinics (25 studies (15%)), dialysis and transplant units (23 studies (13%)), hospital/outpatient (22 studies (12%)) and analysis of collected laboratory or genetic samples (16 studies (9%)).Based on CONSIDER reporting checklist, research governance was reported in two studies research prioritisation based on Indigenous stakeholder perspectives or empirical data was not reported in any study and the methodological approach to the inclusion of Indigenous participants was reported in 34 studies. Table  Of the en = 9), biology or geographical origins (n = 43) or racism (n = 5) as causes of health inequity for Indigenous participants  studies investigated culture (% studiesInvestigator teams interpreted the findings of their research to indicate that colonisation and racism were determinants of chronic kidney disease risk and outcomes in Indigenous Peoples in 46 (26%) studies. In four studies, it was identified that increased understanding of culturally-specific beliefs and practices such as the return of tissue or the handling of samples led to changes in clinical practice. The investigators of these studies reported that increased understanding of cultural practices led to improved acceptability of treatment to Indigenous Peoples. The investigators also reported the need for non-Indigenous health professionals to increase cultural competencies when working with Indigenous Peoples , 66, 70.Social status includes socio-economic status, race, gender, age and marital status. In 27 studies (15%), researchers identified socio-economic factors as determinants of patient outcomes related to chronic kidney disease in Indigenous patients. Reported factors included rurality and socioeconomic status. In eight of these studies, investigators reported that poverty and access to quality health services were factors associated with health outcomes for Indigenous Peoples with chronic kidney disease. No studies evaluated the intersection between race, social status and chronic kidney disease epidemiology.Surface causes include individual health-related behaviours such as smoking and alcohol use, stress, psychosocial resources and medical care. Medical care in the David R Williams framework refers to the health system, physician care and clinical care practices such as transplantation and dialysis. Medical care was the focus of 68 studies (38%) including studies investigating transplantation and dialysis treatment patterns. Six studies all published since 2014, reported clinical care as a source of inequities in chronic kidney disease. These studies also reported improved health outcomes in Indigenous patients following clinical interventions tailored to prevent chronic kidney disease through point of contact screening in rural locations. In 21 (12%) studies, investigators reported on Indigenous patient experiences. These studies reported that Indigenous patients’ education and relationships with health providers were important aspects of their care. The studies also highlighted patient perceptions of unequal treatment, clinician bias and barriers to care such as geographical accessibility. Investigators in two studies explored screening for chronic kidney disease in primary care. Treatment pathways for Indigenous patients were investigated in 8 (4%) studies. These studies reported ways to address accessibility barriers such as point of contact screening, early prevention and education about diabetes and kidney disease, and clinical practice screening solutions .Sixty-three studies (41%) reported on personal health behaviours including smoking, alcohol use and modifiable lifestyle factors including diet as contributing factors to inequities in chronic kidney disease in Indigenous Peoples.Biological processes include central nervous, endocrine, metabolic, immune and cardiovascular systems. Biological processes were the most frequently cited determinants of chronic kidney disease outcomes in the eligible studies. Investigators in 91 (51%) of the eligible studies concluded that Indigenous Peoples had increased risks of chronic kidney disease and kidney failure compared to non-Indigenous participants and that Indigenous Peoples had a higher prevalence of identifiable risk factors, such as type 2 diabetes and cardiovascular disease. Investigation of biological processes within the eligible studies was predominantly focused on endocrine (35 studies) and metabolic (30 studies) processes associated with chronic kidney disease, particularly hypertension and type 2 diabetes.Health status in the framework refers to morbidity, mortality, prognosis, incidence, disability, mental health and wellbeing. Investigators of included studies analysed mortality and hospitalisations in Indigenous Peoples with chronic kidney disease in 22 (12%) studies. Investigators in 18 (10%) studies evaluated differences in incidence and prevalence of chronic kidney disease in Indigenous Peoples in comparison with non-Indigenous peoples. All of these studies identified a higher burden of chronic kidney disease when compared with a non-Indigenous cohort.n = 7) [A subgroup analysis by publication date identified that prior to 2004 there were only a small number of studies published investigating kidney disease in Indigenous Peoples (n = 7) , 81–84. n = 7) , 78, 85.n = 7) , 67, 78.We used the meta-synthesis of epidemiological studies approach incorporating Indigenous methodologies to explore the reported sources of health inequities in Indigenous Peoples with or at risk or chronic kidney disease. The analysis employed a Kaupapa Māori approach using the David R Williams framework for studying racial differences in health. The key finding was that epidemiological investigators most frequently reported biological processes of chronic kidney disease, particularly type 2 diabetes and cardiovascular disease as the principal causes of inequities in the burden of chronic kidney disease for colonised Indigenous Peoples. Social and basic causes of unequal health including the influences of economic, political and legal structures on