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2. Potent roots on the move:calumba and abutua as African, imperial, and global medicines, c. 1700s–1900s

Author

Kananoja, K. (Kalle), Hokkanen, M. (Markku), Kananoja, K. (Kalle), and Hokkanen, M. (Markku)

Abstract

Calumba (Jateorhiza calumba / J. palmata) and abutua (Cissampelos pareira) are multi-purpose medicinal plants, whose roots have been used in Eastern, Southern, and West-Central Africa for a considerable time. In the early modern era, the Portuguese adapted the roots, which became commercially traded in the Portuguese empire across the Indian and Atlantic Oceans. By the early nineteenth century, the roots were recognized also by the British and North American pharmacopoeias, but there was confusion and secrecy surrounding their origins and quality. Engaging with recent historiography about African and imperial plant medicines, we demonstrate that calumba and abutua had long, dynamic, and mobile continuities on the continent—first in Portuguese imperial settings and then in appropriation by British botanists and colonial officials in East Africa. Exploring African agency in the making of knowledge about calumba and abutua is problematic, however. While in the longue durée, calumba and abutua maintained their value and meanings within Africa, in certain moments, these plants became objects of scientific curiosity and heightened commercial interest in the West.

Published
2022

5. Effect of hydrolyzed infant formula vs conventional formula on risk of type 1 diabetes the TRIGR randomized clinical trial

