Preparing healthcare facilities in sub-Saharan Africa for future outbreaks: insights from a multi-country digital self-assessment of COVID-19 preparedness.

Africa COVID-19 Digital tools Epidemic preparedness Quality improvement

Journal

BMC health services research
ISSN: 1472-6963
Titre abrégé: BMC Health Serv Res
Pays: England
ID NLM: 101088677

Informations de publication

Date de publication:
28 Feb 2024
Historique:
received: 14 08 2023
accepted: 20 02 2024
medline: 28 2 2024
pubmed: 28 2 2024
entrez: 27 2 2024
Statut: epublish

Résumé

Despite previous experience with epidemics, African healthcare systems were inadequately prepared and substantially impacted by the coronavirus disease 2019 (COVID-19) pandemic. Limited information about the level of COVID-19 preparedness of healthcare facilities in Africa hampers policy decision-making to fight future outbreaks in the region, while maintaining essential healthcare services running. Between May-November 2020, we performed a survey study with SafeCare4Covid - a free digital self-assessment application - to evaluate the COVID-19 preparedness of healthcare facilities in Africa following World Health Organization guidelines. The tool assessed (i) COVID-19-related capabilities with 31 questions; and (ii) availability of essential medical supplies with a 23-supplies checklist. Tailored quality improvement plans were provided after assessments. Information about facilities' location, type, and ownership was also collected. Four hundred seventy-one facilities in 11 African countries completed the capability assessment; 412 also completed the supplies checklist. The average capability score on a scale of 0-100 (n=471) was 58.0 (interquartile range 40.0-76.0), and the average supplies score (n=412) was 61.6 (39.0-83.0). Both scores were significantly lower in rural (capability score, mean 53.6 [95%CI:50.3-57.0]/supplies score, 59.1 [55.5-62.8]) versus urban facilities (capability score, 65.2 [61.7-68.7]/supplies score, 70.7 [67.2-74.1]) (P<0.0001 for both comparisons). Likewise, lower scores were found for public versus private clinics, and for primary healthcare centres versus hospitals. Guidelines for triage and isolation, clinical management of COVID-19, staff mental support, and contact tracing forms were largely missing. Handwashing stations were partially equipped in 33% of facilities. The most missing medical supply was COVID-19 specimen collection material (71%), while 43% of facilities did not have N95/FFP2 respirators and 19% lacked medical masks. A large proportion of public and private African facilities providing basic healthcare in rural areas, lacked fundamental COVID-19-related capabilities and life-saving personal protective equipment. Decentralization of epidemic preparedness efforts in these settings is warranted to protect healthcare workers and patients alike in future epidemics. Digital tools are of great value to timely measure and improve epidemic preparedness of healthcare facilities, inform decision-making, create a more stakeholder-broad approach and increase health-system resilience for future disease outbreaks.

Sections du résumé

BACKGROUND BACKGROUND
Despite previous experience with epidemics, African healthcare systems were inadequately prepared and substantially impacted by the coronavirus disease 2019 (COVID-19) pandemic. Limited information about the level of COVID-19 preparedness of healthcare facilities in Africa hampers policy decision-making to fight future outbreaks in the region, while maintaining essential healthcare services running.
METHODS METHODS
Between May-November 2020, we performed a survey study with SafeCare4Covid - a free digital self-assessment application - to evaluate the COVID-19 preparedness of healthcare facilities in Africa following World Health Organization guidelines. The tool assessed (i) COVID-19-related capabilities with 31 questions; and (ii) availability of essential medical supplies with a 23-supplies checklist. Tailored quality improvement plans were provided after assessments. Information about facilities' location, type, and ownership was also collected.
RESULTS RESULTS
Four hundred seventy-one facilities in 11 African countries completed the capability assessment; 412 also completed the supplies checklist. The average capability score on a scale of 0-100 (n=471) was 58.0 (interquartile range 40.0-76.0), and the average supplies score (n=412) was 61.6 (39.0-83.0). Both scores were significantly lower in rural (capability score, mean 53.6 [95%CI:50.3-57.0]/supplies score, 59.1 [55.5-62.8]) versus urban facilities (capability score, 65.2 [61.7-68.7]/supplies score, 70.7 [67.2-74.1]) (P<0.0001 for both comparisons). Likewise, lower scores were found for public versus private clinics, and for primary healthcare centres versus hospitals. Guidelines for triage and isolation, clinical management of COVID-19, staff mental support, and contact tracing forms were largely missing. Handwashing stations were partially equipped in 33% of facilities. The most missing medical supply was COVID-19 specimen collection material (71%), while 43% of facilities did not have N95/FFP2 respirators and 19% lacked medical masks.
CONCLUSIONS CONCLUSIONS
A large proportion of public and private African facilities providing basic healthcare in rural areas, lacked fundamental COVID-19-related capabilities and life-saving personal protective equipment. Decentralization of epidemic preparedness efforts in these settings is warranted to protect healthcare workers and patients alike in future epidemics. Digital tools are of great value to timely measure and improve epidemic preparedness of healthcare facilities, inform decision-making, create a more stakeholder-broad approach and increase health-system resilience for future disease outbreaks.

