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antibiotics-for-sore-throat.rm5
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antibiotics-for-sore-throat.rm5
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<?xml version="1.0" encoding="ISO-8859-1"?><COCHRANE_REVIEW DESCRIPTION="I worry there may be an error in the SoF Table (Day 7 soreness)" DOI="10.1002/14651858.CD000023.pub4" GROUP_ID="ARI" ID="972299090211411677" MERGED_FROM="" MODIFIED="2016-05-03 01:41:27 +0100" MODIFIED_BY="Justin Clark" REVIEW_NO="A017" REVMAN_SUB_VERSION="5.2.11 " REVMAN_VERSION="5" SPLIT_FROM="" STAGE="R" STATUS="A" TYPE="INTERVENTION" VERSION_NO="22.1">
<COVER_SHEET MODIFIED="2016-05-03 01:41:27 +0100" MODIFIED_BY="Justin Clark">
<TITLE>Antibiotics for sore throat</TITLE>
<CONTACT MODIFIED="2016-05-03 01:41:27 +0100" MODIFIED_BY="Justin Clark"><PERSON ID="18155" ROLE="AUTHOR"><PREFIX>Ms</PREFIX><FIRST_NAME>Anneliese</FIRST_NAME><LAST_NAME>Spinks</LAST_NAME><SUFFIX>BSc (Hon) BA</SUFFIX><POSITION>Research Fellow</POSITION><EMAIL_1>anneliese.spinks@csiro.au</EMAIL_1><EMAIL_2>a.spinks@griffith.edu.au</EMAIL_2><ADDRESS><DEPARTMENT>School of Medicine</DEPARTMENT><ORGANISATION>Griffith University</ORGANISATION><ADDRESS_1>University Drive</ADDRESS_1><CITY>Meadowbrook</CITY><ZIP>4031</ZIP><REGION>Queensland</REGION><COUNTRY CODE="AU">Australia</COUNTRY><PHONE_1>+61 7 3382 1353</PHONE_1><FAX_1>+61 7 3382 1338</FAX_1></ADDRESS></PERSON></CONTACT>
<CREATORS MODIFIED="2016-05-03 01:41:27 +0100" MODIFIED_BY="Justin Clark"><PERSON ID="18155" ROLE="AUTHOR"><PREFIX>Ms</PREFIX><FIRST_NAME>Anneliese</FIRST_NAME><LAST_NAME>Spinks</LAST_NAME><SUFFIX>BSc (Hon) BA</SUFFIX><POSITION>Research Fellow</POSITION><EMAIL_1>anneliese.spinks@csiro.au</EMAIL_1><EMAIL_2>a.spinks@griffith.edu.au</EMAIL_2><ADDRESS><DEPARTMENT>School of Medicine</DEPARTMENT><ORGANISATION>Griffith University</ORGANISATION><ADDRESS_1>University Drive</ADDRESS_1><CITY>Meadowbrook</CITY><ZIP>4031</ZIP><REGION>Queensland</REGION><COUNTRY CODE="AU">Australia</COUNTRY><PHONE_1>+61 7 3382 1353</PHONE_1><FAX_1>+61 7 3382 1338</FAX_1></ADDRESS></PERSON><PERSON ID="4655" ROLE="AUTHOR"><PREFIX>Prof</PREFIX><FIRST_NAME>Paul</FIRST_NAME><MIDDLE_INITIALS>P</MIDDLE_INITIALS><LAST_NAME>Glasziou</LAST_NAME><POSITION>Professor</POSITION><EMAIL_1>pglaszio@bond.edu.au</EMAIL_1><ADDRESS><DEPARTMENT>Centre for Research in Evidence-Based Practice (CREBP)</DEPARTMENT><ORGANISATION>Bond University</ORGANISATION><ADDRESS_1>University Drive</ADDRESS_1><CITY>Gold Coast</CITY><ZIP>4229</ZIP><REGION>Queensland</REGION><COUNTRY CODE="AU">Australia</COUNTRY><PHONE_1>+61 7 5595 4482</PHONE_1><FAX_1>+61 7 5595 1652</FAX_1></ADDRESS></PERSON><PERSON ID="12249" ROLE="AUTHOR"><PREFIX>Prof</PREFIX><FIRST_NAME>Chris</FIRST_NAME><MIDDLE_INITIALS>B</MIDDLE_INITIALS><LAST_NAME>Del Mar</LAST_NAME><SUFFIX>MA MB BChir MD FRACGP FAFPHM</SUFFIX><POSITION>Professor</POSITION><EMAIL_1>cdelmar@bond.edu.au</EMAIL_1><URL>http://ari.cochrane.org</URL><MOBILE_PHONE>+61 403 220080</MOBILE_PHONE><ADDRESS><DEPARTMENT>Centre for Research in Evidence-Based Practice (CREBP)</DEPARTMENT><ORGANISATION>Bond University</ORGANISATION><ADDRESS_1>University Drive</ADDRESS_1><CITY>Gold Coast</CITY><ZIP>4229</ZIP><REGION>Queensland</REGION><COUNTRY CODE="AU">Australia</COUNTRY><PHONE_1>+61 7 5595 2504</PHONE_1><FAX_1>+61 7 5595 1652</FAX_1><FAX_2>+61 7 5595 1271</FAX_2></ADDRESS></PERSON></CREATORS>
<DATES MODIFIED="2014-01-28 07:31:12 +1000" MODIFIED_BY="Liz Dooley">
<UP_TO_DATE>
<DATE DAY="11" MONTH="7" YEAR="2013"/>
</UP_TO_DATE>
<LAST_SEARCH>
<DATE DAY="11" MONTH="7" YEAR="2013"/>
</LAST_SEARCH>
<NEXT_STAGE>
<DATE DAY="11" MONTH="7" YEAR="2015"/>
</NEXT_STAGE>
<PROTOCOL_PUBLISHED ISSUE="1" YEAR="1997"/>
<REVIEW_PUBLISHED ISSUE="2" YEAR="1997"/>
<LAST_CITATION_ISSUE ISSUE="11" YEAR="2013"/>
</DATES>
<WHATS_NEW MODIFIED="2014-01-28 07:32:23 +1000" MODIFIED_BY="[Empty name]">
<WHATS_NEW_ENTRY EVENT="FEEDBACK" MODIFIED="2014-01-28 07:32:23 +1000" MODIFIED_BY="[Empty name]">
<DATE DAY="28" MONTH="1" YEAR="2014"/>
<DESCRIPTION>
<P>Feedback comment and author reply added to the review.</P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
</WHATS_NEW>
<HISTORY MODIFIED="2014-01-28 07:31:45 +1000" MODIFIED_BY="[Empty name]">
<WHATS_NEW_ENTRY EVENT="NEW_CITATION_OLD_CONCLUSIONS" MODIFIED="2014-01-28 07:31:45 +1000" MODIFIED_BY="[Empty name]">
<DATE DAY="11" MONTH="7" YEAR="2013"/>
<DESCRIPTION>
<P>Our conclusions remain unchanged.</P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
<WHATS_NEW_ENTRY EVENT="UPDATE" MODIFIED="2014-01-28 07:31:42 +1000" MODIFIED_BY="[Empty name]">
<DATE DAY="11" MONTH="7" YEAR="2013"/>
<DESCRIPTION>
<P>Searches conducted. We did not identify any new trials for inclusion but we excluded three new trials (<LINK REF="STD-Kapur-2011" TYPE="STUDY">Kapur 2011</LINK>; <LINK REF="STD-Kolobukhina-2011" TYPE="STUDY">Kolobukhina 2011</LINK>; <LINK REF="STD-Supajatura-2012" TYPE="STUDY">Supajatura 2012</LINK>).</P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
<WHATS_NEW_ENTRY EVENT="UPDATE" MODIFIED="2013-08-15 20:06:30 +1000" MODIFIED_BY="[Empty name]">
<DATE DAY="18" MONTH="5" YEAR="2011"/>
<DESCRIPTION>
<P>Searches conducted. No new studies were identified and our conclusions remain unchanged. </P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
<WHATS_NEW_ENTRY EVENT="AMENDMENT" MODIFIED="2010-08-05 12:00:57 +1000" MODIFIED_BY="Liz Dooley">
<DATE DAY="17" MONTH="2" YEAR="2010"/>
<DESCRIPTION>
<P>Contact details updated.</P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
<WHATS_NEW_ENTRY EVENT="AMENDMENT" MODIFIED="2010-02-18 09:39:18 +1000" MODIFIED_BY="Liz Dooley">
<DATE DAY="21" MONTH="1" YEAR="2010"/>
<DESCRIPTION>
<P>Contact details updated.</P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
<WHATS_NEW_ENTRY EVENT="UPDATE" MODIFIED="2010-01-21 10:18:00 +1000" MODIFIED_BY="Liz Dooley">
<DATE DAY="25" MONTH="11" YEAR="2008"/>
<DESCRIPTION>
<P>Searches conducted. No new studies were identified and conclusions remain unchanged.</P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
<WHATS_NEW_ENTRY EVENT="FEEDBACK" MODIFIED="2009-05-06 09:56:27 +1000" MODIFIED_BY="Liz Dooley">
<DATE DAY="27" MONTH="8" YEAR="2008"/>
<DESCRIPTION>
<P>Typographical error in the Abstract corrected.</P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
<WHATS_NEW_ENTRY EVENT="AMENDMENT" MODIFIED="2008-11-10 08:37:24 +1000" MODIFIED_BY="Liz Dooley">
<DATE DAY="12" MONTH="7" YEAR="2008"/>
<DESCRIPTION>
<P>Converted to new review format.</P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
<WHATS_NEW_ENTRY EVENT="FEEDBACK" MODIFIED="2009-05-06 09:56:29 +1000" MODIFIED_BY="Liz Dooley">
<DATE DAY="18" MONTH="10" YEAR="2006"/>
<DESCRIPTION>
<P>Feedback added.</P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
<WHATS_NEW_ENTRY EVENT="UPDATE" MODIFIED="2011-07-11 17:51:38 +1000" MODIFIED_BY="[Empty name]">
<DATE DAY="9" MONTH="3" YEAR="2006"/>
<DESCRIPTION>
<P>In this 2006 update there is an addition of data from one new study by <LINK REF="STD-Zwart-2003" TYPE="STUDY">Zwart 2003</LINK>.<BR/>Additionally, reported statistics were changed from odds ratios to more clinically meaningful relative risks (using a random-effects model).<BR/>Since the update for this review was submitted to <I>The Cochrane Library</I> (Issue 4, 2006), we have been alerted to an error in the data extraction. This error involved switching the number of participants experiencing headache on day three between the intervention and placebo groups for the study by <LINK REF="STD-El_x002d_Daher-1991" TYPE="STUDY">El-Daher 1991</LINK>. We therefore incorrectly concluded that antibiotics conferred no benefit for the symptom of headache, whereas in fact the meta-analysis does show a significant protective effect (RR 0.47; 95% CI 0.38 to 0.58).</P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
<WHATS_NEW_ENTRY EVENT="UPDATE" MODIFIED="2008-07-14 09:02:33 +1000" MODIFIED_BY="Liz Dooley">
<DATE DAY="22" MONTH="5" YEAR="2003"/>
<DESCRIPTION>
<P>Searches conducted.</P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
<WHATS_NEW_ENTRY EVENT="UPDATE" MODIFIED="2008-07-14 08:50:36 +1000" MODIFIED_BY="Liz Dooley">
<DATE DAY="8" MONTH="5" YEAR="2000"/>
<DESCRIPTION>
<P>Searches conducted.</P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
<WHATS_NEW_ENTRY EVENT="UPDATE" MODIFIED="2008-07-14 08:49:23 +1000" MODIFIED_BY="Liz Dooley">
<DATE DAY="30" MONTH="6" YEAR="1999"/>
<DESCRIPTION>
<P>Searches conducted.</P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
<WHATS_NEW_ENTRY EVENT="UPDATE" MODIFIED="2008-07-14 08:47:11 +1000" MODIFIED_BY="Liz Dooley">
<DATE DAY="31" MONTH="3" YEAR="1996"/>
<DESCRIPTION>
<P>Searches conducted.</P>
</DESCRIPTION>
</WHATS_NEW_ENTRY>
</HISTORY>
<SOURCES_OF_SUPPORT>
<INTERNAL_SOURCES>
<SOURCE>
<NAME>Bond University (2006 update)</NAME>
<COUNTRY CODE="AU">Australia</COUNTRY>
<DESCRIPTION/>
</SOURCE>
<SOURCE>
<NAME>University of Oxford</NAME>
<COUNTRY CODE="GB">UK</COUNTRY>
<DESCRIPTION/>
</SOURCE>
<SOURCE>
<NAME>Griffith University</NAME>
<COUNTRY CODE="AU">Australia</COUNTRY>
<DESCRIPTION/>
</SOURCE>
</INTERNAL_SOURCES>
<EXTERNAL_SOURCES>
<SOURCE>
<NAME>NHS support</NAME>
<COUNTRY CODE="GB">UK</COUNTRY>
<DESCRIPTION/>
</SOURCE>
</EXTERNAL_SOURCES>
</SOURCES_OF_SUPPORT>
<MESH_TERMS VERIFIED="NO"/>
<KEYWORDS/>
</COVER_SHEET>
<MAIN_TEXT MODIFIED="2013-10-25 14:56:46 +1000" MODIFIED_BY="[Empty name]">
<SUMMARY MODIFIED="2013-10-25 10:48:57 +1000" MODIFIED_BY="[Empty name]">
<TITLE MODIFIED="2009-01-28 08:39:38 +1000" MODIFIED_BY="Liz Dooley">Antibiotics for people with sore throats</TITLE>
<SUMMARY_BODY MODIFIED="2013-10-25 10:48:57 +1000" MODIFIED_BY="[Empty name]">
<P>
<B>Question</B>
</P>
<P>This review sought to determine whether antibiotics are effective for treating the symptoms and reducing the potential complications associated with sore throats.</P>