Author

Knip M., Akerblom H. K., Altaji E., Becker D., Bruining J., Castano L., Danne T., De Beaufort C., Dosch H. -M., Dupre J., Fraser W. D., Howard N., Ilonen J., Konrad D., Kordonouri O., Krischer J. P., Lawson M. L., Ludvigsson J., Madacsy L., Mahon J. L., Ormisson A., Palmer J. P., Pozzilli P., Savilahti E., Serrano-Rios M., Songini M., Taback S., Vaarala O., White N. H., Virtanen S. M., Wasikowa R., Mandrup-Poulsen T., Arjas E., Lernmark A., Laara E., Schmidt B., Hyytinen M., Koski K., Koski M., Merentie K., Pajakkala E., Reunanen A., Salonen M., Terhonen T., Virkkunen S., Cuthbertson D., Gainer B., Hadley D., Malloy J., Nallamshetty L., Shanker L., Bradley B., Lough G., Fraser W., Sermer M., Taback S. P., Franciscus M., Nucci A., Palmer J., Alahuhta K., Barlund S., Korhonen T., Kovanen L., Lehtonen E., Niinisto S., Pekkala M., Sorkio S., Toivanen L., Vahatalo L., Uusitalo U., Ohman T., Bongiorno R., Catteau J., Fraser G., Lloyd M., Crock P., Giles M., Siech K., See D. W., Brown C., Craig M., Johnston A., Bere L. J., Clarson C. L., Jenner M., McManus R., Renato N., Lovell M., Higo D., Kent N., Kwan J., Marshall C., Metzger D., Chanoine J. -P., Stewart L., Thompson D., Edwards A., Lange I., Mercer J., Pacaud D., Josephine H., Schwarz W., Stephure D. K., Boer J., Chatur T., Chick C., Couch B., Demianczuk N., Girgis R., Marks S., Ryan E., Thompson M., Dean H. J., Grant L., Hamelin K., LaForte J., Murphy L., Catte D., Schneider C., Sellers E. A. C., Woo V., Boland A., Clark H. D., Cooper T., Gruslin A., Karovitch A., Keely E., Malcolm J. C., Sauro V., Tawagi G. F., Andrighetti S., Arnold G., Barrett J., Blumer I., Daneman D., Donat D., Ehrlich R., Feig D., Gottesman I., Gysler M., Karkanis S., Kenshole A., Knight B., Lackie E., Lewis V., Martin M. J., Maxwell C., Oliver G., Panchum P., Shilletto N., Simone A., Skidmore M., Turrini T., Wong S., Allen C., Belanger L., Bouchard I., Ferland S., Frenette L., Garrido-Russo M., Leblanc M., Imbeault J., Morin V., Olivier G., Weisnagell J., Costain G., Dornan J., Heath K., MacSween M. -C., McGibbon A., Ramsay C., Sanderson F., Sanderson S., Benabdesselam L., Gonthier M., Huot C., Thibeault M., Laforte D., Legault L., Perron P., Armson A., Canning P., Cummings E. A., Ivanko V., McLeod L., Mokashi A., Scott K., Bridger T., Crane J., Crummell C., Curtis J. C., Dawson C., Joyce C., Newhook L. A., Newman S., Druken E., Begum-Hasan J., Breen A., Houlden R., Woods M., Carrson G., Kelly S., Martel M. J., Penner M., Sankaran K., Hardy-Brown K., King N., White R. A., Park M., Popkin J., Robson L., Coles K., Al Taji E., Cerna M., Cerny M., Francova H., Hainerova I., Kothankova H., Koukalova R., Krakorova V., Mendlova P., Sitova R., Stechova K., Vavrinec J., Vosahlo J., Zlatohlavkova B., Brazdova L., Faksova P., Gregorova D., Kantor L., Malkova K., Venhacova J., Venhacova P., Cipra A., Skvor J., Budejovice C., Tomsikova Z., Botkova-Krauseova H., Mockova A., Paterova P., Gogelova P., Kandrnalova J., Einberg U., Jakovlev U., Posiadlo S., Rannaste E., Raukas R., Riikjarv M. -A., Valla K., Astover V., Kirss A., Retpap J., Taht E., Tillmann V., Vahtra S., Heikkila M., Hirvasniemi M., Luopajarvi K., Johansson S., Kleemola P., Laukkanen E., Parkkola A., Pigg H. -M., Puttonen H., Renlund M., Salonen K., Suomalainen H., Tenkula T., Teramo K., Jarvenpaa A. -L., Hamalainen A. -M., Jussila R., Kiiveri S., Haavisto H., Holopainen S., Kupiainen H., Leeve T., Lumme K., Nironen T., Tenhola S., Tiilikainen T., Keinonen H., Lautala P., Salonen P., Vesanto M., Aspholm A. S., Asunta P., Ikavalko H., Jason E., Jaminki S., Kekki P., Koskinen M., Lehtimaki S., Lahde J., Makela M., Peltoniemi S., Poutiainen L., Ranta K., Salonsaari T., Sarviharju-Tujula S. -L., Selvenius J., Siljander H., Haanpaa P. -L., Holm C., Juutilainen A., Jarvelainen V., Kangaskolkka-Keskilohko A. -M., Laino E., Marjamaki L., Suominen E., Ylitalo S., Hokkanen M., Lounamaa R., Matikainen M., Nuuja A., Paalanen I., Puupponen A. R., Salo-Edwards H., Alanne S., Kultti T., Linjama H., Muhonen K., Vaaraniemi M., Talvitie T., Backman M., Hanhijarvi R., Koivula P., Lindstrom K., Martikainen A., Nurmi P., Bjork A., Huopio H., Komulainen J., Lehtomaki S., Muikku E., Pesola J., Sankilampi U., Arkkola T., Hekkala A., Jurvakainen S., Koivikko M. -L., Kahonen M., Leinonen E., Mykkanen T., Pohjola H., Riikonen K., Niittyvuopio A., Stenius A., Tapanainen P., Veijola R., Alar A., Jovio S., Korpela P., Makinen E., Hietanen L., Kivisto J., Kaar M. -L., Lehtimaki P., Mustila T., Popov E., Saatela S., Taittonen L., Ahtiainen K., Laaksonen N., Luoto M., Viitala J., Virransalo R., Nykanen P., Paajanen S., Parkkinen S., Pyrhonen H., Sarkka T., Aschemeier B., Bektas S., Biester T., Datz N., Deiss D., Fath M., Lupke K., Muller B., Nestoris C., Rothes S., Sadeghian E., Semler K., Arato A., Krikovszky D., Nobilis A., Szenasi J., Benevento D., Anguissola G. B., Biagioni M., Bizzarri C., Cherubini V., Ferrito L., Giordano C., Giorgetti C., Khazrai Y. M., Kyanvash S., Maddaloni E., Napoli A., Piergiovanni F., Pitocco D., Suraci T., Tabacco G., Valente L., Visalli N., Carboni M. B., Cavallo R., Cau V., Isola C., Ledda A., Loddo M., Mannu C., Pettinau M., Pisano S., Porceddu M., Putzu C., Rita A., Peters D., Schierloh U., Bisschoff M., Blonk L., Lappenschaar T., Manai B., Seesink M., Sperling-Conrad M., Verhagen M., Zoethout J. A., Basiak A., Chalas M., Chesiak M., Gramza A., Iwankiewicz J., Sieradzan E., Wikiera B., Ciechanowska M., Dziatkowiak H., Futona B., Gorska A., Glowacka-Wony M., Kaim I., Klich B., Starzyk J., Wolanin M., Tokarska L., Chucherco D., Deja G., Firek-Pedras M., Jarosz-Chobot P., Kalina M., Kutrowska-Adamusiak K., Minkina-Pedras M., Muchaka-Bianga M., Bodalski J., Mlynarski W., Szadkowska A., Cieslak A., Cypryk K., Dziatosz K., Jastzebowska J., Krysiak A., Szymanska U., Wilcznski J., Zawodniak-Szalapska M., Aguay A., Bilbao J. R., Chueca M., Cortazar A., Echarte G., Frutos T. G., Jimenez P., Martul P., Moreno A., Oyarzabal M., Rica I., Salgado Y., Martinez-Larrad M. T., Hawkins F. G., Hernandez R., Herranz L., Pallardo L. F., Deibarra L. S., Fernandez B. H., Luis J. L., Ortiz-Quintana L., Recarte P. P., Arnau D. R., Aronsson L., Boden S., Fredriksson J., Isacsson E., Johansson I., Karlsson E., Lock C., Sandstrom A. -M., Konefal M. S., Andreasson C., Dahlstrom U., Hanas R., Lundqvist K., Windell L., Jansson I., Karlsson A. -K., Lindbladh B., Odenman I., Pettersson C., Sundberg F., Sundqvist M., Aronsson S., Bellman I., Bengtsson A. -B., Lyden G. -B., Nilsson N. -O., Soderblom M., Unt C., Augustsson M., Bengtsson M., Fors H., Helmrich A., Johansson T. O., Andersson A. -C., Boiard-Stomlid A., Hellgren G., Kallsholm H., Lindqvist J., Nilsson M., Nordwall M., Stromstedt C., Ahsberg C., Lindh A., Lindhe C., Samuelsson C., Wiik A., Edenwall H., Ljumgcrantz M., Persson I. -B., Strigard E., Svensson B. -L., Aman J., Breivik G. -E., Detlofsson I. -L., Kroon M., Sarnblad S., Johansson C., Ilvered R., Lundberg A., Akesson K., Beccarelli A., Gadient M., Rappold-Amrein C., Schoenle E., Daftary A., Damagro-Elias M. E., Gilmour C., Klein M. B., Lain C., Salerno D., Smith M. E., Vats K., Pfaff D. J., Malone P., Mansfield P., Munns M., Nickel K., Pompilio K., Siemion W., Taculad R., Van Horn K., Zdanadewic M., Chambliss C., Jones J., Sadler M., Tanner-Blasiar M., Bell C., Camper N., Devaskar S., Devaskar U., Horowitz H., Rogers L., Shannahan R., Silk K., Bermudez Z., Colon R., Frazer T., Martinez-Nieves B., Torres J., Vega J., Chan M., Cook S., Goland R., Greenberg E., Jules N., Montes J., Nelson M., Parra-Valencia Z., Schachner H., Softness B., Kiviniemi M., Suomenin R., Alexander A., Hyrckowian E., Nichol L., Trucco M., Karjalainen E., Louhio T., Sarnesto A., Valtonen E., Davydova B., Helander S., Hamalainen J., Harkonen T., Joutsjoki L., Kararic M., Latva-Koivisto M., Lonn E., Nurmi T., Ollila I., Rinkinen J., Ronkainen M., Tukiainen H., Cederlof A., Kiikeri M., Tsupari S., Cheng R., Bryant K., Chan Y., Maezawa Y., Paltser G., Rasavi R., Tsui H., Winer S., Wu P., Yantha J., Pediatrics, Knip M., Akerblom H.K., Altaji E., Becker D., Bruining J., Castano L., Danne T., De Beaufort C., Dosch H.-M., Dupre J., Fraser W.D., Howard N., Ilonen J., Konrad D., Kordonouri O., Krischer J.P., Lawson M.L., Ludvigsson J., Madacsy L., Mahon J.L., Ormisson A., Palmer J.P., Pozzilli P., Savilahti E., Serrano-Rios M., Songini M., Taback S., Vaarala O., White N.H., Virtanen S.M., Wasikowa R., Mandrup-Poulsen T., Arjas E., Lernmark A., Laara E., Schmidt B., Hyytinen M., Koski K., Koski M., Merentie K., Pajakkala E., Reunanen A., Salonen M., Terhonen T., Virkkunen S., Cuthbertson D., Gainer B., Hadley D., Malloy J., Nallamshetty L., Shanker L., Bradley B., Lough G., Fraser W., Sermer M., Taback S.P., Franciscus M., Nucci A., Palmer J., Alahuhta K., Barlund S., Korhonen T., Kovanen L., Lehtonen E., Niinisto S., Pekkala M., Sorkio S., Toivanen L., Vahatalo L., Uusitalo U., Ohman T., Bongiorno R., Catteau J., Fraser G., Lloyd M., Crock P., Giles M., Siech K., See D.W., Brown C., Craig M., Johnston A., Bere L.J., Clarson C.L., Jenner M., McManus R., Renato N., Lovell M., Higo D., Kent N., Kwan J., Marshall C., Metzger D., Chanoine J.-P., Stewart L., Thompson D., Edwards A., Lange I., Mercer J., Pacaud D., Josephine H., Schwarz W., Stephure D.K., Boer J., Chatur T., Chick C., Couch B., Demianczuk N., Girgis R., Marks S., Ryan E., Thompson M., Dean H.J., Grant L., Hamelin K., LaForte J., Murphy L., Catte D., Schneider C., Sellers E.A.C., Woo V., Boland A., Clark H.D., Cooper T., Gruslin A., Karovitch A., Keely E., Malcolm J.C., Sauro V., Tawagi G.F., Andrighetti S., Arnold G., Barrett J., Blumer I., Daneman D., Donat D., Ehrlich R., Feig D., Gottesman I., Gysler M., Karkanis S., Kenshole A., Knight B., Lackie E., Lewis V., Martin M.J., Maxwell C., Oliver G., Panchum P., Shilletto N., Simone A., Skidmore M., Turrini T., Wong S., Allen C., Belanger L., Bouchard I., Ferland S., Frenette L., Garrido-Russo M., Leblanc M., Imbeault J., Morin V., Olivier G., Weisnagell J., Costain G., Dornan J., Heath K., MacSween M.-C., McGibbon A., Ramsay C., Sanderson F., Sanderson S., Benabdesselam L., Gonthier M., Huot C., Thibeault M., Laforte D., Legault L., Perron P., Armson A., Canning P., Cummings E.A., Ivanko V., McLeod L., Mokashi A., Scott K., Bridger T., Crane J., Crummell C., Curtis J.C., Dawson C., Joyce C., Newhook L.A., Newman S., Druken E., Begum-Hasan J., Breen A., Houlden R., Woods M., Carrson G., Kelly S., Martel M.J., Penner M., Sankaran K., Hardy-Brown K., King N., White R.A., Park M., Popkin J., Robson L., Coles K., Al Taji E., Cerna M., Cerny M., Francova H., Hainerova I., Kothankova H., Koukalova R., Krakorova V., Mendlova P., Sitova R., Stechova K., Vavrinec J., Vosahlo J., Zlatohlavkova B., Brazdova L., Faksova P., Gregorova D., Kantor L., Malkova K., Venhacova J., Venhacova P., Cipra A., Skvor J., Budejovice C., Tomsikova Z., Botkova-Krauseova H., Mockova A., Paterova P., Gogelova P., Kandrnalova J., Einberg U., Jakovlev U., Posiadlo S., Rannaste E., Raukas R., Riikjarv M.-A., Valla K., Astover V., Kirss A., Retpap J., Taht E., Tillmann V., Vahtra S., Heikkila M., Hirvasniemi M., Luopajarvi K., Johansson S., Kleemola P., Laukkanen E., Parkkola A., Pigg H.-M., Puttonen H., Renlund M., Salonen K., Suomalainen H., Tenkula T., Teramo K., Jarvenpaa A.-L., Hamalainen A.-M., Jussila R., Kiiveri S., Haavisto H., Holopainen S., Kupiainen H., Leeve T., Lumme K., Nironen T., Tenhola S., Tiilikainen T., Keinonen H., Lautala P., Salonen P., Vesanto M., Aspholm A.S., Asunta P., Ikavalko H., Jason E., Jaminki S., Kekki P., Koskinen M., Lehtimaki S., Lahde J., Makela M., Peltoniemi S., Poutiainen L., Ranta K., Salonsaari T., Sarviharju-Tujula S.-L., Selvenius J., Siljander H., Haanpaa P.-L., Holm C., Juutilainen A., Jarvelainen V., Kangaskolkka-Keskilohko A.-M., Laino E., Marjamaki L., Suominen E., Ylitalo S., Hokkanen M., Lounamaa R., Matikainen M., Nuuja A., Paalanen I., Puupponen A.R., Salo-Edwards H., Alanne S., Kultti T., Linjama H., Muhonen K., Vaaraniemi M., Talvitie T., Backman M., Hanhijarvi R., Koivula P., Lindstrom K., Martikainen A., Nurmi P., Bjork A., Huopio H., Komulainen J., Lehtomaki S., Muikku E., Pesola J., Sankilampi U., Arkkola T., Hekkala A., Jurvakainen S., Koivikko M.-L., Kahonen M., Leinonen E., Mykkanen T., Pohjola H., Riikonen K., Niittyvuopio A., Stenius A., Tapanainen P., Veijola R., Alar A., Jovio S., Korpela P., Makinen E., Hietanen L., Kivisto J., Kaar M.-L., Lehtimaki P., Mustila T., Popov E., Saatela S., Taittonen L., Ahtiainen K., Laaksonen N., Luoto M., Viitala J., Virransalo R., Nykanen P., Paajanen S., Parkkinen S., Pyrhonen H., Sarkka T., Aschemeier B., Bektas S., Biester T., Datz N., Deiss D., Fath M., Lupke K., Muller B., Nestoris C., Rothes S., Sadeghian E., Semler K., Arato A., Krikovszky D., Nobilis A., Szenasi J., Benevento D., Anguissola G.B., Biagioni M., Bizzarri C., Cherubini V., Ferrito L., Giordano C., Giorgetti C., Khazrai Y.M., Kyanvash S., Maddaloni E., Napoli A., Piergiovanni F., Pitocco D., Suraci T., Tabacco G., Valente L., Visalli N., Carboni M.B., Cavallo R., Cau V., Isola C., Ledda A., Loddo M., Mannu C., Pettinau M., Pisano S., Porceddu M., Putzu C., Rita A., Peters D., Schierloh U., Bisschoff M., Blonk L., Lappenschaar T., Manai B., Seesink M., Sperling-Conrad M., Verhagen M., Zoethout J.A., Basiak A., Chalas M., Chesiak M., Gramza A., Iwankiewicz J., Sieradzan E., Wikiera B., Ciechanowska M., Dziatkowiak H., Futona B., Gorska A., Glowacka-Wony M., Kaim I., Klich B., Starzyk J., Wolanin M., Tokarska L., Chucherco D., Deja G., Firek-Pedras M., Jarosz-Chobot P., Kalina M., Kutrowska-Adamusiak K., Minkina-Pedras M., Muchaka-Bianga M., Bodalski J., Mlynarski W., Szadkowska A., Cieslak A., Cypryk K., Dziatosz K., Jastzebowska J., Krysiak A., Szymanska U., Wilcznski J., Zawodniak-Szalapska M., Aguay A., Bilbao J.R., Chueca M., Cortazar A., Echarte G., Frutos T.G., Jimenez P., Martul P., Moreno A., Oyarzabal M., Rica I., Salgado Y., Martinez-Larrad M.T., Hawkins F.G., Hernandez R., Herranz L., Pallardo L.F., Deibarra L.S., Fernandez B.H., Luis J.L., Ortiz-Quintana L., Recarte P.P., Arnau D.R., Aronsson L., Boden S., Fredriksson J., Isacsson E., Johansson I., Karlsson E., Lock C., Sandstrom A.-M., Konefal M.S., Andreasson C., Dahlstrom U., Hanas R., Lundqvist K., Windell L., Jansson I., Karlsson A.-K., Lindbladh B., Odenman I., Pettersson C., Sundberg F., Sundqvist M., Aronsson S., Bellman I., Bengtsson A.-B., Lyden G.-B., Nilsson N.-O., Soderblom M., Unt C., Augustsson M., Bengtsson M., Fors H., Helmrich A., Johansson T.O., Andersson A.-C., Boiard-Stomlid A., Hellgren G., Kallsholm H., Lindqvist J., Nilsson M., Nordwall M., Stromstedt C., Ahsberg C., Lindh A., Lindhe C., Samuelsson C., Wiik A., Edenwall H., Ljumgcrantz M., Persson I.-B., Strigard E., Svensson B.-L., Aman J., Breivik G.-E., Detlofsson I.-L., Kroon M., Sarnblad S., Johansson C., Ilvered R., Lundberg A., Akesson K., Beccarelli A., Gadient M., Rappold-Amrein C., Schoenle E., Daftary A., Damagro-Elias M.E., Gilmour C., Klein M.B., Lain C., Salerno D., Smith M.E., Vats K., Pfaff D.J., Malone P., Mansfield P., Munns M., Nickel K., Pompilio K., Siemion W., Taculad R., Van Horn K., Zdanadewic M., Chambliss C., Jones J., Sadler M., Tanner-Blasiar M., Bell C., Camper N., Devaskar S., Devaskar U., Horowitz H., Rogers L., Shannahan R., Silk K., Bermudez Z., Colon R., Frazer T., Martinez-Nieves B., Torres J., Vega J., Chan M., Cook S., Goland R., Greenberg E., Jules N., Montes J., Nelson M., Parra-Valencia Z., Schachner H., Softness B., Kiviniemi M., Suomenin R., Alexander A., Hyrckowian E., Nichol L., Trucco M., Karjalainen E., Louhio T., Sarnesto A., Valtonen E., Davydova B., Helander S., Hamalainen J., Harkonen T., Joutsjoki L., Kararic M., Latva-Koivisto M., Lonn E., Nurmi T., Ollila I., Rinkinen J., Ronkainen M., Tukiainen H., Cederlof A., Kiikeri M., Tsupari S., Cheng R., Bryant K., Chan Y., Maezawa Y., Paltser G., Rasavi R., Tsui H., Winer S., Wu P., Yantha J., University of Zurich, and Knip, Mikael