chronic kidney disease burden were infrequently reported or absent in existing literature.This systematic analysis raises the possibility that a research focus on biological process and surface causes has provided a foundation of understanding of potential causative factors of inequities in chronic kidney disease experienced by Indigenous Peoples. This may have resulted in a more restricted understanding of the roles of political and economic domains as root causes of inequities for Indigenous Peoples with chronic kidney disease, limiting effective policy and practice responses , 12, 79.This review identified that there is still a need for greater understanding of the impact of political and social structures on Indigenous health inequities, and requires research partnerships that are enabled to consider, and explore a wider range of causes of inequity in non-communicable diseases. A strength-based process could assist to expand the influence of research from a focus on immediate biological factors, to research that is inclusive of, and driven by, Indigenous understanding, knowledge and experiences that considers racism social justice and wider socio-political factors, to inform policy and practices to address health inequities. The recognition of the impact of power on Indigenous health outcomes ultimately leads to research that is inclusive of Indigenous knowledge , 15, 90 This review identified that between 2012 and 2019 there was an increase in studies incorporating Indigenous research methodologies, principles and Indigenous led research. It is plausible that the increase in Indigenous stakeholder involvement directly corelates to the higher number of research protocols/guidelines that identify the need for partnership with Indigenous stakeholders , 94–97. The strengths of this study include the systematic meta-analytical approach, application of David R Williams framework to the synthesis of eligible studies, the use of Indigenous research-reporting criteria (CONSIDER) to assess the completeness of reporting and utilisation of a Kaupapa Māori methodology. There are limitations of this review that need to be considered when interpreting the findings. The inclusion criteria for the studies were limited to research inclusive of Indigenous Peoples of Aotearoa New Zealand, Australia, Canada, Taiwan, Hawaii, the United States of America, and experiences of Indigenous Peoples from outside these nations have not been included. Eligible studies were limited to the English language. The David R Williams framework was initially developed to investigate differences in health based on race, rather than Indigeneity, and may not be fully applicable to the elements of coloniality that are specific to Indigenous health outcomes.In this systematic review with meta-synthesis, a Kaupapa Māori methodology and the David R Williams framework was used to evaluate reported causes of health differences in chronic kidney disease in Indigenous Peoples. Current epidemiological practice is focussed on biological processes and surface causes of inequity, with limited reporting of the basic and social causes of disparities such as racism, economic and political/legal structures and socioeconomic status as sources of inequities.


As stakeholders in the transformative medical research ecosystem, real-world evidence researchers must conduct observational research with an awareness of racism. Advancements in understanding of the impact of racism on health outcomes, the abundance of health care data, and innovations in health information technology provide tools that create opportunities to conduct more focused research that illustrates how racism in health care deters the advancement of equity. RWE research provides facts and evidence for decision and policy makers. The coronavirus pandemic and the cell phone documentation of police brutality that led to George Floyd's murder expose society's burdens of inequity, injustice, and racism. Health care in the United States is not immune to these burdens.2 The tradition of RWE research has identified racial disparities in obstetrics and gynecology,3 the challenges of minority participation in clinical trials,4 as well as racial and economic factors for COVID-19 disease outcomes.5 Building on experience, health care information technology, and a renewed recognition that it is important to measure racism, not socially assigned “race,”7 RWE researchers have the opportunity to generate trusted RWE that leads to evidence-based policies to undo racism that potentially address the more elusive problem: inequity. RWE research must now be conducted with an awareness of racism.Real-world evidence (RWE)8 The inability to acknowledge and address the history and legacy of racism contributes to our contemporary systems of inequity in health care and limits the impact of medical science innovations, particularly for African Americans, Indigenous/Native peoples, and religious and immigrant groups (both past and present). The increased dialogue and commentary about the impact of race in medicine and health care are encouraging.9 Going forward, RWE research can address racism by acknowledging its presence in our real world, asking tough research questions that focus on dismantling racism, use 21st century digital health care/social data, and apply big data analytics tools/technologies to measure outcomes that move facts forward to provide evidence to policy makers.Events of 2020 expose the legacy of racism and its impact on health.10 Sadly, exploitative events with Henrietta Lacks justify some suspicions of medical research.11 Marginalized communities are aware of, and concerned about, biases in algorithms that limit access to potential life-saving resources.12 Researchers can consider questions that account for mistrust in participation in medical research.13 Step two: Build upon the work of veteran scholars of racism research in health care that provides guidance for evidence and research needs to measure racism in health care.14 RWE research has identified disparities