<P>
<B>Background</B>
</P>
<P>Sore throats are infections caused by bacteria or viruses. People usually recover quickly (usually after three or four days), although some develop complications. A serious but rare complication is rheumatic fever, which affects the heart and joints. Antibiotics reduce bacterial infections but they can cause diarrhea, rash and other adverse effects and communities build resistance to them.</P>
<P>
<B>Study characteristics</B>
</P>
<P>The review is current to July 2013 and included 27 trials with 12,835 cases of sore throat. All of the included studies were randomised, placebo-controlled trials which sought to determine if antibiotics helped reduce symptoms of either sore throat, fever and headache or the occurrence of more serious complications. Studies were conducted among both children and adults.</P>
<P>
<B>Key results</B>
</P>
<P>The review found that antibiotics shorten the duration of pain symptoms by an average of about one day and can reduce the chance of rheumatic fever by more than two-thirds in communities where this complication is common. Other complications associated with sore throat are also reduced through antibiotic use.</P>
<P>
<B>Quality of evidence</B>
</P>
<P>The quality of the included studies was moderate to high. However, there were very few recent trials included in the review (only three since 2000), hence it is unclear if changes in bacterial resistance in the community may have affected the effectiveness of antibiotics.</P>
</SUMMARY_BODY>
</SUMMARY>
<ABSTRACT MODIFIED="2013-10-23 12:09:17 +1000" MODIFIED_BY="[Empty name]">
<ABS_BACKGROUND MODIFIED="2009-03-11 14:01:26 +1000" MODIFIED_BY="[Empty name]">
<P>Sore throat is a common reason for people to present for medical care. Although it remits spontaneously, primary care doctors commonly prescribe antibiotics for it.</P>
</ABS_BACKGROUND>
<ABS_OBJECTIVES MODIFIED="2011-05-18 08:19:13 +1000" MODIFIED_BY="Liz Dooley">
<P>To assess the benefits of antibiotics for sore throat for patients in primary care settings.</P>
</ABS_OBJECTIVES>
<ABS_SEARCH_STRATEGY MODIFIED="2013-09-11 21:18:09 +1000" MODIFIED_BY="[Empty name]">
<P>We searched CENTRAL 2013, Issue 6, MEDLINE (January 1966 to July week 1, 2013) and EMBASE (January 1990 to July 2013).</P>
</ABS_SEARCH_STRATEGY>
<ABS_SELECTION_CRITERIA MODIFIED="2011-05-18 08:21:56 +1000" MODIFIED_BY="Liz Dooley">
<P>Randomised controlled trials (RCTs) or quasi-RCTs of antibiotics versus control assessing typical sore throat symptoms or complications.</P>
</ABS_SELECTION_CRITERIA>
<ABS_DATA_COLLECTION MODIFIED="2011-07-11 02:12:27 +1000" MODIFIED_BY="[Empty name]">
<P>Two review authors independently screened studies for inclusion and extracted data. We resolved differences in opinion by discussion. We contacted trial authors from three studies for additional information.</P>
</ABS_DATA_COLLECTION>
<ABS_RESULTS MODIFIED="2013-10-23 12:09:17 +1000" MODIFIED_BY="[Empty name]">
<P>We included 27 trials with 12,835 cases of sore throat. We did not identify any new trials in this 2013 update.</P>
<P>
<B>1. Symptoms</B>
<BR/>Throat soreness and fever were reduced by about half by using antibiotics. The greatest difference was seen at day three. The number needed to treat to benefit (NNTB) to prevent one sore throat at day three was less than six; at week one it was 21.</P>
<P>
<B>2. Non-suppurative complications</B>
<BR/>The trend was antibiotics protecting against acute glomerulonephritis but there were too few cases to be sure. Several studies found antibiotics reduced acute rheumatic fever by more than two-thirds within one month (risk ratio (RR) 0.27; 95% confidence interval (CI) 0.12 to 0.60).</P>
<P>
<B>3. Suppurative complications</B>
<BR/>Antibiotics reduced the incidence of acute otitis media within 14 days (RR 0.30; 95% CI 0.15 to 0.58); acute sinusitis within 14 days (RR 0.48; 95% CI 0.08 to 2.76); and quinsy within two months (RR 0.15; 95% CI 0.05 to 0.47) compared to those taking placebo.</P>
<P>
<B>4. Subgroup analyses of symptom reduction</B>
<BR/>Antibiotics were more effective against symptoms at day three (RR 0.58; 95% CI 0.48 to 0.71) if throat swabs were positive for <I>Streptococcus</I>, compared to RR 0.78; 95% CI 0.63 to 0.97 if negative. Similarly at week one the RR was 0.29 (95% CI 0.12 to 0.70) for positive and 0.73 (95% CI 0.50 to 1.07) for negative <I>Streptococcus </I>swabs.</P>
</ABS_RESULTS>
<ABS_CONCLUSIONS MODIFIED="2011-05-18 09:19:50 +1000" MODIFIED_BY="Liz Dooley">
<P>Antibiotics confer relative benefits in the treatment of sore throat. However, the absolute benefits are modest. Protecting sore throat sufferers against suppurative and non-suppurative complications in high-income countries requires treating many with antibiotics for one to benefit. This NNTB may be lower in low-income countries. Antibiotics shorten the duration of symptoms by about 16 hours overall.</P>
</ABS_CONCLUSIONS>
</ABSTRACT>
<BODY MODIFIED="2013-10-25 10:49:13 +1000" MODIFIED_BY="[Empty name]">
<BACKGROUND MODIFIED="2013-09-11 21:17:20 +1000" MODIFIED_BY="[Empty name]">
<CONDITION MODIFIED="2011-05-18 08:35:38 +1000" MODIFIED_BY="Liz Dooley">
<P>Sore throat is a very common reason for people to attend primary care settings (<LINK REF="REF-ABS-1985" TYPE="REFERENCE">ABS 1985</LINK>). Moreover, four to six times as many people suffering sore throat do not seek care (<LINK REF="REF-Goslings-1963" TYPE="REFERENCE">Goslings 1963</LINK>; <LINK REF="REF-Horder-1954" TYPE="REFERENCE">Horder 1954</LINK>). Sore throat is a disease that remits spontaneously, that is, 'cure' is not dependent on treatment (<LINK REF="REF-Del-Mar-1992c" TYPE="REFERENCE">Del Mar 1992c</LINK>). Nonetheless, primary care doctors commonly prescribe antibiotics for sore throat and other upper respiratory tract infections. There are large differences in clinical practice between countries (<LINK REF="REF-Froom-1990" TYPE="REFERENCE">Froom 1990</LINK>) and between primary care doctors (<LINK REF="REF-Howie-1971" TYPE="REFERENCE">Howie 1971</LINK>).</P>
</CONDITION>
<INTERVENTION MODIFIED="2013-09-11 21:17:20 +1000" MODIFIED_BY="[Empty name]">
<P>The administration of antibiotics is likely to shorten the time to the remittance of symptoms and reduce the likelihood of complications in patients whose sore throat has a bacteriological aetiology (<LINK REF="REF-van-Driel-2013" TYPE="REFERENCE">van Driel 2013</LINK>). However, their benefits may be limited in the treatment of sore throat more generally (<LINK REF="REF-Reveiz-2013" TYPE="REFERENCE">Reveiz 2013</LINK>). Traditionally, doctors have attempted to decide whether the cause of the infection is bacterial, especially when caused by the group A beta-haemolytic <I>Streptococcus</I> (GABHS) (which can cause acute rheumatic fever and acute glomerulonephritis). However, deciding the aetiological agent is difficult (<LINK REF="REF-Del-Mar-1992b" TYPE="REFERENCE">Del Mar 1992b</LINK>).</P>
</INTERVENTION>
<THEORY MODIFIED="2011-07-11 02:17:23 +1000" MODIFIED_BY="[Empty name]">
<P>Antibiotics target bacteria which are potentially responsible for sore throat symptoms and possible subsequent suppurative and non-suppurative sequelae. Successful eradication of bacteria may promote faster healing and prevention of secondary complications. However, not all sore throat cases are of bacteriologic origin and bacteria may resist antibiotic treatment which could limit the overall effectiveness of the intervention.</P>
</THEORY>
<IMPORTANCE MODIFIED="2011-07-11 02:17:42 +1000" MODIFIED_BY="[Empty name]">
<P>Whether or not to prescribe antibiotics for sore throat is controversial. The issue is important because it is a very common disease and differences in prescribing result in large cost differences. Moreover, increased prescribing increases patient attendance rates (<LINK REF="REF-Howie-1978" TYPE="REFERENCE">Howie 1978</LINK>; <LINK REF="STD-Little-1997" TYPE="STUDY">Little 1997</LINK>). This review is built on an early meta-analysis (<LINK REF="REF-Del-Mar-1992a" TYPE="REFERENCE">Del Mar 1992a</LINK>) and is an update of previous Cochrane Reviews (<LINK REF="REF-Del-Mar-1997" TYPE="REFERENCE">Del Mar 1997</LINK>; <LINK REF="REF-Del-Mar-2000" TYPE="REFERENCE">Del Mar 2000</LINK>; <LINK REF="REF-Del-Mar-2004" TYPE="REFERENCE">Del Mar 2004</LINK>; <LINK REF="REF-Del-Mar-2006" TYPE="REFERENCE">Del Mar 2006</LINK>; <LINK REF="REF-Spinks-2009" TYPE="REFERENCE">Spinks 2009</LINK>).</P>
</IMPORTANCE>
</BACKGROUND>
<OBJECTIVES MODIFIED="2013-08-21 10:52:37 +1000" MODIFIED_BY="Liz Dooley">
<P>To assess the benefits of antibiotics for sore throat for patients in primary care settings.</P>
</OBJECTIVES>
<METHODS MODIFIED="2013-09-11 21:17:20 +1000" MODIFIED_BY="[Empty name]">
<SELECTION_CRITERIA MODIFIED="2013-09-11 21:17:20 +1000" MODIFIED_BY="[Empty name]">
<CRIT_STUDIES MODIFIED="2011-05-18 08:39:29 +1000" MODIFIED_BY="Liz Dooley">
<P>Randomised controlled trials (RCTs) or quasi-RCTs.</P>
</CRIT_STUDIES>
<CRIT_PARTICIPANTS MODIFIED="2011-05-18 08:39:55 +1000" MODIFIED_BY="Liz Dooley">
<P>Patients presenting to primary care facilities with symptoms of sore throat.</P>
</CRIT_PARTICIPANTS>
<CRIT_INTERVENTIONS MODIFIED="2011-05-18 08:40:01 +1000" MODIFIED_BY="Liz Dooley">
<P>Antibiotics or placebo control.</P>
</CRIT_INTERVENTIONS>
<CRIT_OUTCOMES MODIFIED="2013-09-11 21:17:20 +1000" MODIFIED_BY="[Empty name]">
<CRIT_OUTCOMES_PRIMARY MODIFIED="2011-07-11 02:17:52 +1000" MODIFIED_BY="[Empty name]">
<OL>
<LI>Symptoms of sore throat on day three.</LI>
<LI>Symptoms of sore throat at one week (days six to eight).</LI>
</OL>
</CRIT_OUTCOMES_PRIMARY>
<CRIT_OUTCOMES_SECONDARY MODIFIED="2013-09-11 21:17:20 +1000" MODIFIED_BY="[Empty name]">
<OL>
<LI>Symptoms of fever at day three.</LI>
<LI>Symptoms of headache at day three.</LI>
