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1. Italy's health performance, 1990–2017: findings from the Global Burden of Disease Study 2017

Author: Monasta, L, Abbafati, C, Logroscino, G, Remuzzi, G, Perico, N, Bikbov, B, Tamburlini, G, Beghi, E, Traini, E, Boston Redford, S, Ariani, F, Borzì, AM, Bosetti, C, Carreras, G, Caso, V, Castelpietra, G, Cirillo, Massimo, Conti, S, Cortesi, PA, Damiani, G, D’Angiolella, LS, Fanzo, J, Farioli, A, Fornari, C, Gallus, S, Giussani, G, Gorini, G, Grosso, G, Guido, D, La Vecchia, C, Lauriola, P, Leonardi, M, Levi, M, Madotto, F, Mondello, S, Naldi, L, Olgiati, S, Palladino, Raffaele, Piccinelli, C, Piccininni, M, Pupillo, P, Raggi, A, Rubino, S, Santalucia, P, Vacante, M, Vidale, S, Violante, FS, Naghavi, M, and Ronfani, Monasta, L, Abbafati, C, Logroscino, G, Remuzzi, G, Perico, N, Bikbov, B, Tamburlini, G, Beghi, E, Traini, E, Boston Redford, S, Ariani, F, Borzì, Am, Bosetti, C, Carreras, G, Caso, V, Castelpietra, G, Cirillo, Massimo, Conti, S, Cortesi, Pa, Damiani, G, D’Angiolella, L, Fanzo, J, Farioli, A, Fornari, C, Gallus, S, Giussani, G, Gorini, G, Grosso, G, Guido, D, La, Vecchia, Lauriola, P, Leonardi, M, Levi, M, Madotto, F, Mondello, S, Naldi, L, Olgiati, S, Palladino, Raffaele, Piccinelli, C, Piccininni, M, Pupillo, P, Raggi, A, Rubino, S, Santalucia, P, Vacante, M, Vidale, S, Violante, F, Naghavi, M, And, Ronfani, GBD 2017 Italy Collaborators, Andrea Farioli, Francesco S. Violante, Monasta, L., Abbafati, C., Logroscino, G., Remuzzi, G., Perico, N., Bikbov, B., Tamburlini, G., Beghi, E., Traini, E., Redford, S. B., Ariani, F., Borzi, A. M., Bosetti, C., Carreras, G., Caso, V., Castelpietra, G., Cirillo, M., Conti, S., Cortesi, P. A., Damiani, G., D'Angiolella, L. S., Fanzo, J., Fornari, C., Gallus, S., Giussani, G., Gorini, G., Grosso, G., Guido, D., La Vecchia, C., Lauriola, P., Leonardi, M., Levi, M., Madotto, F., Mondello, S., Naldi, L., Olgiati, S., Palladino, R., Piccinelli, C., Piccininni, M., Pupillo, E., Raggi, A., Rubino, S., Santalucia, P., Vacante, M., Vidale, S., Violante, F. S., Naghavi, M., Ronfani, L., Redford, S, Borzì, A, Cirillo, M, Cortesi, P, D'Angiolella, L, La Vecchia, C, Palladino, R, Pupillo, E, and Ronfani, L
Subjects: Male, GBD 2017 Italy Collaborators, Health Status, Demographic transition, Disease, Global Health, 01 natural sciences, Global Burden of Disease, Health Statu, 0302 clinical medicine, Universal Health Insurance, Cause of Death, Health care, Medicine, 030212 general & internal medicine, Public, Environmental & Occupational Health, global burden of disease, Italy, health performance, health-care system, lcsh:Public aspects of medicine, Mortality rate, 1. No poverty, Italian health loss, 3. Good health, Female, TERRITORIES, Life Sciences & Biomedicine, Human, Population ageing, medicine.medical_specialty, Cost Control, Waiting Lists, GBD, 195 COUNTRIES, World Health Organization, Article, 03 medical and health sciences, Life Expectancy, SYSTEMATIC ANALYSIS, Delivery of Health Care, Humans, 0101 mathematics, Science & Technology, SEX-SPECIFIC MORTALITY, health care system, business.industry, DISABILITY, Public health, 010102 general mathematics, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, xxx, Years of potential life lost, Life expectancy, INJURIES, GBD Italy, business, Demography
Abstract: Summary Background Through a comprehensive analysis of Italy's estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we aimed to understand the patterns of health loss and response of the health-care system, and offer evidence-based policy indications in light of the demographic transition and government health spending in the country. Methods Estimates for Italy were extracted from GBD 2017. Data on Italy are presented for 1990 and 2017, on prevalence, causes of death, years of life lost, years lived with disability, disability-adjusted life-years (DALYs), life expectancy at birth and at age 65 years, healthy life expectancy, and Healthcare Access and Quality (HAQ) Index. We compared the estimates for Italy with those of 15 other western European countries. Findings The quality of the universal health system and healthy behaviours contribute to favourable overall health, even in comparison with other western European countries. In 2017, life expectancy and HAQ Index score in Italy were among the highest globally, with life expectancy at birth reaching 85·3 years for females and 80·8 for males in 2017, ranking Italy eighth globally for females and sixth for males, and an HAQ Index score of 94·9 in 2016 compared with 81·54 in 1990, keeping Italy ranked as ninth globally. Between 1990 and 2017 age-standardised death rates for cardiovascular diseases decreased by 53·7% (95% uncertainty interval −56·1 to −51·4), for neoplasms decreased by 28·2% (−32·3 to −24·6), and for transport injuries decreased by 62·1% (−64·6 to −59·2). However, population ageing is causing an increase in the burden of specific diseases, such as Alzheimer's disease and other dementias (DALYs increased by 77·9% [68·4 to 87·2]) and pancreatic (DALYs increased by 39·7% [28·4 to 51·7]) and uterine cancers (DALYs increased by 164·7% [129·7 to 202·5]). Behavioural risk factors, which are potentially modifiable, still have a strong effect, particularly on cardiovascular diseases and neoplasms. For instance, in 2017, 44 400 (41 200 to 47 800) cancer deaths were attributed to smoking, 12 000 (9600 to 14 800) to alcohol use, and 9500 (5400 to 14 200) to high body-mass index, while 47 000 (31 100 to 65 700) deaths due to cardiovascular diseases could be attributed to high LDL cholesterol, 28 700 (19 700 to 38 500) to diets low in whole grains, and 15 900 (8500 to 24 900) to low physical activity. Interpretation Italy provides an interesting example of the results that can be achieved by a mix of relatively healthy lifestyles and a universal health system. Two main issues require attention, population ageing and gradual decrease of public health financing, which both pose several challenges to the future of Italy's health status. Our findings should be useful to Italy's policy makers and health system experts elsewhere. Funding Bill & Melinda Gates Foundation.
Published: 2019
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2. Comparison of the effect of MFAT and MFAT + PRP on treatment of hip osteoarthritis : an observational, intention-to-treat study at one year

Author: Delgado, Diego, Sanchez, Mikel, Heidari, N, Slevin, M, Zeinolabediny, Y, Meloni, D, Olgiati, S, Wilson, A, Noorani, A, Azamfirei, L, Delgado, Diego, Sanchez, Mikel, Heidari, N, Slevin, M, Zeinolabediny, Y, Meloni, D, Olgiati, S, Wilson, A, Noorani, A, and Azamfirei, L
Abstract: Hip osteoarthritis (OA) is a major contributor to reduced quality of life and concomitant disability associated with lost working life months. Intra-articular injection of various biological materials has shown promise in alleviating symptoms and potentially slowing down the degenerative process. Here, we compared the effects of treatment of a cohort of 147 patients suffering from grade 1–4 hip OA; with either micro-fragmented adipose tissue (MFAT), or a combination of MFAT with platelet-rich plasma (PRP). We found significant improvements in both the visual analogue score for pain (VAS) and Oxford hip score (OHS) that were similar for both treatments with over 60% having an improvement in the VAS score of 20 points or more. These results suggest a positive role for intra-articular injection of MFAT + PRP as a treatment for hip osteoarthritis which may be important particularly in low body mass index (BMI) patients where the difficulty in obtaining sufficient MFAT for treatment could be offset by using this combination of biologicals.
Published: 2022

3. Past, present, and future of global health financing: A review of development assistance, government, out-of-pocket, and other private spending on health for 195 countries, 1995-2050

Author: Chang, A, Cowling, K, Micah, A, Chapin, A, Chen, C, Ikilezi, G, Sadat, N, Tsakalos, G, Wu, J, Younker, T, Zhao, Y, Zlavog, B, Abbafati, C, Ahmed, A, Alam, K, Alipour, V, Aljunid, S, Almalki, M, Alvis-Guzman, N, Ammar, W, Andrei, C, Anjomshoa, M, Antonio, C, Arabloo, J, Aremu, O, Ausloos, M, Avila-Burgos, L, Awasthi, A, Ayanore, M, Azari, S, Azzopardi-Muscat, N, Bagherzadeh, M, Barnighausen, T, Baune, B, Bayati, M, Belay, Y, Belete, H, Berbada, D, Berman, A, Beuran, M, Bijani, A, Busse, R, Cahuana-Hurtado, L, Camera, L, Catala-Lopez, F, Chauhan, B, Constantin, M, Crowe, C, Cucu, A, Dalal, K, De Neve, J, Deiparine, S, Demeke, F, Do, H, Dubey, M, Tantawi, M, Eskandarieh, S, Esmaeili, R, Fakhar, M, Fazaeli, A, Fischer, F, Foigt, N, Fukumoto, T, Fullman, N, Galan, A, Gamkrelidze, A, Gezae, K, Ghajar, A, Ghashghaee, A, Goginashvili, K, Haakenstad, A, Bidgoli, H, Hamidi, S, Harb, H, Hasanpoor, E, Hassen, H, Hay, S, Hendrie, D, Henok, A, Heredia-Pi, I, Herteliu, C, Hoang, C, Hole, M, Rad, E, Hossain, N, Hosseinzadeh, M, Hostiuc, S, Ilesanmi, O, Irvani, S, Jakovljevic, M, Jalali, A, James, S, Jonas, J, Jurisson, M, Kadel, R, Matin, B, Kasaeian, A, Kasaye, H, Kassaw, M, Karyani, A, Khabiri, R, Khan, J, Khan, M, Khang, Y, Kisa, A, Kissimova-Skarbek, K, Kohler, S, Koyanagi, A, Krohn, K, Leung, R, Lim, L, Lorkowski, S, Majeed, A, Malekzadeh, R, Mansourian, M, Mantovani, L, Massenburg, B, Mckee, M, Mehta, V, Meretoja, A, Meretoja, T, Kostova, N, Miller, T, Mirrakhimov, E, Mohajer, B, Darwesh, A, Mohammed, S, Mohebi, F, Mokdad, A, Morrison, S, Mousavi, S, Muthupandian, S, Nagarajan, A, Nangia, V, Negoi, I, Nguyen, C, Nguyen, H, Nguyen, S, Nosratnejad, S, Oladimeji, O, Olgiati, S, Olusanya, J, Onwujekwe, O, Otstavnov, S, Pana, A, Pereira, D, Piroozi, B, Prada, S, Qorbani, M, Rabiee, M, Rabiee, N, Rafiei, A, Rahim, F, Rahimi-Movaghar, V, Ram, U, Ranabhat, C, Ranta, A, Rawaf, D, Rawaf, S, Rezaei, S, Roro, E, Rostami, A, Rubino, S, Salahshoor, M, Samy, A, Sanabria, J, Santos, J, Milicevic, M, Jose, B, Savic, M, Schwendicke, F, Sepanlou, S, Sepehrimanesh, M, Sheikh, A, Shrime, M, Sisay, S, Soltani, S, Soofi, M, Srinivasan, V, Tabares-Seisdedos, R, Torre, A, Tovani-Palone, M, Tran, B, Tran, K, Undurraga, E, Valdez, P, Van Boven, J, Vargas, V, Veisani, Y, Violante, F, Vladimirov, S, Vlassov, V, Vollmer, S, Vu, G, Wolfe, C, Yonemoto, N, Younis, M, Yousefifard, M, Zaman, S, Zangeneh, A, Zegeye, E, Ziapour, A, Chew, A, Murray, C, Dieleman, J, Chang A. Y., Cowling K., Micah A. E., Chapin A., Chen C. S., Ikilezi G., Sadat N., Tsakalos G., Wu J., Younker T., Zhao Y., Zlavog B. S., Abbafati C., Ahmed A. E., Alam K., Alipour V., Aljunid S. M., Almalki M. J., Alvis-Guzman N., Ammar W., Andrei C. L., Anjomshoa M., Antonio C. A. T., Arabloo J., Aremu O., Ausloos M., Avila-Burgos L., Awasthi A., Ayanore M. A., Azari S., Azzopardi-Muscat N., Bagherzadeh M., Barnighausen T. W., Baune B. T., Bayati M., Belay Y. B., Belay Y. A., Belete H., Berbada D. A., Berman A. E., Beuran M., Bijani A., Busse R., Cahuana-Hurtado L., Camera L. A., Catala-Lopez F., Chauhan B. G., Constantin M. -M., Crowe C. S., Cucu A., Dalal K., De Neve J. -W., Deiparine S., Demeke F. M., Do H. P., Dubey M., Tantawi M. E., Eskandarieh S., Esmaeili R., Fakhar M., Fazaeli A. A., Fischer F., Foigt N. A., Fukumoto T., Fullman N., Galan A., Gamkrelidze A., Gezae K. E., Ghajar A., Ghashghaee A., Goginashvili K., Haakenstad A., Bidgoli H. H., Hamidi S., Harb H. L., Hasanpoor E., Hassen H. Y., Hay S. I., Hendrie D., Henok A., Heredia-Pi I., Herteliu C., Hoang C. L., Hole M. K., Rad E. H., Hossain N., Hosseinzadeh M., Hostiuc S., Ilesanmi O. S., Irvani S. S. N., Jakovljevic M., Jalali A., James S. L., Jonas J. B., Jurisson M., Kadel R., Matin B. K., Kasaeian A., Kasaye H. K., Kassaw M. W., Karyani A. K., Khabiri R., Khan J., Khan M. N., Khang Y. -H., Kisa A., Kissimova-Skarbek K., Kohler S., Koyanagi A., Krohn K. J., Leung R., Lim L. -L., Lorkowski S., Majeed A., Malekzadeh R., Mansourian M., Mantovani L. G., Massenburg B. B., Mckee M., Mehta V., Meretoja A., Meretoja T. J., Kostova N. M., Miller T. R., Mirrakhimov E. M., Mohajer B., Darwesh A. M., Mohammed S., Mohebi F., Mokdad A. H., Morrison S. D., Mousavi S. M., Muthupandian S., Nagarajan A. J., Nangia V., Negoi I., Nguyen C. T., Nguyen H. L. T., Nguyen S. H., Nosratnejad S., Oladimeji O., Olgiati S., Olusanya J. O., Onwujekwe O. E., Otstavnov S. S., Pana A., Pereira D. M., Piroozi B., Prada S. I., Qorbani M., Rabiee M., Rabiee N., Rafiei A., Rahim F., Rahimi-Movaghar V., Ram U., Ranabhat C. L., Ranta A., Rawaf D. L., Rawaf S., Rezaei S., Roro E. M., Rostami A., Rubino S., Salahshoor M., Samy A. M., Sanabria J., Santos J. V., Milicevic M. M. S., Jose B. P. S., Savic M., Schwendicke F., Sepanlou S. G., Sepehrimanesh M., Sheikh A., Shrime M. G., Sisay S., Soltani S., Soofi M., Srinivasan V., Tabares-Seisdedos R., Torre A., Tovani-Palone M. R., Tran B. X., Tran K. B., Undurraga E. A., Valdez P. R., Van Boven J. F. M., Vargas V., Veisani Y., Violante F. S., Vladimirov S. K., Vlassov V., Vollmer S., Vu G. T., Wolfe C. D. A., Yonemoto N., Younis M. Z., Yousefifard M., Zaman S. B., Zangeneh A., Zegeye E. A., Ziapour A., Chew A., Murray C. J. L., Dieleman J. L., Chang, A, Cowling, K, Micah, A, Chapin, A, Chen, C, Ikilezi, G, Sadat, N, Tsakalos, G, Wu, J, Younker, T, Zhao, Y, Zlavog, B, Abbafati, C, Ahmed, A, Alam, K, Alipour, V, Aljunid, S, Almalki, M, Alvis-Guzman, N, Ammar, W, Andrei, C, Anjomshoa, M, Antonio, C, Arabloo, J, Aremu, O, Ausloos, M, Avila-Burgos, L, Awasthi, A, Ayanore, M, Azari, S, Azzopardi-Muscat, N, Bagherzadeh, M, Barnighausen, T, Baune, B, Bayati, M, Belay, Y, Belete, H, Berbada, D, Berman, A, Beuran, M, Bijani, A, Busse, R, Cahuana-Hurtado, L, Camera, L, Catala-Lopez, F, Chauhan, B, Constantin, M, Crowe, C, Cucu, A, Dalal, K, De Neve, J, Deiparine, S, Demeke, F, Do, H, Dubey, M, Tantawi, M, Eskandarieh, S, Esmaeili, R, Fakhar, M, Fazaeli, A, Fischer, F, Foigt, N, Fukumoto, T, Fullman, N, Galan, A, Gamkrelidze, A, Gezae, K, Ghajar, A, Ghashghaee, A, Goginashvili, K, Haakenstad, A, Bidgoli, H, Hamidi, S, Harb, H, Hasanpoor, E, Hassen, H, Hay, S, Hendrie, D, Henok, A, Heredia-Pi, I, Herteliu, C, Hoang, C, Hole, M, Rad, E, Hossain, N, Hosseinzadeh, M, Hostiuc, S, Ilesanmi, O, Irvani, S, Jakovljevic, M, Jalali, A, James, S, Jonas, J, Jurisson, M, Kadel, R, Matin, B, Kasaeian, A, Kasaye, H, Kassaw, M, Karyani, A, Khabiri, R, Khan, J, Khan, M, Khang, Y, Kisa, A, Kissimova-Skarbek, K, Kohler, S, Koyanagi, A, Krohn, K, Leung, R, Lim, L, Lorkowski, S, Majeed, A, Malekzadeh, R, Mansourian, M, Mantovani, L, Massenburg, B, Mckee, M, Mehta, V, Meretoja, A, Meretoja, T, Kostova, N, Miller, T, Mirrakhimov, E, Mohajer, B, Darwesh, A, Mohammed, S, Mohebi, F, Mokdad, A, Morrison, S, Mousavi, S, Muthupandian, S, Nagarajan, A, Nangia, V, Negoi, I, Nguyen, C, Nguyen, H, Nguyen, S, Nosratnejad, S, Oladimeji, O, Olgiati, S, Olusanya, J, Onwujekwe, O, Otstavnov, S, Pana, A, Pereira, D, Piroozi, B, Prada, S, Qorbani, M, Rabiee, M, Rabiee, N, Rafiei, A, Rahim, F, Rahimi-Movaghar, V, Ram, U, Ranabhat, C, Ranta, A, Rawaf, D, Rawaf, S, Rezaei, S, Roro, E, Rostami, A, Rubino, S, Salahshoor, M, Samy, A, Sanabria, J, Santos, J, Milicevic, M, Jose, B, Savic, M, Schwendicke, F, Sepanlou, S, Sepehrimanesh, M, Sheikh, A, Shrime, M, Sisay, S, Soltani, S, Soofi, M, Srinivasan, V, Tabares-Seisdedos, R, Torre, A, Tovani-Palone, M, Tran, B, Tran, K, Undurraga, E, Valdez, P, Van Boven, J, Vargas, V, Veisani, Y, Violante, F, Vladimirov, S, Vlassov, V, Vollmer, S, Vu, G, Wolfe, C, Yonemoto, N, Younis, M, Yousefifard, M, Zaman, S, Zangeneh, A, Zegeye, E, Ziapour, A, Chew, A, Murray, C, Dieleman, J, Chang A. Y., Cowling K., Micah A. E., Chapin A., Chen C. S., Ikilezi G., Sadat N., Tsakalos G., Wu J., Younker T., Zhao Y., Zlavog B. S., Abbafati C., Ahmed A. E., Alam K., Alipour V., Aljunid S. M., Almalki M. J., Alvis-Guzman N., Ammar W., Andrei C. L., Anjomshoa M., Antonio C. A. T., Arabloo J., Aremu O., Ausloos M., Avila-Burgos L., Awasthi A., Ayanore M. A., Azari S., Azzopardi-Muscat N., Bagherzadeh M., Barnighausen T. W., Baune B. T., Bayati M., Belay Y. B., Belay Y. A., Belete H., Berbada D. A., Berman A. E., Beuran M., Bijani A., Busse R., Cahuana-Hurtado L., Camera L. A., Catala-Lopez F., Chauhan B. G., Constantin M. -M., Crowe C. S., Cucu A., Dalal K., De Neve J. -W., Deiparine S., Demeke F. M., Do H. P., Dubey M., Tantawi M. E., Eskandarieh S., Esmaeili R., Fakhar M., Fazaeli A. A., Fischer F., Foigt N. A., Fukumoto T., Fullman N., Galan A., Gamkrelidze A., Gezae K. E., Ghajar A., Ghashghaee A., Goginashvili K., Haakenstad A., Bidgoli H. H., Hamidi S., Harb H. L., Hasanpoor E., Hassen H. Y., Hay S. I., Hendrie D., Henok A., Heredia-Pi I., Herteliu C., Hoang C. L., Hole M. K., Rad E. H., Hossain N., Hosseinzadeh M., Hostiuc S., Ilesanmi O. S., Irvani S. S. N., Jakovljevic M., Jalali A., James S. L., Jonas J. B., Jurisson M., Kadel R., Matin B. K., Kasaeian A., Kasaye H. K., Kassaw M. W., Karyani A. K., Khabiri R., Khan J., Khan M. N., Khang Y. -H., Kisa A., Kissimova-Skarbek K., Kohler S., Koyanagi A., Krohn K. J., Leung R., Lim L. -L., Lorkowski S., Majeed A., Malekzadeh R., Mansourian M., Mantovani L. G., Massenburg B. B., Mckee M., Mehta V., Meretoja A., Meretoja T. J., Kostova N. M., Miller T. R., Mirrakhimov E. M., Mohajer B., Darwesh A. M., Mohammed S., Mohebi F., Mokdad A. H., Morrison S. D., Mousavi S. M., Muthupandian S., Nagarajan A. J., Nangia V., Negoi I., Nguyen C. T., Nguyen H. L. T., Nguyen S. H., Nosratnejad S., Oladimeji O., Olgiati S., Olusanya J. O., Onwujekwe O. E., Otstavnov S. S., Pana A., Pereira D. M., Piroozi B., Prada S. I., Qorbani M., Rabiee M., Rabiee N., Rafiei A., Rahim F., Rahimi-Movaghar V., Ram U., Ranabhat C. L., Ranta A., Rawaf D. L., Rawaf S., Rezaei S., Roro E. M., Rostami A., Rubino S., Salahshoor M., Samy A. M., Sanabria J., Santos J. V., Milicevic M. M. S., Jose B. P. S., Savic M., Schwendicke F., Sepanlou S. G., Sepehrimanesh M., Sheikh A., Shrime M. G., Sisay S., Soltani S., Soofi M., Srinivasan V., Tabares-Seisdedos R., Torre A., Tovani-Palone M. R., Tran B. X., Tran K. B., Undurraga E. A., Valdez P. R., Van Boven J. F. M., Vargas V., Veisani Y., Violante F. S., Vladimirov S. K., Vlassov V., Vollmer S., Vu G. T., Wolfe C. D. A., Yonemoto N., Younis M. Z., Yousefifard M., Zaman S. B., Zangeneh A., Zegeye E. A., Ziapour A., Chew A., Murray C. J. L., and Dieleman J. L.
Abstract: Background: Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries. Methods: We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories-government, out-of-pocket, and prepaid private health spending-and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more reso
Published: 2019

4. Tracking development assistance for health and for COVID-19: a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050

Author: Micah A, Cogswell I, Cunningham B, Ezoe S, Harle A, Maddison E, McCracken D, Nomura S, Simpson K, Stutzman H, Tsakalos G, Wallace L, Zhao Y, Zende R, Abbafati C, Abdelmasseh M, Abedi A, Abegaz K, Abhilash E, Abolhassani H, Abrigo M, Adhikari T, Afzal S, Ahinkorah B, Ahmadi S, Ahmed H, Ahmed M, Rashid T, Ajami M, Aji B, Akalu Y, Akunna C, Al Hamad H, Alam K, Alanezi F, Alanzi T, Alemayehu Y, Alhassan R, Alinia C, Aljunid S, Almustanyir S, Alvis-Guzman N, Alvis-Zakzuk N, Amini S, Amini-Rarani M, Amu H, Ancuceanu R, Andrei C, Andrei T, Angell B, Anjomshoa M, Antonio C, Antony C, Aqeel M, Arabloo J, Arab-Zozani M, Aripov T, Arrigo A, Ashraf T, Atnafu D, Ausloos M, Avila-Burgos L, Awan A, Ayano G, Ayanore M, Azari S, Azhar G, Babalola T, Bahrami M, Baig A, Banach M, Barati N, Barnighausen T, Barrow A, Basu S, Baune B, Bayati M, Benzian H, Berman A, Bhagavathula A, Bhardwaj N, Bhardwaj P, Bhaskar S, Bibi S, Bijani A, Bodolica V, Bragazzi N, Braithwaite D, Breitborde N, Breusov A, Briko N, Busse R, Cahuana-Hurtado L, Callander E, Camera L, Castaneda-Orjuela C, Catala-Lopez F, Charan J, Chatterjee S, Chattu S, Chattu V, Chen S, Cicero A, Dadras O, Dahlawi S, Dai X, Dalal K, Dandona L, Dandona R, Davitoiu D, De Neve J, de Sa A, Denova-Gutierrez E, Dhamnetiya D, Dharmaratne S, Doshmangir L, Dube J, Ehsani-Chimeh E, Zaki M, El Tantawi M, Eskandarieh S, Farzadfar F, Ferede T, Fischer F, Foigt N, Freitas A, Friedman S, Fukumoto T, Fullman N, Gaal P, Gad M, Garcia-Gordillo M, Garg T, Ghafourifard M, Ghashghaee A, Gholamian A, Gholamrezanezhad A, Ghozali G, Gilani S, Glavan I, Glushkova E, Goharinezhad S, Golechha M, Goli S, Guha A, Gupta V, Haakenstad A, Haider M, Hailu A, Hamidi S, Hanif A, Harapan H, Hartono R, Hasaballah A, Hassan S, Hassanein M, Hayat K, Hegazy M, Heidari G, Hendrie D, Heredia-Pi I, Herteliu C, Hezam K, Holla R, Hossain S, Hosseinzadeh M, Hostiuc S, Huda T, Hwang B, Iavicoli I, Idrisov B, Ilesanmi O, Irvani S, Islam S, Ismail N, Isola G, Jahani M, Jahanmehr N, Jakovljevic M, Janodia M, Javaheri T, Jayapal S, Jayawardena R, Jazayeri S, Jha R, Jonas J, Joo T, Joukar F, Jurisson M, Kaambwa B, Kalhor R, Kanchan T, Kandel H, Matin B, Karimi S, Kassahun G, Kayode G, Karyani A, Keikavoosi-Arani L, Khader Y, Khajuria H, Khalilov R, Khammarnia M, Khan J, Khubchandani J, Kianipour N, Kim G, Kim Y, Kisa A, Kisa S, Kohler S, Kosen S, Koteeswaran R, Laxminarayana S, Koyanagi A, Krishan K, Kumar G, Kusuma D, Lamnisos D, Lansingh V, Larsson A, Lasrado S, Le L, Lee S, Lee Y, Lim S, Lobo S, Lozano R, Abd El Razek H, Abd El Razek M, Mahdavi M, Majeed A, Makki A, Maleki A, Malekzadeh R, Manda A, Mansour-Ghanaei F, Mansournia M, Arnedo C, Martinez-Valle A, Masoumi S, Maude R, Mckee M, Medina-Solis C, Menezes R, Meretoja A, Meretoja T, Mesregah M, Mestrovic T, Kostova N, Miller T, Mini G, Mirica A, Mirrakhimov E, Mohajer B, Mohamed T, Mohammadi M, Mohammadian-Hafshejani A, Mohammed S, Moitra M, Mokdad A, Molokhia M, Moni M, Moradi Y, Morze J, Mousavi S, Mpundu-Kaambwa C, Muriithi M, Muthupandian S, Nagarajan A, Naimzada M, Nangia V, Naqvi A, Narayana A, Nascimento B, Naveed M, Nayak B, Nazari J, Ndejjo R, Negoi I, Kandel S, Nguyen T, Nonvignon J, Noubiap J, Nwatah V, Oancea B, Ojelabi F, Olagunju A, Olakunde B, Olgiati S, Olusanya J, Onwujekwe O, Otoiu A, Otstavnov N, Otstavnov S, Owolabi M, Padubidri J, Palladino R, Panda-Jonas S, Park E, Kan F, Pawar S, Toroudi H, Pereira D, Perianayagam A, Pesudovs K, Piccinelli C, Postma M, Prada S, Rabiee M, Rabiee N, Rahim F, Rahimi-Movaghar V, Rahman M, Rahmani A, Ram U, Ranabhat C, Ranasinghe P, Rao C, Rathi P, Rawaf D, Rawaf S, Rawal L, Rawassizadeh R, Reiner R, Renzaho A, Reshmi B, Riaz M, Ripon R, Saad A, Sahraian M, Sahu M, Salama J, Salehi S, Samy A, Sanabria J, Sanmarchi F, Santos J, Santric-Milicevic M, Sathian B, Savic M, Saxena D, Sayyah M, Schwendicke F, Senthilkumaran S, Sepanlou S, Seylani A, Shahabi S, Shaikh M, Sheikh A, Shetty A, Shetty P, Shibuya K, Shrime M, Shuja K, Singh J, Skryabin V, Skryabina A, Soltani S, Soofi M, Spurlock E, Stefan S, Szerencses V, Szocska M, Tabares-Seisdedos R, Taddele B, Tefera Y, Thavamani A, Tobe-Gai R, Topor-Madry R, Tovani-Palone M, Tran B, Car L, Ullah A, Ullah S, Umar N, Undurraga E, Valdez P, Vasankari T, Villafane J, Violante F, Vlassov V, Vo B, Vollmer S, Vos T, Vu G, Vu L, Wamai R, Werdecker A, Woldekidan M, Wubishet B, Xu G, Yaya S, Yazdi-Feyzabadi V, Yigit V, Yip P, Yirdaw B, Yonemoto N, Younis M, Yu C, Yunusa I, Moghadam T, Zandian H, Zastrozhin M, Zastrozhina A, Zhang Z, Ziapour A, Zuniga Y, Hay S, Murray C, Dieleman J, and Global Burden Dis Hlth Financing
Abstract: Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
Published: 2021