and inequities. When researchers identify variations in outcomes based on socially assigned “race” categories, they must ask why multiple times.15 Step three: RWE researchers must acknowledge and account for skepticism about medical research in communities impacted by racism. Formulate research questions aligned with those who experience racism. Avoid speculation. Step four: RWE researchers must begin to understand and learn the power of antiracist thinking in health care as displayed in the United Kingdom16 and the United States.17 When the scientific research community understands the possibilities of antiracism, we broaden our curiosity about why humanity is being damaged by burdens that focus on socially assigned “race” groups.18High quality research begins with posing important research questions. The tough research questions begin with acknowledgment that racism and racist medical research practices have sabotaged trust in medical research for certain groups of people. Step one in formulating tough research questions: RWE researchers must be educated about (and respect) the legacy and scars of the Tuskegee Study and its contemporary relevance in African American communities.19 Research capacity that prioritizes RWE studies that address racism and inequality can provide important peer-reviewed studies to help undo these historical and contemporary deterrents to better health outcomes.Empowered with awareness and new ways of thinking, RWE researchers can formulate better research questions that address racism. RWE researchers can respectfully engage and collaborate with victimized communities to partner for research. Through informed engagement, RWE researchers can actively listen to concerns and questions these communities have not only about the research process, but also how the experiences of racism and inequity impact their health. With this information, health care outcomes and research study endpoints that matter most to victims of racism can be identified and studied. Partnerships and collaborations with community members must be formed to socialize the RWE research process, ensuring transparency and equity in representation in RWE results. Without more direct engagement with communities victimized by racism, and research questions crafted from the perspective of those directly impacted by racism, current (and future) RWE research questions, though useful for regulatory decision making, will have limited impact on evidence-based policies that reduce inequities in health care. Despite these challenges, and missed opportunities of the past, RWE research must move forward to build new and better research capacity through transparency, collaboration, and engagement at more holistic levels with community and research organizations, human and behavior science disciplines, and include economic/financial implications of racism.20 is the currency of transformative RWE and an important component of new and better research capacity that addresses racism and inequities. We have richer and more comprehensive RWD assets that can help answer our tougher RWE research questions. The RWE research community must demand data standards, data quality, and data aggregation practices that include all populations. Interoperability technologies can help create a digital health care data-supported RWE research agenda that links all relevant population data.21 Safe, secure, privacy-protected, and accurate data from Medicaid and Medicare sources must be more accessible to RWE researchers. Data vendors, policy makers, and technologists who organize RWD must understand that RWD must be representative and inclusive to account for all populations.22 Recent Office of the National Coordinator (ONC) information blocking rules improve all patients' access to their health care data.23 These rules can leverage safe and secure Sustainable Medical Applications and Reusable Technologies (SMART)24 to connect different health care data types (some controlled by patients) to gather additional sources of data to conduct RWE research that addresses racism and inequality. With linked, comprehensive, and representative RWD, big data analytics and technologies can analyze complex data sets25 that lead to new insights into the impact of inequity due racism in health care.The path to high-quality research goes through high-quality data. Real-world data (RWD)26Just as tough research questions about why some “race” groups have different outcomes than others, high-quality antiracism research leverages 21st century RWD. The impact of RWE research, unlike randomized controlled trials research, is its use for patient- and population-level policy. Like our contemporary real world, RWD and RWE research are messy, difficult, and complicated. Despite these realities, RWE researchers must lean in with confidence that our skills, experiences, focus, better data, big data analytics capabilities, and our abilities to collaborate can collectively produce evidence that generates policies to dismantle systems of racism and inequity in health care. RWE research can build paths to policy for equality and help create an antiracist health care system.RWE researchers now have tools to generate RWE that can quantify, understand, and account for racism and its impact on health care outcomes, and generate data-driven evidence to influence important policies. The RWE research community is now armed with 21st century tools that include knowledge and awareness of the mistakes of our past, new ways to formulate antiracist research questions that focus on inequity, collaborations and partnerships with communities, science stakeholders , digital health care, social data technology, and big data analytics. RWE researchers can feel emboldened to push forward into the challenge of conducting RWE research for equity. 21st century RWE research can leverage the best of our 21st century tools, and thinking, to generate RWE that leads to policies for a health care system that is antidehumanizing and more equitable for every human being.