<LI>Incidence of suppurative complications:</LI>
<OL>
<LI>quinsy;</LI>
<LI>acute otitis media;</LI>
<LI>acute sinusitis.</LI>
</OL>
<LI>Incidence of non-suppurative complications:</LI>
<OL>
<LI>incidence of acute rheumatic fever within two months;</LI>
<LI>acute glomerulonephritis within one month.</LI>
</OL>
</OL>
</CRIT_OUTCOMES_SECONDARY>
</CRIT_OUTCOMES>
</SELECTION_CRITERIA>
<SEARCH_METHODS MODIFIED="2013-09-11 20:19:34 +1000" MODIFIED_BY="[Empty name]">
<ELECTRONIC_SEARCHES MODIFIED="2013-09-11 20:19:34 +1000" MODIFIED_BY="[Empty name]">
<P>For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2013, Issue 6, part of <I>The Cochrane Library, </I>
<A HREF="http://www.thecochranelibrary.com">www.thecochranelibrary.com</A> (accessed 11 July 2013), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (May 2011 to July week 1, 2013) and EMBASE (May 2011 to July 2013). See <LINK REF="APP-01" TYPE="APPENDIX">Appendix 1</LINK> for details of previous searches.</P>
<P>MEDLINE and CENTRAL were searched using the search strategy shown below. We combined the MEDLINE search string with the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity and precision-maximising version (2008 revision) (<LINK REF="REF-Lefebvre-2011" TYPE="REFERENCE">Lefebvre 2011</LINK>). We adapted the search string for EMBASE (<LINK REF="APP-02" TYPE="APPENDIX">Appendix 2</LINK>). There were no language or publication restrictions.</P>
<SUBSECTION>
<HEADING LEVEL="5">MEDLINE (Ovid)</HEADING>
<P>1 exp Pharyngitis/<BR/>2 pharyngit*.tw.<BR/>3 exp Nasopharyngitis/<BR/>4 (nasopharyngit* or rhinopharyngit*).tw.<BR/>5 exp Tonsillitis/<BR/>6 tonsillit*.tw.<BR/>7 (tonsil* adj2 (inflam* or infect*)).tw.<BR/>8 ((throat* or pharyn*) adj3 (infect* or inflam* or strep*)).tw.<BR/>9 (sore* adj2 throat*).tw.<BR/>10 or/1-9<BR/>11 exp Anti-Bacterial Agents/<BR/>12 antibiot*.tw,nm.<BR/>13 (azithromycin* or clarithromycin* or erythromycin* or roxithromycin* or macrolide* or cefamandole* or cefoperazone* or cefazolin* or cefonicid* or cefsulodin* or cephacetrile* or cefotaxime* or cephalothin* or cephapirin* or cephalexin* or cephaclor* or cephadroxil* or cephaloglycin* or cephradine* or cephaloridine* or ceftazidime* or cephamycin* or cefmetazole* or cefotetan* or cefoxitin* or cephalosporin* or cefpodoxime* or cefuroxime* or cefixime* or amoxicillin* or amoxycillin* or ampicillin* or sulbactum* or tetracyclin* or clindamycin* or lincomycin* or doxycyclin* or fluoroquinolone* or ciprofloxacin* or fleroxacin* or enoxacin* or norfloxacin* or ofloxacin* or pefloxacin* or moxifloxacin* or esparfloxacin* or clindamicin* or penicillin* or ticarcillin* or beta-lactam* or levofloxacin* or trimethoprim* or co-trimoxazole).tw,nm.<BR/>14 or/11-13<BR/>15 10 and 14</P>
</SUBSECTION>
</ELECTRONIC_SEARCHES>
<OTHER_SEARCHES MODIFIED="2013-07-11 16:38:12 +1000" MODIFIED_BY="[Empty name]">
<P>We searched ClinicalTrials.gov and WHO ICTRP (11 July 2013) for completed and ongoing trials. We hand-checked references of selected studies and relevant reviews to find additional studies. </P>
</OTHER_SEARCHES>
</SEARCH_METHODS>
<DATA_COLLECTION MODIFIED="2013-09-11 21:17:20 +1000" MODIFIED_BY="[Empty name]">
<STUDY_SELECTION MODIFIED="2013-08-21 11:25:36 +1000" MODIFIED_BY="[Empty name]">
<P>Two review authors (AS, CD) independently screened abstracts of potential studies and retrieved full articles for those that were trials. Two review authors (AS, CD)<B> </B>examined the full articles and either selected for inclusion or rejected to the excluded studies list. We resolved differences in opinion by discussion.</P>
</STUDY_SELECTION>
<DATA_EXTRACTION MODIFIED="2011-07-11 02:19:23 +1000" MODIFIED_BY="[Empty name]">
<P>Two review authors (AS, CDM) independently extracted data from the included studies based on patient-relevant outcomes: namely the complications and symptoms listed above. Data extraction involved reading from tables, graphs and, in some cases, contacting trial authors for raw data (<LINK REF="STD-Dagnelie-1996" TYPE="STUDY">Dagnelie 1996</LINK>; <LINK REF="STD-Little-1997" TYPE="STUDY">Little 1997</LINK>; <LINK REF="STD-Zwart-2000" TYPE="STUDY">Zwart 2000</LINK>; <LINK REF="STD-Zwart-2003" TYPE="STUDY">Zwart 2003</LINK>).</P>
</DATA_EXTRACTION>
<QUALITY_ASSESSMENT MODIFIED="2013-08-21 11:26:16 +1000" MODIFIED_BY="[Empty name]">
<P>We assessed risk of bias according to the approach indicated in the <I>Cochrane Handbook for Systematic Reviews of Interventions</I> (<LINK REF="REF-Higgins-2011" TYPE="REFERENCE">Higgins 2011</LINK>). We used the following six criteria: adequate sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting and other bias.</P>
</QUALITY_ASSESSMENT>
<EFFECT_MEASURES MODIFIED="2011-07-11 02:19:32 +1000" MODIFIED_BY="[Empty name]">
<P>All treatment effect outcomes were dichotomous data, reported as risk ratios (RR). We reported occurrence of complications during the study period for suppurative and non-suppurative complications. We assessed the presence of symptoms (sore throat, fever, headache) when possible at day three and week one (days six to eight). We also calculated numbers needed to treat to benefit (NNTB) for the primary outcomes.</P>
</EFFECT_MEASURES>
<MISSING_DATA MODIFIED="2011-06-02 10:00:06 +1000" MODIFIED_BY="Liz Dooley">
<P>We performed an intention-to treat (ITT) analysis for all outcomes.</P>
</MISSING_DATA>
<HETEROGENEITY_ASSESSMENT MODIFIED="2013-09-11 21:17:20 +1000" MODIFIED_BY="[Empty name]">
<P>We assessed heterogeneity by using the Chi<SUP>2</SUP> test with the significance level set at 0.1. We determined the effect of heterogeneity by the I<SUP>2</SUP> statistic which indicates the proportion of total variability which can be explained by heterogeneity. We interpreted values of the I<SUP>2 </SUP>statistic greater than 50% as indicating substantial heterogeneity, in accordance with the <I>Cochrane Handbook for Systematic Reviews of Interventions</I> (<LINK REF="REF-Higgins-2011" TYPE="REFERENCE">Higgins 2011</LINK>).</P>
</HETEROGENEITY_ASSESSMENT>
<DATA_SYNTHESIS MODIFIED="2011-05-18 09:23:39 +1000" MODIFIED_BY="Liz Dooley">
<P>We combined data where possible in order to perform meta-analyses to report RR for all relevant outcomes. We used a random-effects meta-analytical method (Mantel-Haenszel) in order to account for heterogeneity that was detected using the methods described above. Not all studies were able to contribute data to each of the meta-analyses performed.</P>
</DATA_SYNTHESIS>
<SUBGROUP_ANALYSIS MODIFIED="2013-09-11 21:17:20 +1000" MODIFIED_BY="Liz Dooley">
<P>We performed a series of subgroup analyses to assess the differences in outcomes across various subgroups within the participant population:</P>
<OL>
<LI>treatment with penicillin (omitting other antibiotics);</LI>
<LI>children compared with adults;</LI>
<LI>positive throat swab versus negative throat swab versus untested and/or inseparable data for group A beta-haemolytic <I>Streptococcus</I> (GABHS).</LI>
</OL>
</SUBGROUP_ANALYSIS>
<SENSITIVITY_ANALYSIS MODIFIED="2011-05-18 09:24:37 +1000" MODIFIED_BY="Liz Dooley">
<P>We performed sensitivity analyses to assess the degree to which results were influenced by the following criteria:</P>
<OL>
<LI>early (pre-1975) versus later (post-1975) studies;</LI>
<LI>blinded versus unblinded studies;</LI>
<LI>antipyretics administered versus no antipyretics administered.</LI>
</OL>
</SENSITIVITY_ANALYSIS>
</DATA_COLLECTION>
</METHODS>
<RESULTS MODIFIED="2013-10-25 10:49:13 +1000" MODIFIED_BY="[Empty name]">
<STUDY_DESCRIPTION MODIFIED="2013-10-25 10:49:13 +1000" MODIFIED_BY="[Empty name]">
<SEARCH_RESULTS MODIFIED="2013-08-29 14:29:10 +1000" MODIFIED_BY="[Empty name]">
<P>A total of 61 studies were considered for the review. Of these, there were 27 controlled studies that met the inclusion criteria and were included in the review. There were no new trials included in this 2013 update. However, three new trials were considered and subsequently excluded.</P>
</SEARCH_RESULTS>
<INCLUDED_STUDIES_DESCR MODIFIED="2013-10-25 10:49:13 +1000" MODIFIED_BY="[Empty name]">
<P>The included studies investigated a total of 12,835 cases of sore throat. The majority of studies were conducted in the 1950s, during which time the rates of serious complications (especially acute rheumatic fever) were much higher than today. Seven studies published in the last 15 years (between 1996 to 2003) were included. However, no new studies have been published since 2003.</P>
<P>The age of participants ranged from less than one year to older than 50 years. The participants of eight early studies were young male recruits from the United States Air Force (<LINK REF="STD-Brink-1951" TYPE="STUDY">Brink 1951</LINK>; <LINK REF="STD-Brumfitt-1957" TYPE="STUDY">Brumfitt 1957</LINK>; <LINK REF="STD-Catanzaro-1954" TYPE="STUDY">Catanzaro 1954</LINK>; <LINK REF="STD-Chamovitz-1954" TYPE="STUDY">Chamovitz 1954</LINK>; <LINK REF="STD-Denny-1950" TYPE="STUDY">Denny 1950</LINK>; <LINK REF="STD-Denny-1953" TYPE="STUDY">Denny 1953</LINK>; <LINK REF="STD-MacDonald-1951" TYPE="STUDY">MacDonald 1951</LINK>; <LINK REF="STD-Wannamaker-1951" TYPE="STUDY">Wannamaker 1951</LINK>). Seven of the remaining studies recruited children up to 18 years of age only (<LINK REF="STD-El_x002d_Daher-1991" TYPE="STUDY">El-Daher 1991</LINK>; <LINK REF="STD-Krober-1985" TYPE="STUDY">Krober 1985</LINK>; <LINK REF="STD-Nelson-1984" TYPE="STUDY">Nelson 1984</LINK>; <LINK REF="STD-Pichichero-1987" TYPE="STUDY">Pichichero 1987</LINK>; <LINK REF="STD-Siegel-1961" TYPE="STUDY">Siegel 1961</LINK>; <LINK REF="STD-Taylor-1977" TYPE="STUDY">Taylor 1977</LINK>; <LINK REF="STD-Zwart-2000" TYPE="STUDY">Zwart 2000</LINK>), three recruited only adults or adolescents aged 15 years or over (<LINK REF="STD-Howe-1997" TYPE="STUDY">Howe 1997</LINK>; <LINK REF="STD-Petersen-1997" TYPE="STUDY">Petersen 1997</LINK>; <LINK REF="STD-Zwart-2003" TYPE="STUDY">Zwart 2003</LINK>) and nine studies recruited both adults and children (<LINK REF="STD-Bennike-1951" TYPE="STUDY">Bennike 1951</LINK>; <LINK REF="STD-Chapple-1956" TYPE="STUDY">Chapple 1956</LINK>; <LINK REF="STD-Dagnelie-1996" TYPE="STUDY">Dagnelie 1996</LINK>; <LINK REF="STD-De-Meyere-1992" TYPE="STUDY">De Meyere 1992</LINK>; <LINK REF="STD-Landsman-1951" TYPE="STUDY">Landsman 1951</LINK>; <LINK REF="STD-Leelarasamee-2000" TYPE="STUDY">Leelarasamee 2000</LINK>; <LINK REF="STD-Little-1997" TYPE="STUDY">Little 1997</LINK>; <LINK REF="STD-Middleton-1988" TYPE="STUDY">Middleton 1988</LINK>; <LINK REF="STD-Whitfield-1981" TYPE="STUDY">Whitfield 1981</LINK>).</P>
