<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article">
 <front>
  <journal-meta>
   <journal-id journal-id-type="publisher-id">
    ojo
   </journal-id>
   <journal-title-group>
    <journal-title>
     Open Journal of Orthopedics
    </journal-title>
   </journal-title-group>
   <issn pub-type="epub">
    2164-3008
   </issn>
   <issn publication-format="print">
    2164-3016
   </issn>
   <publisher>
    <publisher-name>
     Scientific Research Publishing
    </publisher-name>
   </publisher>
  </journal-meta>
  <article-meta>
   <article-id pub-id-type="doi">
    10.4236/ojo.2024.1412055
   </article-id>
   <article-id pub-id-type="publisher-id">
    ojo-138699
   </article-id>
   <article-categories>
    <subj-group subj-group-type="heading">
     <subject>
      Articles
     </subject>
    </subj-group>
    <subj-group subj-group-type="Discipline-v2">
     <subject>
      Medicine 
     </subject>
     <subject>
       Healthcare
     </subject>
    </subj-group>
   </article-categories>
   <title-group>
    Long Term Outcomes of Management of Open Fractures of Long Bone among Patients with a Surgical Implant Generation Network Nail at Kumi Orthopaedic Center, Uganda
   </title-group>
   <contrib-group>
    <contrib contrib-type="author" xlink:type="simple">
     <name name-style="western">
      <surname>
       John
      </surname>
      <given-names>
       Ekure
      </given-names>
     </name> 
     <xref ref-type="aff" rid="aff1"> 
      <sup>1</sup>
     </xref>
    </contrib>
    <contrib contrib-type="author" xlink:type="simple">
     <name name-style="western">
      <surname>
       Naomi
      </surname>
      <given-names>
       Amuron
      </given-names>
     </name> 
     <xref ref-type="aff" rid="aff2"> 
      <sup>2</sup>
     </xref>
    </contrib>
    <contrib contrib-type="author" xlink:type="simple">
     <name name-style="western">
      <surname>
       Douglas
      </surname>
      <given-names>
       Kilama
      </given-names>
     </name> 
     <xref ref-type="aff" rid="aff1"> 
      <sup>1</sup>
     </xref>
    </contrib>
    <contrib contrib-type="author" xlink:type="simple">
     <name name-style="western">
      <surname>
       Phillip
      </surname>
      <given-names>
       Buluma
      </given-names>
     </name> 
     <xref ref-type="aff" rid="aff1"> 
      <sup>1</sup>
     </xref>
    </contrib>
    <contrib contrib-type="author" xlink:type="simple">
     <name name-style="western">
      <surname>
       Andrew
      </surname>
      <given-names>
       Iloket
      </given-names>
     </name> 
     <xref ref-type="aff" rid="aff1"> 
      <sup>1</sup>
     </xref>
    </contrib>
    <contrib contrib-type="author" xlink:type="simple">
     <name name-style="western">
      <surname>
       Akellot
      </surname>
      <given-names>
       Daniella
      </given-names>
     </name> 
     <xref ref-type="aff" rid="aff1"> 
      <sup>1</sup>
     </xref>
    </contrib>
    <contrib contrib-type="author" xlink:type="simple">
     <name name-style="western">
      <surname>
       Faith
      </surname>
      <given-names>
       Akello
      </given-names>
     </name> 
     <xref ref-type="aff" rid="aff1"> 
      <sup>1</sup>
     </xref>
    </contrib>
   </contrib-group> 
   <aff id="aff1">
    <addr-line>
     aKumi Orthopaedic Center, Kumi, Uganda
    </addr-line> 
   </aff> 
   <aff id="aff2">
    <addr-line>
     aCollege of Health Sciences, Soroti University, Soroti, Uganda
    </addr-line> 
   </aff> 
   <pub-date pub-type="epub">
    <day>
     06
    </day> 
    <month>
     12
    </month>
    <year>
     2024
    </year>
   </pub-date> 
   <volume>
    14
   </volume> 
   <issue>
    12
   </issue>
   <fpage>
    589
   </fpage>
   <lpage>
    597
   </lpage>
   <history>
    <date date-type="received">
     <day>
      5,
     </day>
     <month>
      November
     </month>
     <year>
      2024
     </year>
    </date>
    <date date-type="published">
     <day>
      28,
     </day>
     <month>
      November
     </month>
     <year>
      2024
     </year> 
    </date> 
    <date date-type="accepted">
     <day>
      28,
     </day>
     <month>
      December
     </month>
     <year>
      2024
     </year> 
    </date>
   </history>
   <permissions>
    <copyright-statement>
     © Copyright 2014 by authors and Scientific Research Publishing Inc. 