5. Tracking development assistance for health and for COVID-19: A review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990–2050

Author: Micah, A.E., Cogswell, I.E., Cunningham, B., Ezoe, S., Harle, A.C., Maddison, E.R., McCracken, D., Nomura, S., Simpson, K.E., Stutzman, H.N., Tsakalos, G., Wallace, L.E., Zhao, Y., Zende, R.R., Abbafati, C., Abdelmasseh, M., Abedi, A., Abegaz, K.H., Abhilash, E.S., Abolhassani, H., Abrigo, M.R.M., Adhikari, T.B., Afzal, S., Ahinkorah, B.O., Ahmadi, S., Ahmed, H., Ahmed, M.B., Ahmed Rashid, T., Ajami, M., Aji, B., Akalu, Y., Akunna, C.J., Al Hamad, H., Alam, K., Alanezi, F.M., Alanzi, T.M., Alemayehu, Y., Alhassan, R.K., Alinia, C., Aljunid, S.M., Almustanyir, S.A., Alvis-Guzman, N., Alvis-Zakzuk, N.J., Amini, S., Amini-Rarani, M., Amu, H., Ancuceanu, R., Andrei, C.L., Andrei, T., Angell, B., Anjomshoa, M., Antonio, C.A.T., Antony, C.M., Aqeel, M., Arabloo, J., Arab-Zozani, M., Aripov, T., Arrigo, A., Ashraf, T., Atnafu, D.D., Ausloos, M., Avila-Burgos, L., Awan, A.T., Ayano, G., Ayanore, M.A., Azari, S., Azhar, G.S., Babalola, T.K., Bahrami, M.A., Baig, A.A., Banach, M., Barati, N., Bärnighausen, T.W., Barrow, A., Basu, S., Baune, B.T., Bayati, M., Benzian, H., Berman, A.E., Bhagavathula, A.S., Bhardwaj, N., Bhardwaj, P., Bhaskar, S., Bibi, S., Bijani, A., Bodolica, V., Bragazzi, N.L., Braithwaite, D., Breitborde, N.J.K., Breusov, A.V., Briko, N.I., Busse, R., Cahuana-Hurtado, L., Callander, E.J., Cámera, L.A., Castañeda-Orjuela, C.A., Catalá-López, F., Charan, J., Chatterjee, S., Chattu, S.K., Chattu, V.K., Chen, S., Cicero, A.F.G., Dadras, O., Dahlawi, S.M.A., Dai, X., Dalal, K., Dandona, L., Dandona, R., Davitoiu, D.V., De Neve, J-W, de Sá-Junior, A.R., Denova-Gutiérrez, E., Dhamnetiya, D., Dharmaratne, S.D., Doshmangir, L., Dube, J., Ehsani-Chimeh, E., El Sayed Zaki, M., El Tantawi, M., Eskandarieh, S., Farzadfar, F., Ferede, T.Y., Fischer, F., Foigt, N.A., Freitas, A., Friedman, S.D., Fukumoto, T., Fullman, N., Gaal, P.A., Gad, M.M., Garcia-Gordillo, M.A., Garg, T., Ghafourifard, M., Ghashghaee, A., Gholamian, A., Gholamrezanezhad, A., Ghozali, G., Gilani, S.A., Glăvan, I-R, Glushkova, E.V., Goharinezhad, S., Golechha, M., Goli, S., Guha, A., Gupta, V.B., Gupta, V.K., Haakenstad, A., Haider, M.R., Hailu, A., Hamidi, S., Hanif, A., Harapan, H., Hartono, R.K., Hasaballah, A.I., Hassan, S., Hassanein, M.H., Hayat, K., Hegazy, M.I., Heidari, G., Hendrie, D., Heredia-Pi, I., Herteliu, C., Hezam, K., Holla, R., Hossain, S.., Hosseinzadeh, M., Hostiuc, S., Huda, T.M., Hwang, B-F, Iavicoli, I., Idrisov, B., Ilesanmi, O.S., Irvani, S.S.N., Islam, S.M.S., Ismail, N.E., Isola, G., Jahani, M.A., Jahanmehr, N., Jakovljevic, M., Janodia, M.D., Javaheri, T., Jayapal, S.K., Jayawardena, R., Jazayeri, S.B., Jha, R.P., Jonas, J.B., Joo, T., Joukar, F., Jürisson, M., Kaambwa, B., Kalhor, R., Kanchan, T., Kandel, H., Karami Matin, B., Karimi, S.E., Kassahun, G., Kayode, G.A., Kazemi Karyani, A., Keikavoosi-Arani, L., Khader, Y.S., Khajuria, H., Khalilov, R., Khammarnia, M., Khan, J., Khubchandani, J., Kianipour, N., Kim, G.R., Kim, Y.J., Kisa, A., Kisa, S., Kohler, S., Kosen, S., Koteeswaran, R., Koulmane Laxminarayana, S.L., Koyanagi, A., Krishan, K., Kumar, G.A., Kusuma, D., Lamnisos, D., Lansingh, V.C., Larsson, A.O., Lasrado, S., Le, L.K.D., Lee, S.W.H., Lee, Y.Y., Lim, S.S., Lobo, S.W., Lozano, R., Magdy Abd El Razek, H., Magdy Abd El Razek, M., Mahdavi, M.M., Majeed, A., Makki, A., Maleki, A., Malekzadeh, R., Manda, A.L., Mansour-Ghanaei, F., Mansournia, M.A., Marrugo Arnedo, C.A., Martinez-Valle, A., Masoumi, S.Z., Maude, Ri.J., McKee, M., Medina-Solís, C.E., Menezes, R.G., Meretoja, A., Meretoja, T.J., Mesregah, M.K., Mestrovic, T., Milevska Kostova, N., Miller, T.R., Mini, G.K., Mirica, A., Mirrakhimov, E.M., Mohajer, B., Mohamed, T.A., Mohammadi, M., Mohammadian-Hafshejani, A., Mohammed, S., Moitra, M., Mokdad, A.H., Molokhia, M., Moni, M.A., Moradi, Y., Morze, J., Mousavi, S.M., Mpundu-Kaambwa, C., Muriithi, M.K, Muthupandian, S., Nagarajan, A.J., Naimzada, M.D., Nangia, V., Naqvi, A.A., Narayana, A.I., Nascimento, B.R., Naveed, M., Nayak, B.P., Nazari, J., Ndejjo, R., Negoi, I., Neupane Kandel, S., Nguyen, T.H., Nonvignon, J., Noubiap, J.J., Nwatah, V.E., Oancea, B., Ojelabi, F.A.O., Olagunju, A.T., Olakunde, B.O., Olgiati, S., Olusanya, J.O., Onwujekwe, O.E., Otoiu, A., Otstavnov, N., Otstavnov, S.S., Owolabi, M.O., Padubidri, J.R., Palladino, R., Panda-Jonas, S., Park, E-C, Pashazadeh Kan, F., Pawar, S., Pazoki Toroudi, H., Pereira, D.M., Perianayagam, A., Pesudovs, K., Piccinelli, C., Postma, M.J., Prada, S.I., Rabiee, M., Rabiee, N., Rahim, F., Rahimi-Movaghar, V., Rahman, M.H.U., Rahman, M., Rahmani, A.M., Ram, U., Ranabhat, C.L., Ranasinghe, P., Rao, C.R., Rathi, P., Rawaf, D.L., Rawaf, S., Rawal, L., Rawassizadeh, R., Reiner Jr, R.C., Renzaho, A.M.N., Reshmi, B., Riaz, M.A., Ripon, R.K., Saad, A.M., Sahraian, M.A., Sahu, M., Salama, J.S., Salehi, S., Samy, A.M., Sanabria, J., Sanmarchi, F., Santos, J.V., Santric-Milicevic, M.M., Sathian, B., Savic, M., Saxena, D., Sayyah, M., Schwendicke, F., Senthilkumaran, S., Sepanlou, S.G., Seylani, A., Shahabi, S., Shaikh, M.A., Sheikh, A., Shetty, A., Shetty, P.H., Shibuya, K., Shrime, M.G., Shuja, K.H., Singh, J.A., Skryabin, V.Y., Skryabina, A.A., Soltani, S., Soofi, M., Spurlock, E.E., Stefan, S.C., Szerencsés, V., Szócska, M., Tabarés-Seisdedos, R., Taddele, B.W., Tefera, Y.G., Thavamani, A., Tobe-Gai, R., Topor-Madry, R., Tovani-Palone, M.R., Tran, B.X., Tudor Car, L., Ullah, A., Ullah, S., Umar, N., Undurraga, E.A., Valdez, P.R., Vasankari, T.J., Villafañe, J.H., Violante, F.S., Vlassov, V., Vo, B., Vollmer, S., Vos, T., Vu, G.T., Vu, L.G., Wamai, R.G., Werdecker, A., Woldekidan, M.A., Wubishet, B.L., Xu, G., Yaya, S., Yazdi-Feyzabadi, V., Yiğit, V., Yip, P., Yirdaw, B.W., Yonemoto, N., Younis, M.Z., Yu, C., Yunusa, I., Zahirian Moghadam, T., Zandian, H., Zastrozhin, M.S., Zastrozhina, A., Zhang, Z-J, Ziapour, A., Zuniga, Y.M.H., Hay, S.I., Murray, C. J.L., Dieleman, J.L., Micah, A.E., Cogswell, I.E., Cunningham, B., Ezoe, S., Harle, A.C., Maddison, E.R., McCracken, D., Nomura, S., Simpson, K.E., Stutzman, H.N., Tsakalos, G., Wallace, L.E., Zhao, Y., Zende, R.R., Abbafati, C., Abdelmasseh, M., Abedi, A., Abegaz, K.H., Abhilash, E.S., Abolhassani, H., Abrigo, M.R.M., Adhikari, T.B., Afzal, S., Ahinkorah, B.O., Ahmadi, S., Ahmed, H., Ahmed, M.B., Ahmed Rashid, T., Ajami, M., Aji, B., Akalu, Y., Akunna, C.J., Al Hamad, H., Alam, K., Alanezi, F.M., Alanzi, T.M., Alemayehu, Y., Alhassan, R.K., Alinia, C., Aljunid, S.M., Almustanyir, S.A., Alvis-Guzman, N., Alvis-Zakzuk, N.J., Amini, S., Amini-Rarani, M., Amu, H., Ancuceanu, R., Andrei, C.L., Andrei, T., Angell, B., Anjomshoa, M., Antonio, C.A.T., Antony, C.M., Aqeel, M., Arabloo, J., Arab-Zozani, M., Aripov, T., Arrigo, A., Ashraf, T., Atnafu, D.D., Ausloos, M., Avila-Burgos, L., Awan, A.T., Ayano, G., Ayanore, M.A., Azari, S., Azhar, G.S., Babalola, T.K., Bahrami, M.A., Baig, A.A., Banach, M., Barati, N., Bärnighausen, T.W., Barrow, A., Basu, S., Baune, B.T., Bayati, M., Benzian, H., Berman, A.E., Bhagavathula, A.S., Bhardwaj, N., Bhardwaj, P., Bhaskar, S., Bibi, S., Bijani, A., Bodolica, V., Bragazzi, N.L., Braithwaite, D., Breitborde, N.J.K., Breusov, A.V., Briko, N.I., Busse, R., Cahuana-Hurtado, L., Callander, E.J., Cámera, L.A., Castañeda-Orjuela, C.A., Catalá-López, F., Charan, J., Chatterjee, S., Chattu, S.K., Chattu, V.K., Chen, S., Cicero, A.F.G., Dadras, O., Dahlawi, S.M.A., Dai, X., Dalal, K., Dandona, L., Dandona, R., Davitoiu, D.V., De Neve, J-W, de Sá-Junior, A.R., Denova-Gutiérrez, E., Dhamnetiya, D., Dharmaratne, S.D., Doshmangir, L., Dube, J., Ehsani-Chimeh, E., El Sayed Zaki, M., El Tantawi, M., Eskandarieh, S., Farzadfar, F., Ferede, T.Y., Fischer, F., Foigt, N.A., Freitas, A., Friedman, S.D., Fukumoto, T., Fullman, N., Gaal, P.A., Gad, M.M., Garcia-Gordillo, M.A., Garg, T., Ghafourifard, M., Ghashghaee, A., Gholamian, A., Gholamrezanezhad, A., Ghozali, G., Gilani, S.A., Glăvan, I-R, Glushkova, E.V., Goharinezhad, S., Golechha, M., Goli, S., Guha, A., Gupta, V.B., Gupta, V.K., Haakenstad, A., Haider, M.R., Hailu, A., Hamidi, S., Hanif, A., Harapan, H., Hartono, R.K., Hasaballah, A.I., Hassan, S., Hassanein, M.H., Hayat, K., Hegazy, M.I., Heidari, G., Hendrie, D., Heredia-Pi, I., Herteliu, C., Hezam, K., Holla, R., Hossain, S.., Hosseinzadeh, M., Hostiuc, S., Huda, T.M., Hwang, B-F, Iavicoli, I., Idrisov, B., Ilesanmi, O.S., Irvani, S.S.N., Islam, S.M.S., Ismail, N.E., Isola, G., Jahani, M.A., Jahanmehr, N., Jakovljevic, M., Janodia, M.D., Javaheri, T., Jayapal, S.K., Jayawardena, R., Jazayeri, S.B., Jha, R.P., Jonas, J.B., Joo, T., Joukar, F., Jürisson, M., Kaambwa, B., Kalhor, R., Kanchan, T., Kandel, H., Karami Matin, B., Karimi, S.E., Kassahun, G., Kayode, G.A., Kazemi Karyani, A., Keikavoosi-Arani, L., Khader, Y.S., Khajuria, H., Khalilov, R., Khammarnia, M., Khan, J., Khubchandani, J., Kianipour, N., Kim, G.R., Kim, Y.J., Kisa, A., Kisa, S., Kohler, S., Kosen, S., Koteeswaran, R., Koulmane Laxminarayana, S.L., Koyanagi, A., Krishan, K., Kumar, G.A., Kusuma, D., Lamnisos, D., Lansingh, V.C., Larsson, A.O., Lasrado, S., Le, L.K.D., Lee, S.W.H., Lee, Y.Y., Lim, S.S., Lobo, S.W., Lozano, R., Magdy Abd El Razek, H., Magdy Abd El Razek, M., Mahdavi, M.M., Majeed, A., Makki, A., Maleki, A., Malekzadeh, R., Manda, A.L., Mansour-Ghanaei, F., Mansournia, M.A., Marrugo Arnedo, C.A., Martinez-Valle, A., Masoumi, S.Z., Maude, Ri.J., McKee, M., Medina-Solís, C.E., Menezes, R.G., Meretoja, A., Meretoja, T.J., Mesregah, M.K., Mestrovic, T., Milevska Kostova, N., Miller, T.R., Mini, G.K., Mirica, A., Mirrakhimov, E.M., Mohajer, B., Mohamed, T.A., Mohammadi, M., Mohammadian-Hafshejani, A., Mohammed, S., Moitra, M., Mokdad, A.H., Molokhia, M., Moni, M.A., Moradi, Y., Morze, J., Mousavi, S.M., Mpundu-Kaambwa, C., Muriithi, M.K, Muthupandian, S., Nagarajan, A.J., Naimzada, M.D., Nangia, V., Naqvi, A.A., Narayana, A.I., Nascimento, B.R., Naveed, M., Nayak, B.P., Nazari, J., Ndejjo, R., Negoi, I., Neupane Kandel, S., Nguyen, T.H., Nonvignon, J., Noubiap, J.J., Nwatah, V.E., Oancea, B., Ojelabi, F.A.O., Olagunju, A.T., Olakunde, B.O., Olgiati, S., Olusanya, J.O., Onwujekwe, O.E., Otoiu, A., Otstavnov, N., Otstavnov, S.S., Owolabi, M.O., Padubidri, J.R., Palladino, R., Panda-Jonas, S., Park, E-C, Pashazadeh Kan, F., Pawar, S., Pazoki Toroudi, H., Pereira, D.M., Perianayagam, A., Pesudovs, K., Piccinelli, C., Postma, M.J., Prada, S.I., Rabiee, M., Rabiee, N., Rahim, F., Rahimi-Movaghar, V., Rahman, M.H.U., Rahman, M., Rahmani, A.M., Ram, U., Ranabhat, C.L., Ranasinghe, P., Rao, C.R., Rathi, P., Rawaf, D.L., Rawaf, S., Rawal, L., Rawassizadeh, R., Reiner Jr, R.C., Renzaho, A.M.N., Reshmi, B., Riaz, M.A., Ripon, R.K., Saad, A.M., Sahraian, M.A., Sahu, M., Salama, J.S., Salehi, S., Samy, A.M., Sanabria, J., Sanmarchi, F., Santos, J.V., Santric-Milicevic, M.M., Sathian, B., Savic, M., Saxena, D., Sayyah, M., Schwendicke, F., Senthilkumaran, S., Sepanlou, S.G., Seylani, A., Shahabi, S., Shaikh, M.A., Sheikh, A., Shetty, A., Shetty, P.H., Shibuya, K., Shrime, M.G., Shuja, K.H., Singh, J.A., Skryabin, V.Y., Skryabina, A.A., Soltani, S., Soofi, M., Spurlock, E.E., Stefan, S.C., Szerencsés, V., Szócska, M., Tabarés-Seisdedos, R., Taddele, B.W., Tefera, Y.G., Thavamani, A., Tobe-Gai, R., Topor-Madry, R., Tovani-Palone, M.R., Tran, B.X., Tudor Car, L., Ullah, A., Ullah, S., Umar, N., Undurraga, E.A., Valdez, P.R., Vasankari, T.J., Villafañe, J.H., Violante, F.S., Vlassov, V., Vo, B., Vollmer, S., Vos, T., Vu, G.T., Vu, L.G., Wamai, R.G., Werdecker, A., Woldekidan, M.A., Wubishet, B.L., Xu, G., Yaya, S., Yazdi-Feyzabadi, V., Yiğit, V., Yip, P., Yirdaw, B.W., Yonemoto, N., Younis, M.Z., Yu, C., Yunusa, I., Zahirian Moghadam, T., Zandian, H., Zastrozhin, M.S., Zastrozhina, A., Zhang, Z-J, Ziapour, A., Zuniga, Y.M.H., Hay, S.I., Murray, C. J.L., and Dieleman, J.L.
Abstract: Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8·8 trillion (95% uncertainty interval [UI] 8·7–8·8) or $1132 (1119–1143) per person. Spending on health varied within and across income groups and geographical regions. Of this tota
Published: 2021

6. Gender-specific response in pain and function to biologic treatment of knee osteoarthritis : a gender-bias-mitigated, observational, intention-to-treat study at two years

Author: Di Matteo, Berardo, Borg, TM, Heidari, N, Noorani, A, Slevin, M, Cullen, A, Olgiati, S, Zerbi, A, Danovi, A, Wilson, A, Di Matteo, Berardo, Borg, TM, Heidari, N, Noorani, A, Slevin, M, Cullen, A, Olgiati, S, Zerbi, A, Danovi, A, and Wilson, A
Abstract: Knee osteoarthritis is a major cause of disability worldwide. Newer modalities of treatment with less morbidity, such as intra-articular injection of microfragmented fat (MFAT), are showing promise. We report on our novel observation that women show a greater improvement in pain and function to MFAT than men. Traditionally, women have been underrepresented in studies and studies with both sexes regularly fail to analyze the results by sex. To mitigate for this bias and quantify it, we describe a technique using reproducible statistical analysis and replicable results with Open Access statistical software R to calculate the magnitude of this difference. Genetic, hormonal, environmental, and age factors play a role in our observed difference between the sexes. There is a need for further studies to identify the molecular basis for this difference and be able to utilize it to improve outcome for both women and men.
Published: 2021

7. Microfragmented Adipose Tissue Injection (MFAT) may be a solution to the rationing of total knee replacement : a prospective, gender-bias mitigated, reproducible analysis at two years

Author: Di Matteo, Berardo, Heidari, N, Borg, TM, Olgiati, S, Slevin, M, Danovi, A, Fish, B, Wilson, A, Noorani, A, Di Matteo, Berardo, Heidari, N, Borg, TM, Olgiati, S, Slevin, M, Danovi, A, Fish, B, Wilson, A, and Noorani, A
Abstract: Background. Knee osteoarthritis (KOA) is a significant cause of disability in a globally ageing population. Knee replacement surgery has been shown to improve function and quality of life. Access to this intervention can be limited for a number of reasons including rationing of care, lack of healthcare provision in austere environments, and more recently, due to the cessation of elective orthopaedic care as a result of the COVID pandemic. Referral for knee replacement surgery is often guided by the patient's Oxford Knee Score (OKS). Recent therapies including treatment with microfragmented adipose tissue (MFAT) have emerged as alternatives to relieve pain and improve function in such patients. Method. We identified all patients with KOA Kellgren-Lawrence grade 3 and 4 in our dataset of patients treated with a single injection of MFAT and applied published OKS thresholds for referral for TKR to separate them into 3 cohorts according to their functional impairment. 220 patients (95 females, 125 males) with KOA were given one MFAT injection. The function (OKS) and quality of life (EuroQol-5) prior to and 24 months after therapy were compared. Results. MFAT injection provided a statistically significant improvement in the quality of life (EQ-5D) at 24 months in patients with a baseline OKS of 39 or less (p value: <0.001) as well as those with OKS of 27 or less who are deemed suitable for a knee replacement (p value: <0.001). Conclusion. MFAT injection improves quality of life in patients with KOA who are deemed suitable for the knee replacement. MFAT is a low-morbidity alternative biological treatment and can delay the need for total knee replacement in suitable patients.
Published: 2021

8. Tracking development assistance for health and for COVID-19: a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050