Subjects
Male, Risk, medicine.medical_specialty, Casein, Breastfeeding, 030209 endocrinology & metabolism, 610 Medicine & health, 2700 General Medicine, Endocrinology and Diabetes, Disease-Free Survival, law.invention, Follow-Up Studie, Nutrition Policy, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, SDG 3 - Good Health and Well-being, law, Internal medicine, Diabetes mellitus, medicine, Humans, Cumulative incidence, 030212 general & internal medicine, Child, Infant Nutritional Physiological Phenomena, Original Investigation, 2. Zero hunger, Type 1 diabetes, business.industry, Hazard ratio, Absolute risk reduction, Infant, Newborn, Caseins, General Medicine, ta3121, medicine.disease, Infant Formula, 3. Good health, Diabetes Mellitus, Type 1, Infant formula, 10036 Medical Clinic, Endokrinologi och diabetes, Female, business, Human, Follow-Up Studies
Abstract

IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes. Funding Agencies|Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [HD040364, HD042444, HD051997]; Canadian Institutes of Health Research; Commission of the European Communities [QLK1-2002-00372]; European Foundation for the Study of Diabates/JDRF/Novo Nordisk; Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) [250114]; Dutch Diabetes Research Foundation; Finnish Diabetes Research Foundation; JDRF

Published
2018

9. Muuttuva afrikkalainen parantaminen ja siirtomaavalta:kohtaamiset, vuorovaikutukset ja kamppailut eteläisessä Afrikassa

Author

Hokkanen, M. (Markku)

Abstract

Tiivistelmä Tässä luvussa käsitellään afrikkalaisen parantamisen ja siirtomaavallan suhteita eteläisessä Afrikassa osana laajempaa parantamisen ja kolonialismin historiaa. Teemoina ovat kamppailut vallasta, määrittelyistä ja käytänteistä, afrikkalaisen parannuskulttuurin monimuotoisuus, joustavuus ja hybridisaatio kolonialistisissa konteksteissa, ja lääkinnän, uskonnon sekä magian ongelmallinen rajanveto oikeudessa, kirkoissa ja kolonialistisessa tiedontuotannossa. Maantieteellisesti luku keskittyy erityisesti britti-imperiumiin kuuluneille alueille (Etelä-Afrikasta Sambiaan ja Malawiin). Portugalin imperiumiin kuuluneet Mosambik ja Angola jäävät käsittelyssä vähemmälle. Todettakoon kuitenkin, että varhaisimmat kohtaamiset afrikkalaisten ja eurooppalaisten välillä, samoin kuin ensimmäiset parannukselliset vuorovaikutustilanteet eteläisessä Afrikassa, tapahtuivat juuri Angolan ja Mosambikin rannikoilla, jonne portugalilaiset perustivat pieniä tukikohtia 1500-luvulta alkaen. Monet portugalilaiset hakeutuivat näiden tukikohtien ympäristössä afrikkalaisten parantajien hoidettaviksi.

Published
2017

10. Ennallistettujen metsien seuranta

Author

Hokkanen, M., Kotiaho, Janne Sakari, Lehtonen, H., Päivinen, J., Similä, M., Tukia, H., Hokkanen, M., Alanen, A., and Aapala, K.

Subjects
monimuotoisuus, ennallistaminen
Abstract

peerReviewed

Published
2005

11. The Aromatase Gene CYP19A1: Several Genetic and Functional Lines of Evidence Supporting a Role in Reading, Speech and Language

Author

Anthoni, H, Sucheston, LE, Lewis, BA, Tapia-Paez, I, Fan, X, Zucchelli, M, Taipale, M, Stein, CM, Hokkanen, M-E, Castren, E, Pennington, BF, Smith, SD, Olson, RK, Tomblin, JB, Schulte-Koerne, G, Noethen, M, Schumacher, J, Mueller-Myhsok, B, Hoffmann, P, Gilger, JW, Hynd, GW, Nopola-Hemmi, J, Leppanen, PHT, Lyytinen, H, Schoumans, J, Nordenskjold, M, Spencer, J, Stanic, D, Boon, WC, Simpson, E, Makela, S, Gustafsson, J-A, Peyrard-Janvid, M, Iyengar, S, Kere, J, Anthoni, H, Sucheston, LE, Lewis, BA, Tapia-Paez, I, Fan, X, Zucchelli, M, Taipale, M, Stein, CM, Hokkanen, M-E, Castren, E, Pennington, BF, Smith, SD, Olson, RK, Tomblin, JB, Schulte-Koerne, G, Noethen, M, Schumacher, J, Mueller-Myhsok, B, Hoffmann, P, Gilger, JW, Hynd, GW, Nopola-Hemmi, J, Leppanen, PHT, Lyytinen, H, Schoumans, J, Nordenskjold, M, Spencer, J, Stanic, D, Boon, WC, Simpson, E, Makela, S, Gustafsson, J-A, Peyrard-Janvid, M, Iyengar, S, and Kere, J

Abstract

Inspired by the localization, on 15q21.2 of the CYP19A1 gene in the linkage region of speech and language disorders, and a rare translocation in a dyslexic individual that was brought to our attention, we conducted a series of studies on the properties of CYP19A1 as a candidate gene for dyslexia and related conditions. The aromatase enzyme is a member of the cytochrome P450 super family, and it serves several key functions: it catalyzes the conversion of androgens into estrogens; during early mammalian development it controls the differentiation of specific brain areas (e.g. local estrogen synthesis in the hippocampus regulates synaptic plasticity and axonal growth); it is involved in sexual differentiation of the brain; and in songbirds and teleost fishes, it regulates vocalization. Our results suggest that variations in CYP19A1 are associated with dyslexia as a categorical trait and with quantitative measures of language and speech, such as reading, vocabulary, phonological processing and oral motor skills. Variations near the vicinity of its brain promoter region altered transcription factor binding, suggesting a regulatory role in CYP19A1 expression. CYP19A1 expression in human brain correlated with the expression of dyslexia susceptibility genes such as DYX1C1 and ROBO1. Aromatase-deficient mice displayed increased cortical neuronal density and occasional cortical heterotopias, also observed in Robo1-/- mice and human dyslexic brains, respectively. An aromatase inhibitor reduced dendritic growth in cultured rat neurons. From this broad set of evidence, we propose CYP19A1 as a candidate gene for human cognitive functions implicated in reading, speech and language.

Published
2012

15. Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ -population-based follow-up of two cluster-randomized trials.