Identifiants

pubmed: 38413977
doi: 10.1186/s12913-024-10761-2
pii: 10.1186/s12913-024-10761-2
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

254

Informations de copyright

© 2024. The Author(s).

Références

Kapata N, Ihekweazu C, Ntoumi F, Raji T, Chanda-Kapata P, Mwaba P, Mukonka V, Bates M, Tembo J, Corman V, et al. Is Africa prepared for tackling the COVID-19 (SARS-CoV-2) epidemic. Lessons from past outbreaks, ongoing pan-african public health efforts, and implications for the future. Int J Infect Dis. 2020;93:233–6.
doi: 10.1016/j.ijid.2020.02.049 pubmed: 32119980 pmcid: 7129026
COVID-19 cases top 10 000 in Africa. - WHO Regional Office for Africa [ https://www.afro.who.int/news/covid-19-cases-top-10-000-africa ]. Accessed 26 Feb 2024.
Novel Coronavirus (2019-nCoV) Global Epidemic – 14 April 2020. https://africacdc.org/disease-outbreak/novel-coronavirus-2019-ncov-global-epidemic-14-april-2020/ . Accessed 26 Feb 2024.
COVID-19 Africa CDC Dashboard. https://africacdc.org/covid-19/ . Accessed 26 Jan 2024.
Okonji EF OO, Mukumbang FC, VanWyk B. Understanding varying COVID-19 mortality rates reported in Africa compared to Europe, United States of America and Asia. Trop Med Int Health. 2021;26(7):716–9.
Groenewald P, Bradshaw D, Daniels J, Zinyakatira N, Matzopoulos R, Bourne D, Shaikh N, Naledi T. Local-level mortality surveillance in resource-limited settings: a case study of Cape Town highlights disparities in health. Bull World Health Organ. 2010;88(6):444–51.
doi: 10.2471/BLT.09.069435 pubmed: 20539858 pmcid: 2878147
Mwananyanda L, Gill CJ, MacLeod W, Kwenda G, Pieciak R, Mupila Z, Lapidot R, Mupeta F, Forman L, Ziko L, et al. Covid-19 deaths in Africa: prospective systematic postmortem surveillance study. BMJ. 2021;372:n334.
doi: 10.1136/bmj.n334 pubmed: 33597166
Cabore JW, Karamagi HC, Kipruto HK, Mungatu JK, Asamani JA, Droti B, Titi-Ofei R, Seydi ABW, Kidane SN, Balde T, et al. COVID-19 in the 47 countries of the WHO African region: a modelling analysis of past trends and future patterns. Lancet Glob Health. 2022;10(8):e1099-1114.
doi: 10.1016/S2214-109X(22)00233-9 pubmed: 35659911 pmcid: 9159735
Bargain O, Aminjonov U. Poverty and COVID-19 in Africa and Latin America. World Dev. 2021;142:105422.
doi: 10.1016/j.worlddev.2021.105422 pubmed: 33612919 pmcid: 7885669
Coronavirus disease. (COVID-19) advice for the public [ https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public ]. Accessed 26 Feb 2024.
Powell-Jackson T, King JJC, Makungu C, Spieker N, Woodd S, Risha P, Goodman C. Infection prevention and control compliance in Tanzanian outpatient facilities: a cross-sectional study with implications for the control of COVID-19. Lancet Glob Health. 2020;8(6):e780-789.
doi: 10.1016/S2214-109X(20)30222-9 pubmed: 32389195 pmcid: 7202838
Chersich MF, Gray G, Fairlie L, Eichbaum Q, Mayhew S, Allwood B, English R, Scorgie F, Luchters S, Simpson G, et al. COVID-19 in Africa: care and protection for frontline healthcare workers. Global Health. 2020;16(1):46.
doi: 10.1186/s12992-020-00574-3 pubmed: 32414379 pmcid: 7227172
Obaseki DE, Osaigbovo II, Ogboghodo EO, Adeleye O, Akoria OA, Oko-Oboh GA, Okwara BU, Omuemu CE, Okugbo S. Preparedness and response of a tertiary hospital to the COVID-19 pandemic in Nigeria: challenges, opportunities and lessons. Trans R Soc Trop Med Hyg. 2021;115(7):727–30.
Wadvalla BA. How Africa has tackled covid-19. BMJ. 2020;370:m2830.
doi: 10.1136/bmj.m2830 pubmed: 32675053
Hasan MK, Nasrullah SM, Quattrocchi A, Arcos Gonzalez P, Castro Delgado R. Hospital Surge Capacity preparedness in disasters and emergencies: protocol for a systematic review. Int J Environ Res Public Health. 2022;19(20):13437.
doi: 10.3390/ijerph192013437 pubmed: 36294015 pmcid: 9603163