Author: Micah, AE, Cogswell, IE, Cunningham, B, Ezoe, S, Harle, AC, Maddison, ER, McCracken, D, Nomura, S, Simpson, KE, Stutzman, HN, Tsakalos, G, Wallace, LE, Zhao, Y, Zende, RR, Abbafati, C, Abdelmasseh, M, Abedi, A, Abegaz, KH, Abhilash, ES, Abolhassani, H, Abrigo, MRM, Adhikari, TB, Afzal, S, Ahinkorah, BO, Ahmadi, S, Ahmed, H, Ahmed, MB, Rashid, TA, Ajami, M, Aji, B, Akalu, Y, Akunna, CJ, Al Hamad, H, Alam, K, Alanezi, FM, Alanzi, TM, Alemayehu, Y, Alhassan, RK, Alinia, C, Aljunid, SM, Almustanyir, SA, Alvis-Guzman, N, Alvis-Zakzuk, NJ, Amini, S, Amini-Rarani, M, Amu, H, Ancuceanu, R, Andrei, CL, Andrei, T, Angell, B, Anjomshoa, M, Antonio, CAT, Antony, CM, Aqeel, M, Arabloo, J, Arab-Zozani, M, Aripov, T, Arrigo, A, Ashraf, T, Atnafu, DD, Ausloos, M, Avila-Burgos, L, Awan, AT, Ayano, G, Ayanore, MA, Azari, S, Azhar, GS, Babalola, TK, Bahrami, MA, Baig, AA, Banach, M, Barati, N, Barnighausen, TW, Barrow, A, Basu, S, Baune, BT, Bayati, M, Benzian, H, Berman, AE, Bhagavathula, AS, Bhardwaj, N, Bhardwaj, P, Bhaskar, S, Bibi, S, Bijani, A, Bodolica, V, Bragazzi, NL, Braithwaite, D, Breitborde, NJK, Breusov, AV, Briko, NI, Busse, R, Cahuana-Hurtado, L, Callander, EJ, Camera, LA, Castaneda-Orjuela, CA, Catala-Lopez, F, Charan, J, Chatterjee, S, Chattu, SK, Chattu, VK, Chen, S, Cicero, AFG, Dadras, O, Dahlawi, SMA, Dai, X, Dalal, K, Dandona, L, Dandona, R, Davitoiu, DV, De Neve, J-W, de Sa-Junior, AR, Denova-Gutierrez, E, Dhamnetiya, D, Dharmaratne, SD, Doshmangir, L, Dube, J, Ehsani-Chimeh, E, Zaki, MES, El Tantawi, M, Eskandarieh, S, Farzadfar, F, Ferede, TY, Fischer, F, Foigt, NA, Freitas, A, Friedman, SD, Fukumoto, T, Fullman, N, Gaal, PA, Gad, MM, Garcia-Gordillo, MA, Garg, T, Ghafourifard, M, Ghashghaee, A, Gholamian, A, Gholamrezanezhad, A, Ghozali, G, Gilani, SA, Glavan, I-R, Glushkova, EV, Goharinezhad, S, Golechha, M, Goli, S, Guha, A, Gupta, VB, Gupta, VK, Haakenstad, A, Haider, MR, Hailu, A, Hamidi, S, Hanif, A, Harapan, H, Hartono, RK, Hasaballah, AI, Hassan, S, Hassanein, MH, Hayat, K, Hegazy, MI, Heidari, G, Hendrie, D, Heredia-Pi, I, Herteliu, C, Hezam, K, Holla, R, Hossain, SJ, Hosseinzadeh, M, Hostiuc, S, Huda, TM, Hwang, B-F, Iavicoli, I, Idrisov, B, Ilesanmi, OS, Irvani, SSN, Islam, SMS, Ismail, NE, Isola, G, Jahani, MA, Jahanmehr, N, Jakovljevic, M, Janodia, MD, Javaheri, T, Jayapal, SK, Jayawardena, R, Jazayeri, SB, Jha, RP, Jonas, JB, Joo, T, Joukar, F, Jurisson, M, Kaambwa, B, Kalhor, R, Kanchan, T, Kandel, H, Matin, BK, Karimi, SE, Kassahun, G, Kayode, GA, Karyani, AK, Keikavoosi-Arani, L, Khader, YS, Khajuria, H, Khalilov, R, Khammarnia, M, Khan, J, Khubchandani, J, Kianipour, N, Kim, GR, Kim, YJ, Kisa, A, Kisa, S, Kohler, S, Kosen, S, Koteeswaran, R, Laxminarayana, SLK, Koyanagi, A, Krishan, K, Kumar, GA, Kusuma, D, Lamnisos, D, Lansingh, VC, Larsson, AO, Lasrado, S, Le, LKD, Lee, SWH, Lee, YY, Lim, SS, Lobo, SW, Lozano, R, Abd El Razek, HM, Abd El Razek, MM, Mahdavi, MM, Majeed, A, Makki, A, Maleki, A, Malekzadeh, R, Manda, AL, Mansour-Ghanaei, F, Mansournia, MA, Arnedo, CAM, Martinez-Valle, A, Masoumi, SZ, Maude, RJ, Mckee, M, Medina-Solis, CE, Menezes, RG, Meretoja, A, Meretoja, TJ, Mesregah, MK, Mestrovic, T, Kostova, NM, Miller, TR, Mini, GK, Mirica, A, Mirrakhimov, EM, Mohajer, B, Mohamed, TA, Mohammadi, M, Mohammadian-Hafshejani, A, Mohammed, S, Moitra, M, Mokdad, AH, Molokhia, M, Moni, MA, Moradi, Y, Morze, J, Mousavi, SM, Mpundu-Kaambwa, C, Muriithi, MK, Muthupandian, S, Nagarajan, AJ, Naimzada, MD, Nangia, V, Naqvi, AA, Narayana, AI, Nascimento, BR, Naveed, M, Nayak, BP, Nazari, J, Ndejjo, R, Negoi, I, Kandel, SN, Trang, HN, Nonvignon, J, Noubiap, JJ, Nwatah, VE, Oancea, B, Ojelabi, FAO, Olagunju, AT, Olakunde, BO, Olgiati, S, Olusanya, JO, Onwujekwe, OE, Otoiu, A, Otstavnov, N, Otstavnov, SS, Owolabi, MO, Padubidri, JR, Palladino, R, Panda-Jonas, S, Park, E-C, Kan, FP, Pawar, S, Toroudi, HP, Pereira, DM, Perianayagam, A, Pesudovs, K, Piccinelli, C, Postma, MJ, Prada, SI, Rabiee, M, Rabiee, N, Rahim, F, Rahimi-Movaghar, V, Rahman, MHU, Rahman, M, Rahmani, AM, Ram, U, Ranabhat, CL, Ranasinghe, P, Rao, CR, Rathi, P, Rawaf, DL, Rawaf, S, Rawal, L, Rawassizadeh, R, Reiner, RC, Renzaho, AMN, Reshmi, B, Riaz, MA, Ripon, RK, Saad, AM, Sahraian, MA, Sahu, M, Salama, JS, Salehi, S, Samy, AM, Sanabria, J, Sanmarchi, F, Santos, JV, Santric-Milicevic, MM, Sathian, B, Savic, M, Saxena, D, Sayyah, M, Schwendicke, F, Senthilkumaran, S, Sepanlou, SG, Seylani, A, Shahabi, S, Shaikh, MA, Sheikh, A, Shetty, A, Shetty, PH, Shibuya, K, Shrime, MG, Shuja, KH, Singh, JA, Skryabin, VY, Skryabina, AA, Soltani, S, Soofi, M, Spurlock, EE, Stefan, SC, Szerencses, V, Szocska, M, Tabares-Seisdedos, R, Taddele, BW, Tefera, YG, Thavamani, A, Tobe-Gai, R, Topor-Madry, R, Tovani-Palone, MR, Bach, XT, Car, LT, Ullah, A, Ullah, S, Umar, N, Undurraga, EA, Valdez, PR, Vasankari, TJ, Villafane, JH, Violante, FS, Vlassov, V, Bay, V, Vollmer, S, Theo, V, Giang, TV, Linh, GV, Wamai, RG, Werdecker, A, Woldekidan, MA, Wubishet, BL, Xu, G, Yaya, S, Yazdi-Feyzabadi, V, Yigit, V, Yip, P, Yirdaw, BW, Yonemoto, N, Younis, MZ, Yu, C, Yunusa, I, Moghadam, TZ, Zandian, H, Zastrozhin, MS, Zastrozhina, A, Zhang, Z-J, Ziapour, A, Zuniga, YMH, Hay, SI, Murray, CJL, Dieleman, JL, Micah, AE, Cogswell, IE, Cunningham, B, Ezoe, S, Harle, AC, Maddison, ER, McCracken, D, Nomura, S, Simpson, KE, Stutzman, HN, Tsakalos, G, Wallace, LE, Zhao, Y, Zende, RR, Abbafati, C, Abdelmasseh, M, Abedi, A, Abegaz, KH, Abhilash, ES, Abolhassani, H, Abrigo, MRM, Adhikari, TB, Afzal, S, Ahinkorah, BO, Ahmadi, S, Ahmed, H, Ahmed, MB, Rashid, TA, Ajami, M, Aji, B, Akalu, Y, Akunna, CJ, Al Hamad, H, Alam, K, Alanezi, FM, Alanzi, TM, Alemayehu, Y, Alhassan, RK, Alinia, C, Aljunid, SM, Almustanyir, SA, Alvis-Guzman, N, Alvis-Zakzuk, NJ, Amini, S, Amini-Rarani, M, Amu, H, Ancuceanu, R, Andrei, CL, Andrei, T, Angell, B, Anjomshoa, M, Antonio, CAT, Antony, CM, Aqeel, M, Arabloo, J, Arab-Zozani, M, Aripov, T, Arrigo, A, Ashraf, T, Atnafu, DD, Ausloos, M, Avila-Burgos, L, Awan, AT, Ayano, G, Ayanore, MA, Azari, S, Azhar, GS, Babalola, TK, Bahrami, MA, Baig, AA, Banach, M, Barati, N, Barnighausen, TW, Barrow, A, Basu, S, Baune, BT, Bayati, M, Benzian, H, Berman, AE, Bhagavathula, AS, Bhardwaj, N, Bhardwaj, P, Bhaskar, S, Bibi, S, Bijani, A, Bodolica, V, Bragazzi, NL, Braithwaite, D, Breitborde, NJK, Breusov, AV, Briko, NI, Busse, R, Cahuana-Hurtado, L, Callander, EJ, Camera, LA, Castaneda-Orjuela, CA, Catala-Lopez, F, Charan, J, Chatterjee, S, Chattu, SK, Chattu, VK, Chen, S, Cicero, AFG, Dadras, O, Dahlawi, SMA, Dai, X, Dalal, K, Dandona, L, Dandona, R, Davitoiu, DV, De Neve, J-W, de Sa-Junior, AR, Denova-Gutierrez, E, Dhamnetiya, D, Dharmaratne, SD, Doshmangir, L, Dube, J, Ehsani-Chimeh, E, Zaki, MES, El Tantawi, M, Eskandarieh, S, Farzadfar, F, Ferede, TY, Fischer, F, Foigt, NA, Freitas, A, Friedman, SD, Fukumoto, T, Fullman, N, Gaal, PA, Gad, MM, Garcia-Gordillo, MA, Garg, T, Ghafourifard, M, Ghashghaee, A, Gholamian, A, Gholamrezanezhad, A, Ghozali, G, Gilani, SA, Glavan, I-R, Glushkova, EV, Goharinezhad, S, Golechha, M, Goli, S, Guha, A, Gupta, VB, Gupta, VK, Haakenstad, A, Haider, MR, Hailu, A, Hamidi, S, Hanif, A, Harapan, H, Hartono, RK, Hasaballah, AI, Hassan, S, Hassanein, MH, Hayat, K, Hegazy, MI, Heidari, G, Hendrie, D, Heredia-Pi, I, Herteliu, C, Hezam, K, Holla, R, Hossain, SJ, Hosseinzadeh, M, Hostiuc, S, Huda, TM, Hwang, B-F, Iavicoli, I, Idrisov, B, Ilesanmi, OS, Irvani, SSN, Islam, SMS, Ismail, NE, Isola, G, Jahani, MA, Jahanmehr, N, Jakovljevic, M, Janodia, MD, Javaheri, T, Jayapal, SK, Jayawardena, R, Jazayeri, SB, Jha, RP, Jonas, JB, Joo, T, Joukar, F, Jurisson, M, Kaambwa, B, Kalhor, R, Kanchan, T, Kandel, H, Matin, BK, Karimi, SE, Kassahun, G, Kayode, GA, Karyani, AK, Keikavoosi-Arani, L, Khader, YS, Khajuria, H, Khalilov, R, Khammarnia, M, Khan, J, Khubchandani, J, Kianipour, N, Kim, GR, Kim, YJ, Kisa, A, Kisa, S, Kohler, S, Kosen, S, Koteeswaran, R, Laxminarayana, SLK, Koyanagi, A, Krishan, K, Kumar, GA, Kusuma, D, Lamnisos, D, Lansingh, VC, Larsson, AO, Lasrado, S, Le, LKD, Lee, SWH, Lee, YY, Lim, SS, Lobo, SW, Lozano, R, Abd El Razek, HM, Abd El Razek, MM, Mahdavi, MM, Majeed, A, Makki, A, Maleki, A, Malekzadeh, R, Manda, AL, Mansour-Ghanaei, F, Mansournia, MA, Arnedo, CAM, Martinez-Valle, A, Masoumi, SZ, Maude, RJ, Mckee, M, Medina-Solis, CE, Menezes, RG, Meretoja, A, Meretoja, TJ, Mesregah, MK, Mestrovic, T, Kostova, NM, Miller, TR, Mini, GK, Mirica, A, Mirrakhimov, EM, Mohajer, B, Mohamed, TA, Mohammadi, M, Mohammadian-Hafshejani, A, Mohammed, S, Moitra, M, Mokdad, AH, Molokhia, M, Moni, MA, Moradi, Y, Morze, J, Mousavi, SM, Mpundu-Kaambwa, C, Muriithi, MK, Muthupandian, S, Nagarajan, AJ, Naimzada, MD, Nangia, V, Naqvi, AA, Narayana, AI, Nascimento, BR, Naveed, M, Nayak, BP, Nazari, J, Ndejjo, R, Negoi, I, Kandel, SN, Trang, HN, Nonvignon, J, Noubiap, JJ, Nwatah, VE, Oancea, B, Ojelabi, FAO, Olagunju, AT, Olakunde, BO, Olgiati, S, Olusanya, JO, Onwujekwe, OE, Otoiu, A, Otstavnov, N, Otstavnov, SS, Owolabi, MO, Padubidri, JR, Palladino, R, Panda-Jonas, S, Park, E-C, Kan, FP, Pawar, S, Toroudi, HP, Pereira, DM, Perianayagam, A, Pesudovs, K, Piccinelli, C, Postma, MJ, Prada, SI, Rabiee, M, Rabiee, N, Rahim, F, Rahimi-Movaghar, V, Rahman, MHU, Rahman, M, Rahmani, AM, Ram, U, Ranabhat, CL, Ranasinghe, P, Rao, CR, Rathi, P, Rawaf, DL, Rawaf, S, Rawal, L, Rawassizadeh, R, Reiner, RC, Renzaho, AMN, Reshmi, B, Riaz, MA, Ripon, RK, Saad, AM, Sahraian, MA, Sahu, M, Salama, JS, Salehi, S, Samy, AM, Sanabria, J, Sanmarchi, F, Santos, JV, Santric-Milicevic, MM, Sathian, B, Savic, M, Saxena, D, Sayyah, M, Schwendicke, F, Senthilkumaran, S, Sepanlou, SG, Seylani, A, Shahabi, S, Shaikh, MA, Sheikh, A, Shetty, A, Shetty, PH, Shibuya, K, Shrime, MG, Shuja, KH, Singh, JA, Skryabin, VY, Skryabina, AA, Soltani, S, Soofi, M, Spurlock, EE, Stefan, SC, Szerencses, V, Szocska, M, Tabares-Seisdedos, R, Taddele, BW, Tefera, YG, Thavamani, A, Tobe-Gai, R, Topor-Madry, R, Tovani-Palone, MR, Bach, XT, Car, LT, Ullah, A, Ullah, S, Umar, N, Undurraga, EA, Valdez, PR, Vasankari, TJ, Villafane, JH, Violante, FS, Vlassov, V, Bay, V, Vollmer, S, Theo, V, Giang, TV, Linh, GV, Wamai, RG, Werdecker, A, Woldekidan, MA, Wubishet, BL, Xu, G, Yaya, S, Yazdi-Feyzabadi, V, Yigit, V, Yip, P, Yirdaw, BW, Yonemoto, N, Younis, MZ, Yu, C, Yunusa, I, Moghadam, TZ, Zandian, H, Zastrozhin, MS, Zastrozhina, A, Zhang, Z-J, Ziapour, A, Zuniga, YMH, Hay, SI, Murray, CJL, and Dieleman, JL
Abstract: BACKGROUND: The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. METHODS: We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. FINDINGS: In 2019, health spending globally reached $8·8 trillion (95% uncertainty interval [UI] 8·7-8·8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this t
Published: 2021

9. An exome study of Parkinsonʼs disease in Sardinia, a Mediterranean genetic isolate: 165

Author: Quadri, M., Yang, X., Cossu, G., Olgiati, S., Saddi, V., Breedveld, G. J., Ouyang, L., Hu, J., Xu, N., Graafland, J., Ricchi, V., Murgia, D., Guedes, Correia L., Mariani, C., Martí, M. J., Tarantino, P., Asselta, R., Valldeoriola, F., Gagliardi, M., Pezzoli, G., Ezquerra, M., Quattrone, A., Ferreira, J., Annesi, G., Goldwurm, S., Tolosa, E., Oostra, B. A., Melis, M., Wang, J., and Bonifati, V.
Published: 2014

10. Early-onset Parkinsonism caused by SYNJ1 p.Arg258Gln homozygous mutation in a new Italian family: 162

Author: Olgiati, S., De Rosa, A., Quadri, M., Criscuolo, C., Breedveld, G. J., Picillo, M., Graafland, J., Pappatá, S., Quarantelli, M., Barone, P., De Michele, G., and Bonifati, V.
Published: 2014

11. New SLC30A10 mutations in Indian families with early-onset dystonia and manganese transport disease: 164

Author: Quadri, M., Kamate, M., Sharma, S., Olgiati, S., Graafland, J., Kori, I., Hattiholi, V., Aneja, S., Kumar, A., Breedveld, G. J., Verheijen, F. W., and Bonifati, V.
Published: 2014

12. EIF2AK2 Missense Variants Associated with Early Onset Generalized Dystonia

Author: Kuipers, D. (Demy), Mandemakers, W.J. (Wim), Lu, C.-S. (Chin-Song), Olgiati, S. (Simone), Breedveld, G.J. (Guido), Fevga, C. (Christina), Tadic, V. (Vera), Carecchio, M. (Miryam), Osterman, B. (Bradley), Sagi-Dain, L. (Lena), Wu-Chou, Y.H. (Yah-Huei), Chen, C.C. (Chiung C.), Chang, H.C. (Hsiu-Chen), Wu, S.-L. (Shey-Lin), Yeh, T.-H. (Tu-Hsueh), Weng, Y.H. (Yi Hsin), Elia, A.E. (Antonio E.), Panteghini, C. (Celeste), Marotta, N. (Nicolas), Pauly, M.G. (Martje G.), Kühn, A.A. (Andrea A.), Volkmann, J. (Jens), Lace, B. (Baiba), Meijer, I.A. (Inge A.), Kandaswamy, K. (Krishna), Quadri, M. (Marialuisa), Garavaglia, B. (Barbara), Lohmann, K. (Katja), Bauer, P. (Peter), Mencacci, N.E. (Niccolo), Lubbe, S.J. (Steven J.), Klein, C. (Christoph), Bertoli Avella, A.M. (Aida), Bonifati, V. (Vincenzo), Kuipers, D. (Demy), Mandemakers, W.J. (Wim), Lu, C.-S. (Chin-Song), Olgiati, S. (Simone), Breedveld, G.J. (Guido), Fevga, C. (Christina), Tadic, V. (Vera), Carecchio, M. (Miryam), Osterman, B. (Bradley), Sagi-Dain, L. (Lena), Wu-Chou, Y.H. (Yah-Huei), Chen, C.C. (Chiung C.), Chang, H.C. (Hsiu-Chen), Wu, S.-L. (Shey-Lin), Yeh, T.-H. (Tu-Hsueh), Weng, Y.H. (Yi Hsin), Elia, A.E. (Antonio E.), Panteghini, C. (Celeste), Marotta, N. (Nicolas), Pauly, M.G. (Martje G.), Kühn, A.A. (Andrea A.), Volkmann, J. (Jens), Lace, B. (Baiba), Meijer, I.A. (Inge A.), Kandaswamy, K. (Krishna), Quadri, M. (Marialuisa), Garavaglia, B. (Barbara), Lohmann, K. (Katja), Bauer, P. (Peter), Mencacci, N.E. (Niccolo), Lubbe, S.J. (Steven J.), Klein, C. (Christoph), Bertoli Avella, A.M. (Aida), and Bonifati, V. (Vincenzo)
Abstract: Objective: The study was undertaken to identify a monogenic cause of early onset, generalized dystonia. Methods: Methods consisted of genome-wide linkage analysis, exome and Sanger sequencing, clinical neurological examination, brain magnetic resonance imaging, and protein expression studies in skin fibroblasts from patients. Results: We identified a heterozygous variant, c.388G>A, p.Gly130Arg, in the eukaryotic tra
Published: 2020
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13. Patient-Centered Outcomes of Microfragmented Adipose Tissue Treatments of Knee Osteoarthritis: An Observational, Intention-to-Treat Study at Twelve Months

Author: Heidari, N, Noorani, A, Slevin, M, Cullen, A, Stark, L, Olgiati, S, Zerbi, A, Wilson, A, Heidari, N, Noorani, A, Slevin, M, Cullen, A, Stark, L, Olgiati, S, Zerbi, A, and Wilson, A
Abstract: © 2020 Nima Heidari et al. Introduction. Microfragmented adipose tissue (MFAT) has been shown to benefit osteoarthritic patients by reducing pain and supporting tissue regeneration through a mesenchymal stem cell (MSC)-related paracrine mechanism. This observational study of 110 knees assessed patient-centered outcomes of pain, functionality, and quality of life, analyzing their variation at twelve months following one ultrasound-guided intra-articular injection of autologous MFAT for the treatment of knee osteoarthritis (KOA). Method. Inclusion criteria were as follows: VAS >50, and the presence of KOA as diagnosed on X-ray and MRI. Exclusion criteria included the following: recent injury (<3 months) of the symptomatic knee, intra-articular steroid injections performed within the last three months, and hyaluronic acid injections prior to this treatment. Changes in VAS, OKS, and EQ-5D were scored at baseline and twelve months following a single intra-articular injection of autologous MFAT. Score variation was analyzed utilizing a nonparametric paired samples Wilcoxon test. The statistical analysis is reproducible with Open Access statistical software R (version 4.0.0 or higher). The study was carried out with full patient consent, in a private practice setting. Results. Median VAS (pain) improved from 70 (IQR 20) to 30 (IQR 58) (p<0.001); median OKS (function) improved from 25 (IQR 11) to 33.5 (IQR 16) (p<0.001); and median EQ-5D (quality of life) improved from 0.62 (IQR 0.41) to 0.69 (IQR 0.28) (p<0.001). No adverse events were reported during the intraoperative, recovery, or postoperative periods. Conclusions. For patients with all grades of knee osteoarthritis who were treated with intra-articular injections of MFAT, statistically significant improvements in pain, function, and quality of life were reported. Although further research is warranted, the results are encouraging and suggest a positive role for intra-articular injection of MFAT as a treatment for knee
Published: 2020

14. Past, present, and future of global health financing: a review of development assistance, government, out-of-pocket, and other private spending on health for 195 countries, 1995–2050

Author: Chang, A.Y., Cowling, K., Micah, A.E., Chapin, A., Chen, C.S., Ikilezi, G., Sadat, N., Tsakalos, G., Wu, J., Younker, T., Zhao, Y., Zlavog, B.S., Abbafati, C., Ahmed, A.E, Alam, K., Alipour, V., Aljunid, S.M., Almalki, M.J., Alvis-Guzman, N., Ammar, W., Andrei, C.L., Anjomshoa, M., Antonio, C.A.T., Arabloo, J., Aremu, O., Ausloos, M., Avila-Burgos, L., Awasthi, A., Ayanore, M.A., Azari, S., Azzopardi-Muscat, N., Bagherzadeh, M., Bärnighausen, T.W., Baune, B.T., Bayati, M., Belay, Y.B., Belay, Y.A., Belete, H., Berbada, D.A., Berman, A.E., Beuran, M., Bijani, A., Busse, R., Cahuana-Hurtado, L., Cámera, L.A., Catalá-López, F., Chauhan, B.G., Constantin, M-M, Crowe, C.S., Cucu, A., Dalal, K., De Neve, J-W, Deiparine, S., Demeke, F.M., Do, H.P., Dubey, M., El Tantawi, M., Eskandarieh, S., Esmaeili, R., Fakhar, M., Fazaeli, A.A., Fischer, F., Foigt, N.A., Fukumoto, T., Fullman, N., Galan, A., Gamkrelidze, A., Gezae, K.E., Ghajar, A., Ghashghaee, A., Goginashvili, K., Haakenstad, A., Haghparast Bidgoli, H., Hamidi, S., Harb, H.L., Hasanpoor, E., Hassen, H.Y., Hay, S.I., Hendrie, D., Henok, A., Heredia-Pi, I., Herteliu, C., Hoang, C.L., Hole, M.K., Homaie Rad, E., Hossain, N., Hosseinzadeh, M., Hostiuc, S., Ilesanmi, O.S., Irvani, S.S.N., Jakovljevic, M., Jalali, A., James, S.L., Jonas, J.B., Jürisson, M., Kadel, R., Karami Matin, B., Kasaeian, A., Kasaye, H.K., Kassaw, M.W., Kazemi Karyani, A., Khabiri, R., Khan, J., Khan, M.N., Khang, Y-H, Kisa, A., Kissimova-Skarbek, K., Kohler, S., Koyanagi, A., Krohn, K.J., Leung, R., Lim, L-L, Lorkowski, S., Majeed, A., Malekzadeh, R., Mansourian, M., Mantovani, L.G., Massenburg, B.B., McKee, M., Mehta, V., Meretoja, A., Meretoja, T.J., Milevska Kostova, N., Miller, T.R., Mirrakhimov, E.M., Mohajer, B., Mohammad Darwesh, A., Mohammed, S., Mohebi, F., Mokdad, A.H., Morrison, S.D., Mousavi, S.M., Muthupandian, S., Nagarajan, A.J., Nangia, V., Negoi, I., Nguyen, C.T., Nguyen, H.L.T., Nguyen, S.H., Nosratnejad, S., Oladimeji, O., Olgiati, S., Olusanya, J.O., Onwujekwe, O.E., Otstavnov, S.S., Pana, A., Pereira, D.M., Piroozi, B., Prada, S.I., Qorbani, M., Rabiee, M., Rabiee, N., Rafiei, A., Rahim, F., Rahimi-Movaghar, V., Ram, U., Ranabhat, C.L., Ranta, A., Rawaf, D.L., Rawaf, S., Rezaei, S., Roro, E.M., Rostami, A., Rubino, S., Salahshoor, M., Samy, A.M., Sanabria, J., Santos, J.V., Santric Milicevic, M.M., Sao Jose, B.P., Savic, M., Schwendicke, F., Sepanlou, S.G., Sepehrimanesh, M., Sheikh, A., Shrime, M.G, Sisay, S., Soltani, S., Soofi, M., Srinivasan, V., Tabarés-Seisdedos, R., Torre, A., Tovani-Palone, M.R., Tran, B.X., Tran, K.B., Undurraga, E.A., Valdez, P.R., van Boven, J.F.M., Vargas, V., Veisani, Y., Violante, F.S., Vladimirov, S.K., Vlassov, V., Vollmer, S., Vu, G.T., Wolfe, C.D.A., Yonemoto, N., Younis, M.Z., Yousefifard, M., Zaman, S.B., Zangeneh, A., Zegeye, El.A., Ziapour, A., Chew, A., Murray, C.J.L., Dieleman, J.L., Chang, A.Y., Cowling, K., Micah, A.E., Chapin, A., Chen, C.S., Ikilezi, G., Sadat, N., Tsakalos, G., Wu, J., Younker, T., Zhao, Y., Zlavog, B.S., Abbafati, C., Ahmed, A.E, Alam, K., Alipour, V., Aljunid, S.M., Almalki, M.J., Alvis-Guzman, N., Ammar, W., Andrei, C.L., Anjomshoa, M., Antonio, C.A.T., Arabloo, J., Aremu, O., Ausloos, M., Avila-Burgos, L., Awasthi, A., Ayanore, M.A., Azari, S., Azzopardi-Muscat, N., Bagherzadeh, M., Bärnighausen, T.W., Baune, B.T., Bayati, M., Belay, Y.B., Belay, Y.A., Belete, H., Berbada, D.A., Berman, A.E., Beuran, M., Bijani, A., Busse, R., Cahuana-Hurtado, L., Cámera, L.A., Catalá-López, F., Chauhan, B.G., Constantin, M-M, Crowe, C.S., Cucu, A., Dalal, K., De Neve, J-W, Deiparine, S., Demeke, F.M., Do, H.P., Dubey, M., El Tantawi, M., Eskandarieh, S., Esmaeili, R., Fakhar, M., Fazaeli, A.A., Fischer, F., Foigt, N.A., Fukumoto, T., Fullman, N., Galan, A., Gamkrelidze, A., Gezae, K.E., Ghajar, A., Ghashghaee, A., Goginashvili, K., Haakenstad, A., Haghparast Bidgoli, H., Hamidi, S., Harb, H.L., Hasanpoor, E., Hassen, H.Y., Hay, S.I., Hendrie, D., Henok, A., Heredia-Pi, I., Herteliu, C., Hoang, C.L., Hole, M.K., Homaie Rad, E., Hossain, N., Hosseinzadeh, M., Hostiuc, S., Ilesanmi, O.S., Irvani, S.S.N., Jakovljevic, M., Jalali, A., James, S.L., Jonas, J.B., Jürisson, M., Kadel, R., Karami Matin, B., Kasaeian, A., Kasaye, H.K., Kassaw, M.W., Kazemi Karyani, A., Khabiri, R., Khan, J., Khan, M.N., Khang, Y-H, Kisa, A., Kissimova-Skarbek, K., Kohler, S., Koyanagi, A., Krohn, K.J., Leung, R., Lim, L-L, Lorkowski, S., Majeed, A., Malekzadeh, R., Mansourian, M., Mantovani, L.G., Massenburg, B.B., McKee, M., Mehta, V., Meretoja, A., Meretoja, T.J., Milevska Kostova, N., Miller, T.R., Mirrakhimov, E.M., Mohajer, B., Mohammad Darwesh, A., Mohammed, S., Mohebi, F., Mokdad, A.H., Morrison, S.D., Mousavi, S.M., Muthupandian, S., Nagarajan, A.J., Nangia, V., Negoi, I., Nguyen, C.T., Nguyen, H.L.T., Nguyen, S.H., Nosratnejad, S., Oladimeji, O., Olgiati, S., Olusanya, J.O., Onwujekwe, O.E., Otstavnov, S.S., Pana, A., Pereira, D.M., Piroozi, B., Prada, S.I., Qorbani, M., Rabiee, M., Rabiee, N., Rafiei, A., Rahim, F., Rahimi-Movaghar, V., Ram, U., Ranabhat, C.L., Ranta, A., Rawaf, D.L., Rawaf, S., Rezaei, S., Roro, E.M., Rostami, A., Rubino, S., Salahshoor, M., Samy, A.M., Sanabria, J., Santos, J.V., Santric Milicevic, M.M., Sao Jose, B.P., Savic, M., Schwendicke, F., Sepanlou, S.G., Sepehrimanesh, M., Sheikh, A., Shrime, M.G, Sisay, S., Soltani, S., Soofi, M., Srinivasan, V., Tabarés-Seisdedos, R., Torre, A., Tovani-Palone, M.R., Tran, B.X., Tran, K.B., Undurraga, E.A., Valdez, P.R., van Boven, J.F.M., Vargas, V., Veisani, Y., Violante, F.S., Vladimirov, S.K., Vlassov, V., Vollmer, S., Vu, G.T., Wolfe, C.D.A., Yonemoto, N., Younis, M.Z., Yousefifard, M., Zaman, S.B., Zangeneh, A., Zegeye, El.A., Ziapour, A., Chew, A., Murray, C.J.L., and Dieleman, J.L.
Abstract: Background Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries. Methods We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories—government, out-of-pocket, and prepaid private health spending—and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more resour
Published: 2019

15. Past, present, and future of global health financing: a review of development assistance, government, out-of-pocket, and other private spending on health for 195 countries, 1995-2050