<P>All studies recruited patients presenting with symptoms of sore throat. The majority of studies did not distinguish between bacterial and viral aetiology. However, seven studies included or analyzed results for group A beta haemolytic <I>Streptococcus</I> (GABHS) positive patients only (<LINK REF="STD-Catanzaro-1954" TYPE="STUDY">Catanzaro 1954</LINK>; <LINK REF="STD-De-Meyere-1992" TYPE="STUDY">De Meyere 1992</LINK>; <LINK REF="STD-El_x002d_Daher-1991" TYPE="STUDY">El-Daher 1991</LINK>; <LINK REF="STD-Krober-1985" TYPE="STUDY">Krober 1985</LINK>; <LINK REF="STD-Middleton-1988" TYPE="STUDY">Middleton 1988</LINK>; <LINK REF="STD-Nelson-1984" TYPE="STUDY">Nelson 1984</LINK>; <LINK REF="STD-Pichichero-1987" TYPE="STUDY">Pichichero 1987</LINK>), one study distinguished differences in outcomes between GABHS-positive and negative patients (<LINK REF="STD-Dagnelie-1996" TYPE="STUDY">Dagnelie 1996</LINK>) and two studies specifically excluded patients who were GABHS-positive (<LINK REF="STD-Petersen-1997" TYPE="STUDY">Petersen 1997</LINK>; <LINK REF="STD-Taylor-1977" TYPE="STUDY">Taylor 1977</LINK>).</P>
</INCLUDED_STUDIES_DESCR>
<EXCLUDED_STUDIES_DESCR MODIFIED="2013-08-15 20:32:18 +1000" MODIFIED_BY="[Empty name]">
<P>The most common reason for exclusion was lack of appropriate control group (n = 13). Other reasons for exclusion were: irrelevant or non-patient centred outcomes (n = 6), main complaint other than acute sore throat (n = 6), inappropriate or no randomisation to treatment (n = 5), an intervention other than antibiotics was being tested (n = 2), the study tracked natural course of illness only (n = 1) or that the study reported previously published data already included (n = 1).</P>
</EXCLUDED_STUDIES_DESCR>
</STUDY_DESCRIPTION>
<STUDY_QUALITY MODIFIED="2013-09-11 21:36:55 +1000" MODIFIED_BY="[Empty name]">
<P>The overall risk of bias is presented graphically in <LINK REF="FIG-01" TYPE="FIGURE">Figure 1</LINK> and summarised in <LINK REF="FIG-02" TYPE="FIGURE">Figure 2</LINK>.</P>
<ALLOCATION MODIFIED="2011-06-02 11:30:32 +1000" MODIFIED_BY="Liz Dooley">
<P>In most early studies, participants were randomised to treatment and control groups by methods that could potentially introduce bias (for example, Air Force serial number, drawing a card from a deck, hospital bed number) or not randomised at all. Allocation methods were generally appropriate in the later studies.</P>
</ALLOCATION>
<BLINDING MODIFIED="2011-05-18 09:29:50 +1000" MODIFIED_BY="Liz Dooley">
<P>Eighteen of the studies were double-blinded and three were single-blinded.</P>
</BLINDING>
<EXCLUSIONS MODIFIED="2013-09-11 21:36:55 +1000" MODIFIED_BY="[Empty name]">
<P>Outcome data were complete for nearly all studies. For one study it was not clear how many participants maintained pain score diaries and some participants who were initially randomised were excluded due to being GABHS-positive (<LINK REF="STD-Petersen-1997" TYPE="STUDY">Petersen 1997</LINK>).</P>
</EXCLUSIONS>
<OTHER_BIAS_SOURCES MODIFIED="2013-09-11 21:17:20 +1000" MODIFIED_BY="[Empty name]">
<P>The use of antipyretic analgesics was not stated in nine studies, administered routinely in five studies and prohibited in four studies. The prohibition of analgesics might exaggerate any small symptomatic benefit of antibiotics over control if antipyretic analgesics are usually recommended in normal practice.</P>
</OTHER_BIAS_SOURCES>
</STUDY_QUALITY>
<INTERVENTION_EFFECTS MODIFIED="2013-09-11 21:28:12 +1000" MODIFIED_BY="[Empty name]">
<SUBSECTION>
<HEADING LEVEL="3">Primary outcomes</HEADING>
<SUBSECTION>
<HEADING LEVEL="4">1. Symptoms of sore throat on day three</HEADING>
<P>At day three of the illness, antibiotics reduced symptoms of sore throat (risk ratio (RR) 0.68; 95% confidence interval (CI) 0.59 to 0.79) (<LINK REF="CMP-001.01" TYPE="ANALYSIS">Analysis 1.1</LINK>). Day three was the greatest time of benefit because the symptoms of only half the participants had settled.</P>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="4">2. Symptoms of sore throat at one week (days six to eight)</HEADING>
<P>At one week (six to eight days) the RR of experiencing sore throat was 0.49 (95% CI 0.32 to 0.76) (<LINK REF="CMP-001.05" TYPE="ANALYSIS">Analysis 1.5</LINK>), although 82% of controls were better by this time.<BR/>
</P>
</SUBSECTION>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="3">Secondary outcomes</HEADING>
<SUBSECTION>
<HEADING LEVEL="4">1. Symptoms of fever at day three</HEADING>
<P>At day three of the illness, antibiotics reduced symptoms of fever (RR 0.71; 95% CI 0.45 to 1.10) (<LINK REF="CMP-002.01" TYPE="ANALYSIS">Analysis 2.1</LINK>).</P>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="4">2. Symptoms of headache at day three</HEADING>
<P>At day three of the illness, antibiotics reduced symptoms of headache (RR 0.44; 95% CI 0.27 to 0.71) (<LINK REF="CMP-003.01" TYPE="ANALYSIS">Analysis 3.1</LINK>).</P>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="4">3. Incidence of suppurative complications</HEADING>
<P>Antibiotics reduced the incidence of acute otitis media to about one-third of that in the placebo group (RR 0.30; 95% CI 0.15 to 0.58) (<LINK REF="CMP-004.04" TYPE="ANALYSIS">Analysis 4.4</LINK>) and reduced the incidence of acute sinusitis to about one-half of that in the placebo group (RR 0.48; 95% CI 0.08 to 2.76) (<LINK REF="CMP-004.06" TYPE="ANALYSIS">Analysis 4.6</LINK>). Data indicate that the incidence of quinsy was also reduced in relation to the placebo group (RR 0.15; 95% CI 0.05 to 0.47) (<LINK REF="CMP-004.07" TYPE="ANALYSIS">Analysis 4.7</LINK>).</P>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="4">4. Incidence of non-suppurative complications</HEADING>
<P>Cases of acute glomerulonephritis only occurred in the control group which suggests protection by antibiotics. However, there were only two cases and only 10 studies reported on acute glomerulonephritis as an endpoint. Therefore, our estimate of the protection has a very wide 95% CI (RR 0.22; 95% CI 0.02 to 2.08) (<LINK REF="CMP-004.08" TYPE="ANALYSIS">Analysis 4.8</LINK>) which precludes us from definitively claiming that antibiotics protect sore throat sufferers from acute glomerulonephritis.</P>
<P>Several studies found benefit from antibiotics for acute rheumatic fever which reduced this complication to about one-quarter of that in the placebo group (RR 0.27; 95% CI 0.12 to 0.60) (<LINK REF="CMP-004.01" TYPE="ANALYSIS">Analysis 4.1</LINK>). Few studies examined antibiotics other than penicillin. Confining the analysis to penicillin alone resulted in no difference in estimated protection (RR 0.27; 95% CI 0.14 to 0.50) (<LINK REF="CMP-004.02" TYPE="ANALYSIS">Analysis 4.2</LINK>).</P>
</SUBSECTION>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="3">Subgroup analysis of symptom reduction</HEADING>
<SUBSECTION>
<HEADING LEVEL="4">1. Blind versus unblinded studies</HEADING>
<P>There was no significant difference between blinded and unblinded studies for symptoms of sore throat at day three (RR 0.65; 95% CI 0.54 to 0.78 and RR 0.79; 95% CI 0.60 to 1.05, respectively) (<LINK REF="CMP-001.02" TYPE="ANALYSIS">Analysis 1.2</LINK>) nor at one week (RR 0.62; 95% CI 0.38 to 1.03 and RR 0.30; 95% CI 0.08 to 1.15, respectively) (<LINK REF="CMP-001.06" TYPE="ANALYSIS">Analysis 1.6</LINK>). Contrary to expectation, the trend was for a greater effect of antibiotics for blind studies at day three.</P>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="4">2. Antipyretics administered versus not administered</HEADING>
<P>Use of antipyretics led to no significant difference between studies in which antipyretics were offered and those in which they were not (RR 0.52; 95% CI 0.33 to 0.81 and RR 0.62; 95% CI 0.55 to 0.70, respectively) (<LINK REF="CMP-001.03" TYPE="ANALYSIS">Analysis 1.3</LINK>).</P>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="4">3. Throat swabs positive for <I>Streptococcus</I> versus negative for <I>Streptococcus</I> versus not tested and/or inseparable combined data</HEADING>
<P>The probability of still experiencing pain on day three is slightly more than one-half (RR 0.58; 95% CI 0.48 to 0.71) for those participants who had positive throat swabs for GABHS, compared to three-quarters (RR 0.78; 95% CI 0.63 to 0.97) for those with negative swabs (<LINK REF="CMP-001.04" TYPE="ANALYSIS">Analysis 1.4</LINK>). There was a similar effect at one week (RR 0.29; 95% CI 0.12 to 0.70 and RR 0.73; 95% CI 0.50 to 1.07, respectively) (<LINK REF="CMP-001.07" TYPE="ANALYSIS">Analysis 1.7</LINK>). That is, the effectiveness of antibiotics is increased in people with <I>Streptococci</I> growing in the throat.</P>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="4">4. Children versus adults</HEADING>
<P>There were few studies that included children (younger than 13 years of age): only 61 cases in total for when fever was evaluated at day three. There was overlap of the RR 95% CI, so that the trend for children to not experience benefits was not significantly different to adults who did (RR 1.27; 95% CI 0.76 to 2.13 and RR 0.29; 95% CI 0.06 to 1.51, respectively) (<LINK REF="CMP-002.03" TYPE="ANALYSIS">Analysis 2.3</LINK>).</P>