    </copyright-statement>
    <copyright-year>
     2014
    </copyright-year>
    <license>
     <license-p>
      This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/
     </license-p>
    </license>
   </permissions>
   <abstract>
    <b>Background:</b> Open fractures are serious injuries with the potential for severe complications such as infection and non-union. Management of open fractures is challenging especially in areas like Uganda where appropriate human resources, infrastructure and medical care are not readily accessible. The introduction of new devices for fracture stabilization and the development of microsurgical procedures for soft tissue reconstruction have greatly improved the management of open fractures. Patients presenting with open fractures of long bones at Kumi Orthopaedic Center are managed with the help of SIGN nail for fracture stabilization. However, long-term outcomes for patients have not been documented. 
    <b>Objective:</b> The objective of this study was to determine the long term outcomes of the management of open fractures of long bones among patients with a Surgical Implant Generation Network (SIGN) nail at Kumi Orthopaedic Center (KOC). 
    <b>Methods:</b> A retrospective study of 39 patients with open fractures who were managed at KOC between 2010 and 2022. Data on patients’ socio-demographic and clinical characteristics and outcomes (both physical and radiographic) was retrieved from the SIGN surgical online database of patients with over 1 year follow up period. 
    <b>Results:</b> The mean age of patients was 40.3 years. The majority were male 32 (82.1%) and the commonest mechanism of injury was Road Traffic Accidents (RTA) 37 (94.9%). The majority did not have a clear record of having received antibiotics immediately after injury 29 (74.4%). However, most had a record of receiving antibiotics 1 hour before surgery 33 (84.6%). The most affected bone was the tibia 33 (84.6%). The commonest fracture type was Gustilo IIIa 18 (46.2%). On follow up; 10 (25.6%) developed an infection (osteomyelitis), 6 (15.4%) did not have a union on x-ray, 4 (10.3%) had a loose screw, 1 had an implant breakage and also 1 patient had a varus deformity. However, there was no amputation recorded. 
    <b>Conclusion: </b>The management of open fractures is still a major challenge in low and middle income countries like Uganda, which is still experiencing relatively high complication rates. Guidelines emphasizing the need for early antibiotic prophylaxis and faster access to surgical treatment are required for better treatment outcomes.
   </abstract>
   <kwd-group> 
    <kwd>
     Open Fractures
    </kwd> 
    <kwd>
      Outcomes
    </kwd> 
    <kwd>
      SIGN
    </kwd>
   </kwd-group>
  </article-meta>
 </front>
 <body>
  <sec id="s1">
   <title>1. Introduction</title>
   <p>Open fractures are a leading cause of musculoskeletal morbidity in low and middle income countries and are more frequent in Sub-Saharan countries due to the rising rate of injuries from increased use of motorized transport <xref ref-type="bibr" rid="scirp.138699-1">
     [1]
    </xref> <xref ref-type="bibr" rid="scirp.138699-2">
     [2]
    </xref>. Open fractures can be managed using several methods <xref ref-type="bibr" rid="scirp.138699-3">
     [3]
    </xref>. However, in low-resource settings i.e., low and middle income Countries (LMICs) like Uganda, many patients with open fractures do not get appropriate care for their injuries <xref ref-type="bibr" rid="scirp.138699-4">
     [4]
    </xref>. This can be attributed to the fact that appropriate human resources and infrastructure (including equipment, implants and surgical supplies) are not readily available and medical care is not readily accessible <xref ref-type="bibr" rid="scirp.138699-5">
     [5]
    </xref>-<xref ref-type="bibr" rid="scirp.138699-7">
     [7]
    </xref>. Individuals with open fractures also prefer to visit traditional bone setters when faced with musculo-skeletal injuries <xref ref-type="bibr" rid="scirp.138699-8">
     [8]
    </xref>. These are not qualified to treat severe injuries like open fractures and are often more likely to worsen and complicate injuries and also delay the seeking of proper care <xref ref-type="bibr" rid="scirp.138699-9">
     [9]