Author: Chang, AY, Cowling, K, Micah, AE, Chapin, A, Chen, CS, Ikilezi, G, Sadat, N, Tsakalos, G, Wu, J, Younker, T, Zhao, Y, Zlavog, BS, Abbafati, C, Ahmed, AE, Alam, K, Alipour, V, Aljunid, SM, Almalki, MJ, Alvis-Guzman, N, Ammar, W, Andrei, CL, Anjomshoa, M, Antonio, CAT, Arabloo, J, Aremu, O, Ausloos, M, Avila-Burgos, L, Awasthi, A, Ayanore, MA, Azari, S, Azzopardi-Muscat, N, Bagherzadeh, M, Baernighausen, TW, Baune, BT, Bayati, M, Belay, YB, Belay, YA, Belete, H, Berbada, DA, Berman, AE, Beuran, M, Bijani, A, Busse, R, Cahuana-Hurtado, L, Alberto Camera, L, Catala-Lopez, F, Chauhan, BG, Constantin, M-M, Crowe, CS, Cucu, A, Dalal, K, De Neve, J-W, Deipatine, S, Demeke, FM, Huyen, PD, Dubey, M, El Tantawi, M, Eskandarieh, S, Esmaeili, R, Fakhar, M, Fazaeli, AA, Fischer, F, Foigt, NA, Fukumoto, T, Fullman, N, Galan, A, Gamkrelidze, A, Gezae, KE, Ghajar, A, Ghashghaee, A, Goginashvili, K, Haakenstad, A, Bidgoli, HH, Hamidi, S, Harb, HL, Hasanpoor, E, Hassen, HY, Hay, S, Hendrie, D, Henok, A, Heredia-Pi, I, Herteliu, C, Hoang, CL, Hole, MK, Rad, EH, Hossain, N, Hosseinzadeh, M, Hostiuc, S, Ilesanmi, OS, Irvani, SSN, Jakovljevic, M, Jalali, A, James, SL, Jonas, JB, Jurisson, M, Kadel, R, Matin, BK, Kasaeian, A, Kasaye, HK, Kassaw, MW, Karyani, AK, Khabiri, R, Khan, J, Khan, MN, Khang, Y-H, Kisa, A, Kissimova-Skarbek, K, Kohler, S, Koyanagi, A, Krohn, KJ, Leung, R, Lim, L-L, Lorkowski, S, Majeed, A, Malekzadeh, R, Mansourian, M, Mantovani, LG, Massenburg, BB, Mckee, M, Mehta, V, Meretoja, A, Meretoja, TJ, Kostova, NM, Miller, TR, Mirrakhimov, EM, Mohajer, B, Darwesh, AM, Mohammed, S, Mohebi, F, Mokdad, AH, Morrison, SD, Mousavi, SM, Muthupandian, S, Nagarajan, AJ, Nangia, V, Cuong, TN, Huong, LTN, Son, HN, Nosratnejad, S, Oladimeji, O, Olgiati, S, Olusanya, JO, Onwujekwe, OE, Otstavnov, SS, Pana, A, Pereira, DM, Piroozi, B, Prada, S, Qorbani, M, Rabiee, M, Rabiee, N, Rafiei, A, Rahim, F, Rahimi-Mcwaghar, V, Ram, U, Ranabhat, CL, Ranta, A, Rawaf, DL, Rawaf, S, Rezaei, S, Roro, EM, Rostami, A, Rubino, S, Salahshoor, M, Samy, AM, Sanabria, J, Santos, JV, Santric Milicevic, MM, Sao Jose, BP, Savic, M, Schwendicke, F, Sepanlou, SG, Sepehrimanesh, M, Sheikh, A, Shrime, MG, Sisay, S, Soltani, S, Soofi, M, Srinivasan, V, Tabares-Seisdedos, R, Torre, A, Tovani-Palone, MR, Bach, XT, Khanh, BT, Undurraga, EA, Valdez, PR, Van Boven, JFM, Vargas, V, Veisani, Y, Violante, FS, Vladimirov, SK, Vlassov, V, Vollmer, S, Giang, TV, Wolfe, CDA, Yonemoto, N, Younis, MZ, Yousefifard, M, Bin Zaman, S, Zangeneh, A, Zegeye, EA, Ziapour, A, Chew, A, Murray, CJL, Dieleman, JL, Chang, AY, Cowling, K, Micah, AE, Chapin, A, Chen, CS, Ikilezi, G, Sadat, N, Tsakalos, G, Wu, J, Younker, T, Zhao, Y, Zlavog, BS, Abbafati, C, Ahmed, AE, Alam, K, Alipour, V, Aljunid, SM, Almalki, MJ, Alvis-Guzman, N, Ammar, W, Andrei, CL, Anjomshoa, M, Antonio, CAT, Arabloo, J, Aremu, O, Ausloos, M, Avila-Burgos, L, Awasthi, A, Ayanore, MA, Azari, S, Azzopardi-Muscat, N, Bagherzadeh, M, Baernighausen, TW, Baune, BT, Bayati, M, Belay, YB, Belay, YA, Belete, H, Berbada, DA, Berman, AE, Beuran, M, Bijani, A, Busse, R, Cahuana-Hurtado, L, Alberto Camera, L, Catala-Lopez, F, Chauhan, BG, Constantin, M-M, Crowe, CS, Cucu, A, Dalal, K, De Neve, J-W, Deipatine, S, Demeke, FM, Huyen, PD, Dubey, M, El Tantawi, M, Eskandarieh, S, Esmaeili, R, Fakhar, M, Fazaeli, AA, Fischer, F, Foigt, NA, Fukumoto, T, Fullman, N, Galan, A, Gamkrelidze, A, Gezae, KE, Ghajar, A, Ghashghaee, A, Goginashvili, K, Haakenstad, A, Bidgoli, HH, Hamidi, S, Harb, HL, Hasanpoor, E, Hassen, HY, Hay, S, Hendrie, D, Henok, A, Heredia-Pi, I, Herteliu, C, Hoang, CL, Hole, MK, Rad, EH, Hossain, N, Hosseinzadeh, M, Hostiuc, S, Ilesanmi, OS, Irvani, SSN, Jakovljevic, M, Jalali, A, James, SL, Jonas, JB, Jurisson, M, Kadel, R, Matin, BK, Kasaeian, A, Kasaye, HK, Kassaw, MW, Karyani, AK, Khabiri, R, Khan, J, Khan, MN, Khang, Y-H, Kisa, A, Kissimova-Skarbek, K, Kohler, S, Koyanagi, A, Krohn, KJ, Leung, R, Lim, L-L, Lorkowski, S, Majeed, A, Malekzadeh, R, Mansourian, M, Mantovani, LG, Massenburg, BB, Mckee, M, Mehta, V, Meretoja, A, Meretoja, TJ, Kostova, NM, Miller, TR, Mirrakhimov, EM, Mohajer, B, Darwesh, AM, Mohammed, S, Mohebi, F, Mokdad, AH, Morrison, SD, Mousavi, SM, Muthupandian, S, Nagarajan, AJ, Nangia, V, Cuong, TN, Huong, LTN, Son, HN, Nosratnejad, S, Oladimeji, O, Olgiati, S, Olusanya, JO, Onwujekwe, OE, Otstavnov, SS, Pana, A, Pereira, DM, Piroozi, B, Prada, S, Qorbani, M, Rabiee, M, Rabiee, N, Rafiei, A, Rahim, F, Rahimi-Mcwaghar, V, Ram, U, Ranabhat, CL, Ranta, A, Rawaf, DL, Rawaf, S, Rezaei, S, Roro, EM, Rostami, A, Rubino, S, Salahshoor, M, Samy, AM, Sanabria, J, Santos, JV, Santric Milicevic, MM, Sao Jose, BP, Savic, M, Schwendicke, F, Sepanlou, SG, Sepehrimanesh, M, Sheikh, A, Shrime, MG, Sisay, S, Soltani, S, Soofi, M, Srinivasan, V, Tabares-Seisdedos, R, Torre, A, Tovani-Palone, MR, Bach, XT, Khanh, BT, Undurraga, EA, Valdez, PR, Van Boven, JFM, Vargas, V, Veisani, Y, Violante, FS, Vladimirov, SK, Vlassov, V, Vollmer, S, Giang, TV, Wolfe, CDA, Yonemoto, N, Younis, MZ, Yousefifard, M, Bin Zaman, S, Zangeneh, A, Zegeye, EA, Ziapour, A, Chew, A, Murray, CJL, and Dieleman, JL
Abstract: BACKGROUND: Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries. METHODS: We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories-government, out-of-pocket, and prepaid private health spending-and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more reso
Published: 2019

16. Past, present, and future of global health financing : A review of development assistance, government, out-of-pocket, and other private spending on health for 195 countries, 1995-2050

Author: Chang, A. Y., Cowling, K., Micah, A. E., Chapin, A., Chen, C. S., Ikilezi, G., Sadat, N., Tsakalos, G., Wu, J., Younker, T., Zhao, Y., Zlavog, B. S., Abbafati, C., Ahmed, A. E., Alam, K., Alipour, V., Aljunid, S. M., Almalki, M. J., Alvis-Guzman, N., Ammar, W., Andrei, C. L., Anjomshoa, M., Antonio, C. A. T., Arabloo, J., Aremu, O., Ausloos, M., Avila-Burgos, L., Awasthi, A., Ayanore, M. A., Azari, S., Azzopardi-Muscat, N., Bagherzadeh, M., BÃ€rnighausen, T. W., Baune, B. T., Bayati, M., Belay, Y. B., Belay, Y. A., Belete, H., Berbada, D. A., Berman, A. E., Beuran, M., Bijani, A., Busse, R., Cahuana-Hurtado, L., CÃ¡mera, L. A., CatalÃ¡-LÃ³pez, F., Chauhan, B. G., Constantin, M. -M, Crowe, C. S., Cucu, A., Dalal, Koustuv, De Neve, J. -W, Deiparine, S., Demeke, F. M., Do, H. P., Dubey, M., Tantawi, M. E., Eskandarieh, S., Esmaeili, R., Fakhar, M., Fazaeli, A. A., Fischer, F., Foigt, N. A., Fukumoto, T., Fullman, N., Galan, A., Gamkrelidze, A., Gezae, K. E., Ghajar, A., Ghashghaee, A., Goginashvili, K., Haakenstad, A., Bidgoli, H. H., Hamidi, S., Harb, H. L., Hasanpoor, E., Hassen, H. Y., Hay, S. I., Hendrie, D., Henok, A., Heredia-Pi, I., Herteliu, C., Hoang, C. L., Hole, M. K., Rad, E. H., Hossain, N., Hosseinzadeh, M., Hostiuc, S., Ilesanmi, O. S., Irvani, S. S. N., Jakovljevic, M., Jalali, A., James, S. L., Jonas, J. B., JÃŒrisson, M., Kadel, R., Matin, B. K., Kasaeian, A., Kasaye, H. K., Kassaw, M. W., Karyani, A. K., Khabiri, R., Khan, J., Khan, M. N., Khang, Y. -H, Kisa, A., Kissimova-Skarbek, K., Kohler, S., Koyanagi, A., Krohn, K. J., Leung, R., Lim, L. -L, Lorkowski, S., Majeed, A., Malekzadeh, R., Mansourian, M., Mantovani, L. G., Massenburg, B. B., Mckee, M., Mehta, V., Meretoja, A., Meretoja, T. J., Kostova, N. M., Miller, T. R., Mirrakhimov, E. M., Mohajer, B., Darwesh, A. M., Mohammed, S., Mohebi, F., Mokdad, A. H., Morrison, S. D., Mousavi, S. M., Muthupandian, S., Nagarajan, A. J., Nangia, V., Negoi, I., Nguyen, C. T., Nguyen, H. L. T., Nguyen, S. H., Nosratnejad, S., Oladimeji, O., Olgiati, S., Olusanya, J. O., Onwujekwe, O. E., Otstavnov, S. S., Pana, A., Pereira, D. M., Piroozi, B., Prada, S. I., Qorbani, M., Rabiee, M., Rabiee, N., Rafiei, A., Rahim, F., Rahimi-Movaghar, V., Ram, U., Ranabhat, C. L., Ranta, A., Rawaf, D. L., Rawaf, S., Rezaei, S., Roro, E. M., Rostami, A., Rubino, S., Salahshoor, M., Samy, A. M., Sanabria, J., Santos, J. V., Milicevic, M. M. S., Jose, B. P. S., Savic, M., Schwendicke, F., Sepanlou, S. G., Sepehrimanesh, M., Sheikh, A., Shrime, M. G., Sisay, S., Soltani, S., Soofi, M., Srinivasan, V., TabarÃ©s-Seisdedos, R., Torre, A., Tovani-Palone, M. R., Tran, B. X., Tran, K. B., Undurraga, E. A., Valdez, P. R., Van Boven, J. F. M., Vargas, V., Veisani, Y., Violante, F. S., Vladimirov, S. K., Vlassov, V., Vollmer, S., Vu, G. T., Wolfe, C. D. A., Yonemoto, N., Younis, M. Z., Yousefifard, M., Zaman, S. B., Zangeneh, A., Zegeye, E. A., Ziapour, A., Chew, A., Murray, C. J. L., Dieleman, J. L., Network, Global Burden of Disease Health Financing Collaborator, Chang, A. Y., Cowling, K., Micah, A. E., Chapin, A., Chen, C. S., Ikilezi, G., Sadat, N., Tsakalos, G., Wu, J., Younker, T., Zhao, Y., Zlavog, B. S., Abbafati, C., Ahmed, A. E., Alam, K., Alipour, V., Aljunid, S. M., Almalki, M. J., Alvis-Guzman, N., Ammar, W., Andrei, C. L., Anjomshoa, M., Antonio, C. A. T., Arabloo, J., Aremu, O., Ausloos, M., Avila-Burgos, L., Awasthi, A., Ayanore, M. A., Azari, S., Azzopardi-Muscat, N., Bagherzadeh, M., BÃ€rnighausen, T. W., Baune, B. T., Bayati, M., Belay, Y. B., Belay, Y. A., Belete, H., Berbada, D. A., Berman, A. E., Beuran, M., Bijani, A., Busse, R., Cahuana-Hurtado, L., CÃ¡mera, L. A., CatalÃ¡-LÃ³pez, F., Chauhan, B. G., Constantin, M. -M, Crowe, C. S., Cucu, A., Dalal, Koustuv, De Neve, J. -W, Deiparine, S., Demeke, F. M., Do, H. P., Dubey, M., Tantawi, M. E., Eskandarieh, S., Esmaeili, R., Fakhar, M., Fazaeli, A. A., Fischer, F., Foigt, N. A., Fukumoto, T., Fullman, N., Galan, A., Gamkrelidze, A., Gezae, K. E., Ghajar, A., Ghashghaee, A., Goginashvili, K., Haakenstad, A., Bidgoli, H. H., Hamidi, S., Harb, H. L., Hasanpoor, E., Hassen, H. Y., Hay, S. I., Hendrie, D., Henok, A., Heredia-Pi, I., Herteliu, C., Hoang, C. L., Hole, M. K., Rad, E. H., Hossain, N., Hosseinzadeh, M., Hostiuc, S., Ilesanmi, O. S., Irvani, S. S. N., Jakovljevic, M., Jalali, A., James, S. L., Jonas, J. B., JÃŒrisson, M., Kadel, R., Matin, B. K., Kasaeian, A., Kasaye, H. K., Kassaw, M. W., Karyani, A. K., Khabiri, R., Khan, J., Khan, M. N., Khang, Y. -H, Kisa, A., Kissimova-Skarbek, K., Kohler, S., Koyanagi, A., Krohn, K. J., Leung, R., Lim, L. -L, Lorkowski, S., Majeed, A., Malekzadeh, R., Mansourian, M., Mantovani, L. G., Massenburg, B. B., Mckee, M., Mehta, V., Meretoja, A., Meretoja, T. J., Kostova, N. M., Miller, T. R., Mirrakhimov, E. M., Mohajer, B., Darwesh, A. M., Mohammed, S., Mohebi, F., Mokdad, A. H., Morrison, S. D., Mousavi, S. M., Muthupandian, S., Nagarajan, A. J., Nangia, V., Negoi, I., Nguyen, C. T., Nguyen, H. L. T., Nguyen, S. H., Nosratnejad, S., Oladimeji, O., Olgiati, S., Olusanya, J. O., Onwujekwe, O. E., Otstavnov, S. S., Pana, A., Pereira, D. M., Piroozi, B., Prada, S. I., Qorbani, M., Rabiee, M., Rabiee, N., Rafiei, A., Rahim, F., Rahimi-Movaghar, V., Ram, U., Ranabhat, C. L., Ranta, A., Rawaf, D. L., Rawaf, S., Rezaei, S., Roro, E. M., Rostami, A., Rubino, S., Salahshoor, M., Samy, A. M., Sanabria, J., Santos, J. V., Milicevic, M. M. S., Jose, B. P. S., Savic, M., Schwendicke, F., Sepanlou, S. G., Sepehrimanesh, M., Sheikh, A., Shrime, M. G., Sisay, S., Soltani, S., Soofi, M., Srinivasan, V., TabarÃ©s-Seisdedos, R., Torre, A., Tovani-Palone, M. R., Tran, B. X., Tran, K. B., Undurraga, E. A., Valdez, P. R., Van Boven, J. F. M., Vargas, V., Veisani, Y., Violante, F. S., Vladimirov, S. K., Vlassov, V., Vollmer, S., Vu, G. T., Wolfe, C. D. A., Yonemoto, N., Younis, M. Z., Yousefifard, M., Zaman, S. B., Zangeneh, A., Zegeye, E. A., Ziapour, A., Chew, A., Murray, C. J. L., Dieleman, J. L., and Network, Global Burden of Disease Health Financing Collaborator
Abstract: Background: Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries. Methods: We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories-government, out-of-pocket, and prepaid private health spending-and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more reso
Published: 2019
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17. Credit risk management and cyclicality of bank lending to non-financial corporations in Italy during the financial crisis: 2008-2012. A modeling study

Author: Olgiati, S. and Alessandro Danovi
Subjects: credit growth rate, Frequent cyclical fluctuations, default rate, retrospective forecasting, steady state function, cyclical sensitivity parameter, Settore SECS-P/08 - Economia e Gestione delle Imprese, lcsh:Business, lcsh:HF5001-6182
Published: 2015

18. Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia

Author: Vrij, F.M.S. (Femke), Bouwkamp, C.G. (Christian), Gunhanlar, N. (Nilhan), Shpak, G. (Guy), Lendemeijer, B. (Bas), Baghdadi, M. (Maarouf), Gopalakrishna, S. (Shreekara), Ghazvini, M. (Mehrnaz), Li, T. (Tracy), Quadri, M. (Marialuisa), Olgiati, S. (Simone), Breedveld, G.J. (Guido), Coesmans, M.P.H. (Michiel), Mientjes, E.J. (Edwin), de Wit, T. (Ton), Verheijen, F.W. (Frans), Beverloo, H.B. (Berna), Cohen, D. (Dan), Kok, R.M. (Rob M.), Bakker, P.R. (Roberto), Nijburg, A. (Aviva), Spijker, A.T. (Anne), Haffmans, P.M.J. (P.M. Judith), Hoencamp, E. (Erik), Bergink, V. (Veerle), Vorstman, J.A.S., Wu, T. (Timothy), Olde Loohuis, L.M. (Loes M.), Amin, N. (Najaf), Langen, C.D. (Carolyn), Hofman, A. (Albert), Hoogendijk, W.J.G. (Witte), van Duijn, C.M. (Cornelia M.), Ikram, M.A. (M. A.), Vernooij, M.W. (Meike), Tiemeier, H.W. (Henning), Uitterlinden, A.G. (André G.), Elgersma, Y. (Ype), Distel, B. (Ben), Gribnau, J.H. (Joost), White, T.J.H. (Tonya), Bonifati, V. (Vincenzo), Kushner, S.A. (Steven A.), Vrij, F.M.S. (Femke), Bouwkamp, C.G. (Christian), Gunhanlar, N. (Nilhan), Shpak, G. (Guy), Lendemeijer, B. (Bas), Baghdadi, M. (Maarouf), Gopalakrishna, S. (Shreekara), Ghazvini, M. (Mehrnaz), Li, T. (Tracy), Quadri, M. (Marialuisa), Olgiati, S. (Simone), Breedveld, G.J. (Guido), Coesmans, M.P.H. (Michiel), Mientjes, E.J. (Edwin), de Wit, T. (Ton), Verheijen, F.W. (Frans), Beverloo, H.B. (Berna), Cohen, D. (Dan), Kok, R.M. (Rob M.), Bakker, P.R. (Roberto), Nijburg, A. (Aviva), Spijker, A.T. (Anne), Haffmans, P.M.J. (P.M. Judith), Hoencamp, E. (Erik), Bergink, V. (Veerle), Vorstman, J.A.S., Wu, T. (Timothy), Olde Loohuis, L.M. (Loes M.), Amin, N. (Najaf), Langen, C.D. (Carolyn), Hofman, A. (Albert), Hoogendijk, W.J.G. (Witte), van Duijn, C.M. (Cornelia M.), Ikram, M.A. (M. A.), Vernooij, M.W. (Meike), Tiemeier, H.W. (Henning), Uitterlinden, A.G. (André G.), Elgersma, Y. (Ype), Distel, B. (Ben), Gribnau, J.H. (Joost), White, T.J.H. (Tonya), Bonifati, V. (Vincenzo), and Kushner, S.A. (Steven A.)
Abstract: Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation of two rare missense mutations in Chondroitin Sulfate Proteoglycan 4 (CSPG4) (c.391G > A [p.A131T], MAF 7.79 × 10−5 and c.2702T > G [p.V901G], MAF 2.51 × 10−3). The CSPG4A131T mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2536 cases, 2543 controls), while the CSPG4V901G mutation was nominally enriched in cases (11 cases vs. 3 controls, P = 0.026, OR 3.77, 95% CI 1.05–13.52). CSPG4/NG2 is a hallmark protein of oligodendrocyte progenitor cells (OPCs). iPSC-derived OPCs from CSPG4A131T mutation carriers exhibited abnormal post-translational processing (P = 0.029), subcellular localization of mutant NG2 (P = 0.007), as well as aberrant cellular morphology (P = 3.0 × 10−8), viability (P = 8.9 × 10−7), and myelination potential (P = 0.038). Moreover, transfection of healthy non-carrier sibling OPCs confirmed a pathogenic effect on cell survival of both the CSPG4A131T (P = 0.006) and CSPG4V901G (P = 3.4 × 10−4) mutations. Finally, in vivo diffusion tensor imaging of CSPG4A131T mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 × 10−5). Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia.
Published: 2018
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19. Evolution and patterns of global health financing 1995-2014: development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries

Author: Dieleman, J, Campbell, M, Chapin, A, Eldrenkamp, E, Fan, VY, Haakenstad, A, Kates, J, Liu, YY, Matyasz, T, Micah, A, Reynolds, A, Sadat, N, Schneider, MT, Sorensen, R, Evans, T, Evans, D, Kurowski, C, Tandon, A, Abbas, KM, Abera, SF, Kiadaliri, AA, Ahmed, KY, Ahmed, MB, Alam, K, Alizadeh-Navaei, R, Alkerwi, A, Amini, E, Ammar, W, Amrock, SM, Antonio, CAT, Atey, TM, Avila-Burgos, L, Awasthi, A, Barac, A, Bernal, OA, Beyene, AS, Beyene, TJ, Birungi, C, Bizuayehu, HM, Breitborde, NJK, Cahuana-Hurtado, L, Castro, RE, Catala-Lopez, F, Dalal, K, Dandona, L, Dandona, R, Jager, P, Dharmaratne, SD, Dubey, M, Sofia e Sa Farinha, C, Faro, A, Feigl, AB, Fischer, F, Fitchett, JRA, Foigt, N, Giref, AZ, Gupta, R, Hamidi, S, Harb, HL, Hay, SI, Hendrie, D, Horino, M, Jurisson, M, Jakovljevic, MB, Javanbakht, M, John, D, Jonas, JB, Karimi, SM, Khang, YH, Khubchandani, J, Kim, YJ, Kinge, JM, Krohn, KJ, Kumar, GA, Abd El Razek, HM, Abd El Razek, MM, Majeed, A, Malekzadeh, R, Masiye, F, Meier, T, Meretoja, A, Miller, TR, Mirrakhimov, EM, Mohammed, S, Nangia, V, Olgiati, S, Osman, AS, Owolabi, MO, Patel, T, Caicedo, AJP, Pereira, DM, Perelman, J, Polinder, Suzanne, Rafay, A, Rahimi-Movaghar, V, Rai, RK, Ram, U, Ranabhat, CL, Roba, HS, Salama, J, Savic, M, Sepanlou, SG, Shrime, MG, Talongwa, RT, Te Ao, BJ, Tediosi, F, Tesema, AG, Thomson, AJ, Tobe-Gai, R, Topor-Madry, R, Undurraga, EA, Vasankari, T, Violante, FS, Werdecker, A, Wijeratne, T, Xu, G, Yonemoto, N, Younis, MZ, Yu, CH, Zaidi, Z, Zaki, ME, Murray, CJL, Global Burden D Hlth, F, and Public Health
Published: 2017

20. Future and potential spending on health 2015-40: development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries

Author: Dieleman, JL, Campbell, M, Chapin, A, Eldrenkamp, E, Fan, VY, Haakenstad, A, Kates, J, Li, ZY, Matyasz, T, Micah, A, Reynolds, A, Sadat, N, Schneider, MT, Sorensen, R, Abbas, KM, Abera, SF, Kiadaliri, AA, Ahmed, MB, Alam, K, Alizadeh-Navaei, R, Alkerwi, A, Amini, E, Ammar, W, Antonio, CAT, Atey, TM, Avila-Burgos, L, Awasthi, A, Barac, A, Berheto, TM, Beyene, AS, Beyene, TJ, Birungi, C, Bizuayehu, HM, Breitborde, NJK, Cahuana-Hurtado, L, Castro, RE, Catala-Lopez, F, Dalal, K, Dandona, L, Dandona, R, Dharmaratne, SD, Dubey, M, Faro, A, Feigl, AB, Fischer, F, Fitchett, JRA, Foigt, N, Giref, AZ, Gupta, R, Hamidi, S, Harb, HL, Hay, SI, Hendrie, D, Horino, M, Jurisson, M, Jakovljevic, MB, Javanbakht, M, John, D, Jonas, JB, Karimi, SM, Khang, YH, Khubchandani, J, Kim, YJ, Kinge, JM, Krohn, KJ, Kumar, GA, Leung, R, Abd El Razek, HM, Abd El Razek, MM, Majeed, A, Malekzadeh, R, Malta, DC, Meretoja, A, Miller, TR, Mirrakhimov, EM, Mohammed, S, Molla, G, Nangia, V, Olgiati, S, Owolabi, MO, Patel, T, Caicedo, AJP, Pereira, DM, Perelman, J, Polinder, Suzanne, Rafay, A, Rahimi-Movaghar, V, Rai, RK, Ram, U, Ranabhat, CL, Roba, HS, Savic, M, Sepanlou, SG, Te Ao, BJ, Tesema, AG, Thomson, AJ, Tobe-Gai, R, Topor-Madry, R, Undurraga, EA, Vargas, V, Vasankari, T, Violante, FS, Wijeratne, T, Xu, GL, Yonemoto, N, Younis, MZ, Yu, CH, Zaidi, Z, Zaki, ME, Murray, CJL, Global Burden D Hlth, F, and Public Health
Published: 2017

21. Evolution and patterns of global health financing 1995-2014: Development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries

Author: Dieleman, J. (Joseph), Campbell, M. (Madeline), Chapin, A. (Abigail), Eldrenkamp, E. (Erika), Fan, V.Y. (Victoria Y.), Haakenstad, A. (Annie), Kates, J. (Jennifer), Liu, Y. (Yingying), Matyasz, T. (Taylor), Micah, A. (Angela), Reynolds, A. (Alex), Sadat, N. (Nafis), Schneider, M.T. (Matthew T.), Sorensen, R. (Reed), Evans, T. (Tim), Evans, D. (David), Kurowski, C. (Christoph), Tandon, A. (Ajay), Abbas, K.M. (Kaja M.), Abera, S.F. (Semaw Ferede), Ahmad Kiadaliri, A. (Aliasghar), Ahmed, K.Y. (Kedir Yimam), Ahmed, M.B. (Muktar Beshir), Alam, K. (Khurshid), Alizadeh-Navaei, R. (Reza), Alkerwi, A. (Ala'a), Amini, E. (Erfan), Ammar, W. (Walid), Amrock, S.M. (Stephen Marc), Antonio, C.A.T. (Carl Abelardo T), Atey, T.M. (Tesfay Mehari), Avila-Burgos, L. (Leticia), Awasthi, A. (Ashish), Barac, A. (Aleksandra), Bernal, O.A. (Oscar Alberto), Beyene, A.S. (Addisu Shunu), Beyene, T.J. (Tariku Jibat), Birungi, C. (Charles), Bizuayehu, H.M. (Habtamu Mellie), Breitborde, N.J.K. (Nicholas J.K.), Cahuana-Hurtado, L. (Lucero), Castro, R.E. (Ruben Estanislao), Catalá-López, F. (Ferrán), Dalal, K. (Koustuv), Dandona, L. (Lalit), Dandona, R. (Rakhi), De Jager, P. (Pieter), Dharmaratne, S.D. (Samath D.), Dubey, M. (Manisha), Farinha, C.S.E.S. (Carla Sofia E. Sa), Faro, A. (Andre), Feigl, A.B. (Andrea B.), Fischer, F. (Florian), Fitchett, J.R.A. (Joseph Robert Anderson), Foigt, N. (Nataliya), Giref, A.Z. (Ababi Zergaw), Gupta, R. (Rahul), Hamidi, S. (Samer), Harb, H.L. (Hilda L.), Hay, S.I. (Simon), Hendrie, D. (Delia), Horino, M. (Masako), Jürisson, M. (Mikk), Jakovljevic, M.B. (Mihajlo B.), Javanbakht, M. (Mehdi), John, D. (Denny), Jonas, J.B. (Jost B.), Karimi, S.M. (Seyed M.), Khang, Y.-H. (Young-Ho), Khubchandani, J. (Jagdish), Kim, Y.J. (Yun Jin), Kinge, J.M. (Jonas M), Krohn, K.J. (Kristopher J.), Kumar, G.A. (G. Anil), Magdy Abd El Razek, H. (Hassan), Magdy Abd El Razek, M. (Mohammed), Majeed, A. (Azeem), Malekzadeh, R. (Reza), Masiye, F. (Felix), Meier, T. (Toni), Meretoja, A. (Atte), Miller, T.R. (Ted R), Mirrakhimov, E.M. (Erkin M.), Mohammed, S. (Shafiu), Nangia, V. (Vinay), Olgiati, S. (Stefano), Osman, A.S. (Abdalla Sidahmed), Owolabi, M.O. (Mayowa O.), Patel, T. (Tejas), Paternina Caicedo, A.J. (Angel J.), Pereira, D.M. (David M.), Perelman, J. (Julian), Polinder, S. (Suzanne), Rafay, A. (Anwar), Rahimi-Movaghar, V. (Vafa), Rai, R.K. (Rajesh Kumar), Ram, U. (Usha), Ranabhat, C.L. (Chhabi Lal), Roba, H.S. (Hirbo Shore), Salama, J. (Joseph), Savic, M. (Miloje), Sepanlou, S.G. (Sadaf G), Shrime, M.G. (Mark G.), Talongwa, R.T. (Roberto Tchio), Te Ao, B.J. (Braden J.), Tediosi, F. (Fabrizio), Tesema, A.G. (Azeb Gebresilassie), Thomson, A.J. (Alan J.), Tobe-Gai, R. (Ruoyan), Topor-Madry, R. (Roman), Undurraga, E.A. (Eduardo A.), Vasankari, T. (Tommi), Violante, F.S. (Francesco S), Werdecker, A. (Andrea), Wijeratne, T. (Tissa), Xu, G. (Gelin), Yonemoto, N. (Naohiro), Younis, M.Z. (Mustafa Z.), Yu, C. (Chuanhua), Zaidi, Z. (Zoubida), El Sayed Zaki, M. (Maysaa), Murray, C.J.L. (Christopher), Dieleman, J. (Joseph), Campbell, M. (Madeline), Chapin, A. (Abigail), Eldrenkamp, E. (Erika), Fan, V.Y. (Victoria Y.), Haakenstad, A. (Annie), Kates, J. (Jennifer), Liu, Y. (Yingying), Matyasz, T. (Taylor), Micah, A. (Angela), Reynolds, A. (Alex), Sadat, N. (Nafis), Schneider, M.T. (Matthew T.), Sorensen, R. (Reed), Evans, T. (Tim), Evans, D. (David), Kurowski, C. (Christoph), Tandon, A. (Ajay), Abbas, K.M. (Kaja M.), Abera, S.F. (Semaw Ferede), Ahmad Kiadaliri, A. (Aliasghar), Ahmed, K.Y. (Kedir Yimam), Ahmed, M.B. (Muktar Beshir), Alam, K. (Khurshid), Alizadeh-Navaei, R. (Reza), Alkerwi, A. (Ala'a), Amini, E. (Erfan), Ammar, W. (Walid), Amrock, S.M. (Stephen Marc), Antonio, C.A.T. (Carl Abelardo T), Atey, T.M. (Tesfay Mehari), Avila-Burgos, L. (Leticia), Awasthi, A. (Ashish), Barac, A. (Aleksandra), Bernal, O.A. (Oscar Alberto), Beyene, A.S. (Addisu Shunu), Beyene, T.J. (Tariku Jibat), Birungi, C. (Charles), Bizuayehu, H.M. (Habtamu Mellie), Breitborde, N.J.K. (Nicholas J.K.), Cahuana-Hurtado, L. (Lucero), Castro, R.E. (Ruben Estanislao), Catalá-López, F. (Ferrán), Dalal, K. (Koustuv), Dandona, L. (Lalit), Dandona, R. (Rakhi), De Jager, P. (Pieter), Dharmaratne, S.D. (Samath D.), Dubey, M. (Manisha), Farinha, C.S.E.S. (Carla Sofia E. Sa), Faro, A. (Andre), Feigl, A.B. (Andrea B.), Fischer, F. (Florian), Fitchett, J.R.A. (Joseph Robert Anderson), Foigt, N. (Nataliya), Giref, A.Z. (Ababi Zergaw), Gupta, R. (Rahul), Hamidi, S. (Samer), Harb, H.L. (Hilda L.), Hay, S.I. (Simon), Hendrie, D. (Delia), Horino, M. (Masako), Jürisson, M. (Mikk), Jakovljevic, M.B. (Mihajlo B.), Javanbakht, M. (Mehdi), John, D. (Denny), Jonas, J.B. (Jost B.), Karimi, S.M. (Seyed M.), Khang, Y.-H. (Young-Ho), Khubchandani, J. (Jagdish), Kim, Y.J. (Yun Jin), Kinge, J.M. (Jonas M), Krohn, K.J. (Kristopher J.), Kumar, G.A. (G. Anil), Magdy Abd El Razek, H. (Hassan), Magdy Abd El Razek, M. (Mohammed), Majeed, A. (Azeem), Malekzadeh, R. (Reza), Masiye, F. (Felix), Meier, T. (Toni), Meretoja, A. (Atte), Miller, T.R. (Ted R), Mirrakhimov, E.M. (Erkin M.), Mohammed, S. (Shafiu), Nangia, V. (Vinay), Olgiati, S. (Stefano), Osman, A.S. (Abdalla Sidahmed), Owolabi, M.O. (Mayowa O.), Patel, T. (Tejas), Paternina Caicedo, A.J. (Angel J.), Pereira, D.M. (David M.), Perelman, J. (Julian), Polinder, S. (Suzanne), Rafay, A. (Anwar), Rahimi-Movaghar, V. (Vafa), Rai, R.K. (Rajesh Kumar), Ram, U. (Usha), Ranabhat, C.L. (Chhabi Lal), Roba, H.S. (Hirbo Shore), Salama, J. (Joseph), Savic, M. (Miloje), Sepanlou, S.G. (Sadaf G), Shrime, M.G. (Mark G.), Talongwa, R.T. (Roberto Tchio), Te Ao, B.J. (Braden J.), Tediosi, F. (Fabrizio), Tesema, A.G. (Azeb Gebresilassie), Thomson, A.J. (Alan J.), Tobe-Gai, R. (Ruoyan), Topor-Madry, R. (Roman), Undurraga, E.A. (Eduardo A.), Vasankari, T. (Tommi), Violante, F.S. (Francesco S), Werdecker, A. (Andrea), Wijeratne, T. (Tissa), Xu, G. (Gelin), Yonemoto, N. (Naohiro), Younis, M.Z. (Mustafa Z.), Yu, C. (Chuanhua), Zaidi, Z. (Zoubida), El Sayed Zaki, M. (Maysaa), and Murray, C.J.L. (Christopher)
Abstract: Background: An adequate amount of prepaid resources for health is important to ensure access to health services and for the pursuit of universal health coverage. Previous studies on global health financing have described the relationship between economic development and health financing. In this study, we further explore global health financing trends and examine how the sources of funds used, types of services purchased, and development assistance for health disbursed change with economic development. We also identify countries that deviate from the trends. Methods: We estimated national health spending by type of care and by source, including development assistance for health, based on a diverse set of data including programme reports, budget data, national estimates, and 964 National Health Accounts. These data represent health spending for 184 countries from 1995 through 2014. We converted these data into a common inflation-adjusted and purchasing power-adjusted currency, and used non-linear regression methods to model the relationship between health financing, time, and economic development. Findings: Between 1995 and 2014, economic development was positively associated with total health spending and a shift away from a reliance on development assistance and out-of-pocket (OOP) towards government spending. The largest absolute increase in spending was in high-income countries, which increased to purchasing power-adjusted $5221 per capita based on an annual growth rate of 3.0%. The largest health spending growth rates were in upper-middle-income (5.9) and lower-middle-income groups (5.0), which both increased spending at more than 5% per year, and spent $914 and $267 per capita in 2014, respectively. Spending in low-income countries grew nearly as fast, at 4.6%, and health spending increased from $51 to $120 per capita. In 2014, 59.2% of all health spending was financed by the government, although in low-income and lower-middle-income countries, 29.1% and 58.0%
Published: 2017
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22. Future and potential spending on health 2015-40: Development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries

Author: Dieleman, J.L. (Joseph L.), Campbell, M. (Madeline), Chapin, A. (Abigail), Eldrenkamp, E. (Erika), Fan, V.Y. (Victoria Y.), Haakenstad, A. (Annie), Kates, J. (Jennifer), Li, Z. (Zhiyin), Matyasz, T. (Taylor), Micah, A. (Angela), Reynolds, A. (Alex), Sadat, N. (Nafis), Schneider, M.T. (Matthew T.), Sorensen, R. (Reed), Abbas, K.M. (Kaja M.), Abera, S.F. (Semaw Ferede), Ahmad Kiadaliri, A. (Aliasghar), Ahmed, M.B. (Muktar Beshir), Alam, K. (Khurshid), Alizadeh-Navaei, R. (Reza), Alkerwi, A. (Ala'a), Amini, E. (Erfan), Ammar, W. (Walid), Antonio, C.A.T. (Carl Abelardo T), Atey, T.M. (Tesfay Mehari), Avila-Burgos, L. (Leticia), Awasthi, A. (Ashish), Barac, A. (Aleksandra), Berheto, T.M. (Tezera Moshago), Beyene, A.S. (Addisu Shunu), Beyene, T.J. (Tariku Jibat), Birungi, C. (Charles), Bizuayehu, H.M. (Habtamu Mellie), Breitborde, N.J.K. (Nicholas J.K.), Cahuana-Hurtado, L. (Lucero), Castro, R.E. (Ruben Estanislao), Catalá-López, F. (Ferrán), Dalal, K. (Koustuv), Dandona, L. (Lalit), Dharmaratne, R.D.S.D. (Rakhi Dandona Samath D.), Dubey, M. (Manisha), Faro, A. (Andé), Feigl, A.B. (Andrea B.), Fischer, F. (Florian), Fitchett, J.R.A. (Joseph R. Anderson), Foigt, N. (Nataliya), Giref, A.Z. (Ababi Zergaw), Gupta, R. (Rahul), Hamidi, S. (Samer), Harb, H.L. (Hilda L.), Hay, S.I. (Simon), Hendrie, D. (Delia), Horino, M. (Masako), Jürisson, M. (Mikk), Jakovljevic, M.B. (Mihajlo B.), Javanbakht, M. (Mehdi), John, D. (Denny), Jonas, J.B. (Jost B.), Karimi, S.M. (Seyed M.), Khang, Y.-H. (Young-Ho), Khubchandani, J. (Jagdish), Kim, Y.J. (Yun Jin), Kinge, J.M. (Jonas M), Krohn, K.J. (Kristopher J.), Kumar, G.A. (G. Anil), Leung, R. (Ricky), Magdy Abd El Razek, H. (Hassan), Magdy Abd El Razek, M. (Mohammed), Majeed, A. (Azeem), Malekzadeh, R. (Reza), Malta, D.C. (Deborah Carvalho), Meretoja, A. (Atte), Miller, T.R. (Ted R), Mirrakhimov, E.M. (Erkin M.), Mohammed, S. (Shafiu), Molla, G. (Gedefaw), Nangia, V. (Vinay), Olgiati, S. (Stefano), Owolabi, M.O. (Mayowa O.), Patel, T. (Tejas), Paternina Caicedo, A.J. (Angel J.), Pereira, D.M. (David M.), Perelman, J. (Julian), Polinder, S. (Suzanne), Rafay, A. (Anwar), Rahimi-Movaghar, V. (Vafa), Rai, R.K. (Rajesh Kumar), Ram, U. (Usha), Ranabhat, C.L. (Chhabi Lal), Roba, H.S. (Hirbo Shore), Savic, M. (Miloje), Sepanlou, S.G. (Sadaf G), Te Ao, B.J. (Braden J.), Tesema, A.G. (Azeb Gebresilassie), Thomson, A.J. (Alan J.), Tobe-Gai, R. (Ruoyan), Topor-Madry, R. (Roman), Undurraga, E.A. (Eduardo A.), Vargas, V. (Veronica), Vasankari, T. (Tuula), Violante, F.S. (Francesco S), Wijeratne, T. (Tissa), Yonemoto, N. (Naohiro), Younis, M.Z. (Mustafa Z.), Yu, C. (Chuanhua), Zaidi, Z. (Zoubida), El Sayed Zaki, M. (Maysaa), Murray, C.J.L. (Christopher), Dieleman, J.L. (Joseph L.), Campbell, M. (Madeline), Chapin, A. (Abigail), Eldrenkamp, E. (Erika), Fan, V.Y. (Victoria Y.), Haakenstad, A. (Annie), Kates, J. (Jennifer), Li, Z. (Zhiyin), Matyasz, T. (Taylor), Micah, A. (Angela), Reynolds, A. (Alex), Sadat, N. (Nafis), Schneider, M.T. (Matthew T.), Sorensen, R. (Reed), Abbas, K.M. (Kaja M.), Abera, S.F. (Semaw Ferede), Ahmad Kiadaliri, A. (Aliasghar), Ahmed, M.B. (Muktar Beshir), Alam, K. (Khurshid), Alizadeh-Navaei, R. (Reza), Alkerwi, A. (Ala'a), Amini, E. (Erfan), Ammar, W. (Walid), Antonio, C.A.T. (Carl Abelardo T), Atey, T.M. (Tesfay Mehari), Avila-Burgos, L. (Leticia), Awasthi, A. (Ashish), Barac, A. (Aleksandra), Berheto, T.M. (Tezera Moshago), Beyene, A.S. (Addisu Shunu), Beyene, T.J. (Tariku Jibat), Birungi, C. (Charles), Bizuayehu, H.M. (Habtamu Mellie), Breitborde, N.J.K. (Nicholas J.K.), Cahuana-Hurtado, L. (Lucero), Castro, R.E. (Ruben Estanislao), Catalá-López, F. (Ferrán), Dalal, K. (Koustuv), Dandona, L. (Lalit), Dharmaratne, R.D.S.D. (Rakhi Dandona Samath D.), Dubey, M. (Manisha), Faro, A. (Andé), Feigl, A.B. (Andrea B.), Fischer, F. (Florian), Fitchett, J.R.A. (Joseph R. Anderson), Foigt, N. (Nataliya), Giref, A.Z. (Ababi Zergaw), Gupta, R. (Rahul), Hamidi, S. (Samer), Harb, H.L. (Hilda L.), Hay, S.I. (Simon), Hendrie, D. (Delia), Horino, M. (Masako), Jürisson, M. (Mikk), Jakovljevic, M.B. (Mihajlo B.), Javanbakht, M. (Mehdi), John, D. (Denny), Jonas, J.B. (Jost B.), Karimi, S.M. (Seyed M.), Khang, Y.-H. (Young-Ho), Khubchandani, J. (Jagdish), Kim, Y.J. (Yun Jin), Kinge, J.M. (Jonas M), Krohn, K.J. (Kristopher J.), Kumar, G.A. (G. Anil), Leung, R. (Ricky), Magdy Abd El Razek, H. (Hassan), Magdy Abd El Razek, M. (Mohammed), Majeed, A. (Azeem), Malekzadeh, R. (Reza), Malta, D.C. (Deborah Carvalho), Meretoja, A. (Atte), Miller, T.R. (Ted R), Mirrakhimov, E.M. (Erkin M.), Mohammed, S. (Shafiu), Molla, G. (Gedefaw), Nangia, V. (Vinay), Olgiati, S. (Stefano), Owolabi, M.O. (Mayowa O.), Patel, T. (Tejas), Paternina Caicedo, A.J. (Angel J.), Pereira, D.M. (David M.), Perelman, J. (Julian), Polinder, S. (Suzanne), Rafay, A. (Anwar), Rahimi-Movaghar, V. (Vafa), Rai, R.K. (Rajesh Kumar), Ram, U. (Usha), Ranabhat, C.L. (Chhabi Lal), Roba, H.S. (Hirbo Shore), Savic, M. (Miloje), Sepanlou, S.G. (Sadaf G), Te Ao, B.J. (Braden J.), Tesema, A.G. (Azeb Gebresilassie), Thomson, A.J. (Alan J.), Tobe-Gai, R. (Ruoyan), Topor-Madry, R. (Roman), Undurraga, E.A. (Eduardo A.), Vargas, V. (Veronica), Vasankari, T. (Tuula), Violante, F.S. (Francesco S), Wijeratne, T. (Tissa), Yonemoto, N. (Naohiro), Younis, M.Z. (Mustafa Z.), Yu, C. (Chuanhua), Zaidi, Z. (Zoubida), El Sayed Zaki, M. (Maysaa), and Murray, C.J.L. (Christopher)
Abstract: Background: The amount of resources, particularly prepaid resources, available for health can affect access to health care and health outcomes. Although health spending tends to increase with economic development, tremendous variation exists among health financing systems. Estimates of future spending can be beneficial for policy makers and planners, and can identify financing gaps. In this study, we estimate future gross domestic product (GDP), all-sector government spending, and health spending disaggregated by source, and we compare expected future spending to potential future spending. Methods: We extracted GDP, government spending in 184 countries from 1980-2015, and health spend data from 1995-2014. We used a series of ensemble models to estimate future GDP, all-sector government spending, development assistance for health, and government, out-of-pocket, and prepaid private health spending through 2040. We used frontier analyses to identify patterns exhibited by the countries that dedicate the most funding to health, and used these frontiers to estimate potential health spending for each low-income or middle-income country. All estimates are inflation and purchasing power adjusted. Findings: We estimated that global spending on health will increase from US$9.21 trillion in 2014 to $24.24 trillion (uncertainty interval [UI] 20.47-29.72) in 2040. We expect per capita health spending to increase fastest in upper-middle-income countries, at 5.3% (UI 4.1-6.8) per year. This growth is driven by continued growth in GDP, government spending, and government health spending. Lower-middle income countries are expected to grow at 4.2% (3.8-4.9). High-income countries are expected to grow at 2.1% (UI 1.8-2.4) and low-income countries are expected to grow at 1.8% (1.0-2.8). Despite this growth, health spending per capita in low-income countries is expected to remain low, at $154 (UI 133-181) per capita in 2030 and $195 (157-258) per capita in 2040. Increases in national hea
Published: 2017
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23. Future and potential spending on health 2015-40: development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries

Author: Dieleman, J., Campbell, M., Chapin, A., Eldrenkamp, E., Fan, V., Haakenstad, A., Kates, J., Li, Z., Matyasz, T., Micah, A., Reynolds, A., Sadat, N., Schneider, M., Sorensen, R., Abbas, K., Abera, S., Kiadaliri, A., Ahmed, M., Alam, K., Alizadeh-Navaei, R., Alkerwi, A., Amini, E., Ammar, W., Antonio, C., Atey, T., Avila-Burgos, L., Awasthi, A., Barac, A., Berheto, T., Beyene, A., Beyene, T., Birungi, C., Bizuayehu, H., Breitborde, N., Cahuana-Hurtado, L., Estanislao Castro, R., Catala-Lopez, F., Dalal, K., Dandona, L., Dandona, R., Dharmaratne, S., Dubey, M., Faro, A., Feigl, A., Fischer, F., Fitchett, J., Foigt, N., Giref, A., Gupta, R., Hamidi, S., Harb, H., Hay, S., Hendrie, D., Horino, M., Jurisson, M., Jakovljevic, M., Javanbakht, M., John, D., Jonas, J., Karimi, S., Khang, Y., Khubchandani, J., Kim, Y., Kinge, J., Krohn, K., Kumar, G., Leung, R., Abd El Razek, H., Abd El Razek, M., Majeed, A., Malekzadeh, R., Malta, D., Meretoja, A., Miller, Ted, Mirrakhimov, E., Mohammed, S., Molla, G., Nangia, V., Olgiati, S., Owolabi, M., Patel, T., Caicedo, A., Pereira, D., Perelman, J., Polinder, S., Rafay, A., Rahimi-Movaghar, V., Rai, R., Ram, U., Ranabhat, C., Roba, H., Savic, M., Sepanlou, S., Te Ao, B., Tesema, A., Thomson, A., Tobe-Gai, R., Topor-Madry, R., Undurraga, E., Vargas, V., Vasankari, T., Violante, F., Wijeratne, T., Xu, G., Yonemoto, N., Younis, M., Yu, C., Zaidi, Z., Zaki, M., Murray, C., Dieleman, J., Campbell, M., Chapin, A., Eldrenkamp, E., Fan, V., Haakenstad, A., Kates, J., Li, Z., Matyasz, T., Micah, A., Reynolds, A., Sadat, N., Schneider, M., Sorensen, R., Abbas, K., Abera, S., Kiadaliri, A., Ahmed, M., Alam, K., Alizadeh-Navaei, R., Alkerwi, A., Amini, E., Ammar, W., Antonio, C., Atey, T., Avila-Burgos, L., Awasthi, A., Barac, A., Berheto, T., Beyene, A., Beyene, T., Birungi, C., Bizuayehu, H., Breitborde, N., Cahuana-Hurtado, L., Estanislao Castro, R., Catala-Lopez, F., Dalal, K., Dandona, L., Dandona, R., Dharmaratne, S., Dubey, M., Faro, A., Feigl, A., Fischer, F., Fitchett, J., Foigt, N., Giref, A., Gupta, R., Hamidi, S., Harb, H., Hay, S., Hendrie, D., Horino, M., Jurisson, M., Jakovljevic, M., Javanbakht, M., John, D., Jonas, J., Karimi, S., Khang, Y., Khubchandani, J., Kim, Y., Kinge, J., Krohn, K., Kumar, G., Leung, R., Abd El Razek, H., Abd El Razek, M., Majeed, A., Malekzadeh, R., Malta, D., Meretoja, A., Miller, Ted, Mirrakhimov, E., Mohammed, S., Molla, G., Nangia, V., Olgiati, S., Owolabi, M., Patel, T., Caicedo, A., Pereira, D., Perelman, J., Polinder, S., Rafay, A., Rahimi-Movaghar, V., Rai, R., Ram, U., Ranabhat, C., Roba, H., Savic, M., Sepanlou, S., Te Ao, B., Tesema, A., Thomson, A., Tobe-Gai, R., Topor-Madry, R., Undurraga, E., Vargas, V., Vasankari, T., Violante, F., Wijeratne, T., Xu, G., Yonemoto, N., Younis, M., Yu, C., Zaidi, Z., Zaki, M., and Murray, C.
Published: 2017

24. Evolution and patterns of global health financing 1995-2014: development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries

Author: Dieleman, J., Campbell, M., Chapin, A., Eldrenkamp, E., Fan, V., Haakenstad, A., Kates, J., Liu, Y., Matyasz, T., Micah, A., Reynolds, A., Sadat, N., Schneider, M., Sorensen, R., Evans, T., Evans, D., Kurowski, C., Tandon, A., Abbas, K., Abera, S., Kiadaliri, A., Ahmed, K., Ahmed, M., Alam, K., Alizadeh-Navaei, R., Alkerwi, A., Amini, E., Ammar, W., Amrock, S., Antonio, C., Atey, T., Avila-Burgos, L., Awasthi, A., Barac, A., Alberto Bernal, O., Beyene, A., Beyene, T., Birungi, C., Bizuayehu, H., Breitborde, N., Cahuana-Hurtado, L., Estanislao Castro, R., Catala-Lopez, F., Dalal, K., Dandona, L., Dandona, R., de Jager, P., Dharmaratne, S., Dubey, M., Farinha, C., Faro, A., Feigl, A., Fischer, F., Fitchett, J., Foigt, N., Giref, A., Gupta, R., Hamidi, S., Harb, H., Hay, S., Hendrie, D., Horino, M., Jurisson, M., Jakovljevic, M., Javanbakht, M., John, D., Jonas, J., Karimi, S., Khang, Y., Khubchandani, J., Kim, Y., Kinge, J., Krohn, K., Kumar, G., Abd El Razek, H., Abd El Razek, M., Majeed, A., Malekzadeh, R., Masiye, F., Meier, T., Meretoja, A., Miller, Ted, Mirrakhimov, E., Mohammed, S., Nangia, V., Olgiati, S., Osman, A., Owolabi, M., Patel, T., Paternina Caicedo, A., Pereira, D., Perelman, J., Polinder, S., Rafay, A., Rahimi-Movaghar, V., Rai, R., Ram, U., Ranabhat, C., Roba, H., Salama, J., Savic, M., Sepanlou, S., Shrime, M., Talongwa, R., Te Ao, B., Tediosi, F., Tesema, A., Thomson, A., Tobe-Gai, R., Topor-Madry, R., Undurraga, E., Vasankari, T., Violante, F., Werdecker, A., Wijeratne, T., Xu, G., Yonemoto, N., Younis, M., Yu, C., Zaidi, Z., Zaki, M., Murray, C., Dieleman, J., Campbell, M., Chapin, A., Eldrenkamp, E., Fan, V., Haakenstad, A., Kates, J., Liu, Y., Matyasz, T., Micah, A., Reynolds, A., Sadat, N., Schneider, M., Sorensen, R., Evans, T., Evans, D., Kurowski, C., Tandon, A., Abbas, K., Abera, S., Kiadaliri, A., Ahmed, K., Ahmed, M., Alam, K., Alizadeh-Navaei, R., Alkerwi, A., Amini, E., Ammar, W., Amrock, S., Antonio, C., Atey, T., Avila-Burgos, L., Awasthi, A., Barac, A., Alberto Bernal, O., Beyene, A., Beyene, T., Birungi, C., Bizuayehu, H., Breitborde, N., Cahuana-Hurtado, L., Estanislao Castro, R., Catala-Lopez, F., Dalal, K., Dandona, L., Dandona, R., de Jager, P., Dharmaratne, S., Dubey, M., Farinha, C., Faro, A., Feigl, A., Fischer, F., Fitchett, J., Foigt, N., Giref, A., Gupta, R., Hamidi, S., Harb, H., Hay, S., Hendrie, D., Horino, M., Jurisson, M., Jakovljevic, M., Javanbakht, M., John, D., Jonas, J., Karimi, S., Khang, Y., Khubchandani, J., Kim, Y., Kinge, J., Krohn, K., Kumar, G., Abd El Razek, H., Abd El Razek, M., Majeed, A., Malekzadeh, R., Masiye, F., Meier, T., Meretoja, A., Miller, Ted, Mirrakhimov, E., Mohammed, S., Nangia, V., Olgiati, S., Osman, A., Owolabi, M., Patel, T., Paternina Caicedo, A., Pereira, D., Perelman, J., Polinder, S., Rafay, A., Rahimi-Movaghar, V., Rai, R., Ram, U., Ranabhat, C., Roba, H., Salama, J., Savic, M., Sepanlou, S., Shrime, M., Talongwa, R., Te Ao, B., Tediosi, F., Tesema, A., Thomson, A., Tobe-Gai, R., Topor-Madry, R., Undurraga, E., Vasankari, T., Violante, F., Werdecker, A., Wijeratne, T., Xu, G., Yonemoto, N., Younis, M., Yu, C., Zaidi, Z., Zaki, M., and Murray, C.
Abstract: Background: An adequate amount of prepaid resources for health is important to ensure access to health services and for the pursuit of universal health coverage. Previous studies on global health financing have described the relationship between economic development and health financing. In this study, we further explore global health financing trends and examine how the sources of funds used, types of services purchased, and development assistance for health disbursed change with economic development. We also identify countries that deviate from the trends. Methods: We estimated national health spending by type of care and by source, including development assistance for health, based on a diverse set of data including programme reports, budget data, national estimates, and 964 National Health Accounts. These data represent health spending for 184 countries from 1995 through 2014. We converted these data into a common inflation-adjusted and purchasing power-adjusted currency, and used non-linear regression methods to model the relationship between health financing, time, and economic development. Findings: Between 1995 and 2014, economic development was positively associated with total health spending and a shift away from a reliance on development assistance and out-of-pocket (OOP) towards government spending. The largest absolute increase in spending was in high-income countries, which increased to purchasing power-adjusted $5221 per capita based on an annual growth rate of 3·0%. The largest health spending growth rates were in upper-middle-income (5·9) and lower-middle-income groups (5·0), which both increased spending at more than 5% per year, and spent $914 and $267 per capita in 2014, respectively. Spending in low-income countries grew nearly as fast, at 4·6%, and health spending increased from $51 to $120 per capita. In 2014, 59·2% of all health spending was financed by the government, although in low-income and lower-middle-income countries, 29·1% and 58·0%
Published: 2017

25. Novel GCH1 variant in Dopa-responsive dystonia and Parkinson's disease

Author: Lewthwaite, A.J., Lambert, T.D., Rolfe, E.B., Olgiati, S., Quadri, M., Simons, E.J., Morrison, K.E., Bonifati, V., and Nicholl, D.J.
Published: 2015
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26. DNAJC6 Mutations Associated with Early-Onset Parkinson's Disease

Author: Olgiati, S. (Simone), Quadri, M. (Marialuisa), Fang, M. (Mingyan), Rood, J.P.M.A. (Janneke P.M.A.), Saute, J.A. (Jonas A.), Chien, H.F. (Hsin Fen), Bouwkamp, C.G. (Christian), Graafland, J. (Josja), Minneboo, M. (Michelle), Breedveld, G.J. (Guido J.), Zhang, J. (Jianguo), Verheijen, F.W. (Frans W.), Boon, A.J.W. (Agnita), Kievit, A.J.A. (Anneke J.A.), Jardim, L.B. (L.), Mandemakers, W.J. (Wim), Barbosa, E.R. (Egberto Reis), Rieder, C.R.M. (Carlos), Leenders, K.L. (Klaus L.), Wang, J. (Jinxia), Bonifati, V. (Vincenzo), Olgiati, S. (Simone), Quadri, M. (Marialuisa), Fang, M. (Mingyan), Rood, J.P.M.A. (Janneke P.M.A.), Saute, J.A. (Jonas A.), Chien, H.F. (Hsin Fen), Bouwkamp, C.G. (Christian), Graafland, J. (Josja), Minneboo, M. (Michelle), Breedveld, G.J. (Guido J.), Zhang, J. (Jianguo), Verheijen, F.W. (Frans W.), Boon, A.J.W. (Agnita), Kievit, A.J.A. (Anneke J.A.), Jardim, L.B. (L.), Mandemakers, W.J. (Wim), Barbosa, E.R. (Egberto Reis), Rieder, C.R.M. (Carlos), Leenders, K.L. (Klaus L.), Wang, J. (Jinxia), and Bonifati, V. (Vincenzo)
Abstract: _Objective_ DNAJC6 mutations were recently described in two families with autosomal recessive juvenile parkinsonism (onset age < 11), prominent atypical signs, poor or absent response to levodopa, and rapid progression (wheelchair-bound within ∼10 years from onset). Here, for the first time, we report DNAJC6 mutations in early-onset Parkinson's disease (PD). _Methods_ The DNAJC6 open reading frame was analyzed in 274 patients with early-onset sporadic or familial PD. Selected variants were followed up by cosegregation, homozygosity mapping, linkage analysis, whole-exome sequencing, and protein studies. _Results_ We identified two families with different novel homozygous DNAJC6 mutations segregating with PD. In each family, the DNAJC6 mutation was flanked by long runs of homozygosity within highest linkage peaks. Exome sequencing did not detect additional pathogenic variants within the linkage regions. In both families, patients showed severely decreased steady-state levels of the auxilin protein in fibroblasts. We also identified a sporadic patient carrying two rare noncoding DNAJC6 variants possibly effecting RNA splicing. All these cases fulfilled the criteria for a clinical diagnosis of early-onset PD, had symptoms onset in the third-to-fifth decade, and slow disease progression. Response to dopaminergic therapies was prominent, but, in some patients, limited by psychiatric side effects. The phenotype overlaps that of other monogenic forms of early-onset PD. _Interpretation_ Our findings delineate a novel form of hereditary early-onset PD. Screening of DNAJC6 is warranted in all patients with early-onset PD compatible with autosomal recessive inheritance. Our data provide further evidence for the involvement of synaptic vesicles endocytosis and trafficking in PD pathogenesis.
Published: 2016
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27. A balanced translocation disrupting BCL2L10 and PNLDC1 segregates with affective psychosis