<P>Some of these results are summarised in <LINK REF="FIG-03" TYPE="FIGURE">Figure 3</LINK>.</P>
<P>A trial from Thailand was included in the 2003 update (<LINK REF="STD-Leelarasamee-2000" TYPE="STUDY">Leelarasamee 2000</LINK>). It is especially important because it is one of the few trials from a non-Western industrial country. Unfortunately we were unable to enter its data into the meta-analysis because of different ways of collecting the data (in particular no data were collected mid-way through the illness). Nevertheless, the use of antibiotics conferred no benefit (nor harms) on symptoms or complications.</P>
</SUBSECTION>
</SUBSECTION>
</INTERVENTION_EFFECTS>
</RESULTS>
<DISCUSSION MODIFIED="2013-10-25 10:49:13 +1000" MODIFIED_BY="[Empty name]">
<SUBSECTION>
<HEADING LEVEL="4">Natural history</HEADING>
<P>In the placebo groups, after three days symptoms of sore throat and fever had disappeared in about 40% and 85%, respectively. Eighty-two percent of participants were symptom-free by one week. This natural history was similar in <I>Streptococcus-</I>positive, negative and untested participants. About 1.7 per 100 placebo participants developed rheumatic fever. However, this complication occurred only in trials reporting before 1961. The background incidence of acute rheumatic fever has continued to decline in Western societies since then.</P>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="4">Benefits of treatment</HEADING>
<P>The absolute benefit of antibiotics for the duration of symptoms was modest. The reduction of illness time is greatest in the middle of the illness period when the mean absolute reduction is about one day at around day three. There are not enough data to draw conclusions about children. The absolute reduction averaged over the whole illness can only be estimated from these data. The difference in the area under the survival curves of sore throat symptoms for those treated with placebo as opposed to antibiotic is about 16 hours for the first week.</P>
<P>Estimates of the number of people with sore throat who must be treated to resolve the symptoms of one by day three (the number needed to treat to benefit (NNTB)) is about 3.7 for those with positive throat swabs for <I>Streptococcus</I>. It is 6.5 for those with a negative swab and 14.4 for those in whom no swab has been taken. The last result is difficult to understand. Intuitively one would expect the NNTB value to lie between both the swab-negative and swab-positive results. Perhaps participants with less severe throat infections were recruited into the three studies in which swabs were not taken.</P>
<P>Antibiotics are effective at reducing the relative complication rate of people suffering sore throat. However, the relative benefit exaggerates the absolute benefit because complication rates are low and the illness is short-lived. Interpretation of these data is aided by estimating the absolute benefit, which we attempt below.</P>
<P>In these trials, conducted mostly in the 1950s, for every 100 participants treated with antibiotics rather than placebo, there was one fewer case of acute rheumatic fever, two fewer cases of acute otitis media and three fewer cases of quinsy. These figures need to be adapted to current circumstances and individuals. For example, the complication rate of acute otitis media among those with sore throats before 1975 was 3%. A NNTB of about 50 to prevent one case of acute otitis media can be estimated from the data. After 1975, this complication rate fell to 0.7% and applying the odds of reducing the complication with antibiotics from the data table yields a NNTB of nearly 200 to prevent one case of acute otitis media. Clinicians will have to exercise judgement in applying these data to their patients.</P>
<P>In particular, in high-income countries (where absolute rates of complications are lower) the NNTB will rise above a rate at which it might be regarded as worthwhile to treat. In low-income countries where the absolute rate may be much higher, the lower NNTB will mean antibiotics are more likely to be effective.</P>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="4">Adverse effects of treatment</HEADING>
<P>We were unable to present the adverse effects of antibiotic use because of inconsistencies in recording these symptoms. In other studies these were principally diarrhea, rashes and thrush (<LINK REF="REF-Venekamp-2013" TYPE="REFERENCE">Venekamp 2013</LINK>). Consideration of the side effects of antibiotics would have been useful in further defining their risk-benefits.</P>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="4">Special risk groups</HEADING>
<P>Acute rheumatic fever is common among people living in some parts of the world (Australian Aborigines living in low socio-economic conditions, for example) and antibiotics may be justified to reduce the complication of acute rheumatic fever in these settings. In other parts of the world the incidence of acute rheumatic fever is so low (one estimate is that it took 12 General Practitioners' working lifetimes to encounter one new case of acute rheumatic fever in Western Scotland in the 1980s (<LINK REF="REF-Howie-1985" TYPE="REFERENCE">Howie 1985</LINK>)) that the risks of serious complications arising from using antibiotics for sore throat might be of the same order as that of acute rheumatic fever.</P>
</SUBSECTION>
<SUMMARY_OF_RESULTS MODIFIED="2013-09-11 21:30:54 +1000" MODIFIED_BY="[Empty name]">
<SUBSECTION>
<HEADING LEVEL="4">1. Symptoms</HEADING>
<P>Throat soreness and fever were reduced by about half when using antibiotics. The greatest difference was seen at day three. The number needed to treat to benefit (NNTB) to prevent one sore throat at day three was less than six; at week one it was 21. Antibiotics were more effective against symptoms at day three and one week if throat swabs were positive for <I>Streptococcus</I> compared to negative throat swabs.</P>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="4">2. Non-suppurative complications</HEADING>
<P>Antibiotics showed a trend for protecting against acute glomerulonephritis but there were too few cases for the results to reach statistical significance. Antibiotics reduced acute rheumatic fever by more than two-thirds.</P>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="4">3. Suppurative complications</HEADING>
<P>Antibiotics significantly reduced the incidence of acute otitis media by two-thirds, acute sinusitis by a half and quinsy by 85% compared to those taking placebo.</P>
</SUBSECTION>
<SUBSECTION>
<HEADING LEVEL="2">Authors' conclusions </HEADING>
<P>Antibiotics confer relative benefits in the treatment of sore throat. However, the absolute benefits are modest. Protecting sore throat sufferers against suppurative and non-suppurative complications in high-income countries requires treating many with antibiotics for one to benefit. This NNTB may be lower in low-income countries. Antibiotics shorten the duration of symptoms by about 16 hours overall.</P>
</SUBSECTION>
</SUMMARY_OF_RESULTS>
<APPLICABILITY_OF_FINDINGS MODIFIED="2011-05-19 16:53:52 +1000" MODIFIED_BY="[Empty name]">
<P>The majority of trials included in this review were conducted prior to 1975, with only three trials published since 2000. The main reason for this is that very few antibiotic trials conducted recently include a placebo control arm. It is therefore unknown whether changes in bacterial resistance and population immunity over time may have altered the applicability of results.</P>
</APPLICABILITY_OF_FINDINGS>
<QUALITY_OF_EVIDENCE MODIFIED="2011-05-19 16:53:52 +1000" MODIFIED_BY="[Empty name]">
<P>The quality of the evidence is considered to be moderate to high. The greatest compromise to evidence quality arose from non-clarity in treatment allocation procedures.</P>
</QUALITY_OF_EVIDENCE>
<POTENTIAL_BIASES MODIFIED="2013-09-11 21:17:20 +1000" MODIFIED_BY="[Empty name]">
<P>Non-reporting of anti-pyretic use in a high number of studies may have constituted a source of bias in the results. Publication bias may also be considered a potential threat to the validity of results, particularly for the earlier studies.</P>
</POTENTIAL_BIASES>
<AGREEMENT MODIFIED="2013-09-11 21:17:20 +1000" MODIFIED_BY="[Empty name]">
<P>A recent review analysing the risk-benefit profile of antimicrobial prescribing for children concluded that antibiotics show little benefit in preventing quinsy following sore throat (<LINK REF="REF-Keith-2010" TYPE="REFERENCE">Keith 2010</LINK>). A clinical evidence review of antibiotic treatment for streptococcal pharyngitis concluded that among patients with signs and symptoms of positive bacterial infection, a specific diagnosis should be determined by performing either a throat culture or rapid antigen-detection test, especially in children (<LINK REF="REF-Wessels-2011" TYPE="REFERENCE">Wessels 2011</LINK>). Antibiotic treatment with penicillin or a first-generation cephalosporin is then recommended in the case of positive bacteriologic assessment.</P>
</AGREEMENT>
</DISCUSSION>
<CONCLUSIONS MODIFIED="2013-09-11 21:17:20 +1000" MODIFIED_BY="[Empty name]">
<IMPLICATIONS_PRACTICE MODIFIED="2011-05-18 09:58:52 +1000" MODIFIED_BY="Liz Dooley">
<P>Antibiotics have a beneficial effect on both suppurative and symptom reduction.</P>
<P>The effect on symptoms is small, so that clinicians must judge with individual cases whether it is clinically justifiable to employ antibiotics to produce this effect. In other words their use should be discretionary rather than either prohibited or mandatory. Since 90% of patients are symptom-free by one week (whether or not treated with antibiotics), the absolute benefit of antibiotics at this time and beyond is vanishingly small.</P>