Author

Lehtinen M, Gray P, Luostarinen T, Eriksson T, Apter D, Bly A, Harjula K, Heikkilä K, Hokkanen M, Kuortti M, Nieminen P, Nummela M, Paavonen J, Palmroth J, Petäjä T, Pimenoff VN, Pukkala E, and Dillner J

Subjects
Humans, Female, Adolescent, Follow-Up Studies, Young Adult, Finland, Adult, Treatment Outcome, Vaccination, Uterine Cervical Dysplasia prevention & control, Uterine Cervical Dysplasia virology, Papillomavirus Vaccines administration & dosage, Papillomavirus Vaccines immunology, Papillomavirus Infections prevention & control, Papillomavirus Infections virology, Uterine Cervical Neoplasms prevention & control, Uterine Cervical Neoplasms virology, Adenocarcinoma in Situ prevention & control, Adenocarcinoma in Situ virology
Abstract

Introduction: We report head-to-head comparison of the bivalent and quadrivalent HPV vaccine efficacies against immediate precursors of cervical cancer from 15 years' country-wide cancer registry follow-up of phase III trial cohorts and an age-aligned cohort of unvaccinated women., Methods: These individually and/or clusterrandomized cohorts of HPV6/11/16/18- and HPV16/18-vaccinated and unvaccinated women were enrolled, respectively, in 2002, 2004, and 2003/2005. The trial cohorts comprised initially 16- to 17-year-old HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866) and HPV16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2,465), and 16,526 initially 16- to 19-year-old unvaccinated controls. After active 4-year clinical follow-up, passive, country-wide Finnish Cancer Registry (FCR) follow-up for cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) was based on consented use of unique personal identifiers and started 6 months after the end of the FUTURE II and PATRICIA trials in 2007 and 2009, and ended at the end of 2019. The follow-up with altogether 229,020 follow-up years was age-aligned to ensure that similarly aged cohorts were passively followed up for 15 years post=vaccination for the intention-to-treat analyses of vaccine efficacy., Results: Overall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, during the FCR-based follow-up. In the unvaccinated cohort, we identified 281 CIN3 cases, 20 AIS cases, and 13 cases with invasive cervical cancer. Vaccine efficacies against CIN3+ were 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals., Discussion: Long-term follow-up of randomized, initially adolescent HPV-vaccinated and unvaccinated cohorts shows, in this head-to-head setting, that the bivalent and quadrivalent HPV vaccines are equally effective against immediate precursors of cervical cancer., Competing Interests: DA, JD, ML, and JPaa have received grants for their HPV vaccination studies from Merck&Co. Inc. DA, JD, ML, and JPaa and GSK Biologicals DA, ML, JPaa. 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 © 2024 Lehtinen, Gray, Luostarinen, Eriksson, Apter, Bly, Harjula, Heikkilä, Hokkanen, Kuortti, Nieminen, Nummela, Paavonen, Palmroth, Petäjä, Pimenoff, Pukkala and Dillner.)

Published
2024
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16. The quality of life of frequently vs. infrequently screened HPV vaccinated women.

Author

Taavela K, Eriksson T, Huhtala H, Bly A, Harjula K, Heikkilä K, Hokkanen M, Nummela M, Kotaniemi-Talonen L, Lehtinen M, and Louvanto K

Subjects
Female, Humans, Human Papillomavirus Viruses, Quality of Life psychology, Human papillomavirus 16, Human papillomavirus 18, Early Detection of Cancer methods, Papillomavirus Infections prevention & control, Papillomavirus Infections diagnosis, Uterine Cervical Neoplasms prevention & control, Uterine Cervical Neoplasms diagnosis
Abstract

Purpose: Cervical lesions caused by human papillomavirus (HPV) are related to decreased quality of life (QoL) of women. Also, cervical cancer (CC) screening can cause psychological adverse effects. It has been assumed that by decreasing the HPV-related disease burden, HPV vaccinations would increase the QoL. This study compares the effect of CC screening on QoL of HPV vaccinated women in two different screening protocols., Methods: A total of 753 HPV16/18 vaccinated women were randomized to frequent (22/25/28 years of age) and infrequent (28 years of age) CC screening arms. QoL questionnaires (EQ VAS, RAND 36, amended CECA 10) were sent at the age of 28., Results: Median EQ VAS scores were 80 (Q 1 -Q 3 75-90) in both screening arms. Mean RAND 36 scores of frequently and infrequently screened women were 78.13/81.64 in Physical role functioning domain and, respectively, 77.93/80.18 in Pain, 69.10/69.12 in General Health, 54.67/53.61 in Energy, 83.72/85.11 in Social functioning, 69.53/69.68 in Emotional role functioning, and 68.16/69.29 in Emotional well-being domain. Among women with a self-reported history of Pap cytology abnormalities, overall mean scores of amended CECA 10 were 69.52/72.07, and among women with a self-reported history of genital warts, 60.09/66.73, respectively., Conclusion: There was no significant difference in the QoL of HPV vaccinated women between the two CC screening arms. Women were mostly satisfied with the screening experience despite the screening frequency. This information is important for the future screening program planning as we need to reach the best possible balance with screening benefits and harms., Trial Registration Number: NCT02149030, date of registration 29/5/2014., (© 2024. The Author(s).)

Published
2024
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17. Association of Chlamydia trachomatis infection with cervical atypia in adolescent women with short-term or long-term use of oral contraceptives: a longitudinal study in HPV vaccinated women.

Author

Adhikari I, Eriksson T, Harjula K, Hokkanen M, Apter D, Nieminen P, Luostarinen T, and Lehtinen M

Subjects
Adolescent, Adult, Chlamydia trachomatis, Contraceptives, Oral, Female, Human papillomavirus 16, Human papillomavirus 18, Humans, Longitudinal Studies, Young Adult, Chlamydia Infections complications, Chlamydia Infections epidemiology, Papillomavirus Infections complications, Papillomavirus Infections epidemiology, Papillomavirus Infections prevention & control, Squamous Intraepithelial Lesions
Abstract

Objective: We assessed the relationship between Chlamydia trachomatis infection, duration of oral contraceptive (OC) use and cervical atypia among young adult Finnish women., Design: A longitudinal study., Setting and Participants: Women who were included in this study participated in a community-randomised trial on the effectiveness of human papillomavirus (HPV) vaccination and C. trachomatis screening at ages 18.5 and 22 years in Finland. They completed questionnaires on both visits about sexual behaviours. The cytology test results at age 18.5 and 22 years were also available for those women. The total number of participants in this study at 18.5 years of age were 11 701 and at 22 years of age were 6618., Main Outcome Measure: ORs with 95% CIs using univariable and multivariable logistic regression were used to assess the association between C. trachomatis infection, duration of OC and squamous intraepithelial lesions (SIL)., Results: There were 940 cytological SIL cases at the first screening visit and 129 cytological SIL cases at the second screening visit. Among the 22 years old, more than fourfold adjusted risk of SIL was associated with C. trachomatis positivity. The HPV16/18, condom use, smoking and number of sexual partners adjusted joint effect of prolonged OC use and C. trachomatis was significantly increased (OR 4.7, 95% CI 1.7 to 12.8) in the 22-year-old women. This observed joint effect was 1.6 times higher than expected on a multiplicative scale. On additive scale, the observed relative excess risk from interaction was 1.8., Conclusion: The risk of SIL in HPV vaccinated women is significantly increased if they are C. trachomatis positive and have used OC for 5 or more years. The biological basis may be lack of condom facilitated protection against sexually transmitted diseases., Trial Registration Number: NCT00534638., Competing Interests: Competing interests: ML and DA have grants from Merck & Co Inc and GSK for HPV vaccination trials through their employers (Tampere University, ML; Family Federation Finland, DA)., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2022
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18. Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial.

Author

Lehtinen M, Lagheden C, Luostarinen T, Eriksson T, Apter D, Bly A, Gray P, Harjula K, Heikkilä K, Hokkanen M, Karttunen H, Kuortti M, Nieminen P, Nummela M, Paavonen J, Palmroth J, Petäjä T, Pukkala E, Soderlund-Strand A, Veivo U, and Dillner J

Subjects
Adolescent, Adult, Female, Follow-Up Studies, Human papillomavirus 16, Human papillomavirus 18, Humans, Vaccine Efficacy, Young Adult, Papillomavirus Infections diagnosis, Papillomavirus Vaccines, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Dysplasia diagnosis
Abstract

Background: Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of randomised cohorts that vaccination provides HPV-type-specific protection against invasive cancer., Methods: Individually and/or cluster randomised cohorts of HPV-vaccinated and non-vaccinated women were enrolled in 2002-2005. HPV vaccine cohorts comprised originally 16-17 year-old HPV 16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2465) and HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866). Altogether, 3341 vaccines were followed by the Finnish Cancer Registry in the same way as 16 526 non-HPV-vaccinated controls. The control cohort stemmed from 15 665 originally 18-19 years-old women enrolled in 2003 (6499) or 2005 (9166) and 861 placebo recipients of the FUTURE II trial. The follow-up started 6 months after the clinical trials in 2007 and 2009 and ended in 2019. It was age aligned for the cohorts., Findings: During a follow-up time of up to 11 years, we identified 17 HPV-positive invasive cancer cases (14 cervical cancers, 1 vaginal cancer, 1 vulvar cancer and 1 tongue cancer) in the non-HPV-vaccinated cohorts and no cases in the HPV-vaccinated cohorts. HPV typing of diagnostic tumour blocks found HPV16 in nine cervical cancer cases, HPV18, HPV33 and HPV52 each in two cases and HPV45 in one cervical cancer case. The vaginal, vulvar and tongue cancer cases were, respectively, positive for HPV16, HPV52/66 and HPV213. Intention-to-treat vaccine efficacy against all HPV-positive cancers was 100% (95% CI 2 to 100, p<0.05)., Interpretation: Vaccination is effective against invasive HPV-positive cancer., Trial Registration Number: NCT00122681, Post-results; NCT00169494, Post-results; NCT00092534, Post-results., Competing Interests: Competing interests: We declare that ML, DA, JD and JPaa have received grants from Merck & Co. Inc. and/or from the GSK group of companies through their respective employers. GSK Biologicals SA was provided the opportunity to review this manuscript but the authors are solely responsible for final content and interpretation., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2021
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19. Effectiveness of various human papillomavirus vaccination strategies: A community randomized trial in Finland.