Author: Bouwkamp, C.G. (Christian G.), Kievit, A.J.A. (Anneke J.A.), Olgiati, S. (Simone), Breedveld, G.J. (Guido), Coesmans, M.P.H. (Michiel), Bonifati, V. (Vincenzo), Kushner, S.A. (Steven), Bouwkamp, C.G. (Christian G.), Kievit, A.J.A. (Anneke J.A.), Olgiati, S. (Simone), Breedveld, G.J. (Guido), Coesmans, M.P.H. (Michiel), Bonifati, V. (Vincenzo), and Kushner, S.A. (Steven)
Abstract: Affective psychoses are a group of severe psychiatric disorders, including schizoaffective disorder and bipolar I disorder, together affecting ∼1% of the population. Despite their high heritability, the molecular genetics and neurobiology of affective psychosis remain largely elusive. Here, we describe the identification of a structural genetic variant segregating with affective psychosis in a family with multiple members suffering from bipolar I disorder or schizoaffective disorder, bipolar type. A balanced translocation involving chromosomes 6 and 15 was detected by karyotyping and fluorescence in-situ hybridization (FISH). Using whole-genome sequencing, we rapidly delineated the translocation breakpoints as corresponding intragenic events disrupting BCL2L10 and PNLDC1. These data warrant further consideration for BCL2L10 and PNLDC1 as novel candidates for affective psychosis.
Published: 2016
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28. Early-onset Parkinsonism caused by SYNJ1 p.Arg258Gln homozygous mutation in a new Italian family

Author: Olgiati, S., De Rosa, A., Quadri, M., Criscuolo, C., Breedveld, G. J., Picillo, M., Graafland, J., Pappata, S., Quarantelli, M., Barone, P., De Michele, G., and Bonifati, V.
Subjects: Parkinsonism, MRI
Published: 2014

29. Mutation in the SYNJ1 gene associated with autosomal recessive, early-onset parkinsonism

Author: Quadri M, Fang M, Picillo M, Olgiati S, Breedveld GJ, Graafland J, Wu B, Xu F, Erro R, Amboni M, Pappatà S, Quarantelli M, Annesi G, Quattrone A, Chien HF, Barbosa ER and The International Parkinsonism Genetics Network, Oostra BA, Barone P, Wang J, Bonifati V.
Published: 2013

30. Beta-propeller protein-associated neurodegeneration (BPAN), a rare form of NBIA: Novel mutations and neuropsychiatric phenotype in three adult patients

Author: Verhoeven, W.M.A., Egger, J.I.M., Koolen, D.A., Yntema, H.G., Olgiati, S., Breedveld, G.J., Bonifati, V., Warrenburg, B.P.C. van de, Verhoeven, W.M.A., Egger, J.I.M., Koolen, D.A., Yntema, H.G., Olgiati, S., Breedveld, G.J., Bonifati, V., and Warrenburg, B.P.C. van de
Abstract: Item does not contain fulltext, Neurodegeneration with brain iron accumulation (NBIA) comprises a group of rare neuropsychiatric syndromes characterized by iron accumulation in the basal ganglia. The pantothenate kinase-associated neurodegeneration (PKAN) was the first NBIA form to be genetically identified almost 15 years ago. Nowadays, eight types can be genetically distinguished. More recently, a novel NBIA was delineated and termed Static Encephalopathy of childhood with Neurodegeneration in Adulthood (SENDA), characterized by early intellectual disability followed by delayed progressive motor and cognitive deterioration with an onset in the second to third decade. Very recently, mutations in the WD repeat-containing protein 45 (WDR45) gene located on Xp11.23 were shown to be the causal factor. The protein encoded by WDR45 propels protein interaction important for autophagy. This form was therefore retermed Beta-propeller Protein Associated Neurodegeneration (BPAN). Here, the first three Dutch patients with genetically proven BPAN are comprehensively described with respect to course and neurological as well as neuropsychiatric phenotypes. All three showed a characteristic delayed progression of neurological symptoms with parkinsonism and prominent dystonia. Treatment with levodopa/carbidopa had limited effects only. Neuropsychiatric symptoms within the autistic and affective spectrum were present in the early phase of the disease. The specific course and prognosis should implicate restrained psychopharmacological interventions. The clinical picture and imaging hallmarks are often highly suggestive and should lead to suspect this specific disorder. However, the identification of a WDR45 mutation is needed for a definite diagnosis of SPAN.
Published: 2014

31. PARK20 caused by SYNJ1 homozygous Arg258Gln mutation in a new Italian family

Author: Olgiati, S. (Simone), Rosa, A. (Anna) de, Quadri, M. (Marialuisa), Criscuolo, C. (Chiara), Breedveld, G.J. (Guido), Picillo, M. (Marina), Pappatà, S. (Sabina), Quarantelli, M. (Mario), Barone, P. (Paolo), Michele, G. (Giuseppe) de, Bonifati, V. (Vincenzo), Olgiati, S. (Simone), Rosa, A. (Anna) de, Quadri, M. (Marialuisa), Criscuolo, C. (Chiara), Breedveld, G.J. (Guido), Picillo, M. (Marina), Pappatà, S. (Sabina), Quarantelli, M. (Mario), Barone, P. (Paolo), Michele, G. (Giuseppe) de, and Bonifati, V. (Vincenzo)
Abstract: SYNJ1 has been recently identified by two independent groups as the gene defective in a novel form of autosomal recessive, early-onset atypical parkinsonism (PARK20). Two consanguineous families were initially reported (one of Sicilian and one of Iranian origins), with the same SYNJ1 homozygous mutation (c.773G>A, p.Arg258Gln) segregating with a similar phenotype of early-onset parkinsonism and additional atypical features. Here, we report the identification of the same SYNJ1 homozygous mutation in two affected siblings of a third pedigree. Both siblings had mild developmental psychomotor delay, followed, during the third decade of life, by progressive parkinsonism, dystonia, and mild cognitive impairment. One sibling suffered one episode of generalized seizures. Neuroimaging studies revealed severe nigrostriatal dopaminergic defects, mild striatal and very mild cortical hypometabolism. Treatment with dopamine agonists and anticholinergics resulted in partial improvements. Genetic analyses revealed in both siblings the SYNJ1 homozygous c.773G>A (p.Arg258Gln) mutation. Haplotype analysis suggests that the mutation has arisen independently in this family and the Sicilian PARK20 family previously described by us, in keeping with the hypothesis of a mutational hot spot. This is the third reported family with autosomal recessive, early-onset parkinsonism associated with the SYNJ1 p.Arg258Gln mutation. This work contributes to the definition of the genetic and clinical aspects of PARK20. This newly recognized form must be considered in the diagnostic work-up of patients with early-onset atypical parkinsonism. The presence of seizures might represent a red flag to suspect PARK20.
Published: 2014
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32. Using DRG to analyze hospital production: A re-classification model based on a linear tree-network topology

Author: Lanzarini, A, Lafranconi, A, Nonis, M, Madotto, F, Grillo, P, Olgiati, S, Cesana, G, LAFRANCONI, ALESSANDRA, MADOTTO, FABIANA, OLGIATI, STEFANO, CESANA, GIANCARLO, Lanzarini, A, Lafranconi, A, Nonis, M, Madotto, F, Grillo, P, Olgiati, S, Cesana, G, LAFRANCONI, ALESSANDRA, MADOTTO, FABIANA, OLGIATI, STEFANO, and CESANA, GIANCARLO
Abstract: Background: Hospital discharge records are widely classified by the Diagnosis Related Group (DRG) system; the version currently used in Italy counts 538 different codes, including thousands of diagnosis and procedures. These numbers reflect the considerable effort towards simplification, yet the current classification system is of little use to evaluate hospital production and performance.Methods: As the case-mix of a given Hospital Unit (HU) is driven by its physicians’ specializations, a grouping of DRG s into a specialization-driven classification system has been conceived through the analysis of HUs discharging and the ICD -9-CM codes. We shall propose a physicians’ competencecentred classification, based on the analysis of 1,670,755 Hospital Discharge Cards (HDC s) produced by Lombardy Hospitals in 2010; it consists of 32 specializations (e.g. Neurosurgery), 124 sub-specialization (e.g. skull surgery) and 337 sub-sub-specialization (e.g. craniotomy).Results: We shall offer a practical application of our classification, based on the production of a Neurosurgical HU; we shall observe synthetically the profile of production (1,305 hospital discharges for 79 different DRG codes of 16 different MDC are divided into few groups of homogeneous DRG codes), a more informative production comparison (through process-specific comparisons, rather than crude or case-mix standardized comparisons) and a potentially more adequate production planning (considering the Neurosurgical HUs of the same city, that produce a limited quote of the whole neurosurgical production, since the same activity can be realized by non-Neurosugical HUs).Conclusions: Our work may help evaluate the hospital production for a rational planning of available resources, blunting information asymmetries between physicians and managers.
Published: 2014

33. Mutation in the SYNJ1 gene associated with autosomal recessive, early-onset Parkinsonism

Author: Quadri, M., Fang, M., Picillo, M., Olgiati, S., Breedveld, G.J., Graafland, J., Wu, B., Xu, F., Erro, R., Amboni, M., Pappata, S., Quarantelli, M., Annesi, G., Quattrone, A., Chien, H.F., Barbosa, E.R., Oostra, B.A., Barone, P., Wang, J, Bonifati, V., Warrenburg, B.P.C. van de, Bloem, B., Quadri, M., Fang, M., Picillo, M., Olgiati, S., Breedveld, G.J., Graafland, J., Wu, B., Xu, F., Erro, R., Amboni, M., Pappata, S., Quarantelli, M., Annesi, G., Quattrone, A., Chien, H.F., Barbosa, E.R., Oostra, B.A., Barone, P., Wang, J, Bonifati, V., Warrenburg, B.P.C. van de, and Bloem, B.
Abstract: Item does not contain fulltext, Autosomal recessive, early-onset Parkinsonism is clinically and genetically heterogeneous. Here, we report the identification, by homozygosity mapping and exome sequencing, of a SYNJ1 homozygous mutation (p.Arg258Gln) segregating with disease in an Italian consanguineous family with Parkinsonism, dystonia, and cognitive deterioration. Response to levodopa was poor, and limited by side effects. Neuroimaging revealed brain atrophy, nigrostriatal dopaminergic defects, and cerebral hypometabolism. SYNJ1 encodes synaptojanin 1, a phosphoinositide phosphatase protein with essential roles in the postendocytic recycling of synaptic vesicles. The mutation is absent in variation databases and in ethnically matched controls, is damaging according to all prediction programs, and replaces an amino acid that is extremely conserved in the synaptojanin 1 homologues and in SAC1-like domains of other proteins. Sequencing the SYNJ1 ORF in unrelated patients revealed another heterozygous mutation (p.Ser1422Arg), predicted as damaging, in a patient who also carries a heterozygous PINK1 truncating mutation. The SYNJ1 gene is a compelling candidate for Parkinsonism; mutations in the functionally linked protein auxilin cause a similar early-onset phenotype, and other findings implicate endosomal dysfunctions in the pathogenesis. Our data delineate a novel form of human Mendelian Parkinsonism, and provide further evidence for abnormal synaptic vesicle recycling as a central theme in the pathogenesis.
Published: 2013

34. The sustainability of the Lombardia health system

Author: Olgiati, S, CESANA, GIANCARLO, OLGIATI, STEFANO, Olgiati, S, CESANA, GIANCARLO, and OLGIATI, STEFANO
Abstract: The cœteris paribus trend of growth of the Lombardia Hospital System epidemiological, demographic, economic and financial variables analyzed in this research in the period 1997-2009 is not sustainable in the long-term, for the purpose of this research to the year 2050. Even if in the period 2002-2009 some financial and epidemiological adjustment has indeed been attempted (as highlighted by the Financial Function), in particular with yearly activity budgetary financial constraints and compulsory transfers from acute to ambulatory care (as highlighted by the Epidemiological Function), by means of which short-term financial equilibrium has temporarily been maintained, this same adjustment does not guarantee long-term epidemiological, demographic, economic and financial sustainability (as highlighted by the Sustainability Function). The Italian Ministero dell’Economia e delle Finanze is indeed intervening in curbing the growth rate of public health expenditure by fixing it at a definite percent of the national gross domestic product (circa 7.2%). Most of the savings are based on the reduction of personnel. Since health funds are pooled and equally allocated on a risk adjusted capitarian basis, the same savings will be required on the part of Lombardia. However, if savings are to be made, the underlying epidemiological trends (increase in complexity, invariance in the acute inpatient cases length of stay, increase in intensity), as highlighted by the Epidemiological Function, have to be addressed as well, which introduces the bi-faced question if such savings are sustainable or if their epidemiological effects are acceptable. If there is an almost general consensus among both health operators and regulators in Italy and Lombardia that both effectiveness and efficiency are the main drivers of the long term sustainability of a health system, it appears from the first applications of the model presented here that the Italian and Lombardia Hospital System is still governed b
Published: 2012

35. Past, present, and future of global health financing: a review of development assistance, government, out-of-pocket, and other private spending on health for 195 countries, 1995–2050

Author: Angela Y. Chang, Krycia Cowling, Angela E. Micah, Abigail Chapin, Catherine S. Chen, Gloria Ikilezi, Nafis Sadat, Golsum Tsakalos, Junjie Wu, Theodore Younker, Yingxi Zhao, Bianca S. Zlavog, Cristiana Abbafati, Anwar E Ahmed, Khurshid Alam, Vahid Alipour, Syed Mohamed Aljunid, Mohammed J. Almalki, Nelson Alvis-Guzman, Walid Ammar, Catalina Liliana Andrei, Mina Anjomshoa, Carl Abelardo T. Antonio, Jalal Arabloo, Olatunde Aremu, Marcel Ausloos, Leticia Avila-Burgos, Ashish Awasthi, Martin Amogre Ayanore, Samad Azari, Natasha Azzopardi-Muscat, Mojtaba Bagherzadeh, Till Winfried Bärnighausen, Bernhard T Baune, Mohsen Bayati, Yared Belete Belay, Yihalem Abebe Belay, Habte Belete, Dessalegn Ajema Berbada, Adam E. Berman, Mircea Beuran, Ali Bijani, Reinhard Busse, Lucero Cahuana-Hurtado, Luis Alberto Cámera, Ferrán Catalá-López, Bal Govind Chauhan, Maria-Magdalena Constantin, Christopher Stephen Crowe, Alexandra Cucu, Koustuv Dalal, Jan-Walter De Neve, Selina Deiparine, Feleke Mekonnen Demeke, Huyen Phuc Do, Manisha Dubey, Maha El Tantawi, Sharareh Eskandarieh, Reza Esmaeili, Mahdi Fakhar, Ali Akbar Fazaeli, Florian Fischer, Nataliya A. Foigt, Takeshi Fukumoto, Nancy Fullman, Adriana Galan, Amiran Gamkrelidze, Kebede Embaye Gezae, Alireza Ghajar, Ahmad Ghashghaee, Ketevan Goginashvili, Annie Haakenstad, Hassan Haghparast Bidgoli, Samer Hamidi, Hilda L. Harb, Edris Hasanpoor, Hamid Yimam Hassen, Simon I. Hay, Delia Hendrie, Andualem Henok, Ileana Heredia-Pi, Claudiu Herteliu, Chi Linh Hoang, Michael K. Hole, Enayatollah Homaie Rad, Naznin Hossain, Mehdi Hosseinzadeh, Sorin Hostiuc, Olayinka Stephen Ilesanmi, Seyed Sina Naghibi Irvani, Mihajlo Jakovljevic, Amir Jalali, Spencer L. James, Jost B. Jonas, Mikk Jürisson, Rajendra Kadel, Behzad Karami Matin, Amir Kasaeian, Habtamu Kebebe Kasaye, Mesfin Wudu Kassaw, Ali Kazemi Karyani, Roghayeh Khabiri, Junaid Khan, Md Nuruzzaman Khan, Young-Ho Khang, Adnan Kisa, Katarzyna Kissimova-Skarbek, Stefan Kohler, Ai Koyanagi, Kristopher J. Krohn, Ricky Leung, Lee-Ling Lim, Stefan Lorkowski, Azeem Majeed, Reza Malekzadeh, Morteza Mansourian, Lorenzo Giovanni Mantovani, Benjamin Ballard Massenburg, Martin McKee, Varshil Mehta, Atte Meretoja, Tuomo J Meretoja, Neda Milevska Kostova, Ted R Miller, Erkin M Mirrakhimov, Bahram Mohajer, Aso Mohammad Darwesh, Shafiu Mohammed, Farnam Mohebi, Ali H Mokdad, Shane Douglas Morrison, Seyyed Meysam Mousavi, Saravanan Muthupandian, Ahamarshan Jayaraman Nagarajan, Vinay Nangia, Ionut Negoi, Cuong Tat Nguyen, Huong Lan Thi Nguyen, Son Hoang Nguyen, Shirin Nosratnejad, Olanrewaju Oladimeji, Stefano Olgiati, Jacob Olusegun Olusanya, Obinna E Onwujekwe, Stanislav S Otstavnov, Adrian Pana, David M. Pereira, Bakhtiar Piroozi, Sergio I Prada, Mostafa Qorbani, Mohammad Rabiee, Navid Rabiee, Alireza Rafiei, Fakher Rahim, Vafa Rahimi-Movaghar, Usha Ram, Chhabi Lal Ranabhat, Anna Ranta, David Laith Rawaf, Salman Rawaf, Satar Rezaei, Elias Merdassa Roro, Ali Rostami, Salvatore Rubino, Mohamadreza Salahshoor, Abdallah M. Samy, Juan Sanabria, João Vasco Santos, Milena M Santric Milicevic, Bruno Piassi Sao Jose, Miloje Savic, Falk Schwendicke, Sadaf G. Sepanlou, Masood Sepehrimanesh, Aziz Sheikh, Mark G Shrime, Solomon Sisay, Shahin Soltani, Moslem Soofi, Vinay Srinivasan, Rafael Tabarés-Seisdedos, Anna Torre, Marcos Roberto Tovani-Palone, Bach Xuan Tran, Khanh Bao Tran, Eduardo A. Undurraga, Pascual R Valdez, Job F M van Boven, Veronica Vargas, Yousef Veisani, Francesco S Violante, Sergey Konstantinovitch Vladimirov, Vasily Vlassov, Sebastian Vollmer, Giang Thu Vu, Charles D A Wolfe, Naohiro Yonemoto, Mustafa Z. Younis, Mahmoud Yousefifard, Sojib Bin Zaman, Alireza Zangeneh, Elias Asfaw Zegeye, Arash Ziapour, Adrienne Chew, Christopher J L Murray, Joseph L Dieleman, Chang A.Y., Cowling K., Micah A.E., Chapin A., Chen C.S., Ikilezi G., Sadat N., Tsakalos G., Wu J., Younker T., Zhao Y., Zlavog B.S., Abbafati C., Ahmed A.E., Alam K., Alipour V., Aljunid S.M., Almalki M.J., Alvis-Guzman N., Ammar W., Andrei C.L., Anjomshoa M., Antonio C.A.T., Arabloo J., Aremu O., Ausloos M., Avila-Burgos L., Awasthi A., Ayanore M.A., Azari S., Azzopardi-Muscat N., Bagherzadeh M., Barnighausen T.W., Baune B.T., Bayati M., Belay Y.B., Belay Y.A., Belete H., Berbada D.A., Berman A.E., Beuran M., Bijani A., Busse R., Cahuana-Hurtado L., Camera L.A., Catala-Lopez F., Chauhan B.G., Constantin M.-M., Crowe C.S., Cucu A., Dalal K., De Neve J.-W., Deiparine S., Demeke F.M., Do H.P., Dubey M., El Tantawi M., Eskandarieh S., Esmaeili R., Fakhar M., Fazaeli A.A., Fischer F., Foigt N.A., Fukumoto T., Fullman N., Galan A., Gamkrelidze A., Gezae K.E., Ghajar A., Ghashghaee A., Goginashvili K., Haakenstad A., Haghparast Bidgoli H., Hamidi S., Harb H.L., Hasanpoor E., Hassen H.Y., Hay S.I., Hendrie D., Henok A., Heredia-Pi I., Herteliu C., Hoang C.L., Hole M.K., Homaie Rad E., Hossain N., Hosseinzadeh M., Hostiuc S., Ilesanmi O.S., Irvani S.S.N., Jakovljevic M., Jalali A., James S.L., Jonas J.B., Jurisson M., Kadel R., Karami Matin B., Kasaeian A., Kasaye H.K., Kassaw M.W., Kazemi Karyani A., Khabiri R., Khan J., Khan M.N., Khang Y.-H., Kisa A., Kissimova-Skarbek K., Kohler S., Koyanagi A., Krohn K.J., Leung R., Lim L.-L., Lorkowski S., Majeed A., Malekzadeh R., Mansourian M., Mantovani L.G., Massenburg B.B., McKee M., Mehta V., Meretoja A., Meretoja T.J., Milevska Kostova N., Miller T.R., Mirrakhimov E.M., Mohajer B., Mohammad Darwesh A., Mohammed S., Mohebi F., Mokdad A.H., Morrison S.D., Mousavi S.M., Muthupandian S., Nagarajan A.J., Nangia V., Negoi I., Nguyen C.T., Nguyen H.L.T., Nguyen S.H., Nosratnejad S., Oladimeji O., Olgiati S., Olusanya J.O., Onwujekwe O.E., Otstavnov S.S., Pana A., Pereira D.M., Piroozi B., Prada S.I., Qorbani M., Rabiee M., Rabiee N., Rafiei A., Rahim F., Rahimi-Movaghar V., Ram U., Ranabhat C.L., Ranta A., Rawaf D.L., Rawaf S., Rezaei S., Roro E.M., Rostami A., Rubino S., Salahshoor M., Samy A.M., Sanabria J., Santos J.V., Santric Milicevic M.M., Sao Jose B.P., Savic M., Schwendicke F., Sepanlou S.G., Sepehrimanesh M., Sheikh A., Shrime M.G., Sisay S., Soltani S., Soofi M., Srinivasan V., Tabares-Seisdedos R., Torre A., Tovani-Palone M.R., Tran B.X., Tran K.B., Undurraga E.A., Valdez P.R., van Boven J.F.M., Vargas V., Veisani Y., Violante F.S., Vladimirov S.K., Vlassov V., Vollmer S., Vu G.T., Wolfe C.D.A., Yonemoto N., Younis M.Z., Yousefifard M., Zaman S.B., Zangeneh A., Zegeye E.A., Ziapour A., Chew A., Murray C.J.L., Dieleman J.L., Global Burden Dis Hlth Financing C, Bill & Melinda Gates Foundation, Chang, A, Cowling, K, Micah, A, Chapin, A, Chen, C, Ikilezi, G, Sadat, N, Tsakalos, G, Wu, J, Younker, T, Zhao, Y, Zlavog, B, Abbafati, C, Ahmed, A, Alam, K, Alipour, V, Aljunid, S, Almalki, M, Alvis-Guzman, N, Ammar, W, Andrei, C, Anjomshoa, M, Antonio, C, Arabloo, J, Aremu, O, Ausloos, M, Avila-Burgos, L, Awasthi, A, Ayanore, M, Azari, S, Azzopardi-Muscat, N, Bagherzadeh, M, Barnighausen, T, Baune, B, Bayati, M, Belay, Y, Belete, H, Berbada, D, Berman, A, Beuran, M, Bijani, A, Busse, R, Cahuana-Hurtado, L, Camera, L, Catala-Lopez, F, Chauhan, B, Constantin, M, Crowe, C, Cucu, A, Dalal, K, De Neve, J, Deiparine, S, Demeke, F, Do, H, Dubey, M, Tantawi, M, Eskandarieh, S, Esmaeili, R, Fakhar, M, Fazaeli, A, Fischer, F, Foigt, N, Fukumoto, T, Fullman, N, Galan, A, Gamkrelidze, A, Gezae, K, Ghajar, A, Ghashghaee, A, Goginashvili, K, Haakenstad, A, Bidgoli, H, Hamidi, S, Harb, H, Hasanpoor, E, Hassen, H, Hay, S, Hendrie, D, Henok, A, Heredia-Pi, I, Herteliu, C, Hoang, C, Hole, M, Rad, E, Hossain, N, Hosseinzadeh, M, Hostiuc, S, Ilesanmi, O, Irvani, S, Jakovljevic, M, Jalali, A, James, S, Jonas, J, Jurisson, M, Kadel, R, Matin, B, Kasaeian, A, Kasaye, H, Kassaw, M, Karyani, A, Khabiri, R, Khan, J, Khan, M, Khang, Y, Kisa, A, Kissimova-Skarbek, K, Kohler, S, Koyanagi, A, Krohn, K, Leung, R, Lim, L, Lorkowski, S, Majeed, A, Malekzadeh, R, Mansourian, M, Mantovani, L, Massenburg, B, Mckee, M, Mehta, V, Meretoja, A, Meretoja, T, Kostova, N, Miller, T, Mirrakhimov, E, Mohajer, B, Darwesh, A, Mohammed, S, Mohebi, F, Mokdad, A, Morrison, S, Mousavi, S, Muthupandian, S, Nagarajan, A, Nangia, V, Negoi, I, Nguyen, C, Nguyen, H, Nguyen, S, Nosratnejad, S, Oladimeji, O, Olgiati, S, Olusanya, J, Onwujekwe, O, Otstavnov, S, Pana, A, Pereira, D, Piroozi, B, Prada, S, Qorbani, M, Rabiee, M, Rabiee, N, Rafiei, A, Rahim, F, Rahimi-Movaghar, V, Ram, U, Ranabhat, C, Ranta, A, Rawaf, D, Rawaf, S, Rezaei, S, Roro, E, Rostami, A, Rubino, S, Salahshoor, M, Samy, A, Sanabria, J, Santos, J, Milicevic, M, Jose, B, Savic, M, Schwendicke, F, Sepanlou, S, Sepehrimanesh, M, Sheikh, A, Shrime, M, Sisay, S, Soltani, S, Soofi, M, Srinivasan, V, Tabares-Seisdedos, R, Torre, A, Tovani-Palone, M, Tran, B, Tran, K, Undurraga, E, Valdez, P, Van Boven, J, Vargas, V, Veisani, Y, Violante, F, Vladimirov, S, Vlassov, V, Vollmer, S, Vu, G, Wolfe, C, Yonemoto, N, Younis, M, Yousefifard, M, Zaman, S, Zangeneh, A, Zegeye, E, Ziapour, A, Chew, A, Murray, C, and Dieleman, J
Subjects: health financing, coverage, 030204 cardiovascular system & hematology, systematic analysis, Global Health, Gross domestic product, DISEASE, burden, project, 0302 clinical medicine, Per capita, Global health, Healthcare Financing, 030212 general & internal medicine, our of pocket, 11 Medical and Health Sciences, Government spending, government, 1. No poverty, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Public Assistance, COVERAGE, Models, Economic, 8. Economic growth, health financing, project, government, our of pocket, BURDEN, Life Sciences & Biomedicine, Human, Gross Domestic Product, Department of Error, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, SYSTEMATIC ANALYSIS, Revenue, Humans, medicine (all), Health policy, Finance, sex-specific mortality, Government, disease, Science & Technology, SEX-SPECIFIC MORTALITY, business.industry, Prepaid Health Plan, International health, Global Burden of Disease Health Financing Collaborator Network, Health Expenditure, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Human medicine, Health Expenditures, business, Prepaid Health Plans
Abstract: Published Erratum. Past, present, and future of global health financing: a review of development assistance, government, out-of-pocket, and other private spending on health for 195 countries, 1995-2050. Lancet. 2021 Sep 11;398(10304):956. doi: 10.1016/S0140-6736(21)01806-7. PMID: 34509230. BACKGROUND: Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries. METHODS: We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories-government, out-of-pocket, and prepaid private health spending-and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more resources for health. FINDINGS: Between 1995 and 2016, health spending grew at a rate of 4·00% (95% uncertainty interval 3·89-4·12) annually, although it grew slower in per capita terms (2·72% [2·61-2·84]) and increased by less than $1 per capita over this period in 22 of 195 countries. The highest annual growth rates in per capita health spending were observed in upper-middle-income countries (5·55% [5·18-5·95]), mainly due to growth in government health spending, and in lower-middle-income countries (3·71% [3·10-4·34]), mainly from DAH. Health spending globally reached $8·0 trillion (7·8-8·1) in 2016 (comprising 8·6% [8·4-8·7] of the global economy and $10·3 trillion [10·1-10·6] in purchasing-power parity-adjusted dollars), with a per capita spending of US$5252 (5184-5319) in high-income countries, $491 (461-524) in upper-middle-income countries, $81 (74-89) in lower-middle-income countries, and $40 (38-43) in low-income countries. In 2016, 0·4% (0·3-0·4) of health spending globally was in low-income countries, despite these countries comprising 10·0% of the global population. In 2018, the largest proportion of DAH targeted HIV/AIDS ($9·5 billion, 24·3% of total DAH), although spending on other infectious diseases (excluding tuberculosis and malaria) grew fastest from 2010 to 2018 (6·27% per year). The leading sources of DAH were the USA and private philanthropy (excluding corporate donations and the Bill & Melinda Gates Foundation). For the first time, we included estimates of China's contribution to DAH ($644·7 million in 2018). Globally, health spending is projected to increase to $15·0 trillion (14·0-16·0) by 2050 (reaching 9·4% [7·6-11·3] of the global economy and $21·3 trillion [19·8-23·1] in purchasing-power parity-adjusted dollars), but at a lower growth rate of 1·84% (1·68-2·02) annually, and with continuing disparities in spending between countries. In 2050, we estimate that 0·6% (0·6-0·7) of health spending will occur in currently low-income countries, despite these countries comprising an estimated 15·7% of the global population by 2050. The ratio between per capita health spending in high-income and low-income countries was 130·2 (122·9-136·9) in 2016 and is projected to remain at similar levels in 2050 (125·9 [113·7-138·1]). The decomposition analysis identified governments' increased prioritisation of the health sector and economic development as the strongest factors associated with increases in government health spending globally. Future government health spending scenarios suggest that, with greater prioritisation of the health sector and increased government spending, health spending per capita could more than double, with greater impacts in countries that currently have the lowest levels of government health spending. INTERPRETATION: Financing for global health has increased steadily over the past two decades and is projected to continue increasing in the future, although at a slower pace of growth and with persistent disparities in per-capita health spending between countries. Out-of-pocket spending is projected to remain substantial outside of high-income countries. Many low-income countries are expected to remain dependent on development assistance, although with greater government spending, larger investments in health are feasible. In the absence of sustained new investments in health, increasing efficiency in health spending is essential to meet global health targets. FUNDING: Bill & Melinda Gates Foundation. Bill & Melinda Gates Foundation Sí
Published: 2019
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36. Tracking development assistance for health and for COVID-19: a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990–2050

