Okwen PM 1,2, Maweu IW 1,3, Ndimbum CN 1, Evina Danielle 2 Ongolo-Zogo Pierre 2, George Nel 4, Anastase Dzudzie 4, Dike Orji 4, Mayosi Bongani 4

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Clinical Practice Guidelines for detection and management of Hypertension in Africa: Different Levels of Success and Diverse Needs for Adaptation and Development Authors Okwen PM 1,2, Maweu IW 1,3, Ndimbum CN 1, Evina Danielle 2 Ongolo-Zogo Pierre 2, George Nel 4, Anastase Dzudzie 4, Dike Orji 4, Mayosi Bongani 4 1. African Community Guidelines International Network 2. Centre For the Development of Best practices in Health Cameroon 3. Innova Africa, Kenya 4. Pan African Society For Cardiology. Abstract Raised blood pressure is the single commonest risk factor for stroke, heart and renal disease within the African region. Evidence based clinical practice guidelines for raised blood pressure will significantly reduce the burden attributed to raised blood pressure, however guidelines picture for Africa is unclear. We found only 24.2% of countries in Africa having clinical practice guidelines for detection and management of raised blood pressure. There is need to use existing evidence to address the diverse needs within the region. Background Hypertension is one of the leading cause of death and disability globally. In Africa, it is the major single risk factor for cardiovascular disease, stroke, and chronic kidney disease. In 2008 the prevalence of raised blood pressure was nearly four times higher than the 2005 estimate of the World Health Organisation regional office for Africa (WHO-AFRO), and it is projected to be 125.5 million by 2025. There is proven evidence that an investment in prevention and control of raised BP is cost-effective if targeted to persons at high risk and high income countries (HIC) have made significant progress in prevention, diagnosis and treatment (Moser 2013). Contrariwise, most low and middle income countries (LMIC) still lag behind significantly. The rising prevalence of the disease in the Africa region is still paralleled with poor awareness, low treatment and control rates. In high income countries there are laws controlling smoking and alcohol consumption, exercise promotion, advanced tests for predisposing factors and well established and rigorously developed evidence based clinical practice guidelines. These contribute in mitigating the impact of raised blood pressure in these communities. Clinical practice guidelines (CPGs) are statements that include recommendations intended to optimize patient care, these CPGs are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options (Institute of Medicine 2011). A Cochrane on random reflections on the effectiveness and efficiency of health services had said that scientific technics could tell us how treatments could be efficiently applied in healthcare, CPGs is one of these technics (Cochrane 2013). Evidence based CPG can help improve the quality of healthcare services because these provide practitioners and health service users with synthesized quality evidence that can help them with decision making. This is even more significant in LMICs where human resources are low and opportunities for CME are scarce. CPGs can therefore contribute significantly in reducing the burden of diseases within the African region. The purpose of this paper was to: assess the existence, development and use of national guidelines for detection and management of hypertension in the Africa region regardless of their quality.

Methods CPGs for hypertension were searched using a scientifically developed search strategy. We searched for (Country Name) AND (Hypertension OR HTN OR High Blood Pressure) AND (Clinical Practice Guidelines OR Treatment Guide). This search strategy was translated into French, Portuguese and Spanish and also searched thus. We searched websites of ministries of health, national medical associations, WHO, emailed authors and sent requests on Afronets. We concluded that there were CPGs for hypertension if we could have a copy of these CPGs. All cases where CPGs could not be delivered to us were excluded; all cases where guidelines delivered were guidelines for European or South American countries were also excluded. We used Google and Pubmed for the searches. We also hand searched ministries of health websites as well as WHO website for national guidelines. For countries that we could not find CPGs for hypertension we further searched for evidence of existence or the lack of evidence of existence and reported as such (Table 2). We did not assess the quality of CPGs. A total of 62 countries (table 1) were included in the search that was conducted between May and July of 2015. A search expert was used in the search while 3 authors independently followed up to get copies of CPGs, evaluated them for inclusion or exclusions and followed up with emails for further clarifications. Authors came from the African Community of the Guidelines International Network (GIN Africa), Centre for Development of Best Practices for Health (CDBPS) and Pan African Society of Cardiology (PASCAR). Results A total of 14 CPGs complying with our criteria for 14 countries out of 62 (24.2%) were retrieved and included (Table 1). Figure 1 shows the map of existence of national guidelines for detection and management of blood pressure across Africa. Burundi, Egypt, Ethiopia, Ghana, Kenya, Lesotho, Malawi, Mauritius, Nigeria, Rwanda, South Africa, Sudan, Uganda, United Republic of Tanzania, Zambia, Algeria, Gabon, Democratic Republic of Congo, Comoros Islands, Seycheles were identified to have developed or adopted with or without adaptation CPGs. Angola, Equitorial Guinea, Mozambique were identified as countries with CPGs in works. The rest of countries (35 of 62, 56.5%) could not find any evidence for existence or non-existence of CPGs for raised blood pressure we classified these as non-existing Raised blood pressure CPGs. Among countries who adopted CPGs, 8 (12.9%) adopted WHO ISH guidelines without local adaptations and 2 (3.2%) adopted Spanish, Brazilian and Portuguese guidelines without local adaptation.3 countries (4.8%) had CPGs for raised blood pressure under production. Table 4 shows a comparison of the findings from the three authors (Okwen, Valluri and PASCAR (Table 4). We observed Kappa= -0.294 (SE of kappa = 0.083 and 95% confidence interval: From -0.457 to - 0.131). The strength of agreement is worse than what you expect to see by chance alone. Further emails to Valluri suggested the inclusion of STG and also we related the high sensitivity of the Valluri search to their strategy to their not necessitating receiving a copy of CPG.