Author

Lehtinen M, Apter D, Eriksson T, Harjula K, Hokkanen M, Natunen K, Nieminen P, Paavonen J, Palmroth J, Petäjä T, Pukkala E, Vänskä S, Cheuvart B, Soila M, Bi D, and Struyf F

Subjects
Adolescent, Child, Female, Finland epidemiology, Humans, Male, Papillomavirus Infections epidemiology, Prevalence, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Mass Vaccination methods, Papillomavirus Infections prevention & control, Papillomavirus Vaccines, Uterine Cervical Neoplasms prevention & control, Uterine Cervical Neoplasms virology
Abstract

Introduction: We conducted a community-randomized trial (NCTBLINDED) in Finland to assess gender-neutral and girls-only vaccination strategies with the AS04-adjuvanted human papillomavirus (HPV)-16/18 (AS04-HPV-16/18)vaccine., Methods: Girls and boys (12-15 years) were invited. We randomized 33 communities (1:1:1 ratio): Arm A: 90% of randomly selected girls and boys received AS04-HPV-16/18 vaccine and 10% received hepatitis B vaccine (HBV); Arm B: 90% of randomly selected girls received AS04-HPV-16/18 vaccine, 10% of girls received HBV, and all boys received HBV; Arm C: all participants received HBV. Effectiveness measurements against prevalence of HPV-16/18 cervical infection were estimated in girls at 18.5 years. The main measures were: (1) overall effectiveness comparing Arms A or B, regardless of vaccination status, vs Arm C; (2) total effectiveness comparing AS04-HPV-16/18 vaccinated girls in pooled Arms A/B vs Arm C; (3) indirect effectiveness (herd effect) comparing girls receiving HBV or unvaccinated in Arm A vs Arm C. Co-primary objectives were overall effectiveness following gender-neutral or girls-only vaccination., Results: Of 80,272 adolescents invited, 34,412 were enrolled. Overall effectiveness was 23.8% (95% confidence interval: -19.0, 51.1; P = 0.232) with gender-neutral vaccination. Following girls-only vaccination, overall effectiveness was 49.6% (20.1, 68.2; P = 0.004). Total effectiveness was over 90% regardless of vaccination strategy. No herd effect was found. Immunogenicity of the AS04-HPV-16/18 vaccine was high in both sexes., Conclusions: This study illustrates the difficulty in conducting community randomized trials. It is not plausible that vaccinating boys would reduce overall effectiveness, and the apparent lack of herd effect was unexpected given findings from other studies. This analysis was likely confounded by several factors but confirms the vaccine's high total effectiveness as in clinical trials., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Published
2021
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20. The effect of postoperative complications on health-related quality of life and survival 12 years after coronary artery bypass grafting - a prospective cohort study.

Author

Hokkanen M, Huhtala H, Laurikka J, and Järvinen O

Subjects
Aged, Cerebrovascular Disorders etiology, Heart Diseases etiology, Heart Diseases mortality, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Prospective Studies, Coronary Artery Bypass adverse effects, Postoperative Complications etiology, Quality of Life
Abstract

Background: Despite the steady improvements in survival and operative safety, postoperative complications still remain a significant cause of morbidity and mortality after coronary artery bypass grafting (CABG). However, less is known on the impact of postoperative complications on health-related quality of life (QoL). The main objective of our study was to investigate the impact of postoperative complications on long-term QoL and survival after CABG surgery., Methods: Data of 508 patients, who underwent isolated CABG was prospectively collected. The RAND-36 Health Survey (RAND-36) was used to evaluate patients' QoL status preoperatively, 1 year and 12 years after the surgery. Predefined postoperative complications were reported during primary and secondary hospital stay. QoL and survival analysis were performed primarily on three patient groups: patients with and without complications and patients with major adverse cardiac and cerebrovascular events (MACCE)., Results: In total 205(40%) of 508 patients had at least one postoperative complication and 73 (14%) experienced MACCE. Patients' thirty-day, 1-year and 10-year survival rates were, 99, 98, 84% without complications, 97, 95, 72% with complications, and 90, 89, 64% with MACCE, respectively (log-rank p < 0.001). Patients without complications showed significant(p < 0.05) improvements in seven and patients with complications in five out of eight RAND-36 QoL dimensions. All patient groups showed significant improvements in RAND-36 summary scores compared with preoperative values. Patients with complications and especially with MACCE had more profound decline in their RAND-36 summary scores while patients without complications maintained their health status best., Conclusions: Despite the constant deterioration, both patients with and without complications showed improvements even 12 years after CABG compared with preoperative state. Postoperative complications and especially MACCE were associated with impaired long-term QoL.

Published
2021
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21. Preterm birth rate after bivalent HPV vaccination: Registry-based follow-up of a randomized clinical trial.

Author

Kalliala I, Eriksson T, Aro K, Hokkanen M, Lehtinen M, Gissler M, and Nieminen P

Subjects
Female, Finland epidemiology, Follow-Up Studies, Human papillomavirus 16, Human papillomavirus 18, Humans, Infant, Newborn, Pregnancy, Registries, Vaccination, Papillomavirus Infections epidemiology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines, Premature Birth epidemiology, Premature Birth prevention & control
Abstract

A registry-based follow-up of pregnancy data until the end of 2014 was conducted based on a community-randomized trial to assess human papillomavirus (HPV) vaccination strategies and a reference cohort from the same community with no intervention. Our objective was to determine whether prophylactic HPV vaccination (three doses of Cervarix® (AS04-HPV-16/18)-vaccine) affects preterm birth (PTB) rates. All identified 80,272 residents in 1992-95 birth cohorts in Finland were eligible for the trial and 20,513 of 39,420 (51.9%) females consented to participate. The final study population consisted of age-aligned 6226 HPV16/18 vaccinated females and 1770 HBV vaccinated (Engerix® B, hepatitis B-virus vaccine) females that did not receive HPV vaccine at the age of 18 from the 1992-93 birth cohorts, and 19,849 females from the 1990-91 non-vaccinated reference birth cohorts. We compared the rates of preterm (22 + 0-36 + 6 pregnancy weeks) and early preterm (22 + 0-31 + 6) per term (at least 37 + 0) singleton births among the HPV- and non-HPV-vaccinated women, using nationwide Medical Birth Registry data. We observed 409 singleton first pregnancies lasting at least 22 + 0 weeks among 6226 HPV-vaccinated and 1923 among 21,619 non-HPV-vaccinated women. In the first pregnancy the PTB rate was 13/409 (3.2%) among the HPV-vaccinated and 98/1923 (5.1%) among the non-HPV-vaccinated (OR 0.61, 95% CI 0.34-1.09). Early preterm birth rate was 0/409 (0%) in the HPV-vaccinated women and 20/1923 (1.0%) in the non-HPV-vaccinated women (p = 0.04). PTB rate, especially early PTB rate, was lower among the HPV-vaccinated women. Reduction of PTB incidence after prophylactic HPV vaccination would lead to public health benefits globally. Trial Registration:NCT00534638., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2021
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22. Baseline findings and safety of infrequent vs. frequent screening of human papillomavirus vaccinated women.

Author

Louvanto K, Eriksson T, Gray P, Apter D, Baussano I, Bly A, Harjula K, Heikkilä K, Hokkanen M, Huhtinen L, Ikonen M, Karttunen H, Nummela M, Söderlund-Strand A, Veivo U, Dillner J, Elfstöm M, Nieminen P, and Lehtinen M

Subjects
Adolescent, Adult, Early Detection of Cancer economics, Female, Humans, Incidence, Pregnancy, Prevalence, Uterine Cervical Neoplasms diagnosis, Vaccination statistics & numerical data, Young Adult, Early Detection of Cancer statistics & numerical data, Papillomavirus Infections prevention & control, Papillomavirus Vaccines therapeutic use, Uterine Cervical Neoplasms epidemiology
Abstract

Less frequent cervical cancer screening in human papillomavirus (HPV) vaccinated birth cohorts could produce considerable savings without increasing cervical cancer incidence and loss of life-years. We report here the baseline findings and interim results of safety and accuracy of infrequent screening among HPV16/18 vaccinated females. The entire 1992-1994 birth-cohorts (30,139 females) were invited to a community-randomized HPV16/18-vaccination trial. A total of 9,482 female trial participants received HPV16/18-vaccination in 2007-2009 at age of 13-15. At age 22, 4,273 (45%) of these females consented to attend a randomized trial on frequent (ages 22/25/28; Arm 1: 2,073 females) vs. infrequent screening (age 28; Arm 2: 2,200 females) in 2014-2017. Females (1,329), who had got HPV16/18 vaccination at age 18 comprised the safety Arm 3. Baseline prevalence and incidence of HPV16/18 and other high-risk HPV types were: 0.5% (53/1,000 follow-up years, 10 4 ) and 25% (2,530/10 4 ) in the frequently screened Arm 1; 0.2% (23/10 4 ) and 24% (2,413/10 4 ) in the infrequently screened Arm 2; and 3.1% (304/10 4 ) and 23% (2,284/10 4 ) in the safety Arm 3. Corresponding prevalence of HSIL/ASC-H and of any abnormal cytological findings were: 0.3 and 4.2% (Arm 1), 0.4 and 5.3% (Arm 2) and 0.3 and 4.7% (Arm 3). Equally rare HSIL/CIN3 findings in the infrequently screened safety Arm A3 (0.4%) and in the frequently screened Arm 1 (0.4%) indicate no safety concerns on infrequent screening despite the up to 10 times higher HPV16/18 baseline prevalence and incidence in the former., (© 2019 UICC.)