Author: Junaid Khan, Blake Angell, Marcel Ausloos, Catherine M. Antony, Elham Ehsani-Chimeh, Edgar Denova-Gutiérrez, Kewal Krishan, Mohamed Kamal Mesregah, Arrigo Francesco Giuseppe Cicero, Simona Cătălina Ştefan, Tanuj Kanchan, Maysaa El Sayed Zaki, Mohamed I Hegazy, Richard James Maude, Salman Rawaf, Viktória Szerencsés, Milena Santric-Milicevic, Martin McKee, Reza Rawassizadeh, Anton C Harle, Neda Milevska Kostova, Hamidreza Pazoki Toroudi, Saravanan Muthupandian, Mohammad Hifz Ur Rahman, Hassan Abolhassani, Christine Mpundu-Kaambwa, Atta Abbas Naqvi, John Dube, Habib Benzian, Cristiano Piccinelli, Kedir Hussein Abegaz, Mohammad Khammarnia, Carlo Eduardo Medina-Solís, Tanvir M. Huda, Fakher Rahim, Modhurima Moitra, Valentin Yurievich Skryabin, Emily Joy Callander, David Laith Rawaf, Saeed Shahabi, Mohsen Bayati, Raffaele Palladino, Shahin Soltani, Mohammad Ali Mansournia, Rafael Lozano, Himal Kandel, João Vasco Santos, MA Garcia-Gordillo, Savita Lasrado, Alexey V Breusov, Nicola Luigi Bragazzi, Deepak Dhamnetiya, Mohammad Amin Bahrami, Teroj Abdulrahman Mohamed, Reinhard Busse, Veer Bala Gupta, Ionut Negoi, Xiaochen Dai, Eun-Cheol Park, Trang Huyen Nguyen, Gulrez Shah Azhar, Annie Haakenstad, Asadollah Gholamian, Vafa Rahimi-Movaghar, Subramanian Senthilkumaran, Ismaeel Yunusa, Hubert Amu, G. K. Mini, Francesco Saverio Violante, Michael Abdelmasseh, Yun Jin Kim, Yousef Moradi, Nataliya Foigt, Afshin Maleki, Pavanchand H Shetty, Mesfin Agachew Woldekidan, Ramesh Holla, Mina Anjomshoa, Seyyed Meysam Mousavi, Azeem Majeed, Bright Opoku Ahinkorah, Hassan Magdy Abd El Razek, Avirup Guha, Telma Zahirian Moghadam, Olayinka Stephen Ilesanmi, Alessandro Arrigo, Neda Kianipour, Marcos Roberto Tovani-Palone, Mosiur Rahman, Tomas Y Ferede, Catalina Liliana Andrei, Alaa Makki, Joseph L Dieleman, Shuhei Nomura, Kanwar Hamza Shuja, Ileana Heredia-Pi, Mukhammad David Naimzada, Ali Kazemi Karyani, Chisom Joyqueenet Akunna, Souranshu Chatterjee, Yonas Akalu, Hanadi Al Hamad, Abdollah Mohammadian-Hafshejani, Hayley N Stutzman, Getinet Ayano, Atte Meretoja, Fahad Alanezi, Aravind Thavamani, Sonu Bhaskar, Claudiu Herteliu, Andreea Mirica, Masood Ali Shaikh, Soewarta Kosen, Nelson J. Alvis-Zakzuk, Emma Elizabeth Spurlock, Ferrán Catalá-López, Samath D Dharmaratne, Stany W. Lobo, Alemayehu Hailu, Sebastian Vollmer, Tarik Ahmed Rashid, Sheikh Mohammed Shariful Islam, Lalit Dandona, Farahnaz Joukar, Jacob Olusegun Olusanya, Befikadu Legesse Wubishet, Sezer Kisa, Songhomitra Panda-Jonas, Nasir Umar, Adrian Otoiu, Yonas Getaye Tefera, Harapan Harapan, Ivo Iavicoli, Jakub Morze, Mihajlo Jakovljevic, Nicholas J K Breitborde, Ian E Cogswell, Mehdi Hosseinzadeh, Sadia Bibi, Stefan Kohler, Florian Fischer, Jagdish Khubchandani, Justice Nonvignon, Salah Eddin Karimi, Yousef Khader, Jan-Walter De Neve, Stanislav S. Otstavnov, Ruoyan Tobe-Gai, Tommi Vasankari, Carlos A Castañeda-Orjuela, Nahlah Elkudssiah Ismail, Khezar Hayat, Chythra R Rao, Priya Rathi, Asma Tahir Awan, Jean Jacques Noubiap, Salime Goharinezhad, Ai Koyanagi, Rafael Tabarés-Seisdedos, Angela E Micah, Rakhi Dandona, Jaykaran Charan, Lorainne Tudor Car, Michael R.M. Abrigo, Kenji Shibuya, Aziz Sheikh, B Reshmi, Rovshan Khalilov, Haroon Ahmed, Andrea Werdecker, Alberto Freitas, Tara Ballav Adhikari, Vasily Vlassov, Risky Kusuma Hartono, Leila Keikavoosi-Arani, Gyu Ri Kim, Ana Laura Manda, Carlos Alberto Marrugo Arnedo, Obinna Onwujekwe, Van C. Lansingh, Miklós Szócska, Gelin Xu, Ted R. Miller, Saad M.A. Dahlawi, Till Bärnighausen, Jagadish Rao Padubidri, Bernhard T. Baune, Fatemeh Pashazadeh Kan, Juan Sanabria, Bruno Ramos Nascimento, Stefano Olgiati, Navid Rabiee, Mark G. Shrime, Mayowa O. Owolabi, V. E. Nwatah, Tesleem Kayode Babalola, Ranil Jayawardena, Robert Kaba Alhassan, Takeshi Fukumoto, Lucero Cahuana-Hurtado, Aparna Ichalangod Narayana, Mohammad Ali Sahraian, Atif Amin Baig, Carl Abelardo T. Antonio, Jost B. Jonas, Dian Kusuma, Priyanga Ranasinghe, Mikhail Sergeevich Zastrozhin, Ali Bijani, Arash Ziapour, Seyed Behzad Jazayeri, Francesco Sanmarchi, Seyed Sina Naghibi Irvani, Allen Seylani, Theo Vos, Tuomo J. Meretoja, Delia Hendrie, Mostafa Amini-Rarani, Manthan D Janodia, Sathish Kumar Jayapal, Sorin Hostiuc, Marjan Ajami, Ali Gholamrezanezhad, Muhammad Aqeel, Muhammed Magdy Abd El Razek, Shaun Wen Huey Lee, Rawlance Ndejjo, Maarten J. Postma, Luis Camera, Chhabi Lal Ranabhat, Sadaf G. Sepanlou, Adnan Kisa, Tahira Ashraf, Tudorel Andrei, Mohammad Ali Jahani, Virginia Bodolica, Chuanhua Yu, Moses K. Muriithi, Pascual R. Valdez, Paul S. F. Yip, Demetris Lamnisos, Amir Masoud Rahmani, Hamed Zandian, Anna Aleksandrovna Skryabina, Yeong Yeh Lee, Sana Salehi, Syed Mohamed Aljunid, Kyle E. Simpson, Sami Almustanyir Almustanyir, Bogdan Oancea, Biswa Prakash Nayak, Omid Dadras, Fariborz Mansour-Ghanaei, Turki Alanzi, Mahaveer Golechha, Bach Xuan Tran, Lal B. Rawal, Shoaib Hassan, Rahul R. Zende, Sandhya Neupane Kandel, Martin Amogre Ayanore, Adam E. Berman, Long Khanh Dao Le, Dragos Virgil Davitoiu, Adithi Shetty, Getinet Kassahun, Birhanu Wubale Yirdaw, Usha Ram, Linh Gia Vu, Emilie R Maddison, Yosef Alemayehu, Ali H. Mokdad, Tomislav Mestrovic, Mavra A Riaz, Muhammad Naveed, Koustuv Dalal, Syed Amir Gilani, Reza Malekzadeh, Nikha Bhardwaj, Desta Debalkie Atnafu, Rohollah Kalhor, Naohiro Yonemoto, Ahmad Ghashghaee, Andre M. N. Renzaho, Amadou Barrow, Christopher J L Murray, Budi Aji, Maitreyi Sahu, Sara D Friedman, Konrad Pesudovs, Robert Reiner, Mohammad Rifat Haider, Mustafa Z. Younis, Aidin Abedi, Sanjay Basu, Nancy Fullman, Darrah McCracken, Rajasekaran Koteeswaran, Falk Schwendicke, Ionela-Roxana Glavan, Mohamed H Hassanein, Sindhura Lakshmi Koulmane Laxminarayana, Javad Nazari, Khurshid Alam, Bulat Idrisov, Nelson Alvis-Guzman, Mokhtar Mohammadi, Golnaz Heidari, Asif Hanif, Ghozali Ghozali, Vijay Kumar Chattu, Leila Doshmangir, Simiao Chen, Maha El Tantawi, Stephen S Lim, Bay Vo, Deepak Saxena, Jasvinder A. Singh, Robert Ancuceanu, Yves Miel H Zuniga, Kamal Hezam, Andrew T Olagunju, Sheikh Jamal Hossain, Lindsey E Wallace, Dejana Braithwaite, Sergio I. Prada, Adolfo Martinez-Valle, Brandon Cunningham, Vivek Gupta, Joseph Salama, Rezaul Karim Ripon, Bing-Fang Hwang, Mokhtar Mahdavi, Tamás Joó, Cristiana Abbafati, Behzad Karami Matin, Tushar Garg, Cyrus Alinia, Yingxi Zhao, Richard G. Wamai, Satoshi Ezoe, Anders Larsson, Seyedeh Zahra Masoumi, Arokiasamy Perianayagam, Sharareh Eskandarieh, Maciej Banach, Billingsley Kaambwa, Nader Jahanmehr, Saeed Amini, Foluke Adetola Ojelabi, Nikolay Ivanovich Briko, Samer Hamidi, Gaetano Isola, Tahereh Javaheri, Gbenga A. Kayode, Nikita Otstavnov, Vahid Yazdi-Feyzabadi, David M. Pereira, Mansour Ghafourifard, Saira Afzal, Ravi Prakash Jha, Erkin M. Mirrakhimov, Ahamarshan Jayaraman Nagarajan, Giang Thu Vu, G Anil Kumar, Vahit Yigit, Farshad Farzadfar, Anasthasia Zastrozhina, Shafiu Mohammed, Leticia Avila-Burgos, Nastaran Barati, Morteza Arab-Zozani, Eduardo A. Undurraga, Muktar Beshir Ahmed, Mohamed M. Gad, Mikk Jürisson, Himanshu Khajuria, Anas M. Saad, Mohammad Rabiee, Abdallah M. Samy, Srinivas Goli, Roman Topor-Madry, Golsum Tsakalos, Mariam Molokhia, Biruk Wogayehu Taddele, Mohammad Ali Moni, E S Abhilash, Timur Aripov, Sepideh Ahmadi, Mehdi Sayyah, Jorge Hugo Villafañe, Peter Andras Gaal, Babayemi O Olakunde, Brijesh Sathian, Anayat Ullah, Ritesh G. Menezes, Samad Azari, Ahmed I. Hasaballah, Soosanna Kumary Chattu, Pankaj Bhardwaj, Sanni Yaya, Zhi-Jiang Zhang, Jalal Arabloo, Saif Ullah, Akshaya Srikanth Bhagavathula, Bahram Mohajer, Ekaterina Vladimirovna Glushkova, Vinay Nangia, Shrikant Pawar, Moslem Soofi, Antonio Reis de Sá-Junior, Simon I. Hay, Miloje Savic, 2. Global Burden of Disease 2020 Health Financing Collaborator Network, Cicero AFG, Network, Global Burden of Disease 2020 Health Financing Collaborator, Bill & Melinda Gates Foundation, Micah, A. E., Cogswell, I. E., Cunningham, B., Ezoe, S., Harle, A. C., Maddison, E. R., Mccracken, D., Nomura, S., Simpson, K. E., Stutzman, H. N., Tsakalos, G., Wallace, L. E., Zhao, Y., Zende, R. R., Abbafati, C., Abdelmasseh, M., Abedi, A., Abegaz, K. H., Abhilash, E. S., Abolhassani, H., Abrigo, M. R. M., Adhikari, T. B., Afzal, S., Ahinkorah, B. O., Ahmadi, S., Ahmed, H., Ahmed, M. B., Ahmed Rashid, T., Ajami, M., Aji, B., Akalu, Y., Akunna, C. J., Al Hamad, H., Alam, K., Alanezi, F. M., Alanzi, T. M., Alemayehu, Y., Alhassan, R. K., Alinia, C., Aljunid, S. M., Almustanyir, S. A., Alvis-Guzman, N., Alvis-Zakzuk, N. J., Amini, S., Amini-Rarani, M., Amu, H., Ancuceanu, R., Andrei, C. L., Andrei, T., Angell, B., Anjomshoa, M., Antonio, C. A. T., Antony, C. M., Aqeel, M., Arabloo, J., Arab-Zozani, M., Aripov, T., Arrigo, A., Ashraf, T., Atnafu, D. D., Ausloos, M., Avila-Burgos, L., Awan, A. T., Ayano, G., Ayanore, M. A., Azari, S., Azhar, G. S., Babalola, T. K., Bahrami, M. A., Baig, A. A., Banach, M., Barati, N., Barnighausen, T. W., Barrow, A., Basu, S., Baune, B. T., Bayati, M., Benzian, H., Berman, A. E., Bhagavathula, A. S., Bhardwaj, N., Bhardwaj, P., Bhaskar, S., Bibi, S., Bijani, A., Bodolica, V., Bragazzi, N. L., Braithwaite, D., Breitborde, N. J. K., Breusov, A. V., Briko, N. I., Busse, R., Cahuana-Hurtado, L., Callander, E. J., Camera, L. A., Castaneda-Orjuela, C. A., Catala-Lopez, F., Charan, J., Chatterjee, S., Chattu, S. K., Chattu, V. K., Chen, S., Cicero, A. F. G., Dadras, O., Dahlawi, S. M. A., Dai, X., Dalal, K., Dandona, L., Dandona, R., Davitoiu, D. V., De Neve, J. -W., de Sa-Junior, A. R., Denova-Gutierrez, E., Dhamnetiya, D., Dharmaratne, S. D., Doshmangir, L., Dube, J., Ehsani-Chimeh, E., El Sayed Zaki, M., El Tantawi, M., Eskandarieh, S., Farzadfar, F., Ferede, T. Y., Fischer, F., Foigt, N. A., Freitas, A., Friedman, S. D., Fukumoto, T., Fullman, N., Gaal, P. A., Gad, M. M., Garcia-Gordillo, M. A., Garg, T., Ghafourifard, M., Ghashghaee, A., Gholamian, A., Gholamrezanezhad, A., Ghozali, G., Gilani, S. A., Glavan, I. -R., Glushkova, E. V., Goharinezhad, S., Golechha, M., Goli, S., Guha, A., Gupta, V. B., Gupta, V. K., Haakenstad, A., Haider, M. R., Hailu, A., Hamidi, S., Hanif, A., Harapan, H., Hartono, R. K., Hasaballah, A. I., Hassan, S., Hassanein, M. H., Hayat, K., Hegazy, M. I., Heidari, G., Hendrie, D., Heredia-Pi, I., Herteliu, C., Hezam, K., Holla, R., Hossain, S. J., Hosseinzadeh, M., Hostiuc, S., Huda, T. M., Hwang, B. -F., Iavicoli, I., Idrisov, B., Ilesanmi, O. S., Irvani, S. S. N., Islam, S. M. S., Ismail, N. E., Isola, G., Jahani, M. A., Jahanmehr, N., Jakovljevic, M., Janodia, M. D., Javaheri, T., Jayapal, S. K., Jayawardena, R., Jazayeri, S. B., Jha, R. P., Jonas, J. B., Joo, T., Joukar, F., Jurisson, M., Kaambwa, B., Kalhor, R., Kanchan, T., Kandel, H., Karami Matin, B., Karimi, S. E., Kassahun, G., Kayode, G. A., Kazemi Karyani, A., Keikavoosi-Arani, L., Khader, Y. S., Khajuria, H., Khalilov, R., Khammarnia, M., Khan, J., Khubchandani, J., Kianipour, N., Kim, G. R., Kim, Y. J., Kisa, A., Kisa, S., Kohler, S., Kosen, S., Koteeswaran, R., Koulmane Laxminarayana, S. L., Koyanagi, A., Krishan, K., Kumar, G. A., Kusuma, D., Lamnisos, D., Lansingh, V. C., Larsson, A. O., Lasrado, S., Le, L. K. D., Lee, S. W. H., Lee, Y. Y., Lim, S. S., Lobo, S. W., Lozano, R., Magdy Abd El Razek, H., Magdy Abd El Razek, M., Mahdavi, M. M., Majeed, A., Makki, A., Maleki, A., Malekzadeh, R., Manda, A. L., Mansour-Ghanaei, F., Mansournia, M. A., Marrugo Arnedo, C. A., Martinez-Valle, A., Masoumi, S. Z., Maude, R. J., Mckee, M., Medina-Solis, C. E., Menezes, R. G., Meretoja, A., Meretoja, T. J., Mesregah, M. K., Mestrovic, T., Milevska Kostova, N., Miller, T. R., Mini, G. K., Mirica, A., Mirrakhimov, E. M., Mohajer, B., Mohamed, T. A., Mohammadi, M., Mohammadian-Hafshejani, A., Mohammed, S., Moitra, M., Mokdad, A. H., Molokhia, M., Moni, M. A., Moradi, Y., Morze, J., Mousavi, S. M., Mpundu-Kaambwa, C., Muriithi, M. K., Muthupandian, S., Nagarajan, A. J., Naimzada, M. D., Nangia, V., Naqvi, A. A., Narayana, A. I., Nascimento, B. R., Naveed, M., Nayak, B. P., Nazari, J., Ndejjo, R., Negoi, I., Neupane Kandel, S., Nguyen, T. H., Nonvignon, J., Noubiap, J. J., Nwatah, V. E., Oancea, B., Ojelabi, F. A. O., Olagunju, A. T., Olakunde, B. O., Olgiati, S., Olusanya, J. O., Onwujekwe, O. E., Otoiu, A., Otstavnov, N., Otstavnov, S. S., Owolabi, M. O., Padubidri, J. R., Palladino, R., Panda-Jonas, S., Park, E. -C., Pashazadeh Kan, F., Pawar, S., Pazoki Toroudi, H., Pereira, D. M., Perianayagam, A., Pesudovs, K., Piccinelli, C., Postma, M. J., Prada, S. I., Rabiee, M., Rabiee, N., Rahim, F., Rahimi-Movaghar, V., Rahman, M. H. U., Rahman, M., Rahmani, A. M., Ram, U., Ranabhat, C. L., Ranasinghe, P., Rao, C. R., Rathi, P., Rawaf, D. L., Rawaf, S., Rawal, L., Rawassizadeh, R., Reiner Jr, R. C., Renzaho, A. M. N., Reshmi, B., Riaz, M. A., Ripon, R. K., Saad, A. M., Sahraian, M. A., Sahu, M., Salama, J. S., Salehi, S., Samy, A. M., Sanabria, J., Sanmarchi, F., Santos, J. V., Santric-Milicevic, M. M., Sathian, B., Savic, M., Saxena, D., Sayyah, M., Schwendicke, F., Senthilkumaran, S., Sepanlou, S. G., Seylani, A., Shahabi, S., Shaikh, M. A., Sheikh, A., Shetty, A., Shetty, P. H., Shibuya, K., Shrime, M. G., Shuja, K. H., Singh, J. A., Skryabin, V. Y., Skryabina, A. A., Soltani, S., Soofi, M., Spurlock, E. E., Stefan, S. C., Szerencses, V., Szocska, M., Tabares-Seisdedos, R., Taddele, B. W., Tefera, Y. G., Thavamani, A., Tobe-Gai, R., Topor-Madry, R., Tovani-Palone, M. R., Tran, B. X., Tudor Car, L., Ullah, A., Ullah, S., Umar, N., Undurraga, E. A., Valdez, P. R., Vasankari, T. J., Villafane, J. H., Violante, F. S., Vlassov, V., Vo, B., Vollmer, S., Vos, T., Vu, G. T., Vu, L. G., Wamai, R. G., Werdecker, A., Woldekidan, M. A., Wubishet, B. L., Xu, G., Yaya, S., Yazdi-Feyzabadi, V., Yigit, V., Yip, P., Yirdaw, B. W., Yonemoto, N., Younis, M. Z., Yu, C., Yunusa, I., Zahirian Moghadam, T., Zandian, H., Zastrozhin, M. S., Zastrozhina, A., Zhang, Z. -J., Ziapour, A., Zuniga, Y. M. H., Hay, S. I., Murray, C. J. L., and Dieleman, J. L.
Subjects: Economic growth, Financing, Government, International Cooperation, HN, HM, Global Health, Gross domestic product, International Agencies/economics, 0302 clinical medicine, RA0421, Per capita, Global health, Healthcare Financing, 11 Medical and Health Sciences, 2. Zero hunger, COVID 19, develompment assistance, health financing, projection 1995-250, INCOME, COVID-19, Development assistance, Health financing, COVID-19/economics, 1. No poverty, Public Health, Global Health, Social Medicine and Epidemiology, Articles, General Medicine, 3. Good health, Government Programs, Health Expenditures/statistics & numerical data, 030220 oncology & carcinogenesis, Transparency (graphic), QR180, Economic Development, International development, Life Sciences & Biomedicine, medicine.medical_specialty, Government Programs/economics, Gross Domestic Product, Context (language use), 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, medicine, Humans, Developing Countries/economics, Developing Countries, Government, Science & Technology, Public health, COVID-19, development assistance, global health, Global Burden of Disease 2020 Health Financing Collaborator Network, International Agencies, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Business, Global Health/economics, Health Expenditures, 030217 neurology & neurosurgery, RC, Financing, Government/economics
Abstract: Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. For complete list of authors see http://dx.doi.org/10.1016/S0140-6736(21)01258-7
Published: 2021
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37. PARK20 caused by SYNJ1 homozygous Arg258Gln mutation in a new Italian family

Author: Paolo Barone, Giuseppe De Michele, Sabina Pappatà, Vincenzo Bonifati, Anna De Rosa, Chiara Criscuolo, Marialuisa Quadri, Guido J. Breedveld, Simone Olgiati, Marina Picillo, Mario Quarantelli, Olgiati, S, DE ROSA, Anna, Quadri, M, Criscuolo, C, Breedveld, Gj, Picillo, M, Pappatà, S, Quarantelli, M, Barone, P, DE MICHELE, Giuseppe, Bonifati, V., and Clinical Genetics
Subjects: Male, Synaptojanin 1, Parkinson's disease, Genes, Recessive, Parkinsonism, Biology, SYNJ1, Cellular and Molecular Neuroscience, Parkinsonian Disorders, Genetics, medicine, Recessive, Humans, Sibling, Genetics (clinical), Family Health, Dystonia, PARK20, Medicine (all), Homozygote, Haplotype, Dopaminergic, Brain, medicine.disease, Phenotype, Phosphoric Monoester Hydrolases, Human genetics, Pedigree, Genes, Italy, Mutation, Female
Abstract: SYNJ1 has been recently identified by two independent groups as the gene defective in a novel form of autosomal recessive, early-onset atypical parkinsonism (PARK20). Two consanguineous families were initially reported (one of Sicilian and one of Iranian origins), with the same SYNJ1 homozygous mutation (c.773G>A, p.Arg258Gln) segregating with a similar phenotype of early-onset parkinsonism and additional atypical features. Here, we report the identification of the same SYNJ1 homozygous mutation in two affected siblings of a third pedigree. Both siblings had mild developmental psychomotor delay, followed, during the third decade of life, by progressive parkinsonism, dystonia, and mild cognitive impairment. One sibling suffered one episode of generalized seizures. Neuroimaging studies revealed severe nigrostriatal dopaminergic defects, mild striatal and very mild cortical hypometabolism. Treatment with dopamine agonists and anticholinergics resulted in partial improvements. Genetic analyses revealed in both siblings the SYNJ1 homozygous c.773G>A (p.Arg258Gln) mutation. Haplotype analysis suggests that the mutation has arisen independently in this family and the Sicilian PARK20 family previously described by us, in keeping with the hypothesis of a mutational hot spot. This is the third reported family with autosomal recessive, early-onset parkinsonism associated with the SYNJ1 p.Arg258Gln mutation. This work contributes to the definition of the genetic and clinical aspects of PARK20. This newly recognized form must be considered in the diagnostic work-up of patients with early-onset atypical parkinsonism. The presence of seizures might represent a red flag to suspect PARK20. © 2014 Springer-Verlag.
Published: 2014
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38. A new Turkish family with homozygous FBXO7 truncating mutation and juvenile atypical parkinsonism

Author: Gul Yalcin-Cakmakli, Vincenzo Bonifati, Bulent Elibol, Pietro Cortelli, Simone Olgiati, Marialuisa Quadri, Guido J. Breedveld, Yalcin-Cakmakli, G., Olgiati, S., Quadri, M., Breedveld, G.J., Cortelli, P., Bonifati, V., and Elibol, B.
Subjects: Male, Adolescent, Turkey, Turkish, Juvenile, Genes, Recessive, Biology, Parkinsonism, Compound heterozygosity, Genetic analysis, Gene, Young Adult, Parkinsonian Disorders, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, FBXO7, F-Box Protein, Genetics, F-Box Proteins, Haplotype, Homozygote, Parkinsonian Disorder, medicine.disease, language.human_language, Pedigree, Neurology, Mutation (genetic algorithm), Mutation, language, Female, Neurology (clinical), Geriatrics and Gerontology, Human
Abstract: Juvenile parkinsonism can be caused by recessive mutations in several genes. Among these, homozygous or compound heterozygous mutations in the F-box only protein 7 gene (FBXO7) cause juvenile parkinsonism with variable degrees of pyramidal disturbances (PARK15). So far, only five families (from Iran, Italy, The Netherlands, Pakistan, and Turkey) have been reported with this form. Here, we describe a new Turkish family with homozygous FBXO7 mutation (c.1492C > T, p.Arg498*). Three out of nine siblings born from consanguineous parents suffered from juvenile-onset progressive parkinsonism. Mental retardation was also documented in two of them. Of note, pyramidal signs were absent. The response to dopaminergic medications was present, but limited by dyskinesias and psychiatric side effects. Further genetic analysis of this Turkish family and the Italian PARK15 family reported previously revealed that the c.1492C > T mutation is present on two different haplotypes in the Italian family, and one of these haplotypes is shared in homozygous state in the Turkish patients. These findings contribute to the ongoing delineation of the genetic and clinical spectrum of PARK15.
Published: 2014

39. The sustainability of the Lombardia health system

Author: OLGIATI, STEFANO, Olgiati, S, and CESANA, GIANCARLO
Subjects: health, sustainability, Lombardia, MED/01 - STATISTICA MEDICA
Abstract: The cœteris paribus trend of growth of the Lombardia Hospital System epidemiological, demographic, economic and financial variables analyzed in this research in the period 1997-2009 is not sustainable in the long-term, for the purpose of this research to the year 2050. Even if in the period 2002-2009 some financial and epidemiological adjustment has indeed been attempted (as highlighted by the Financial Function), in particular with yearly activity budgetary financial constraints and compulsory transfers from acute to ambulatory care (as highlighted by the Epidemiological Function), by means of which short-term financial equilibrium has temporarily been maintained, this same adjustment does not guarantee long-term epidemiological, demographic, economic and financial sustainability (as highlighted by the Sustainability Function). The Italian Ministero dell’Economia e delle Finanze is indeed intervening in curbing the growth rate of public health expenditure by fixing it at a definite percent of the national gross domestic product (circa 7.2%). Most of the savings are based on the reduction of personnel. Since health funds are pooled and equally allocated on a risk adjusted capitarian basis, the same savings will be required on the part of Lombardia. However, if savings are to be made, the underlying epidemiological trends (increase in complexity, invariance in the acute inpatient cases length of stay, increase in intensity), as highlighted by the Epidemiological Function, have to be addressed as well, which introduces the bi-faced question if such savings are sustainable or if their epidemiological effects are acceptable. If there is an almost general consensus among both health operators and regulators in Italy and Lombardia that both effectiveness and efficiency are the main drivers of the long term sustainability of a health system, it appears from the first applications of the model presented here that the Italian and Lombardia Hospital System is still governed by a tendency to manage the short term effects of rising medical, labor and variable costs in general, than by a much more challenging direct intervention into the epidemiological and operational parameters governing the health system in the long term. Certainly, an excellent clinical effectiveness has been achieved, even if, in order to be sustainable in the long term, increases in clinical quality must be proportional to the reduction in the economic waste of financial resources, both in the form of excess costs of the public providers and excess profits in the private ones. Once again, the authors of this paper argue that there can be no health without equity, no equity without quality, and no quality without sustainability.
Published: 2012

40. A Gender-Bias-Mitigated, Data-Driven Precision Medicine System to Assist in the Selection of Biological Treatments of Grade 3 and 4 Knee Osteoarthritis: Development and Preliminary Validation of precisionKNEE.