    </xref>. These complications due to delayed seeking of appropriate care make management even more difficult. At KOC, patients with open fractures are managed using various surgical techniques including SIGN intramedullary (IM) nails, plates and screws, and external fixation. KOC is one of the SIGN supported centers using SIGN nails to treat the majority of the long bone fractures. SIGN surgeons are required to record case reports and follow ups in the SIGN Online Surgical Data base (SOSD) by SIGN Fracture CARE International. However, the long term outcomes of these patients following treatment have not been well documented. Therefore, the aim of the study was to determine the long term outcomes of the management of open fractures of long bones among patients with a Surgical Implant Generation Network (SIGN) nail at Kumi Orthopaedic Center (KOC).</p>
  </sec><sec id="s2">
   <title>2. Methods</title>
   <sec id="s2_1">
    <title>2.1. Study Design</title>
    <p>This is a hospital-based retrospective cohort study conducted in Kumi Orthopaedic Center, which was located in semi-urban Uganda between January 2010 and December 2022. The hospital is a specialized Center serving a majority of the population in Eastern Uganda. All patients that present with an open fracture of a long bone are managed with the help of a SIGN nail.</p>
   </sec>
   <sec id="s2_2">
    <title>2.2. Study Population</title>
    <p>The study included patients that had an open fracture(s) of long bones ranging from Gustilo I to Gustilo IIIc, managed at KOC as either a primary hospital or referred case and had a follow up visit recorded after 1 year (365 days). None of the patients that met the inclusion criteria were excluded.</p>
   </sec>
   <sec id="s2_3">
    <title>2.3. Data Collection and Analysis</title>
    <p>Data was retrieved from the SIGN online Surgical Data base (SOSD) using the semi-structured data abstraction tools. This included data on the patient socio-demographic characteristics, clinical characteristics and outcomes (both physical and radiographic).</p>
    <p>The data was then extracted into excel sheets and analyzed using Stata version 17.0. Descriptive statistics were used to analyze the data and results presented as frequencies and percentages.</p>
   </sec>
   <sec id="s2_4">
    <title>2.4. Ethical Issues</title>
    <p>Ethical approval and waiver of consent were granted by Mbale Regional Referral Hospital Research and Ethics Committee (Ref no MRRH-2023-333) and the Uganda National Council of Science and Technology (Ref no HS3238ES).</p>
   </sec>
  </sec><sec id="s3">
   <title>3. Results</title>
   <p>At the time of the study, 174 patients with Open fractures were found in the SOSD, of these 39 met the inclusion criteria of having a recorded follow up visit of one year and above. Of the 39 cases, 32 (82.0%) were male and 7 (18.0%) were female. The median age was 41 years with the youngest being 23 and the oldest being 76 years at the time of surgery. The commonest mechanism of injury was Road Traffic Accidents, 37 (94.9%) as shown in <xref ref-type="table" rid="table1">
     Table 1
    </xref> below.</p>
   <table-wrap id="table1">
    <label>
     <xref ref-type="table" rid="table1">
      Table 1
     </xref></label>
    <caption>
     <title>
      <xref ref-type="bibr" rid="scirp.138699-"></xref>Table 1. Socio-demographic characteristics of the 39 participants.</title>
    </caption>
    <table class="MsoTableGrid custom-table" border="0" cellspacing="0" cellpadding="0"> 
     <tr> 
      <td class="custom-bottom-td custom-top-td acenter" width="70.47%"><p style="text-align:center">Variable</p></td> 
      <td class="custom-bottom-td custom-top-td acenter" width="70.47%"><p style="text-align:center">Frequency n = 39(%)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td custom-top-td acenter" width="70.47%"><p style="text-align:center">Age (Median, IQR)</p></td> 
      <td class="custom-bottom-td custom-top-td acenter" width="70.47%"><p style="text-align:center">41 (30 - 49)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center">Sex</p></td> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="70.47%"><p style="text-align:center">Male</p></td> 
      <td class="acenter" width="70.47%"><p style="text-align:center">32 (82.0)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">Female</p></td> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">7 (18.0)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center">Mechanism of injury</p></td> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="70.47%"><p style="text-align:center">RTA</p></td> 
      <td class="acenter" width="70.47%"><p style="text-align:center">37 (94.1)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">Gunshot</p></td> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">2 (5.1)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center">Type of admission</p></td> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="70.47%"><p style="text-align:center">Primary</p></td> 