Published
2020
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23. Effectiveness of the AS04-adjuvanted HPV-16/18 vaccine in reducing oropharyngeal HPV infections in young females-Results from a community-randomized trial.

Author

Lehtinen M, Apter D, Eriksson T, Harjula K, Hokkanen M, Lehtinen T, Natunen K, Damaso S, Soila M, Bi D, and Struyf F

Subjects
Adolescent, Adult, Aluminum Hydroxide administration & dosage, Female, Finland epidemiology, Humans, Lipid A administration & dosage, Lipid A analogs & derivatives, Oropharyngeal Neoplasms epidemiology, Oropharyngeal Neoplasms immunology, Oropharyngeal Neoplasms prevention & control, Oropharyngeal Neoplasms virology, Oropharynx immunology, Papillomavirus Infections immunology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines immunology, Pharyngeal Diseases immunology, Pharyngeal Diseases prevention & control, Pharyngeal Diseases virology, Seroepidemiologic Studies, Young Adult, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Oropharynx virology, Papillomavirus Infections epidemiology, Papillomavirus Vaccines administration & dosage, Pharyngeal Diseases epidemiology
Abstract

We studied effectiveness of the AS04-adjuvanted HPV-16/18 (AS04-HPV-16/18) vaccine against human papillomavirus (HPV) oropharyngeal infections associated with the increase of head/neck cancers in western countries. All 38,631 resident adolescents from 1994 to 1995 birth cohorts of 33 Finnish communities were invited in this community-randomized trial (NCT00534638). During 2008-2009, 11,275 girls and 6,129 boys were enrolled in three arms of 11 communities each. In Arm A, 90% of vaccinated girls/boys, and in Arm B, 90% of vaccinated girls received AS04-HPV-16/18 vaccine. Other Arm A/B and all Arm C vaccinated participants received control vaccine. All Arm A participants and Arm B female participants were blinded to vaccine allocation. Oropharyngeal samples were analyzed from 4,871 18.5-year-old females who attended follow-up visit 3-6 years postvaccination. HPV DNA prevalence was determined by SPF-10 LiPA and Multiplex type-specific PCR. Total vaccine effectiveness (VE) was defined as relative reduction of oropharyngeal HPV prevalence in pooled Arms A/B HPV-vaccinated females vs. all Arm C females. VE against oropharyngeal HPV-16/18, HPV-31/45 and HPV-31/33/45 infections were 82.4% (95% confidence intervals [CI]: 47.3-94.1), 75.3% (95%CI: 12.7-93.0) and 69.9% (95% CI: 29.6-87.1), respectively. In conclusion, the AS04-HPV-16/18 vaccine showed effectiveness against vaccine and nonvaccine HPV-types oropharyngeal infections in adolescent females up to 6 years postvaccination., (© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Published
2020
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24. Safety of the AS04-adjuvanted human papillomavirus (HPV)-16/18 vaccine in adolescents aged 12-15 years: end-of-study results from a community-randomized study up to 6.5 years.

Author

Bi D, Apter D, Eriksson T, Hokkanen M, Zima J, Damaso S, Soila M, Dubin G, Lehtinen M, and Struyf F

Subjects
Adjuvants, Immunologic, Adolescent, Female, Finland epidemiology, Human papillomavirus 16, Human papillomavirus 18, Humans, Male, Pregnancy, Alphapapillomavirus, Papillomavirus Infections epidemiology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines adverse effects, Uterine Cervical Neoplasms
Abstract

This manuscript discloses end-of-study safety data of a community-randomized controlled trial in Finland (NCT00534638), assessing the effectiveness of two vaccination strategies (gender-neutral versus females only) using the AS04-adjuvanted human papillomavirus (HPV)-16/18 (AS04-HPV-16/18) vaccine. The total vaccination cohort included 32,175 adolescents aged 12-15 y at vaccination of whom 14,837 received the AS04-HPV-16/18 vaccine and 17,338 received the hepatitis-B virus vaccine (control). Spontaneous reporting of serious adverse events (SAEs) combined with surveillance using nation-wide health registries showed an acceptable safety profile of the AS04-HPV-16/18 vaccine. During the study period (up to 6.5 y), the incidences (per 100,000 person-years) of reported SAEs considered as possibly related to vaccination were 39.1 (95% confidence interval [CI]: 25.3-57.7) and 39.8 (95%CI: 26.8-56.8) in the HPV and control groups, respectively. The most frequently reported new-onset autoimmune diseases (NOADs) were ulcerative colitis (incidence rates of 28.2 and 33.1 per 100,000 person-years in the HPV and control groups, respectively), insulin-dependent diabetes mellitus (21.9 and 37.1), Crohn's disease (15.6 and 22.5), celiac disease (15.6 and 21.2), and juvenile idiopathic arthritis (14.1 and 15.9). Of 1,344 pregnancies reported (777 and 567 in the HPV and control groups, respectively), most resulted in elective termination (58.4% and 58.6%), birth of a live infant (32.7% and 32.3%), or in spontaneous abortion (8.0% and 7.9%). No major, registered congenital anomalies were identified. The incidence rates of NOADs and pregnancy outcomes were generally balanced between groups. No specific safety signals were identified in the population-based health registry surveillance. Plain Language Summary What is the context? ● Since first licensure in 2007 of the AS04-adjuvanted human papillomavirus (HPV)-16/18 vaccine ( Cervarix , GSK), large quantity of safety data has been collected and confirmed its safety profile. This study provides further unique, population-based safety data from vaccinated Finnish adolescents monitored via health registries up to 6.5 y of follow-up. What is new? ● The vaccine has shown an acceptable safety profile in girls and boys. The risk of new-onset autoimmune diseases (NOADs) was similar between the HPV vaccine group and the control group and in line with the expectations for the studied population. ● The study supports that safety surveillance via national health registries is in general more sensitive than the conventional safety reporting, notably for monitoring specific chronic diseases, e.g. autoimmune disorders. What is the impact? ● This study highlights the importance of health registries in long-term vaccination safety surveillance. The population-based safety data reported in this study further support the routine administration of the HPV vaccine to girls and boys.

Published
2020
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25. Diabetics have Inferior Long-Term Survival and Quality of Life after CABG.

Author

Järvinen O, Hokkanen M, and Huhtala H

Abstract

A prevalence of diabetes is increasing among the patients undergoing coronary artery bypass grafting (CABG). Data on whether health-related quality of life improves similarly after CABG in diabetics and nondiabetics are limited. We assessed long-term mortality and changes in quality of life (RAND-36 Health Survey) after CABG. Seventy-four of the 508 patients (14.6%) operated on in a single institution had a history of diabetes and were compared with nondiabetics. The RAND-36 Health Survey was used as an indicator of quality of life. Assessments were made preoperatively and repeated 1 and 12 years later. Thirty-day mortality was 2.7 versus 1.6 ( p  = 0.511) in the diabetics and nondiabetics. One- and 10-year survival rates in the diabetics and nondiabetics were 94.6% versus 97.0% ( p  = 0.287) and 63.5% versus 81.6% ( p  < 0.001), respectively. After 1 year, diabetics improved significantly ( p  < 0.005) in seven, and nondiabetics ( p  < 0.001) in all eight RAND-36 dimensions. Despite an ongoing decline in quality of life over the 12-year follow-up, an improvement was maintained in four out of eight dimensions among diabetics and in seven dimensions among nondiabetics. Physical and mental component summary scores on the RAND-36 improved significantly ( p  < 0.001) in both groups after 1 year, and at least slight improvement was maintained during the 12-year follow-up time. Diabetics have inferior long-term survival after CABG as compared with nondiabetics. They gain similar improvement of quality of life in 1 year after surgery, but they have a stronger decline tendency over the years.

Published
2019
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26. Gender-neutral vaccination provides improved control of human papillomavirus types 18/31/33/35 through herd immunity: Results of a community randomized trial (III).

Author

Lehtinen M, Luostarinen T, Vänskä S, Söderlund-Strand A, Eriksson T, Natunen K, Apter D, Baussano I, Harjula K, Hokkanen M, Kuortti M, Palmroth J, Petäjä T, Pukkala E, Rekonen S, Siitari-Mattila M, Surcel HM, Tuomivaara L, Paavonen J, Nieminen P, Dillner J, Dubin G, and Garnett G

Subjects
Adolescent, Child, Cohort Studies, Female, Finland epidemiology, Follow-Up Studies, Humans, Male, Papillomavirus Infections epidemiology, Papillomavirus Infections immunology, Prognosis, Sex Factors, Immunity, Herd immunology, Papillomaviridae classification, Papillomaviridae immunology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines therapeutic use
Abstract

With optimal strategy, human papillomavirus (HPV) vaccines have the potential to control HPV. We have assessed vaccine efficacy (VE), herd effect (HE) of HPV vaccination and overall protective effectiveness (PE) against high-risk HPV infections by HPV type and vaccination strategy in a community-randomized trial using the bivalent HPV16/18 vaccine. We randomized 33 communities to gender-neutral HPV vaccination (Arm A), HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (Arm B) and gender-neutral HBV vaccination (Arm C). Entire 1992-1995 male (40,852) and female (39,420) birth cohorts were invited, and 11,662 males and 20,513 females vaccinated with 20-30% and 45% coverage in 2007-2010. During 2010-2014, 11,396 cervicovaginal samples were collected from 13,545 18.5-year-old attendees. HPV typing was performed by a high-throughput PCR. VE was calculated for HPV vaccinated women and HE for non-HPV-vaccinated women, using the HBV vaccinated, for HE all non-HPV vaccinated, Arm C women as controls. PE was calculated as coverage rate-weighted mean of VE + HE. HPV16/18/45 and 31/33/35 VEs varied between 86-94% and 30-66%, respectively. Only the gender-neutral vaccination provided significant HEs against HPV18 (61%) and HPV31 (72%) in the 1995 birth cohort-increased HEs against HPV33 (39%) and HPV35 (42%) were also observed. Due to the increased HEs, PEs for HPV16/18/45 and HPV31/33/35 were comparable in the gender-neutral arm 1995 birth cohort. High vaccine efficacy against HPV16/18/45 and, gender-neutral vaccination-enforced, herd effect against HPV18/31/33/35 by the bivalent vaccine rapidly provides comparable overall protective effectiveness against six oncogenic HPV types: 16/18/31/33/35/45., (© 2018 UICC.)