Author: Heidari N, Olgiati S, Meloni D, Parkin J, Fish B, Slevin M, and Azamfirei L
Abstract: Objective To identify key variables predictive of patient responses to microfragmented adipose tissue (MFAT) treatment in knee osteoarthritis (KOA) and evaluate its potential to delay or mitigate the need for total knee replacement (TKR). Methods We utilised a dataset comprising 329 patients treated with MFAT for KOA, incorporating variables such as gender, age, BMI, arthritic aetiology, radiological grade, and Oxford Knee Scores (OKS) pre- and post-treatment. We employed random forest regressors for model training and testing, with gender bias mitigation and outlier detection to enhance prediction accuracy. Model performance was assessed through root mean squared error (RMSE) and mean absolute error (MAE), with further validation in a TKR-suitable patient subset. Results The model achieved a test RMSE of 6.72 and an MAE of 5.38, reflecting moderate predictive accuracy across the patient cohort. Stratification by gender revealed no statistically significant differences between actual and predicted OKS improvements (p-values: males = 0.93, females = 0.92). For the subset of patients suitable for TKR, the model presented an increased RMSE of 9.77 and MAE of 7.81, indicating reduced accuracy in this group. The decision tree analysis identified pre-operative OKS, radiological grade, and gender as significant predictors of post-treatment outcomes, with pre-operative OKS being the most critical determinant. Patients with lower pre-operative OKS showed varying responses based on radiological severity and gender, suggesting a nuanced interaction between these factors in determining treatment efficacy. Conclusion This study highlights the potential of MFAT as a non-surgical alternative for KOA treatment, emphasising the importance of personalised patient assessments. While promising, the predictive model warrants further refinement and validation with a larger, more diverse dataset to improve its utility in clinical decision-making for KOA management., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Heidari et al.)
Published: 2024
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41. A Quantum-Enhanced Precision Medicine Application to Support Data-Driven Clinical Decisions for the Personalized Treatment of Advanced Knee Osteoarthritis: The Development and Preliminary Validation of precisionKNEE_QNN.

Author: Heidari N, Olgiati S, Meloni D, Slevin M, Noorani A, Pirovano F, and Azamfirei L
Abstract: Background Quantum computing and quantum machine learning (QML) are promising experimental technologies that can improve precision medicine applications by reducing the computational complexity of algorithms driven by big, unstructured, real-world data. The clinical problem of knee osteoarthritis is that, although some novel therapies are safe and effective, the response is variable, and defining the characteristics of an individual who will respond remains a challenge. In this study, we tested a quantum neural network (QNN) application to support precision data-driven clinical decisions to select personalized treatments for advanced knee osteoarthritis. Methodology After obtaining patients' consent and Research Ethics Committee approval, we collected the clinicodemographic data before and after the treatment from 170 patients eligible for knee arthroplasty (Kellgren-Lawrence grade ≥3, Oxford Knee Score (OKS) ≤27, age ≥64 years, and idiopathic aetiology of arthritis) treated over a two-year period with a single injection of microfragmented fat. Gender classes were balanced (76 males and 94 females) to mitigate gender bias. A patient with an improvement ≥7 OKS was considered a responder. We trained our QNN classifier on a randomly selected training subset of 113 patients to classify responders from non-responders (73 responders and 40 non-responders) in pain and function at one year. Outliers were hidden from the training dataset but not from the validation set. Results We tested our QNN classifier on a randomly selected test subset of 57 patients (34 responders, 23 non-responders) including outliers. The no information rate was 0.59. Our application correctly classified 28 responders out of 34 and 6 non-responders out of 23 (sensitivity = 0.82, specificity = 0.26, F1 Statistic = 0.71). The positive and negative likelihood ratios were 1.11 and 0.68, respectively. The diagnostic odds ratio was 2. Conclusions Preliminary results on a small validation dataset showed that QML applied to data-driven clinical decisions for the personalized treatment of advanced knee osteoarthritis is a promising technology to reduce computational complexity and improve prognostic performance. Our results need further research validation with larger, real-world unstructured datasets, as well as clinical validation with an artificial intelligence clinical trial to test model efficacy, safety, clinical significance, and relevance at a public health level., Competing Interests: Some parts of the Quantum Circuits and Artificial Intelligence algorithms are copyrighted and the authors are likely to patent some of the contents., (Copyright © 2024, Heidari et al.)
Published: 2024
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42. Transcriptome Profiling of Porcine Naïve, Intermediate and Terminally Differentiated CD8 + T Cells.

Author: Lagumdzic E, Pernold C, Viano M, Olgiati S, Schmitt MW, Mair KH, and Saalmüller A
Subjects: Animals, Gene Expression Profiling, Ionomycin metabolism, Mice, Swine, T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Lymphocyte Activation
Abstract: The pig has the potential to become a leading research model for human diseases, pharmacological and transplantation studies. Since there are many similarities between humans and pigs, especially concerning anatomy, physiology and metabolism, there is necessity for a better understanding of the porcine immune system. In adaptive immunity, cytotoxic T lymphocytes (CTLs) are essential for host defense. However, most data on CTLs come from studies in mice, non-human primates and humans, while detailed information about porcine CD8 + CTLs is still sparse. Aim of this study was to analyze transcriptomes of three subsets of porcine CD8β + T-cell subsets by using next-generation sequencing technology. Specifically, we described transcriptional profiles of subsets defined by their CD11a/CD27 expression pattern, postulated as naïve (CD8β + CD27 + CD11a low ), intermediate differentiated (CD8β + CD27 dim CD11a + ), and terminally differentiated cells (CD8β + CD27 - CD11a high ). Cells were analyzed in ex vivo condition as well as upon in vitro stimulation with concanavalin A (ConA) and PMA/ionomycin. Our analyses show that the highest number of differentially expressed genes was identified between naïve and terminally differentiated CD8 + T-cell subsets, underlining their difference in gene expression signature and respective differentiation stages. Moreover, genes related to early ( IL7-R , CCR7 , SELL , TCF7, LEF1 , BACH2 , SATB1 , ZEB1 and BCL2 ) and late ( KLRG1 , TBX21 , PRDM1 , CX3CR1, ZEB2 , ZNF683 , BATF , EZH2 and ID2 ) stages of CD8 + T-cell differentiation were highly expressed in the naïve and terminally differentiated CD8 + T-cell subsets, respectively. Intermediate differentiated CD8 + T-cell subsets shared a more comparable gene expression profile associated with later stages of T-cell differentiation. Genes associated with cytolytic activity ( GNLY , PRF1 , GZMB , FASL , IFNG and TNF ) were highly expressed in terminally and intermediate differentiated CD8 + T-cell subsets, while naïve CD8 + T cells lacked expression even after in vitro stimulation. Overall, PMA/ionomycin stimulation induced much stronger upregulation of genes compared to stimulation with ConA. Taken together, we provided comprehensive results showing transcriptional profiles of three differentiation stages of porcine CD8 + T-cell subsets. In addition, our study provides a powerful toolbox for the identification of candidate markers to characterize porcine immune cell subsets in more detail., Competing Interests: MV and SO are employed by Istituto di Ricerche Biomediche “A. Marxer” RBM S.p.A. MS is employed by Merck Healthcare KGaA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lagumdzic, Pernold, Viano, Olgiati, Schmitt, Mair and Saalmüller.)
Published: 2022
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43. Comparison of the Effect of MFAT and MFAT + PRP on Treatment of Hip Osteoarthritis: An Observational, Intention-to-Treat Study at One Year.

Author: Heidari N, Slevin M, Zeinolabediny Y, Meloni D, Olgiati S, Wilson A, Noorani A, and Azamfirei L
Abstract: Hip osteoarthritis (OA) is a major contributor to reduced quality of life and concomitant disability associated with lost working life months. Intra-articular injection of various biological materials has shown promise in alleviating symptoms and potentially slowing down the degenerative process. Here, we compared the effects of treatment of a cohort of 147 patients suffering from grade 1-4 hip OA; with either micro-fragmented adipose tissue (MFAT), or a combination of MFAT with platelet-rich plasma (PRP). We found significant improvements in both the visual analogue score for pain (VAS) and Oxford hip score (OHS) that were similar for both treatments with over 60% having an improvement in the VAS score of 20 points or more. These results suggest a positive role for intra-articular injection of MFAT + PRP as a treatment for hip osteoarthritis which may be important particularly in low body mass index (BMI) patients where the difficulty in obtaining sufficient MFAT for treatment could be offset by using this combination of biologicals.
Published: 2022
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44. Microfragmented Adipose Tissue Injection (MFAT) May Be a Solution to the Rationing of Total Knee Replacement: A Prospective, Gender-Bias Mitigated, Reproducible Analysis at Two Years.

Author: Heidari N, Borg TM, Olgiati S, Slevin M, Danovi A, Fish B, Wilson A, and Noorani A
Abstract: Background: Knee osteoarthritis (KOA) is a significant cause of disability in a globally ageing population. Knee replacement surgery has been shown to improve function and quality of life. Access to this intervention can be limited for a number of reasons including rationing of care, lack of healthcare provision in austere environments, and more recently, due to the cessation of elective orthopaedic care as a result of the COVID pandemic. Referral for knee replacement surgery is often guided by the patient's Oxford Knee Score (OKS). Recent therapies including treatment with microfragmented adipose tissue (MFAT) have emerged as alternatives to relieve pain and improve function in such patients., Method: We identified all patients with KOA Kellgren-Lawrence grade 3 and 4 in our dataset of patients treated with a single injection of MFAT and applied published OKS thresholds for referral for TKR to separate them into 3 cohorts according to their functional impairment. 220 patients (95 females, 125 males) with KOA were given one MFAT injection. The function (OKS) and quality of life (EuroQol-5) prior to and 24 months after therapy were compared., Results: MFAT injection provided a statistically significant improvement in the quality of life (EQ-5D) at 24 months in patients with a baseline OKS of 39 or less ( p value: <0.001) as well as those with OKS of 27 or less who are deemed suitable for a knee replacement ( p value: <0.001)., Conclusion: MFAT injection improves quality of life in patients with KOA who are deemed suitable for the knee replacement. MFAT is a low-morbidity alternative biological treatment and can delay the need for total knee replacement in suitable patients., Competing Interests: N.H., A.N., and S.O. have participations in Medical Artificial Intelligence Companies which have received in the past and are likely to receive in the future private and public funding for predictive computational medicine, AI clinical trials, and precision medicine modeling in the field of regenerative medicine. The other authors declare no conflict of interest., (Copyright © 2021 Nima Heidari et al.)
Published: 2021
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45. EIF2AK2 Missense Variants Associated with Early Onset Generalized Dystonia.

Author: Kuipers DJS, Mandemakers W, Lu CS, Olgiati S, Breedveld GJ, Fevga C, Tadic V, Carecchio M, Osterman B, Sagi-Dain L, Wu-Chou YH, Chen CC, Chang HC, Wu SL, Yeh TH, Weng YH, Elia AE, Panteghini C, Marotta N, Pauly MG, Kühn AA, Volkmann J, Lace B, Meijer IA, Kandaswamy K, Quadri M, Garavaglia B, Lohmann K, Bauer P, Mencacci NE, Lubbe SJ, Klein C, Bertoli-Avella AM, and Bonifati V
Subjects: Adolescent, Adult, Age of Onset, Asian People, Brain diagnostic imaging, Child, Child, Preschool, Dystonic Disorders metabolism, Dystonic Disorders physiopathology, Female, Genome-Wide Association Study, Humans, Infant, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Missense, Pedigree, White People, Exome Sequencing, Young Adult, eIF-2 Kinase metabolism, Dystonic Disorders genetics, Fibroblasts metabolism, eIF-2 Kinase genetics
Abstract: Objective: The study was undertaken to identify a monogenic cause of early onset, generalized dystonia., Methods: Methods consisted of genome-wide linkage analysis, exome and Sanger sequencing, clinical neurological examination, brain magnetic resonance imaging, and protein expression studies in skin fibroblasts from patients., Results: We identified a heterozygous variant, c.388G>A, p.Gly130Arg, in the eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) gene, segregating with early onset isolated generalized dystonia in 5 patients of a Taiwanese family. EIF2AK2 sequencing in 191 unrelated patients with unexplained dystonia yielded 2 unrelated Caucasian patients with an identical heterozygous c.388G>A, p.Gly130Arg variant, occurring de novo in one case, another patient carrying a different heterozygous variant, c.413G>C, p.Gly138Ala, and one last patient, born from consanguineous parents, carrying a third, homozygous variant c.95A>C, p.Asn32Thr. These 3 missense variants are absent from gnomAD, and are located in functional domains of the encoded protein. In 3 patients, additional neurological manifestations were present, including intellectual disability and spasticity. EIF2AK2 encodes a kinase (protein kinase R [PKR]) that phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α), which orchestrates the cellular stress response. Our expression studies showed abnormally enhanced activation of the cellular stress response, monitored by PKR-mediated phosphorylation of eIF2α, in fibroblasts from patients with EIF2AK2 variants. Intriguingly, PKR can also be regulated by PRKRA (protein interferon-inducible double-stranded RNA-dependent protein kinase activator A), the product of another gene causing monogenic dystonia., Interpretation: We identified EIF2AK2 variants implicated in early onset generalized dystonia, which can be dominantly or recessively inherited, or occur de novo. Our findings provide direct evidence for a key role of a dysfunctional eIF2α pathway in the pathogenesis of dystonia. ANN NEUROL 2021;89:485-497., (© 2020 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Published: 2021
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46. Gender-Specific Response in Pain and Function to Biologic Treatment of Knee Osteoarthritis: A Gender-Bias-Mitigated, Observational, Intention-to-Treat Study at Two Years.

Author: Borg TM, Heidari N, Noorani A, Slevin M, Cullen A, Olgiati S, Zerbi A, Danovi A, and Wilson A
Abstract: Knee osteoarthritis is a major cause of disability worldwide. Newer modalities of treatment with less morbidity, such as intra-articular injection of microfragmented fat (MFAT), are showing promise. We report on our novel observation that women show a greater improvement in pain and function to MFAT than men. Traditionally, women have been underrepresented in studies and studies with both sexes regularly fail to analyze the results by sex. To mitigate for this bias and quantify it, we describe a technique using reproducible statistical analysis and replicable results with Open Access statistical software R to calculate the magnitude of this difference. Genetic, hormonal, environmental, and age factors play a role in our observed difference between the sexes. There is a need for further studies to identify the molecular basis for this difference and be able to utilize it to improve outcome for both women and men., Competing Interests: N.H., A.N., and S.O. have participations in Medical Artificial Intelligence Companies which have received in the past and are likely to receive in the future private and public funding for predictive computational medicine, AI clinical trials, and precision medicine modeling in the field of regenerative medicine. The other authors declare no conflict of interest., (Copyright © 2021 Tiffanie-Marie Borg et al.)
Published: 2021
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47. Patient-Centered Outcomes of Microfragmented Adipose Tissue Treatments of Knee Osteoarthritis: An Observational, Intention-to-Treat Study at Twelve Months.

Author: Heidari N, Noorani A, Slevin M, Cullen A, Stark L, Olgiati S, Zerbi A, and Wilson A
Abstract: Introduction: Microfragmented adipose tissue (MFAT) has been shown to benefit osteoarthritic patients by reducing pain and supporting tissue regeneration through a mesenchymal stem cell (MSC)-related paracrine mechanism. This observational study of 110 knees assessed patient-centered outcomes of pain, functionality, and quality of life, analyzing their variation at twelve months following one ultrasound-guided intra-articular injection of autologous MFAT for the treatment of knee osteoarthritis (KOA)., Method: Inclusion criteria were as follows: VAS >50, and the presence of KOA as diagnosed on X-ray and MRI. Exclusion criteria included the following: recent injury (<3 months) of the symptomatic knee, intra-articular steroid injections performed within the last three months, and hyaluronic acid injections prior to this treatment. Changes in VAS, OKS, and EQ-5D were scored at baseline and twelve months following a single intra-articular injection of autologous MFAT. Score variation was analyzed utilizing a nonparametric paired samples Wilcoxon test. The statistical analysis is reproducible with Open Access statistical software R (version 4.0.0 or higher). The study was carried out with full patient consent, in a private practice setting., Results: Median VAS (pain) improved from 70 (IQR 20) to 30 (IQR 58) ( p < 0.001); median OKS (function) improved from 25 (IQR 11) to 33.5 (IQR 16) ( p < 0.001); and median EQ-5D (quality of life) improved from 0.62 (IQR 0.41) to 0.69 (IQR 0.28) ( p < 0.001). No adverse events were reported during the intraoperative, recovery, or postoperative periods., Conclusions: For patients with all grades of knee osteoarthritis who were treated with intra-articular injections of MFAT, statistically significant improvements in pain, function, and quality of life were reported. Although further research is warranted, the results are encouraging and suggest a positive role for intra-articular injection of MFAT as a treatment for knee osteoarthritis., Competing Interests: S.O. has received in the past and is likely to receive in the future private and public funding for predictive computational medicine, predictive clinical trials, and predictive modeling in the field of regenerative medicine. The other authors declare no conflict of interest., (Copyright © 2020 Nima Heidari et al.)
Published: 2020
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48. Late-onset phenotype associated with a homozygous GJC2 missense mutation in a Turkish family.

Author: Kuipers DJS, Tufekcioglu Z, Bilgiç B, Olgiati S, Dremmen MHG, van IJcken WFJ, Breedveld GJ, Mancini GMS, Hanagasi HA, Emre M, and Bonifati V
Subjects: Age of Onset, Aged, Ataxia pathology, Ataxia physiopathology, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Missense, Parkinsonian Disorders pathology, Parkinsonian Disorders physiopathology, Pedigree, Phenotype, Siblings, Turkey, White Matter diagnostic imaging, Ataxia genetics, Connexins genetics, Parkinsonian Disorders genetics, White Matter pathology
Abstract: Objective: Recessive mutations in the Gap Junction Protein Gamma 2 (GJC2) gene cause Pelizaeus-Merzbacher-like disease type 1, a severe infantile-onset hypomyelinating leukodystrophy. Milder, late-onset phenotypes including complicated spastic paraplegia in one family (SPG44), and mild tremor in one case, were reported associated to GJC2 homozygous missense mutations. Here, we report a new family with two siblings carrying a different homozygous GJC2 mutation, presenting with late-onset ataxic and pyramidal disturbances, and parkinsonism in one of them., Methods: Two affected siblings were studied by neurological examination and brain MRI. Genetic analyses included genome-wide homozygosity mapping in both siblings, and whole exome sequencing in one sib. The resulting candidate gene variant was validated by Sanger sequencing., Results: The affected siblings share a novel homozygous GJC2 missense mutation (c.820G>C, p.Val274Leu), predicted as pathogenic by all used in-silico tools. Brain MRI showed hyperintense signal in T2-weighted images in the internal capsule and subcortical and periventricular white matter, consistent with hypomyelination., Conclusions: Our findings confirm and further expand the late-onset phenotypes of GJC2 mutations, to include prominent ataxia, pyramidal disturbances and mild parkinsonism, and confirm the distinctive associated MRI pattern., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
Published: 2019
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49. Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia.

Author: de Vrij FM, Bouwkamp CG, Gunhanlar N, Shpak G, Lendemeijer B, Baghdadi M, Gopalakrishna S, Ghazvini M, Li TM, Quadri M, Olgiati S, Breedveld GJ, Coesmans M, Mientjes E, de Wit T, Verheijen FW, Beverloo HB, Cohen D, Kok RM, Bakker PR, Nijburg A, Spijker AT, Haffmans PMJ, Hoencamp E, Bergink V, Vorstman JA, Wu T, Olde Loohuis LM, Amin N, Langen CD, Hofman A, Hoogendijk WJ, van Duijn CM, Ikram MA, Vernooij MW, Tiemeier H, Uitterlinden AG, Elgersma Y, Distel B, Gribnau J, White T, Bonifati V, and Kushner SA
Subjects: Adult, Antigens genetics, Cell Differentiation physiology, Chondroitin Sulfate Proteoglycans metabolism, Diffusion Tensor Imaging, Family, Female, Humans, Induced Pluripotent Stem Cells metabolism, Male, Membrane Proteins metabolism, Mutation genetics, Oligodendrocyte Precursor Cells physiology, Oligodendroglia metabolism, Pedigree, Proteoglycans genetics, Schizophrenia metabolism, White Matter metabolism, Chondroitin Sulfate Proteoglycans genetics, Membrane Proteins genetics, Oligodendrocyte Precursor Cells metabolism, Schizophrenia genetics
Abstract: Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation of two rare missense mutations in Chondroitin Sulfate Proteoglycan 4 (CSPG4) (c.391G > A [p.A131T], MAF 7.79 × 10 -5 and c.2702T > G [p.V901G], MAF 2.51 × 10 -3 ). The CSPG4 A131T mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2536 cases, 2543 controls), while the CSPG4 V901G mutation was nominally enriched in cases (11 cases vs. 3 controls, P = 0.026, OR 3.77, 95% CI 1.05-13.52). CSPG4/NG2 is a hallmark protein of oligodendrocyte progenitor cells (OPCs). iPSC-derived OPCs from CSPG4 A131T mutation carriers exhibited abnormal post-translational processing (P = 0.029), subcellular localization of mutant NG2 (P = 0.007), as well as aberrant cellular morphology (P = 3.0 × 10 -8 ), viability (P = 8.9 × 10 -7 ), and myelination potential (P = 0.038). Moreover, transfection of healthy non-carrier sibling OPCs confirmed a pathogenic effect on cell survival of both the CSPG4 A131T (P = 0.006) and CSPG4 V901G (P = 3.4 × 10 -4 ) mutations. Finally, in vivo diffusion tensor imaging of CSPG4 A131T mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 × 10 -5 ). Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia.
Published: 2019
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50. LRP10 genetic variants in familial Parkinson's disease and dementia with Lewy bodies: a genome-wide linkage and sequencing study.

Author: Quadri M, Mandemakers W, Grochowska MM, Masius R, Geut H, Fabrizio E, Breedveld GJ, Kuipers D, Minneboo M, Vergouw LJM, Carreras Mascaro A, Yonova-Doing E, Simons E, Zhao T, Di Fonzo AB, Chang HC, Parchi P, Melis M, Correia Guedes L, Criscuolo C, Thomas A, Brouwer RWW, Heijsman D, Ingrassia AMT, Calandra Buonaura G, Rood JP, Capellari S, Rozemuller AJ, Sarchioto M, Fen Chien H, Vanacore N, Olgiati S, Wu-Chou YH, Yeh TH, Boon AJW, Hoogers SE, Ghazvini M, IJpma AS, van IJcken WFJ, Onofrj M, Barone P, Nicholl DJ, Puschmann A, De Mari M, Kievit AJ, Barbosa E, De Michele G, Majoor-Krakauer D, van Swieten JC, de Jong FJ, Ferreira JJ, Cossu G, Lu CS, Meco G, Cortelli P, van de Berg WDJ, and Bonifati V
Subjects: Brain pathology, Chromosomes, Human, Pair 14 genetics, Dementia epidemiology, Dementia etiology, Dementia genetics, Family, Female, Genetic Linkage, Genome-Wide Association Study, Heterozygote, Humans, Italy, Lewy Body Disease epidemiology, Male, Middle Aged, Parkinson Disease complications, Parkinson Disease epidemiology, Pedigree, Pluripotent Stem Cells metabolism, RNA, Messenger chemistry, RNA, Messenger genetics, LDL-Receptor Related Proteins genetics, Lewy Body Disease genetics, Parkinson Disease genetics
Abstract: Background: Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the development of these disorders., Methods: Our study was done in three stages. First, we did genome-wide linkage analysis of an Italian family with dominantly inherited Parkinson's disease to identify the disease locus. Second, we sequenced the candidate gene in an international multicentre series of unrelated probands who were diagnosed either clinically or pathologically with Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. As a control, we used gene sequencing data from individuals with abdominal aortic aneurysms (who were not examined neurologically). Third, we enrolled an independent series of patients diagnosed clinically with Parkinson's disease and controls with no signs or family history of Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies from centres in Portugal, Sardinia, and Taiwan, and screened them for specific variants. We also did mRNA and brain pathology studies in three patients from the international multicentre series carrying disease-associated variants, and we did functional protein studies in in-vitro models, including neurons from induced pluripotent stem-like cells., Findings: Molecular studies were done between Jan 1, 2008, and Dec 31, 2017. In the initial kindred of ten affected Italian individuals (mean age of disease onset 59·8 years [SD 8·7]), we detected significant linkage of Parkinson's disease to chromosome 14 and nominated LRP10 as the disease-causing gene. Among the international series of 660 probands, we identified eight individuals (four with Parkinson's disease, two with Parkinson's disease dementia, and two with dementia with Lewy bodies) who carried different, rare, potentially pathogenic LRP10 variants; one carrier was found among 645 controls with abdominal aortic aneurysms. In the independent series, two of these eight variants were detected in three additional Parkinson's disease probands (two from Sardinia and one from Taiwan) but in none of the controls. Of the 11 probands from the international and independent cohorts with LRP10 variants, ten had a positive family history of disease and DNA was available from ten affected relatives (in seven of these families). The LRP10 variants were present in nine of these ten relatives, providing independent-albeit limited-evidence of co-segregation with disease. Post-mortem studies in three patients carrying distinct LRP10 variants showed severe Lewy body pathology. Of nine variants identified in total (one in the initial family and eight in stage 2), three severely affected LRP10 expression and mRNA stability (1424+5delG, 1424+5G→A, and Ala212Serfs*17, shown by cDNA analysis), four affected protein stability (Tyr307Asn, Gly603Arg, Arg235Cys, and Pro699Ser, shown by cycloheximide-chase experiments), and two affected protein localisation (Asn517del and Arg533Leu; shown by immunocytochemistry), pointing to loss of LRP10 function as a common pathogenic mechanism., Interpretation: Our findings implicate LRP10 gene defects in the development of inherited forms of α-synucleinopathies. Future elucidation of the function of the LRP10 protein and pathways could offer novel insights into mechanisms, biomarkers, and therapeutic targets., Funding: Stichting ParkinsonFonds, Dorpmans-Wigmans Stichting, Erasmus Medical Center, ZonMw-Memorabel programme, EU Joint Programme Neurodegenerative Disease Research (JPND), Parkinson's UK, Avtal om Läkarutbildning och Forskning (ALF) and Parkinsonfonden (Sweden), Lijf and Leven foundation, and cross-border grant of Alzheimer Netherlands-Ligue Européene Contre la Maladie d'Alzheimer (LECMA)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
Published: 2018
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