<P>Acute rheumatic fever is common among people living in some parts of the world (Australian Aborigines living in low socio-economic conditions, for example) and antibiotics may be justified to reduce the incidence of this complication in these settings. For other settings where rheumatic fever is rare, there is a balance to be made between modest symptom reduction and the hazards of antimicrobial resistance.</P>
</IMPLICATIONS_PRACTICE>
<IMPLICATIONS_RESEARCH MODIFIED="2013-09-11 21:17:20 +1000" MODIFIED_BY="[Empty name]">
<P>More trials are needed in low-income countries, in socio-economically deprived sections of high-income countries and also in children. In high-income countries, better prognostic studies are called for which can predict which patients may develop suppurative and non-suppurative complications. This will help to further define which patients benefit from antibiotics.</P>
<P>Studies which use patient-centred outcome measures compatible with those presented here would be greatly beneficial, in terms of easier comparison and analysis of results and ready inclusion into future updates of this review.</P>
<P>Few trials have attempted to measure the severity of symptoms. If antibiotics reduce the severity as well as the duration of symptoms, their benefit will have been underestimated in this meta-analysis.</P>
</IMPLICATIONS_RESEARCH>
</CONCLUSIONS>
</BODY>
<ACKNOWLEDGEMENTS MODIFIED="2013-09-11 20:39:11 +1000" MODIFIED_BY="[Empty name]">
<P>A previous update was completed with the help of a Glaxo sponsored educational support grant from the Australasian Cochrane Centre. The 2006 update was supported by a grant from the UK NHS through the Acute Respiratory Infections Group, based in Australia (at Bond University).</P>
<P>Thanks to Prof Jim Dickinson for helpful suggestions about dividing the studies into early and late last century to examine the idea that the pathogenesis of this illness, and/or its sequelae, have changed with time. Thanks to Ian Thomas and Michael Thomas for research assistance. Thanks to Beth Clewer and Katie Farmer who in January 1999 drew our attention to mistakes in the data extraction by their careful checking of original studies as part of their medical student project at the University of Bristol Medical School. The authors wish to thank the following people for commenting on the 2006 draft of this updated review: Craig Mellis, Mark Jones and Tom Fahey.</P>
</ACKNOWLEDGEMENTS>
<CONFLICT_OF_INTEREST MODIFIED="2013-10-25 14:56:46 +1000" MODIFIED_BY="Liz Dooley">
<P>Paul Glasziou is on the board of Therapeutic Guidelines Limited and holds a research grant from the NHMRC on antibiotic resistance.</P>
<P>Chris Del Mar has received funding from the NHMRC for antibiotic resistance, funding the ARI Cochrane Group, and from some consultancies (GSK for advice about vaccines for otitis media; and a local pharmaceutical company contemplating analgesic ear drops for otitis media). </P>
<P>Anneliese Spinks does not have any interests to declare relevant to this review.<BR/>
</P>
</CONFLICT_OF_INTEREST>
<CONTRIBUTIONS MODIFIED="2011-07-11 02:25:31 +1000" MODIFIED_BY="[Empty name]">
<P>Chris Del Mar first conceived the review, presenting it as a meta-analysis in a journal (<LINK REF="REF-Del-Mar-1992a" TYPE="REFERENCE">Del Mar 1992a</LINK>; <LINK REF="REF-Del-Mar-1992b" TYPE="REFERENCE">Del Mar 1992b</LINK>). It was subsequently improved and modified for <I>The Cochrane Library</I> with Paul Glasziou (who improved the subgroup analyses) and Anneliese Spinks (who updated searches and completed the analyses).</P>
</CONTRIBUTIONS>
<PRO_REV_DIFF/>
<PUBLIC_NOTES MODIFIED="2013-08-21 11:40:54 +1000" MODIFIED_BY="[Empty name]"/>
</MAIN_TEXT>
<STUDIES_AND_REFERENCES MODIFIED="2013-09-11 21:08:16 +1000" MODIFIED_BY="[Empty name]">
<STUDIES MODIFIED="2013-09-11 21:05:12 +1000" MODIFIED_BY="[Empty name]">
<INCLUDED_STUDIES MODIFIED="2013-09-11 21:01:41 +1000" MODIFIED_BY="[Empty name]">
<STUDY DATA_SOURCE="PUB" ID="STD-Bennike-1951" NAME="Bennike 1951" YEAR="1951">
<REFERENCE NOTES="<p>Bennike TBMK, Kjaer E, Skadhauge K, Trolle E. Penicillin therapy in acute tonsillitis, phlegmonous tonsillitis and ulcerative tonsillitis. Acta Media Scand. 1951;139:253-274.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Bennike TBMK, Kjaer E, Skadhauge K, Trolle E</AU>
<TI>Penicillin therapy in acute tonsillitis, phlegmonous tonsillitis and ulcerative tonsillitis</TI>
<SO>Acta Medica Scandinavica</SO>
<YR>1951</YR>
<VL>139</VL>
<PG>253-74</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Brink-1951" NAME="Brink 1951" YEAR="1951">
<REFERENCE NOTES="<p>Brink WRR, Denny FW, Wannamaker LW. Effect of penicillin and aureomycin on the natural course of streptococcal tonsillitis and pharyngitis. Am J Med. 1951;10:300-308.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Brink WRR, Denny FW, Wannamaker LW</AU>
<TI>Effect of penicillin and aureomycin on the natural course of streptococcal tonsillitis and pharyngitis</TI>
<SO>American Journal of Medicine</SO>
<YR>1951</YR>
<VL>10</VL>
<PG>300-8</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Brumfitt-1957" NAME="Brumfitt 1957" YEAR="1957">
<REFERENCE NOTES="<p>Brumfitt WS, Slater DH. Treatment of acute sore throat with penicillin: a controlled trial among young soldiers. Lancet 1957;1:8-11.<br>Brumfitt 1957 <br>Lancet 1957 272(6958):8-11</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Brumfitt WS, Slater DH</AU>
<TI>Treatment of acute sore throat with penicillin: a controlled trial among young soldiers</TI>
<SO>Lancet</SO>
<YR>1957</YR>
<VL>272</VL>
<NO>6958</NO>
<PG>8-11</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Catanzaro-1954" NAME="Catanzaro 1954" YEAR="1954">
<REFERENCE NOTES="<p>Catanzaro 1954 (CHANGE TO TITLE AND ADDED ISSUE NO. AS PER PUBMED CITATION) <br>Catanzaro FJ, Morris AJ, Chamovitz R, Rammelkamp CH, Stolzer B, Perry WD. The role of Streptococcus in the pathogenesis of rheumatic fever. American Journal of Medicine 1954;17(6):749-56 </p><p></p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Catanzaro FJ, Morris AJ, Chamovitz R, Rammelkamp CH, Stolzer B, Perry WD</AU>
<TI>The role of Streptococcus in the pathogenesis of rheumatic fever</TI>
<SO>American Journal of Medicine</SO>
<YR>1954</YR>
<VL>17</VL>
<NO>6</NO>
<PG>749-56</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Chamovitz-1954" NAME="Chamovitz 1954" YEAR="1954">
<REFERENCE NOTES="<p>Chamovitz R, Stetson CA, Rammelkamp CH. Prevention of rheumatic fever by treatment of previous streptococcal infections. N Engl J Med 1954;251:466-471.<br>Chamovitz 1954 <br>New England Journal of Medicine 1954;251(12):466-71</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Chamovitz R, Stetson CA, Rammelkamp CH</AU>
<TI>Prevention of rheumatic fever by treatment of previous streptococcal infections</TI>
<SO>New England Journal of Medicine</SO>
<YR>1954</YR>
<VL>251</VL>
<NO>12</NO>
<PG>466-71</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Chapple-1956" NAME="Chapple 1956" YEAR="1956">
<REFERENCE NOTES="<p>Chapple LM, Paulett JD, Tuckman E, Woodall JT, Tomlinson AJH, McDonald JC. Treatment of acute sore throat in general practice. BMJ. 1956; March: 705-708.<br>Chapple 1956 <br>British Medical Journal 1956 Mar 31;(4969):705-8</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Chapple LM, Paulett JD, Tuckman E, Woodall JT, Tomlinson AJH, McDonald JC</AU>
<TI>Treatment of acute sore throat in general practice</TI>
<SO>British Medical Journal</SO>
<YR>1956</YR>
<VL>March</VL>
<NO>4969</NO>
<PG>705-8</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="MIX" ID="STD-Dagnelie-1996" NAME="Dagnelie 1996" YEAR="1996">
<REFERENCE NOTES="<p>Dagnelie CF, van-der-Graaf Y, De Melker RA. Do patients with sore throat benefit from penicillin? A randomised double-blind placebo-controlled clinical trial with penicillin V in general practice. Br J Gen Pract. 1996;46(411):589-93.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Dagnelie CF, van-der-Graaf Y, De Melker RA</AU>
<TI>Do patients with sore throat benefit from penicillin? A randomised double-blind placebo-controlled clinical trial with penicillin V in general practice</TI>
<SO>British Journal of General Practice</SO>
<YR>1996</YR>
<VL>46</VL>
<NO>411</NO>
<PG>589-93</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-De-Meyere-1992" NAME="De Meyere 1992" YEAR="1992">
<REFERENCE NOTES="<p>De Meyere M, Mervielde Y, Verschraegen G, Bogaert M. Effect of penicillin on the clinical course of streptococcal pharngitis in general practice. Euro J Clin Pharmacol. 1992;43:581-585.<br>De Meyere 1992 <br>European Journal of Clinical Pharmacology 1992;43(6):581-5</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>De Meyere M, Mervielde Y, Verschraegen G, Bogaert M</AU>
<TI>Effect of penicillin on the clinical course of streptococcal pharyngitis in general practice</TI>
<SO>European Journal of Clinical Pharmacology</SO>
<YR>1992</YR>
<VL>43</VL>
<NO>6</NO>
<PG>581-5</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Denny-1950" NAME="Denny 1950" YEAR="1950">
<REFERENCE NOTES="<p>Denny LW, Brink WR, Rammelkamp CH, Custer EA. Prevention of rhuematic fever: treatment of the preceding streptococcal infection. JAMA. 1950;143:151-153.<br>Denny 1950 <br>Journal of the American Medical Association 1950;143(2):151-3.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Denny LW, Brink WR, Rammelkamp CH, Custer EA</AU>
<TI>Prevention of rheumatic fever: treatment of the preceding streptococcal infection</TI>
<SO>Journal of the American Medical Association</SO>
<YR>1950</YR>
<VL>143</VL>
<NO>2</NO>
<PG>151-3</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Denny-1953" MODIFIED="2009-01-07 14:17:18 +1000" MODIFIED_BY="[Empty name]" NAME="Denny 1953" YEAR="1953">