Causey K, Fullman N, Sorensen RJD, Galles NC, Zheng P, Aravkin A, Danovaro-Holliday MC, Martinez-Piedra R, Sodha SV, Velandia-Gonzalez MP, et al. Estimating global and regional disruptions to routine childhood vaccine coverage during the COVID-19 pandemic in 2020: a modelling study. Lancet. 2021;398(10299):522–34.
doi: 10.1016/S0140-6736(21)01337-4 pubmed: 34273292 pmcid: 8285122
Guglielmi G. Pandemic drives largest drop in childhood vaccinations in 30 years. Nature. 2022;608(7922):253.
doi: 10.1038/d41586-022-02051-w pubmed: 35883006
Vaccine-preventable disease outbreaks on the rise in Africa [ https://www.afro.who.int/news/vaccine-preventable-disease-outbreaks-rise-africa ]. Accessed 26 Feb 2024.
The impact of COVID-19 on HIV, TB and malaria services and systems for health: a snapshot from 502 health facilities across Africa and Asia [ https://www.theglobalfund.org/media/10776/covid-19_2020-disruption-impact_report_en.pdf ]. Accessed 26 Feb 2024.
Kc A, Gurung R, Kinney MV, Sunny AK, Moinuddin M, Basnet O, Paudel P, Bhattarai P, Subedi K, Shrestha MP, et al. Effect of the COVID-19 pandemic response on intrapartum care, stillbirth, and neonatal mortality outcomes in Nepal: a prospective observational study. Lancet Glob Health. 2020;8(10):e1273-1281.
doi: 10.1016/S2214-109X(20)30345-4 pubmed: 32791117 pmcid: 7417164
Shapira G, Ahmed T, Drouard SHP, Amor Fernandez P, Kandpal E, Nzelu C, Wesseh CS, Mohamud NA, Smart F, Mwansambo C, et al. Disruptions in maternal and child health service utilization during COVID-19: analysis from eight sub-saharan African countries. Health Policy Plan. 2021;36(7):1140–51.
doi: 10.1093/heapol/czab064 pubmed: 34146394
Ahmed S, Ajisola M, Azeem K, Bakibinga P, Chen YF, Choudhury NN, Fayehun O, Griffiths F, Harris B, Kibe P, et al. Impact of the societal response to COVID-19 on access to healthcare for non-COVID-19 health issues in slum communities of Bangladesh, Kenya, Nigeria and Pakistan: results of pre-COVID and COVID-19 lockdown stakeholder engagements. BMJ Glob Health. 2020;5(8):e003042.
doi: 10.1136/bmjgh-2020-003042 pubmed: 32819917
Venkatesan P. Global monkeypox outbreak. Lancet Infect Dis. 2022;22(7):950.
doi: 10.1016/S1473-3099(22)00379-6 pubmed: 35752185 pmcid: 9533939
eBioMedicine. Ebola outbreak in Uganda: urgent call for better prevention and surveillance. EBioMedicine. 2022;85:104366.
doi: 10.1016/j.ebiom.2022.104366 pubmed: 36371089 pmcid: 9669767
Zhang X, Zhang W, Chen S. Shanghai’s life-saving efforts against the current omicron wave of the COVID-19 pandemic. Lancet. 2022;399(10340):2011–2.
doi: 10.1016/S0140-6736(22)00838-8 pubmed: 35533708 pmcid: 9075855
Allen T, Murray KA, Zambrana-Torrelio C, Morse SS, Rondinini C, Di Marco M, Breit N, Olival KJ, Daszak P. Global hotspots and correlates of emerging zoonotic diseases. Nat Commun. 2017;8(1):1124.
doi: 10.1038/s41467-017-00923-8 pubmed: 29066781 pmcid: 5654761
Jones KE, Patel NG, Levy MA, Storeygard A, Balk D, Gittleman JL, Daszak P. Global trends in emerging infectious diseases. Nature. 2008;451(7181):990–3.
doi: 10.1038/nature06536 pubmed: 18288193 pmcid: 5960580
Oppenheim B, Gallivan M, Madhav NK, Brown N, Serhiyenko V, Wolfe ND, Ayscue P. Assessing global preparedness for the next pandemic: development and application of an epidemic preparedness index. BMJ Glob Health. 2019;4(1): e001157.
doi: 10.1136/bmjgh-2018-001157 pubmed: 30775006 pmcid: 6352812
Uniting Epidemic Preparedness and Response with Primary Health Care to Build More Resilient Health Systems. [ https://www.path.org/resources/uniting-epidemic-preparedness-and-response-primary-health-care-build-more-resilient-health-systems/ ]. Accessed 26 Feb 2024.
Action, Brief. Use of a Digital Tool Available Worldwide for an Integrated Approach to Improving the Quality Of Health Service Delivery During COVID-19. World Health Organization - Global Learning Laboratory for quality universal health coverage [ https://drive.google.com/file/d/1phhCYvEQ4J87gp2RV5-ED6P1paV-2Kji/view ]. Accessed 26 Feb 2024.