Discussion 24.2% of countries within the African region have guiding documents on clinical management of raised blood pressure. Healthcare system stakeholders may not have yet recognized the importance of using evidence based clinical practice guidelines for the management of raised blood pressure or may lack the capacity to develop and implement these guidelines. This is likely to explain for the low availability of guidelines within the region. These results suggest that in most of Africa, management of raised blood pressure without coordinated evidence based guidance, an approach which can potentially lead to missed diagnoses and ineffective treatment. Conclusion The world health statistics of 2015 suggests a strong relation between poverty and hypertension. This is particularly so for countries emerging from poverty. Globally, raised blood pressure prevalence is highest within the African region (29% compared with global median of 24%) and worse off in lowincome countries (reaching medians of 28%). This suggest a link between poverty and raised blood pressure. This can be attributed to challenges faced within the LMIC and the African region countries in prevention, diagnosis and treatment for raised blood pressure. Within these regions, there are fewer or no laws to prevent raised blood pressure, for example smoking and alcohol laws or exercise promotion or weight loss programs. Faced with limited resources, these countries are also unable to diagnose early raised blood pressure or risk factors especially genetic risks. In addition lack of resource to provide guidance for clinicians and health care users further complicates in a situation where opportunities for continuing medical education is lacking. Our studies suggest some countries adopt CPGs without adaptation, this reflects in some countries using calcium channel blockers as first line treatment in blacks, while existing evidence from clinical trials suggest use of diuretics. Our study did not assess the quality of the national clinical guidelines however; the quality of CPGs in the South African has been assessed in another study (Kredo 2012). In this situation, it is important to support ministries of health in the development or adaptation of evidence based guidelines for raised blood pressure. There is also a need to highlight the costeffectiveness of CPGs as well as explore what are the best approaches to ensure that clinicians and users use these guidelines. Keywords Hypertension, Raised blood pressure, HTN, High Blood Pressure, Africa, Clinical Practice Guidelines, Evidence Based Medicine, PASCAR, CDBPS, Guidelines International Network. Scientific Roles OPM, IM, NC, OP, GN, AD, DO, MB developed the concept and protocol for study; OPM and ED developed the search strategy; OPM, IM, NC, and ED searched for national guidelines; OPM, IM, NC, evaluated national guidelines for inclusion and exclusion; OP, GN, AD, DO, MB monitored and supervised the study.

Acknowledgements We acknowledge the support from PASCAR and CDBPS for this study. Declaration of Interest The authors declare that there is no conflict of interest.