<REFERENCE MODIFIED="2009-01-07 14:17:18 +1000" MODIFIED_BY="[Empty name]" NOTES="<p>Denny LW, Hahn EO. Comparative effects of penicillin, aureomycin and terramycin on streptococcal tonsillitis and pharygitis. Pediatr. 1953;11:7- 14.<br>Denny 1953 <br>Pediatrics 1953;11(1):7-14 </p><p></p>" NOTES_MODIFIED="2009-01-07 14:17:18 +1000" NOTES_MODIFIED_BY="[Empty name]" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Denny LW, Hahn EO</AU>
<TI>Comparative effects of penicillin, aureomycin and terramycin on streptococcal tonsillitis and pharyngitis</TI>
<SO>Pediatrics</SO>
<YR>1953</YR>
<VL>11</VL>
<NO>1</NO>
<PG>7-14</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-El_x002d_Daher-1991" NAME="El-Daher 1991" YEAR="1991">
<REFERENCE PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>El-Daher NT, Hijazi SS, Rawashdeh NM, Al-Khalil IA, Abu-Ektaish FM, Abdel-Latif DI</AU>
<TI>Immediate vs. delayed treatment of Group A beta-hemolytic streptococcal pharyngitis with penicillin V</TI>
<SO>Pediatric Infectious Diseases Journal</SO>
<YR>1991</YR>
<VL>10</VL>
<NO>2</NO>
<PG>126-30</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="MIX" ID="STD-Howe-1997" NAME="Howe 1997" YEAR="1997">
<REFERENCE NOTES="<p>Howe RW, Millar MR, Coast J, Whitfield M, Peters TJ, Brookes S. A randomized controlled trial of antibiotics on symptom resolution in patients presenting to their general practitioner with a sore throat. Br J Gen Practice. 1997;47(418):280-4.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Howe RW, Millar MR, Coast J, Whitfield M, Peters TJ, Brookes S</AU>
<TI>A randomized controlled trial of antibiotics on symptom resolution in patients presenting to their general practitioner with a sore throat</TI>
<SO>British Journal of General Practice</SO>
<YR>1997</YR>
<VL>47</VL>
<NO>418</NO>
<PG>280-4</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Krober-1985" MODIFIED="2011-07-11 02:33:57 +1000" MODIFIED_BY="[Empty name]" NAME="Krober 1985" YEAR="1985">
<REFERENCE MODIFIED="2011-07-11 02:33:57 +1000" MODIFIED_BY="[Empty name]" NOTES="<p>Krober JW, Michels GN. Streptococcal pharyngitis: placebo controlled double blind evaluation of clinical repsonse to penicillin therapy. JAMA. 1985;253:1271-1274.<br>Krober 1985 <br>Journal of the American Medical Association 1985;253(9):1271-4</p>" NOTES_MODIFIED="2011-07-11 02:33:57 +1000" NOTES_MODIFIED_BY="[Empty name]" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Krober JW, Michels GN</AU>
<TI>Streptococcal pharyngitis: Placebo controlled double blind evaluation of clinical response to penicillin therapy</TI>
<SO>JAMA</SO>
<YR>1985</YR>
<VL>253</VL>
<NO>9</NO>
<PG>1271-4</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Landsman-1951" NAME="Landsman 1951" YEAR="1951">
<REFERENCE NOTES="<p>Landsman JB, Grist NR, Black R, McFarlane D, Blair W. Sore throat in general practice. BMJ. 1951;1:326-329.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Landsman JB, Grist NR, Black R, McFarlane D, Blair W</AU>
<TI>Sore throat in general practice</TI>
<SO>British Medical Journal</SO>
<YR>1951</YR>
<VL>1</VL>
<PG>326-9</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Leelarasamee-2000" MODIFIED="2011-05-18 07:56:29 +1000" MODIFIED_BY="Liz Dooley" NAME="Leelarasamee 2000" YEAR="2000">
<REFERENCE MODIFIED="2011-05-18 07:56:29 +1000" MODIFIED_BY="Liz Dooley" NOTES="<p>Leelarasamee 2000 <br>International Journal of Infectious Diseases 2000;4(2):70-4.</p>" NOTES_MODIFIED="2011-05-18 07:56:29 +1000" NOTES_MODIFIED_BY="Liz Dooley" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Leelarasamee A, Leowattana W, Tobunluepop P, Chub-upakarn S, Artavetakan W, Jarupoonphol V, et al</AU>
<TI>Amoxycillin for fever and sore throat due to non-exudative pharyngotonsillitis: beneficial or harmful?</TI>
<SO>International Journal of Infectious Diseases</SO>
<YR>2000</YR>
<VL>4</VL>
<NO>2</NO>
<PG>70-4</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="MIX" ID="STD-Little-1997" MODIFIED="2011-05-25 10:02:32 +1000" MODIFIED_BY="[Empty name]" NAME="Little 1997" YEAR="1997">
<REFERENCE NOTES="<p>Little P, Gould C, Williamson I, Warner G, Gantley M, Kinmonth AL. Reattendance and complications in a randomised trial of prescribing strategies for sore throat: the medicaliseing efect of prescribing antibiotics. BMJ. 1997;315:350-2. Little 1997 <br>BMJ 1997;315(7104):350-2</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Little P, Gould C, Williamson I, Warner G, Gantley M, Kinmonth AL</AU>
<TI>Reattendance and complications in a randomised trial of prescribing strategies for sore throat: the medicalising effect of prescribing antibiotics</TI>
<SO>BMJ</SO>
<YR>1997</YR>
<VL>315</VL>
<NO>7104</NO>
<PG>350-2</PG>
<IDENTIFIERS/>
</REFERENCE>
<REFERENCE MODIFIED="2011-05-25 10:02:32 +1000" MODIFIED_BY="[Empty name]" PRIMARY="YES" TYPE="JOURNAL_ARTICLE">
<AU>Little P, Williamson I, Warner G, Gould C, Gantley M, Kinmonth AL</AU>
<TI>Open randomised trial of prescribing strategies in managing sore throat</TI>
<SO>BMJ</SO>
<YR>1997</YR>
<VL>314</VL>
<PG>722-7</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-MacDonald-1951" NAME="MacDonald 1951" YEAR="1951">
<REFERENCE NOTES="<p>MacDonald TC, Watson IH. Sulphonamides and acute tonsillitis: a controlled experiment in a Royal Airforce community. BMJ. 1951;1:323-326.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>MacDonald TC, Watson IH</AU>
<TI>Sulphonamides and acute tonsillitis: a controlled experiment in a Royal Airforce community</TI>
<SO>British Medical Journal</SO>
<YR>1951</YR>
<VL>1</VL>
<PG>323-6</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Middleton-1988" MODIFIED="2011-05-18 07:57:40 +1000" MODIFIED_BY="Liz Dooley" NAME="Middleton 1988" YEAR="1988">
<REFERENCE MODIFIED="2011-05-18 07:57:40 +1000" MODIFIED_BY="Liz Dooley" NOTES="<p>Middleton 1988 <br>The Journal of Pediatrics 1988;113(6):1089-94</p>" NOTES_MODIFIED="2011-05-18 07:57:40 +1000" NOTES_MODIFIED_BY="Liz Dooley" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Middleton DB, D'Amico F, Merenstein JH</AU>
<TI>Standardized symptomatic treatment versus penicillin as initial therapy for streptococcal pharyngitis</TI>
<SO>Journal of Pediatrics</SO>
<YR>1988</YR>
<VL>113</VL>
<NO>6</NO>
<PG>1089-94</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Nelson-1984" NAME="Nelson 1984" YEAR="1984">
<REFERENCE NOTES="<p>Nelson JD. The effect of penicillin therapy on the symptoms and signs of streptococcal pharyngitis. Ped Inf Dis. 1984;3:10-13.<br>Nelson 1984 <br>Pediatric Infectious Disease 1984;3(1):10-3</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Nelson JD</AU>
<TI>The effect of penicillin therapy on the symptoms and signs of streptococcal pharyngitis</TI>
<SO>Pediatric Infectious Disease</SO>
<YR>1984</YR>
<VL>3</VL>
<NO>1</NO>
<PG>10-3</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Petersen-1997" MODIFIED="2011-07-11 02:34:07 +1000" MODIFIED_BY="[Empty name]" NAME="Petersen 1997" YEAR="1997">
<REFERENCE MODIFIED="2011-07-11 02:34:07 +1000" MODIFIED_BY="[Empty name]" NOTES="<p>Peterson K, Phillips RS, Soukup J, Komaroff AL, Aronson M. The effect of Erythromycin on resolution of symptoms among adults with pharyngitis not caused by Group A Atreptococcus. J Gen Intern Med. 1997;12:95-101.<br>Petersen 1997 <br>Journal of General Internal Medicine 1997;12(2):95-101</p>" NOTES_MODIFIED="2011-07-11 02:34:07 +1000" NOTES_MODIFIED_BY="[Empty name]" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Peterson K, Phillips RS, Soukup J, Komaroff AL, Aronson M</AU>
<TI>The effect of erythromycin on resolution of symptoms among adults with pharyngitis not caused by Group A Streptococcus</TI>
<SO>Journal of General Internal Medicine</SO>
<YR>1997</YR>
<VL>12</VL>
<NO>2</NO>
<PG>95-101</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Pichichero-1987" MODIFIED="2013-09-11 21:01:41 +1000" MODIFIED_BY="[Empty name]" NAME="Pichichero 1987" YEAR="1987">
<REFERENCE MODIFIED="2013-09-11 21:01:41 +1000" MODIFIED_BY="[Empty name]" NOTES="<p>Pichichero FA, Talpey WB, Green JL, Francis AB, Roghmann KJ, Hoekelman RA. Adverse and beneficial effects of immediate treatment of Group A Beta Haemolytic Streptococcal pharyngitis with penicillin. Ped Inf Dis. 1987;6:635-643.<br>Pichichero 1987 <br>Pediatric Infectious Disease 1987;6(7):635-43</p>" NOTES_MODIFIED="2013-09-11 21:01:41 +1000" NOTES_MODIFIED_BY="[Empty name]" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Pichichero FA, Talpey WB, Green JL, Francis AB, Roghmann KJ, Hoekelman RA</AU>
<TI>Adverse and beneficial effects of immediate treatment of group A beta haemolytic streptococcal pharyngitis with penicillin</TI>
<SO>Pediatric Infectious Disease</SO>
<YR>1987</YR>
<VL>6</VL>
<NO>7</NO>
<PG>635-43</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Siegel-1961" NAME="Siegel 1961" YEAR="1961">
<REFERENCE NOTES="<p>Siegel EE, Stollerman GH. Controlled studies of streptococcal pharyngitis in a pediatric population. N Engl J Med. 1961;265:559- 565.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Siegel EE, Stollerman GH</AU>
<TI>Controlled studies of streptococcal pharyngitis in a pediatric population</TI>
<SO>New England Journal of Medicine</SO>
<YR>1961</YR>
<VL>265</VL>
<PG>559-65</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Taylor-1977" MODIFIED="2011-07-11 02:34:17 +1000" MODIFIED_BY="[Empty name]" NAME="Taylor 1977" YEAR="1977">
<REFERENCE MODIFIED="2011-07-11 02:34:17 +1000" MODIFIED_BY="[Empty name]" NOTES="<p>Taylor GD, McKerr M, Fergusson DM. Amoxycillin and co- trimoxazole in presumed viral respiratory infections of childhood: placebo controlled trial. BMJ. 1977;2:552-554.<br>Taylor 1977 <br>British Medical Journal 1977;2(6086):552-4</p>" NOTES_MODIFIED="2011-07-11 02:34:17 +1000" NOTES_MODIFIED_BY="[Empty name]" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Taylor B, Abbott GD, McKerr M, Fergusson DM</AU>
<TI>Amoxycillin and co-trimoxazole in presumed viral respiratory infections of childhood: placebo controlled trial</TI>