Johnson MC, Schellekens O, Stewart J, van Ostenberg P, de Wit TR, Spieker N. SafeCare: an innovative Approach for improving Quality through standards, Benchmarking, and improvement in low- and Middle- Income Countries. Jt Comm J Qual Patient Saf. 2016;42(8):350–71.
pubmed: 27456416
Chigbu UE. Rurality as a choice: towards ruralising rural areas in sub-saharan African countries. Dev South Afr. 2013;30(6):812–25.
doi: 10.1080/0376835X.2013.859067
Veronica Bucket. https://en.wikipedia.org/wiki/Veronica_Bucket . Accessed 26 Feb 2024.
Staines A, Amalberti R, Berwick DM, Braithwaite J, Lachman P, Vincent CA. COVID-19: patient safety and quality improvement skills to deploy during the surge. Int J Qual Health Care. 2021;33(1):mzaa050.
doi: 10.1093/intqhc/mzaa050 pubmed: 32400870
Suite of health service capacity assessments in the context of the COVID-19 pandemic. https://www.who.int/teams/integrated-health-services/monitoring-health-services . Accessed 26 Feb 2024.
Interim Infection Prevention and Control Recommendations for Healthcare Personnel During the Coronavirus Disease 2019 (COVID-19) Pandemic. https://www.cdc.gov/coronavirus/2019-ncov/hcp/infection-control-recommendations.html . Accessed 26 Feb 2024.
Oladipo EK, Ajayi AF, Odeyemi AN, Akindiya OE, Adebayo ET, Oguntomi AS, Oyewole MP, Jimah EM, Oladipo AA, Ariyo OE, et al. Laboratory diagnosis of COVID-19 in Africa: availability, challenges and implications. Drug Discov Ther. 2020;14(4):153–60.
doi: 10.5582/ddt.2020.03067 pubmed: 32908070
Usher AD. Medical oxygen crisis: a belated COVID-19 response. Lancet. 2021;397(10277):868–9.
doi: 10.1016/S0140-6736(21)00561-4 pubmed: 33676621 pmcid: 9752211
Sikakulya FK, Ssebuufu R, Mambo SB, Pius T, Kabanyoro A, Kamahoro E, Mulumba Y, Muhongya JK, Kyamanywa P. Use of face masks to limit the spread of the COVID-19 among western ugandans: knowledge, attitude and practices. PLoS ONE. 2021;16(3):e0248706.
doi: 10.1371/journal.pone.0248706 pubmed: 33760882 pmcid: 7990295
Prevention, identification and management of health worker infection in the context of COVID-19 [ https://www.who.int/publications/i/item/10665-336265 ]. Accessed 26 Feb 2024.
Hui KPY, Cheung MC, Perera R, Ng KC, Bui CHT, Ho JCW, Ng MMT, Kuok DIT, Shih KC, Tsao SW, et al. Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures. Lancet Respir Med. 2020;8(7):687–95.
doi: 10.1016/S2213-2600(20)30193-4 pubmed: 32386571 pmcid: 7252187
Infection prevention and control for the safe management of a dead body in the context of COVID-19: interim guidance. https://www.who.int/publications/i/item/infection-prevention-and-control-for-the-safe-management-of-a-dead-body-in-the-context-of-covid-19-interim-guidance . Accessed 26 Feb 2024.
Jones SA, Gopalakrishnan S, Ameh CA, White S, van den Broek NR. Women and babies are dying but not of Ebola’: the effect of the Ebola virus epidemic on the availability, uptake and outcomes of maternal and newborn health services in Sierra Leone. BMJ Glob Health. 2016;1(3): e000065.
doi: 10.1136/bmjgh-2016-000065 pubmed: 28588954 pmcid: 5321347
Walker PG, White MT, Griffin JT, Reynolds A, Ferguson NM, Ghani AC. Malaria morbidity and mortality in Ebola-affected countries caused by decreased health-care capacity, and the potential effect of mitigation strategies: a modelling analysis. Lancet Infect Dis. 2015;15(7):825–32.
doi: 10.1016/S1473-3099(15)70124-6 pubmed: 25921597 pmcid: 4824180
Hogan AB, Jewell BL, Sherrard-Smith E, Vesga JF, Watson OJ, Whittaker C, Hamlet A, Smith JA, Winskill P, Verity R, et al. Potential impact of the COVID-19 pandemic on HIV, Tuberculosis, and malaria in low-income and middle-income countries: a modelling study. Lancet Glob Health. 2020;8(9):e1132-1141.
doi: 10.1016/S2214-109X(20)30288-6 pubmed: 32673577 pmcid: 7357988