      <td class="acenter" width="70.47%"><p style="text-align:center">29 (74.4)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">Referral</p></td> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">10 (25.6)</p></td> 
     </tr> 
    </table>
   </table-wrap>
   <p>The most affected bone was the tibia 33 (84.6%) especially the middle portion 18 (46.1%). The commonest fracture type was Gustilo IIIa 18 (46.1%) and the least was Gustilo I 3 (7.7%). Majority of the patients received antibiotics before surgery 33 (84.6%). However, majority did not have a known record of having received antibiotics immediately after injury 29 (74.4%). The media time to debridement following presentation was 8 hours. The median time to skin closure was 1 days with majority 19 (48.7%) having primary skin closure as illustrated in <xref ref-type="table" rid="table2">
     Table 2
    </xref> below.</p>
   <table-wrap id="table2">
    <label>
     <xref ref-type="table" rid="table2">
      Table 2
     </xref></label>
    <caption>
     <title>
      <xref ref-type="bibr" rid="scirp.138699-"></xref>Table 2. Clinical characteristics of the 39 participants.</title>
    </caption>
    <table class="MsoTableGrid custom-table" border="0" cellspacing="0" cellpadding="0"> 
     <tr> 
      <td class="custom-bottom-td custom-top-td acenter" width="67.88%"><p style="text-align:center">Variable</p></td> 
      <td class="custom-bottom-td custom-top-td acenter" width="32.12%"><p style="text-align:center">Frequency n = 39(%)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td custom-top-td acenter" width="67.88%"><p style="text-align:center">Time to surgery (days) (Median, IQR)</p></td> 
      <td class="custom-bottom-td custom-top-td acenter" width="32.12%"><p style="text-align:center">3 (2 - 5)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="67.88%"><p style="text-align:center">Antibiotic use after injury</p></td> 
      <td class="custom-top-td acenter" width="32.12%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="67.88%"><p style="text-align:center">Yes</p></td> 
      <td class="acenter" width="32.12%"><p style="text-align:center">10 (25.6)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="67.88%"><p style="text-align:center">Unknown</p></td> 
      <td class="custom-bottom-td acenter" width="32.12%"><p style="text-align:center">29 (74.4)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="67.88%"><p style="text-align:center">Antibiotic use before surgery</p></td> 
      <td class="custom-top-td acenter" width="32.12%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="67.88%"><p style="text-align:center">Yes</p></td> 
      <td class="acenter" width="32.12%"><p style="text-align:center">33 (84.6)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="67.88%"><p style="text-align:center">Unknown</p></td> 
      <td class="custom-bottom-td acenter" width="32.12%"><p style="text-align:center">6 (15.4)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="67.88%"><p style="text-align:center">Bone</p></td> 
      <td class="custom-top-td acenter" width="32.12%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="67.88%"><p style="text-align:center">Femur</p></td> 
      <td class="acenter" width="32.12%"><p style="text-align:center">6 (15.4)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="67.88%"><p style="text-align:center">Tibia</p></td> 
      <td class="custom-bottom-td acenter" width="32.12%"><p style="text-align:center">33 (84.6)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="67.88%"><p style="text-align:center">Location</p></td> 
      <td class="custom-top-td acenter" width="32.12%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="67.88%"><p style="text-align:center">Proximal</p></td> 
      <td class="acenter" width="32.12%"><p style="text-align:center">4 (10.3)</p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="67.88%"><p style="text-align:center">Middle</p></td> 
      <td class="acenter" width="32.12%"><p style="text-align:center">18 (46.1)</p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="67.88%"><p style="text-align:center">Distal</p></td> 
      <td class="acenter" width="32.12%"><p style="text-align:center">16 (41.0)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="67.88%"><p style="text-align:center">Segmental</p></td> 
      <td class="custom-bottom-td acenter" width="32.12%"><p style="text-align:center">1 (2.6)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="67.88%"><p style="text-align:center">Type of fracture</p></td> 