<SO>British Medical Journal</SO>
<YR>1977</YR>
<VL>2</VL>
<NO>6086</NO>
<PG>552-4</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Wannamaker-1951" NAME="Wannamaker 1951" YEAR="1951">
<REFERENCE NOTES="<p>Wannamaker LW, Rammelkamp CH, Denny FW, Brink WR, Houser HB, Hahn EO. Prophylaxis of acute rheumatic fever by treatment of the preceding streptococcal infection with various amounts of depot penicillin. Am J Med. 1951;10: 673-694.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Wannamaker LW, Rammelkamp CH, Denny FW, Brink WR, Houser HB, Hahn EO</AU>
<TI>Prophylaxis of acute rheumatic fever by treatment of the preceding streptococcal infection with various amounts of depot penicillin</TI>
<SO>American Journal of Medicine</SO>
<YR>1951</YR>
<VL>10</VL>
<PG>673-94</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Whitfield-1981" NAME="Whitfield 1981" YEAR="1981">
<REFERENCE NOTES="<p>Whitfield AO. Penicillin in sore throat. Pract. 1981;225:234-239.<br>Whitfield 1981 <br>Penicillin in sore throat. Practitioner 1981;225(1352):234-9</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Whitfield MJ, Hughes AO</AU>
<TI>Penicillin in sore throat</TI>
<SO>Practitioner</SO>
<YR>1981</YR>
<VL>225</VL>
<NO>1352</NO>
<PG>234-9</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="MIX" ID="STD-Zwart-2000" MODIFIED="2009-01-12 08:49:21 +1000" MODIFIED_BY="[Empty name]" NAME="Zwart 2000" YEAR="2000">
<REFERENCE MODIFIED="2009-01-12 08:49:21 +1000" MODIFIED_BY="[Empty name]" NOTES="<p>Zwart 2000 <br>BMJ 2000;320(7228):150-4</p>" NOTES_MODIFIED="2009-01-12 08:49:21 +1000" NOTES_MODIFIED_BY="[Empty name]" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Zwart S, Sachs AP, Rujis GJ, Gubbels JW, Hoes AW, de Melker RA</AU>
<TI>Penicillin for acute sore throat: randomised double blind trial seven days versus three days treatment or placebo in adults</TI>
<SO>BMJ</SO>
<YR>2000</YR>
<VL>320</VL>
<NO>7228</NO>
<PG>150-4</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Zwart-2003" NAME="Zwart 2003" YEAR="2003">
<REFERENCE NOTES="<p>Zwart 2003 <br>BMJ 2003;327(7427):1324-8</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Zwart S, Rovers MM, de Melker RA, Hoes AW</AU>
<TI>Penicillin for acute sore throat in children: randomised, double blind trial</TI>
<SO>BMJ</SO>
<YR>2003</YR>
<VL>327</VL>
<NO>7427</NO>
<PG>1324-8</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
</INCLUDED_STUDIES>
<EXCLUDED_STUDIES MODIFIED="2013-09-11 21:05:12 +1000" MODIFIED_BY="[Empty name]">
<STUDY DATA_SOURCE="PUB" ID="STD-Barwitz-1999" NAME="Barwitz 1999" YEAR="1999">
<REFERENCE PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Barwitz HJK</AU>
<TI>Common cold - trial to rationalize management in general practice by recommendation</TI>
<TO>Erkaltung: eine Handlungsempfehlung</TO>
<SO>Zeitschrift fur Allgemeinmedizin</SO>
<YR>1999</YR>
<VL>75</VL>
<PG>932-8</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Bass-1986" MODIFIED="2011-07-11 02:34:27 +1000" MODIFIED_BY="[Empty name]" NAME="Bass 1986" YEAR="1986">
<REFERENCE MODIFIED="2011-07-11 02:34:27 +1000" MODIFIED_BY="[Empty name]" NOTES="<p>Bass J. Treatment of streptococcal pharyngitis revisted. JAMA. 1986;256:740-743.</p>" NOTES_MODIFIED="2011-07-11 02:34:27 +1000" NOTES_MODIFIED_BY="[Empty name]" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Bass J</AU>
<TI>Treatment of streptococcal pharyngitis revisited</TI>
<SO>JAMA</SO>
<YR>1986</YR>
<VL>256</VL>
<PG>740-3</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Bishop-1952" NAME="Bishop 1952" YEAR="1952">
<REFERENCE NOTES="<p>Bishop JM, Peden AS, Prankerd TAJ, Cawley RH. Acute sore throat. Clinical features, aetiology and treatment. The Lancet, 1952;1:1183-1187.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Bishop JM, Peden AS, Prankerd TAJ, Cawley RH</AU>
<TI>Acute sore throat. Clinical features, aetiology and treatment</TI>
<SO>Lancet</SO>
<YR>1952</YR>
<VL>1</VL>
<PG>1183-7</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Catanzaro-1958" NAME="Catanzaro 1958" YEAR="1958">
<REFERENCE NOTES="<p>Catanzaro FJ, Chamovitz R. Prevention of rheumatic fever by treatment of streptococcal infections: factors responsible for failures. N Engl J Med. 1958.259:51-57.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Catanzaro FJ, Chamovitz R</AU>
<TI>Prevention of rheumatic fever by treatment of streptococcal infections: factors responsible for failures</TI>
<SO>New England Journal of Medicine</SO>
<YR>1958</YR>
<VL>259</VL>
<PG>51-7</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Cruickshank-1960" NAME="Cruickshank 1960" YEAR="1960">
<REFERENCE NOTES="<p>Cruickshank R. Sore throat: a controlled therapeutic trial in young adults. Controlled Clinical Trials: paper delivered at the conference convened by the Council for International Organisation of Medical Sciences. Oxford Blackwell. 1960:38-44.</p>" PRIMARY="NO" TYPE="CONFERENCE_PROC">
<AU>Cruickshank R</AU>
<TI>Sore throat: a controlled therapeutic trial in young adults</TI>
<SO>Controlled Clinical Trials: paper delivered at the conference convened by the Council for International Organisation of Medical Sciences</SO>
<YR>1960</YR>
<PG>38-44</PG>
<PB>Blackwell</PB>
<CY>Oxford</CY>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Dowell-2001" NAME="Dowell 2001" YEAR="2001">
<REFERENCE PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Dowell J, Pitkethly M, Bain J, Martin S</AU>
<TI>A randomised controlled trial of delayed antibiotic prescribing as a strategy for managing uncomplicated respiratory tract infection in primary care</TI>
<SO>British Journal of General Practice</SO>
<YR>2001</YR>
<VL>51</VL>
<PG>200-5</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Gerber-1985" NAME="Gerber 1985" YEAR="1985">
<REFERENCE PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Gerber MA, Spadaccini LJ, Wright LL, Deutsch L, Kaplan EL</AU>
<TI>Twice-daily penicillin in the treatment of streptococcal pharyngitis</TI>
<SO>American Journal of Diseases of Children</SO>
<YR>1985</YR>
<VL>139</VL>
<PG>1145-8</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Gerber-1989" NAME="Gerber 1989" YEAR="1989">
<REFERENCE NOTES="<p>Gerber MA, Randolph MF. Failure of once-daily penicillin v therapy for streptococcal pharyngitis. Am J Dis Child. 1989;143:153-5.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Gerber MA, Randolph MF</AU>
<TI>Failure of once-daily penicillin V therapy for streptococcal pharyngitis</TI>
<SO>American Journal of Diseases of Children</SO>
<YR>1989</YR>
<VL>143</VL>
<PG>153-5</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Ginsburg-1980" MODIFIED="2009-01-12 08:49:44 +1000" MODIFIED_BY="[Empty name]" NAME="Ginsburg 1980" YEAR="1980">
<REFERENCE MODIFIED="2009-01-12 08:49:44 +1000" MODIFIED_BY="[Empty name]" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Ginsburg CM, McCracken GH, Crow SD, Steinberg JB, Cope F</AU>
<TI>A controlled comparative study of penicillin V and cefadroxil therapy on Group A streptococcal tonsillopharyngitis</TI>
<SO>Journal of International Medical Research</SO>
<YR>1980</YR>
<VL>8</VL>
<NO>Suppl 1</NO>
<PG>82-6</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Guthrie-1988" MODIFIED="2011-07-11 02:34:39 +1000" MODIFIED_BY="[Empty name]" NAME="Guthrie 1988" YEAR="1988">
<REFERENCE MODIFIED="2011-07-11 02:34:39 +1000" MODIFIED_BY="[Empty name]" NOTES="<p>Guthrie RR, Rofman BA. Aetiology of acute pharyngitis and clinical response to empirical therapy with erythromycin versus amoxicillin. Fam Pract. 1988;5:29-35.</p>" NOTES_MODIFIED="2011-07-11 02:34:39 +1000" NOTES_MODIFIED_BY="[Empty name]" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Guthrie RM, Ruoff GE, Rofman BA, Ginsberg D, Karp RR, Brown SM, et al</AU>
<TI>Aetiology of acute pharyngitis and clinical response to empirical therapy with erythromycin versus amoxicillin</TI>
<SO>Family Practice</SO>
<YR>1988</YR>
<VL>5</VL>
<PG>29-35</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Haverkorn-1971" NAME="Haverkorn 1971" YEAR="1971">
<REFERENCE NOTES="<p>Haverkorn MV, Goslings WRO. Streptococcal pharyngitis in the general population. A controlled study of streptococcal pharyngitis and its complications in the Netherlands. J Infect Dis. 1971;124:339-347.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Haverkorn MV, Goslings WRO</AU>
<TI>Streptococcal pharyngitis in the general population. A controlled study of streptococcal pharyngitis and its complications in the Netherlands</TI>
<SO>Journal of Infectious Diseases</SO>
<YR>1971</YR>
<VL>124</VL>
<PG>339-47</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Herz-1988" NAME="Herz 1988" YEAR="1988">
<REFERENCE NOTES="<p>Herz MJ. Antibiotics and the adult sore throat - an unnecessary ceremony. Family Pract. 1988;5:196-199.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Herz MJ</AU>
<TI>Antibiotics and the adult sore throat - an unnecessary ceremony</TI>
<SO>Family Practice</SO>
<YR>1988</YR>
<VL>5</VL>
<PG>196-9</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Howie-1970" NAME="Howie 1970" YEAR="1970">
<REFERENCE NOTES="<p>Howie JGR, Clark GA. Double-blind trial of early demethylchlortetracycline in minor respiratory illness in general practice The Lancet. 1970; Nov 28:1099-1102.</p>" PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Howie JGR, Clark GA</AU>
<TI>Double-blind trial of early demethylchlortetracycline in minor respiratory illness in general practice</TI>
<SO>Lancet</SO>
<YR>1970</YR>
<VL>Nov 28</VL>
<PG>1099-102</PG>
<IDENTIFIERS/>
</REFERENCE>
<IDENTIFIERS/>
</STUDY>
<STUDY DATA_SOURCE="PUB" ID="STD-Jensen-1991" NAME="Jensen 1991" YEAR="1991">
<REFERENCE PRIMARY="NO" TYPE="JOURNAL_ARTICLE">
<AU>Jensen JH, Larsen SB</AU>
<TI>Treatment of recurrent acute tonsillitis with clindamycin. An alternative to tonsillectomy?</TI>