Abraha HE, Gessesse Z, Gebrecherkos T, Kebede Y, Weldegiorgis AW, Tequare MH, Welderifael AL, Zenebe D, Gebremariam AG, Dawit TC, et al. Clinical features and risk factors Associated with Morbidity and Mortality among COVID-19 patients in Northern Ethiopia. Int J Infect Dis. 2021;105:776–83.
doi: 10.1016/j.ijid.2021.03.037 pubmed: 33741488 pmcid: 7962557
Western Cape Department of Health in collaboration with the National Institute for Communicable Diseases, South Africa. Risk Factors for Coronavirus Disease 2019 (COVID-19) Death in a Population Cohort Study from the Western Cape Province, South Africa. Clin Infect Dis. 2021;73(7):e2005–15.
Tiete J, Guatteri M, Lachaux A, Matossian A, Hougardy JM, Loas G, Rotsaert M. Mental Health Outcomes in Healthcare Workers in COVID-19 and Non-COVID-19 care units: a cross-sectional survey in Belgium. Front Psychol. 2020;11:612241.
doi: 10.3389/fpsyg.2020.612241 pubmed: 33469439
Fang XH, Wu L, Lu LS, Kan XH, Wang H, Xiong YJ, Ma DC, Wu GC. Mental health problems and social supports in the COVID-19 healthcare workers: a Chinese explanatory study. BMC Psychiatry. 2021;21(1):34.
doi: 10.1186/s12888-020-02998-y pubmed: 33435867 pmcid: 7802988
Debes JD, Quadri NS, Sultan A, Yousif M, Ali SI, Kayandabila J, Ijeoma I, Ssebambulidde K, Ochola L, Moussa A. Risk of Healthcare Worker Burnout in Africa during the COVID-19 pandemic. Ann Glob Health. 2021;87(1):5.
doi: 10.5334/aogh.3150 pubmed: 33505864 pmcid: 7792458
Corina Knoll AW, Rothfeld M. ‘I Couldn’t Do Anything’: The Virus and an E.R. Doctor’s Suicide. In: The New York Times. 2020.
Hand hygiene self-assessment framework 2010. https://www.who.int/publications/m/item/hand-hygiene-self-assessment-framework-2010 . Accessed 26 Feb 2024.
Strasser R, Kam SM, Regalado SM. Rural Health Care Access and Policy in developing countries. Annu Rev Public Health. 2016;37:395–412.
doi: 10.1146/annurev-publhealth-032315-021507 pubmed: 26735432
The African Regional Health Report 2014 - The health of the people: what works [ https://www.afro.who.int/publications/african-regional-health-report-2014-health-people-what-works#:~:text=Publications-,The%20African%20Regional%20Health%20Report%202014%20%2D%20The,of%20the%20people%3A%20what%20works&text=This%20report%20provides%20an%20assessment,the%20six%20regions%20of%20WHO ]. Accessed 26 Feb 2024.
Rinke de Wit TF, Janssens W, Antwi M, Milimo E, Mutegi N, Marwa H, Ndili N, Owino W, Waiyaiya E, Garcia Rojas DC, et al. Digital health systems strengthening in Africa for rapid response to COVID-19. Front Health Serv. 2022;2:987828.
The World Bank - Rural population (% of total population) - Sub-Saharan Africa. https://data.worldbank.org/indicator/SP.RUR.TOTL.ZS?locations=ZG . Accessed 26 Feb 2024.
Ugo O, Ezinne EA, Modupe O, Nicole S, Winifred E, Kelechi O. Improving quality of Care in Primary Health-Care facilities in Rural Nigeria: successes and challenges. Health Serv Res Manag Epidemiol. 2016;3:2333392816662581.
pubmed: 28462280 pmcid: 5266458
The business of health in Africa: partnering with the private sector to improve people’s lives. International Finance Corporation Washington, D.C.: World Bank Group. https://documents.worldbank.org/en/publication/documents-reports/documentdetail/878891468002994639/the-business-of-health-in-africa-partnering-with-the-private-sector-to-improve-peoples-lives . Accessed 26 Feb 2024.
Integrating Health in Africa: The Role of the Private Sector. https://www.afro.who.int/regional-director/speeches-messages/integrating-health-africa-role-private-sector . Accessed 26 Feb 2024.
Ebola outbreak in Uganda, as of 11 January 2023 - European Centre for Disease Prevention and Control. https://www.ecdc.europa.eu/en/news-events/ebola-outbreak-uganda#:~:text=On%2020%20September%202022%2C%20the,sub%2Dcounty%20in%20Mubende%20District . Accessed 26 Feb 2024.