      <td class="custom-top-td acenter" width="32.12%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="67.88%"><p style="text-align:center">Gustilo I</p></td> 
      <td class="acenter" width="32.12%"><p style="text-align:center">3 (7.7)</p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="67.88%"><p style="text-align:center">Gustilo II</p></td> 
      <td class="acenter" width="32.12%"><p style="text-align:center">6 (15.4)</p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="67.88%"><p style="text-align:center">Gustilo IIIa</p></td> 
      <td class="acenter" width="32.12%"><p style="text-align:center">18 (46.1)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="67.88%"><p style="text-align:center">Gustilo IIIb</p></td> 
      <td class="custom-bottom-td acenter" width="32.12%"><p style="text-align:center">12 (30.8)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td custom-top-td acenter" width="67.88%"><p style="text-align:center">Time to debridement (hours) (Median, IQR)</p></td> 
      <td class="custom-bottom-td custom-top-td acenter" width="32.12%"><p style="text-align:center">8 (0 - 24)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td custom-top-td acenter" width="67.88%"><p style="text-align:center">Days to skin closure (Median, IQR)</p></td> 
      <td class="custom-bottom-td custom-top-td acenter" width="32.12%"><p style="text-align:center">1 (0 - 5)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="67.88%"><p style="text-align:center">Type of wound closure</p></td> 
      <td class="custom-top-td acenter" width="32.12%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="67.88%"><p style="text-align:center">Primary</p></td> 
      <td class="acenter" width="32.12%"><p style="text-align:center">19 (48.7)</p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="67.88%"><p style="text-align:center">Secondary</p></td> 
      <td class="acenter" width="32.12%"><p style="text-align:center">6 (15.4)</p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="67.88%"><p style="text-align:center">Skin graft</p></td> 
      <td class="acenter" width="32.12%"><p style="text-align:center">7 (17.9)</p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="67.88%"><p style="text-align:center">Muscle flap</p></td> 
      <td class="acenter" width="32.12%"><p style="text-align:center">5 (12.8)</p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="67.88%"><p style="text-align:center">Fascio-cutaneous flap</p></td> 
      <td class="acenter" width="32.12%"><p style="text-align:center">1 (2.6)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="67.88%"><p style="text-align:center">Unknown</p></td> 
      <td class="custom-bottom-td acenter" width="32.12%"><p style="text-align:center">1 (2.6)</p></td> 
     </tr> 
    </table>
   </table-wrap>
   <p>The infection rate on follow up was 25.6%. However, majority of the participants had healing on x-ray 33 (84.6%). There was no case of amputation recorded with only one case of varus deformity and implant breakage noted. On Physical examination, majority had painless full weight bearing 33 (84.6%) and had flexion more than 90 degrees 36 (92.3%) as indicated in <xref ref-type="table" rid="table3">
     Table 3
    </xref> below.</p>
   <table-wrap id="table3">
    <label>
     <xref ref-type="table" rid="table3">
      Table 3
     </xref></label>
    <caption>
     <title>
      <xref ref-type="bibr" rid="scirp.138699-"></xref>Table 3. Patient outcomes of the 39 participants.</title>
    </caption>
    <table class="MsoTableGrid custom-table" border="0" cellspacing="0" cellpadding="0"> 
     <tr> 
      <td class="custom-bottom-td custom-top-td acenter" width="70.47%"><p style="text-align:center">Variable</p></td> 
      <td class="custom-bottom-td custom-top-td acenter" width="70.47%"><p style="text-align:center">Frequency n = 39(%)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center">Painless full weight bearing</p></td> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="70.47%"><p style="text-align:center">Yes</p></td> 
      <td class="acenter" width="70.47%"><p style="text-align:center">33 (84.6)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">No</p></td> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">6 (15.4)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center">Healing on X-ray</p></td> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="70.47%"><p style="text-align:center">Yes</p></td> 
