{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:08:48Z","timestamp":1789193328797,"version":"build-2803163510"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,12,18]]},"abstract":"\n Background<\/jats:title>\n \n Acute rheumatic fever (\n ARF<\/jats:styled-content>\n ) and rheumatic heart disease cause substantial burdens worldwide. Long\u2010term antibiotic secondary prophylaxis is used to prevent disease progression, but evidence for benefits of different adherence levels is limited. Using data from northern Australia, we identified factors associated with adherence, and the association between adherence and\n ARF<\/jats:styled-content>\n recurrence, progression to rheumatic heart disease, worsening or improvement of rheumatic heart disease, and mortality.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Factors associated with adherence (percent of doses administered) were analyzed using logistic regression. Nested case\u2013control and case\u2013crossover designs were used to investigate associations with clinical outcomes; conditional logistic regression was used to estimate odds ratios (\n OR<\/jats:styled-content>\n ) with 95% CIs Adherence estimates (7728) were analyzed. Being female, younger, having more\u2010severe disease, and living remotely were associated with higher adherence. Alcohol misuse was associated with lower adherence. The risk of\n ARF<\/jats:styled-content>\n recurrence did not decrease until \u224840% of doses had been administered. Receiving <80% was associated with a 4\u2010fold increase in the odds of\n ARF<\/jats:styled-content>\n recurrence (case\u2013control\n OR<\/jats:styled-content>\n : 4.00 [95%\n CI<\/jats:styled-content>\n : 1.7\u20139.29], case\u2013crossover\n OR<\/jats:styled-content>\n : 3.31 [95%\n CI<\/jats:styled-content>\n : 1.09\u201310.07]) and appeared to be associated with increased all\u2010cause mortality (case\u2013control\n OR<\/jats:styled-content>\n : 1.90 [95%\n CI<\/jats:styled-content>\n : 0.89\u20134.06]; case\u2013crossover\n OR<\/jats:styled-content>\n 1.91 [95%\n CI<\/jats:styled-content>\n : 0.51\u20137.12]).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n We show for the first time that increased adherence to penicillin prophylaxis is associated with reduced\n ARF<\/jats:styled-content>\n recurrence, and a likely reduction in mortality, in our setting. These findings can motivate patients to receive doses since even relatively low adherence can be beneficial, and additional doses further reduce adverse clinical outcomes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.010223","type":"journal-article","created":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T10:00:40Z","timestamp":1544608840000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["How Many Doses Make a Difference? An Analysis of Secondary Prevention of Rheumatic Fever and Rheumatic Heart Disease"],"prefix":"10.1161","volume":"7","author":[{"given":"Jessica Langloh","family":"de Dassel","sequence":"first","affiliation":[{"name":"Menzies School of Health Research Charles Darwin University Darwin Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"de Klerk","sequence":"additional","affiliation":[{"name":"Telethon Kids Institute University of Western Australia Perth Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan Rhys","family":"Carapetis","sequence":"additional","affiliation":[{"name":"Telethon Kids Institute University of Western Australia Perth Australia"},{"name":"Princess Margaret Hospital for Children Perth Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna P.","family":"Ralph","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research Charles Darwin University Darwin Australia"},{"name":"Royal Darwin Hospital Darwin Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603693"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(54)90220-X"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM195409162511203"},{"key":"e_1_3_1_5_2","volume-title":"Rheumatic Fever and Rheumatic Heart Disease: Report of a WHO Expert Consultation Geneva, 29 October\u20131 November 2001","author":"World Health Organization","year":"2004","unstructured":"World Health Organization . 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