Published
2018
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27. The effect of obesity on long-term survival and health-related quality of life after coronary artery bypass grafting: a 12-year follow-up.

Author

Hokkanen M, Järvinen O, Huhtala H, and Laurikka J

Subjects
Adult, Aged, Aged, 80 and over, Body Mass Index, Coronary Artery Disease complications, Coronary Artery Disease mortality, Coronary Artery Disease physiopathology, Female, Health Status, Humans, Male, Middle Aged, Obesity mortality, Obesity physiopathology, Prospective Studies, Risk Factors, Time Factors, Treatment Outcome, Coronary Artery Bypass adverse effects, Coronary Artery Bypass mortality, Coronary Artery Disease surgery, Obesity complications, Quality of Life
Abstract

Objective: The proportion of obese patients undergoing coronary artery bypass graft (CABG) surgery is increasing. In this study, our main objective was to assess the effect of obesity on long-term mortality and changes in quality of life (QoL) after GABG., Materials and Methods: Data of 508 patients who underwent isolated GABG were prospectively collected. RAND-36 Health Survey (RAND-36) was used as an indicator of QoL. BMI was used to assess obesity, and the analysis was based primarily on two patient groups: BMI less than 30 kg/m (408 patients) and BMI of at least 30 (100 patients). All assessments were made preoperatively and repeated 1 and 12 years after CABG surgery. The follow-up of the cohort was complete in 95 and 84% of the alive patients at 1 and 12 years, respectively., Results: Thirty-day, 1-year, and 10-year survival rates were 99.0, 97.0, and 78.0%, respectively, in the obese and 98.0, 96.8, and 79.2%, respectively, in the nonobese group. Obese showed significant (P<0.05) improvements only in four and nonobese in seven of eight RAND-36 dimensions of QoL. In both obese and nonobese patients, improved RAND-36 physical component summary and mental component summary scores were seen in comparison with the preoperative values. Yet, obese patients had a more pronounced diminution in their physical component summary and mental component summary scores, whereas nonobese patients maintained their physical and mental health status better., Conclusion: Despite an on-going decline in 12 years after the CABG, both patient groups showed improvements in their health status in comparison with preoperative values. Obese patients gained less benefit in terms of QoL dimension, but there was no significant difference in overall mortality in the long-term follow-up.

Published
2018
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28. Impact of gender-neutral or girls-only vaccination against human papillomavirus-Results of a community-randomized clinical trial (I).

Author

Lehtinen M, Söderlund-Strand A, Vänskä S, Luostarinen T, Eriksson T, Natunen K, Apter D, Baussano I, Harjula K, Hokkanen M, Kuortti M, Palmroth J, Petäjä T, Pukkala E, Rekonen S, Siitari-Mattila M, Surcel HM, Tuomivaara L, Paavonen J, Dillner J, Dubin G, and Garnett G

Subjects
Adolescent, Adult, Female, Finland epidemiology, Humans, Incidence, Male, Papillomavirus Infections epidemiology, Papillomavirus Infections virology, Prognosis, Uterine Cervical Neoplasms epidemiology, Uterine Cervical Neoplasms virology, Vaccination, Young Adult, Papillomaviridae pathogenicity, Papillomavirus Infections prevention & control, Papillomavirus Vaccines therapeutic use, Uterine Cervical Neoplasms prevention & control
Abstract

Human papillomavirus (HPV) vaccine is efficacious but the real-life effectiveness of gender-neutral and girls-only vaccination strategies is unknown. We report a community-randomized trial on the protective effectiveness [(PE) = vaccine efficacy (VE) + herd effect (HE)] of the two strategies among females in virtually HPV vaccination naïve population. We randomized 33 Finnish communities into Arm A) gender-neutral vaccination with AS04-adjuvanted HPV16/18 vaccine (11 communities), Arm B) HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (11 communities) or Arm C) gender-neutral HBV vaccination (11 communities). All resident 39,420 females and 40,852 males born 1992-95 were invited in 2007-09. Virtually all (99%) 12- to 15-year-old participating males (11,662) and females (20,513) received three doses resulting in uniform 20-30% male and 50% female vaccination coverage by birth cohort. Four years later (2010-14) 11,396 cervicovaginal samples obtained from 18.5 year-old women were tested for HPV DNA, and prevalence of cervical HPV infections by trial arm and birth cohort was the main outcome measure. VEs against HPV16/18 varied between 89.2% and 95.2% across birth cohorts in arms A and B. The VEs against non-vaccine types consistent with cross-protection were highest in those born 1994-95 for HPV45 (VE A 82.8%; VE B 86.1%) and for HPV31 (VE A 77.6%, VE B 84.6%). The HEs in the non HPV-vaccinated were statistically significant in those born 1994-95 for HPV18 (HE A 51.0%; 95% CI 8.3-73.8, HE B 47.2%; 6.5-70.2) and for HPV31/33 in arm A (HE A 53.7%; 22.1-72.5). For HPV16 and 45 no significant herd effects were detected. PE estimates against HPV16/18 were similar by both strategies (PE A 58.1%; 45.1-69.4; PE B 55.7%; 42.9-66.6). PE estimates against HPV31/33 were higher by the gender-neutral vaccination (PE A 60.5%; 43.6-73.4; PE B 44.5%; 24.9-60.6). In conclusion, while gender-neutral strategy enhanced the effectiveness of HPV vaccination for cross-protected HPV types with low to moderate coverage, high coverage in males appears to be key to providing a substantial public health benefit also to unvaccinated females. Trial registration www.clinicaltrials.gov.com NCT000534638., (© 2017 UICC.)

Published
2018
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29. Safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in adolescents aged 12-15 years: Interim analysis of a large community-randomized controlled trial.

Author

Lehtinen M, Eriksson T, Apter D, Hokkanen M, Natunen K, Paavonen J, Pukkala E, Angelo MG, Zima J, David MP, Datta S, Bi D, Struyf F, and Dubin G

Subjects
Adolescent, Aluminum Hydroxide administration & dosage, Autoimmune Diseases chemically induced, Autoimmune Diseases epidemiology, Child, Drug-Related Side Effects and Adverse Reactions pathology, Female, Finland, Hepatitis B Vaccines administration & dosage, Hepatitis B Vaccines adverse effects, Humans, Lipid A administration & dosage, Lipid A adverse effects, Male, Papillomavirus Vaccines administration & dosage, Aluminum Hydroxide adverse effects, Drug-Related Side Effects and Adverse Reactions epidemiology, Lipid A analogs & derivatives, Papillomavirus Infections prevention & control, Papillomavirus Vaccines adverse effects
Abstract

This community-randomized controlled trial was initiated to assess the overall and herd effects of 2 different human papillomavirus (HPV) immunization strategies in over 80,000 girls and boys aged 12-15 y in 33 communities in Finland (ClinicalTrials.gov NCT00534638). Overall, 14,838 adolescents received HPV-16/18 vaccine (2,440 boys and 12,398 girls) and 17,338 received hepatitis-B virus (HBV) vaccine (9,221 boys and 8,117 girls). In an interim analysis, vaccine safety was assessed by active monitoring and surveillance via health registry linkage. Active monitoring showed that the HPV-16/18 vaccine has acceptable safety and reactogenicity in boys. In all study participants, the observed incidences (per 100,000 person-years) of serious adverse events (SAEs) possibly related to vaccination were 54.3 (95% Confidence Interval [CI]: 34.0-82.1) in the HPV-16/18 group and 64.0 (95% CI: 43.2-91.3) in the HBV group. During the follow-up period for this interim analysis, the most common new-onset autoimmune diseases (NOADs; with incidence rate ≥15 per 100,000) in any group based on hospital discharge registry (HILMO) download were ulcerative colitis, juvenile arthritis, celiac disease, insulin-dependent diabetes mellitus (IDDM) and Crohn's disease. No increased NOAD incidences were observed in HPV-16/18 vaccine recipients compared to HBV vaccine recipients. In both the SAE possibly related- and HILMO-analyses, a lower incidence of IDDM was observed in HPV-16/18 vaccinees compared to HBV vaccinees (relative risks, 0.26 [95% CI: 0.03-1.24] and 0.16 [95% CI: 0.03-0.55], respectively).

Published
2016
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30. The long-term effect of perioperative myocardial infarction on health-related quality-of-life after coronary artery bypass grafting.