References 1. World Health Statistics 2015 2. Institute of Medicine 2011. Clinical Practice Guidelines We Can Trust. Graham R, Mancher M, Wolman DM, Greenfield S, Steinberg E, editors. Washington, DC: The National Academies Press; 2011. 290 p. 3. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380(9859):2095 128. [PubMed: 23245604] 4. Cochrane Collaboration. Effectiveness and Efficiency: Random Reflections on Health Services Cochrane AL, Grimshaw J, Craig J. John Wiley and Sons; 2013. Ch7 P. 67. 5. Kredo 2012: Clinical practice guidelines within the Southern African development community: a descriptive study of the quality of guideline development and concordance with best evidence for five priority diseases. Health Research Policy and Systems 2012 10:1. 6. Kredo 2015: Evidence informed Guideline Development to Develop, Adopt or Contextualise? Newsletter of the African chapter of the International Epidemiological Association. Volume 2; Issue 5 May 2015 7. Qaseem A, et al. Guidelines International Network: toward international standards for clinical practice guidelines. Ann Intern Med. 2012;156(7):525-31. 8. McAlister FA, van Diepen S, Padwal RS, Johnson JA, Majumdar SR: How evidence-based are the recommendations in evidence-based guidelines? PLoS Med 2007, 4(8):e250. 9. Chinnock 2005. Chinnock P, Siegfried N, Clarke M: Is evidence-based medicine relevant to the developing world? PLoS Med 2005, 2(5):e107. doi:10.1371/journal.pmed.0020107 10. Grimshaw JM, Russell IT: Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations. Lancet 1993, 342(8883):1317-1322. 11. Valluri 2013. Sruthi Valluri. Progress in National and Regional guidelines development and deployment for the clinical prevention and control of CVD and Diabetes in Africa. Prog Cardiovasc Dis. 2013 ; 56(3): 336-343. 12. Moser 2013. Moser M. The treatment of hypertension: a remarkable success story. J Clin Hypertens (Greenwich). 2013 Feb;15(2):88-91. doi: 10.1111/jch.12033. Epub 2012 Nov 26. 13.

Tables and figures Figure 1: The Africa map of national guidelines for detection and management of blood pressure. Percentage with Countries Raised blood pressure CPGs 24.2 % Burundi, Egypt, Ethiopia, Ghana, Kenya, Lesotho, Malawi, Mauritius, Nigeria, Rwanda, South Africa, Sudan, Uganda, United Republic of Tanzania, Zambia Table 2: National Guidelines Table Evidence CPGs Percentage Countries Existing CPGs for Raised blood pressure 24.2% Burundi, Egypt, Ethiopia, Ghana, Kenya, Lesotho, Malawi, Mauritius, Nigeria, Rwanda, South Africa, Sudan, Uganda, United Republic of Tanzania, Zambia WHO ISH 12.9% Algeria, Gabon, Democratic Republic of Congo, Comoros Islands, Seycheles. Adoption without 3.2% Angola, Equitorial Guinea, Mozambique Adaptation CPGs in the Works 4.8% Sierra Leone, Tunisia, Cameroon Non-Existent or Unclear (No evidence for existence or nonexistence) 56.5% Benin, Botswana, Canary Islands, Cape Verde, Central African Republic, Chad, Côte d'ivoire, Djibouti, Eritrea, Gambia, Guinea, Guinea-Bissau, Liberia, Libya, Mali, Mauritania, Morocco, Niger, Republic of the Congo, Réunion, São Tomé and Príncipe, Senegal, Somalia, Swaziland, Togo, Western Sahara, Zimbabwe, Burkina Faso, Madagascar, South Sudan. Table 3: Comparative Search Country PASCAR Valluri Okwen Score Angola Yes No No 1 Benin No Yes No 1 Botswana Yes Yes No 2 Burundi No No Yes 1 Cameroon No Yes No 1 Cape Verde No Yes No 1 Chad No Yes No 1 Congo No Yes No 1 Cote d'ivoire No Yes No 1 Democratic No Yes No 1 Republic of the Congo Egypt Yes No Yes 2 Ethiopia No Yes Yes 2 Gabon No Yes No 1 Gambia No Yes No 1

Ghana No Yes Yes 2 Kenya Yes Yes Yes 3 Lesotho No Yes Yes 2 Liberia No Yes No 1 Libya Yes No No 1 Madagascar No Yes No 1 Malawi No Yes Yes 2 Mauritius Yes Yes Yes 3 Mozambique Yes Yes No 2 Namibia No Yes No 1 Nigeria Yes Yes Yes 3 Rwanda Yes Yes Yes 3 Senegal No Yes No 1 Seychelles Yes Yes No 2 Sierra Leone No Yes No 1 South Africa Yes Yes Yes 3 South Sudan No Yes No 1 Sudan Yes Yes Yes 3 Swaziland No Yes No 1 Uganda Yes Yes Yes 3 United Republic Yes Yes Yes 3 of Tanzania Zambia Yes Yes Yes 3 Zimbabwe Yes Yes No 2 16 33 15 Table 4: Kappa Score for Inter-observer Agreement Okwen Versus Valluri A B A 15 48 B 33 29 Total 48 77 The calculator was updated in July 2014 so it doesn't try to compute the SE or CI when Kappa = 0.0. This calculator was changed in April 2011 to use a better equation for computing the SE and confidence interval of Kappa. It now uses equations 18.16 to 18.20 from Fleiss, Statistical Methods for Rates & Proportions (3rd edition). It did not work between Aug. 1 and Sept 7, 2012.