Auteurs

Gloria P Gómez-Pérez (GP)

PharmAccess Foundation, Amsterdam, The Netherlands. p.gomez@pharmaccess.org.
Amsterdam Institute for Global Health and Development, University of Amsterdam, Amsterdam, The Netherlands. p.gomez@pharmaccess.org.

Aafke E de Graaff (AE)

PharmAccess Foundation, Amsterdam, The Netherlands.

John T Dekker (JT)

PharmAccess Foundation, Amsterdam, The Netherlands.

Bonifacia B Agyei (BB)

PharmAccess Ghana, Accra, Ghana.

Ibironke Dada (I)

PharmAccess Nigeria, Lagos, Nigeria.

Emmanuel Milimo (E)

PharmAccess Kenya, Nairobi, Kenya.

Marilyn S Ommeh (MS)

PharmAccess Kenya, Nairobi, Kenya.

Peter Risha (P)

PharmAccess Tanzania, Dar es Salaam, Tanzania.

Tobias F Rinke de Wit (TF)

PharmAccess Foundation, Amsterdam, The Netherlands.
Amsterdam Institute for Global Health and Development, University of Amsterdam, Amsterdam, The Netherlands.

Nicole Spieker (N)

PharmAccess Foundation, Amsterdam, The Netherlands.

Classifications MeSH