Author

Järvinen O, Hokkanen M, and Huhtala H

Subjects
Adult, Aged, Aged, 80 and over, Case-Control Studies, Coronary Artery Bypass mortality, Electrocardiography, Female, Humans, Kaplan-Meier Estimate, Longitudinal Studies, Male, Middle Aged, Myocardial Infarction diagnosis, Myocardial Infarction etiology, Myocardial Infarction mortality, Risk Factors, Surveys and Questionnaires, Time Factors, Coronary Artery Bypass adverse effects, Myocardial Infarction psychology, Quality of Life, Survivors psychology
Abstract

Objectives: To evaluate the long-term effect of perioperative myocardial infarction (PMI) on outcomes and health-related quality-of-life (QOL) after coronary artery bypass grafting (CABG)., Methods: Eighty of the 501 patients (16%) fulfilled electrocardiogram or cardiac enzyme criteria for PMI and were compared with patients with no PMI. The RAND-36 Health Survey was used as an indicator of QOL. Assessments were made preoperatively and repeated 1 year and 12 years later., Results: Thirty-day mortality was adversely affected by PMI (6.3 vs 1.0%, P = 0.001). One-year survival rates for PMI and no-PMI patients were 92.5 and 97.6%, 10-year rates being 72.5 and 79.8%. One year after the surgery, PMI patients improved in seven and no-PMI patients in all the eight RAND-36 dimensions. In the 12-year follow-up, the scores showed a general decline tendency. PMI patients still maintained a significant improvement in four and no-PMI patients in seven of eight dimensions when compared with the baseline scores. A highly significant improvement was seen in the RAND-36 mental and physical component summary scores in the no-PMI group 1 year after CABG. PMI patients improved also significantly although the magnitude of change was lower. In the 12-year follow-up, there was a general decline tendency in the scores. Both groups showed similar freedom from anginal symptoms at 12 years., Conclusions: Although PMI has a negative impact on health-related QOL 1 year after CABG, this effect is only minor in the long term. PMI increases 30-day mortality but shows no effect on later mortality.

Published
2014
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31. A 12-year follow-up on the changes in health-related quality of life after coronary artery bypass graft surgery.

Author

Hokkanen M, Järvinen O, Huhtala H, and Tarkka MR

Subjects
Aged, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Male, Mental Health, Treatment Outcome, Coronary Artery Bypass, Quality of Life
Abstract

Objectives: Improvement in quality of life (QoL) and survival benefit are the primary objectives of coronary artery bypass graft (CABG) surgery. The profile of patients undergoing isolated CABG has altered towards higher age with more preoperative comorbidities. Thus, the importance of QoL over the quantity of life among elderly patients is getting more emphasized. In this study, our main goal was to evaluate the long-term changes in QoL, overall performance status and symptomatic status after the CABG., Methods: Comprehensive data of 508 patients who underwent isolated CABG in a single institution were prospectively collected. The RAND-36 Health Survey (RAND-36) was used as an indicator of QoL. Karnofsky dependency category was used to evaluate overall performance status, and symptomatic status was assessed using New York Heart Association (NYHA) class. All assessment were made preoperatively and repeated 1 year and 12 years later. The follow-up of the study cohort was complete in 95 and 84% of the alive patients at 1 year and 12 years, respectively. Analysis was based mainly on three age groups: ≤64 years (282 patients), 65-74 years (175 patients) and ≥75 years (51 patients)., Results: Thirty-day, 1-year and 10-year survival rates were 98, 97 and 79%, respectively. Twelve years after the surgery significant improvement (P<0.05) was seen in all but one RAND-36 dimensions of the QoL (general health, P=0.76) as well as in functional capacity (P<0.001) and NYHA class. All age groups showed improvements in RAND-36 physical component summary (PCS) and mental component summary (MCS) scores compared with the preoperative values. The youngest subgroup maintained their physical and mental health status best, whereas older subgroups had more pronounced decreases in their PCS and MCS scores., Conclusions: Despite an ongoing deterioration 12 years after the CABG, there was significant improvement in most dimensions of the QoL and functional capacity in comparison with the preoperative values. The elderly gain less long-term benefit from CABG regarding the QoL and survival.

Published
2014
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32. Quality of life 12 years after on-pump and off-pump coronary artery bypass grafting.

Author

Järvinen O, Hokkanen M, and Huhtala H

Subjects
Adult, Aged, Aged, 80 and over, Coronary Artery Disease diagnosis, Coronary Artery Disease mortality, Coronary Artery Disease physiopathology, Female, Finland, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Prospective Studies, Recovery of Function, Risk Factors, Surveys and Questionnaires, Time Factors, Treatment Outcome, Cardiopulmonary Bypass adverse effects, Cardiopulmonary Bypass mortality, Coronary Artery Bypass adverse effects, Coronary Artery Bypass mortality, Coronary Artery Bypass, Off-Pump adverse effects, Coronary Artery Bypass, Off-Pump mortality, Coronary Artery Disease surgery, Quality of Life
Abstract

Objective: To assess whether the use of either the on-pump or the off-pump method affects changes in health-related quality of life (QOL) in the long term after coronary artery bypass graft (CABG) surgery., Methods: Four hundred and fifty-two (89.0%) of the 508 patients in a single institution were operated on-pump and 56 (11.0%) were operated off-pump. The RAND-36 Health Survey (RAND-36) was used as an indicator of QOL. Assessments were performed preoperatively and repeated 1 year and 12 years later. Symptomatic status was estimated according to New York Heart Association class., Results: After 1 year, on-pump patients improved significantly (P<0.001) in all eight RAND-36 dimensions. Also, in off-pump patients, positive changes were observed in all RAND-36 dimensions and these changes were statistically significant (P<0.05) in six dimensions. Despite an ongoing decrease in QOL over the 12-year follow-up, on-pump patients still maintained a significant (P<0.05) improvement in all and off-pump patients in seven out of eight RAND-36 dimensions. A highly significant (P<0.001) pattern of change after 1 year was observed in the RAND-36 Mental Component Summary and Physical Component Summary scores in both operative groups, and despite the general declining trend, significant improvement was maintained during the 12-year follow-up time. Both groups showed almost identical relief from anginal symptoms at 12 years., Conclusion: A majority of patients experience significant improvement in health-related QOL in the long term after CABG. Cardiopulmonary bypass has no impact on patients' subsequent health-related QOL.

Published
2013
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33. Impact of HPV16/18 vaccination on quality of life: a pilot study.

Author

Eriksson T, Torvinen S, Woodhall SC, Lehtinen M, Apter D, Harjula K, Hokkanen M, Rissanen P, Paavonen J, and Lehtinen M

Subjects
Adolescent, Adult, Condylomata Acuminata prevention & control, Female, Finland, Follow-Up Studies, Hepatitis A prevention & control, Hepatitis A Vaccines, Humans, Pilot Projects, Sexual Behavior, Surveys and Questionnaires, Uterine Cervical Dysplasia prevention & control, Young Adult, Papillomavirus Infections prevention & control, Papillomavirus Vaccines, Quality of Life psychology, Vaccination psychology
Abstract

Objectives: Genital human papillomavirus (HPV) infections and associated precancerous lesions adversely affect health-related quality of life (HRQoL). HPV vaccines provide effective protection against these conditions. We therefore investigated the impact of HPV vaccination on HRQoL in young women five years after participation in a phase III HPV vaccination trial., Methods: A total of 4808 originally 16- to 17-year-old Finnish girls had participated in the PATRICIA trial and received either bivalent HPV 16/18 vaccine or hepatitis A-virus (HAV) vaccine in 2004 to 2005. Unvaccinated girls (n = 9602), from adjacent birth cohorts, had participated in the control cohort in 2005. From 2009 to 2011, at 22 to 23 years of age, all participants received a questionnaire consisting of two generic HRQoL instruments (RAND36 and EQ VAS) and a disease-specific questionnaire (CECA10)., Results: We analysed responses of 1143 HPV 16/18-vaccinated, 980 HAV-vaccinated, and 3753 unvaccinated young women. The unadjusted mean outcome measures of the different HRQoL estimates were similar in the three different responder cohorts., Conclusions: Five years after vaccination the health-related quality of life of HPV 16/ 18- vaccinated young women did not differ from those of HAV-vaccinated or unvaccinated controls representing the general population.

Published
2013
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34. Moral transgression, disease and holistic health in the Livingstonia Mission in late nineteenth and early twentieth-century Malawi.

Author

Hokkanen M

Subjects
Alcoholic Beverages economics, Alcoholic Beverages history, History, 19th Century, History, 20th Century, Malawi ethnology, Missionaries, Religion history, Sexual Behavior ethnology, Sexual Behavior history, Sexual Behavior physiology, Sexual Behavior psychology, Social Behavior, Social Conditions economics, Social Conditions history, Social Responsibility, Social Values ethnology, Alcoholism economics, Alcoholism ethnology, Alcoholism history, Alcoholism psychology, Disease economics, Disease ethnology, Disease history, Disease psychology, Morals, Public Health economics, Public Health education, Public Health history, Religious Missions economics, Religious Missions history, Religious Missions psychology, Sexuality ethnology, Sexuality history, Sexuality physiology, Sexuality psychology, Social Problems economics, Social Problems ethnology, Social Problems history, Social Problems psychology
Abstract

This article examines ideas of morality and health, and connections between moral transgression and disease in both Scottish missionary and Central African thought in the context of the Livingstonia Mission of the Presbyterian Free Church of Scotland in Malawi during the late nineteenth and early twentieth centuries. By concentrating on debates, conflicts and co-operation between missionaries and Africans over the key issues of beer drinking and sexual morality, this article explores the emergence of a new "moral hygiene" among African Christian communities in Northern Malawi.

Published
2009
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35. Anticipated acceptance of HPV vaccination at the baseline of implementation: a survey of parental and adolescent knowledge and attitudes in Finland.

Author

Woodhall SC, Lehtinen M, Verho T, Huhtala H, Hokkanen M, and Kosunen E

Subjects
Adolescent, Adult, Analysis of Variance, Female, Finland, Humans, Logistic Models, Male, Middle Aged, Probability, Risk Assessment, Surveys and Questionnaires, Vaccination trends, Health Knowledge, Attitudes, Practice, Papillomavirus Infections prevention & control, Papillomavirus Vaccines administration & dosage, Parental Consent statistics & numerical data, Patient Acceptance of Health Care statistics & numerical data, Vaccination standards
Abstract

We evaluated acceptance of human papillomavirus (HPV) vaccination by adolescents and their parents, 83% and 86% of whom accepted vaccination. Improving knowledge and awareness of HPV, and addressing parental concerns about vaccinating adolescents, most notably on vaccinating against a sexually transmitted disease, should help tackle factors associated with being resistant to accepting HPV vaccination.

Published
2007
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