      <td class="acenter" width="70.47%"><p style="text-align:center">33 (84.6)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">No</p></td> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">6 (15.4)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center">Flexion more than 90 degrees</p></td> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="70.47%"><p style="text-align:center">Yes</p></td> 
      <td class="acenter" width="70.47%"><p style="text-align:center">36 (92.3)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">No</p></td> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">3 (7.7)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center">Infection (Osteomyelitis)</p></td> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="70.47%"><p style="text-align:center">Yes</p></td> 
      <td class="acenter" width="70.47%"><p style="text-align:center">10 (25.6)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">No</p></td> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">29 (74.4)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center">Loose screw</p></td> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="70.47%"><p style="text-align:center">Yes</p></td> 
      <td class="acenter" width="70.47%"><p style="text-align:center">4 (10.3)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">No</p></td> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">35 (89.7)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center">Implant breakage</p></td> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="70.47%"><p style="text-align:center">Yes</p></td> 
      <td class="acenter" width="70.47%"><p style="text-align:center">1 (2.6)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">No</p></td> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">38 (97.4)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center">Amputation</p></td> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="70.47%"><p style="text-align:center">Yes</p></td> 
      <td class="acenter" width="70.47%"><p style="text-align:center">0 (0)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">No</p></td> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">39 (100.0)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center">Deformity</p></td> 
      <td class="custom-top-td acenter" width="70.47%"><p style="text-align:center"></p></td> 
     </tr> 
     <tr> 
      <td class="acenter" width="70.47%"><p style="text-align:center">Yes</p></td> 
      <td class="acenter" width="70.47%"><p style="text-align:center">1 (2.6)</p></td> 
     </tr> 
     <tr> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">No</p></td> 
      <td class="custom-bottom-td acenter" width="70.47%"><p style="text-align:center">38 (97.4)</p></td> 
     </tr> 
    </table>
   </table-wrap>
  </sec><sec id="s4">
   <title>4. Discussion</title>
   <p>Open fractures are serious injuries and significant sources of morbidity and mortality. These are difficult to treat because of the increased risk of complications specifically infections with rates ranging as high as 52% <xref ref-type="bibr" rid="scirp.138699-10">
     [10]
    </xref>. The infection rate in this study of 25.6% is lower compared to the 30% that was obtained by a systematic review done on studies in different parts of Africa <xref ref-type="bibr" rid="scirp.138699-11">
     [11]
    </xref> and the 31.4% infection rate found in Cameroon <xref ref-type="bibr" rid="scirp.138699-12">
     [12]
    </xref>. However, it is higher than 8.1% found in the USA <xref ref-type="bibr" rid="scirp.138699-13">
     [13]
    </xref> and 14.6% found in China <xref ref-type="bibr" rid="scirp.138699-14">
     [14]
    </xref>.</p>
   <p>The higher infection rate can be attributed to high energy injuries with heavy contamination as evidenced by the majority of the fractures being Gustilo IIIa (46.1%) and Gustilo IIIb (30.8%) in this study. These fractures have been shown to be more prone to infection <xref ref-type="bibr" rid="scirp.138699-15">
     [15]
    </xref> <xref ref-type="bibr" rid="scirp.138699-16">
     [16]
    </xref>.</p>
   <p>Delayed administration of antibiotics following injury could also explain the high infection rate. Early antibiotic prophylaxis has been demonstrated to unequivocally reduce the risk of infection following an open fracture <xref ref-type="bibr" rid="scirp.138699-17">
     [17]
    </xref>-<xref ref-type="bibr" rid="scirp.138699-19">
     [19]
    </xref>. Most surgeons deem a period of less than 1 hour as the optimal time for antibiotic administration, which is substantiated in the literature <xref ref-type="bibr" rid="scirp.138699-16">
     [16]
    </xref> <xref ref-type="bibr" rid="scirp.138699-17">
     [17]
    </xref>.</p>
   <p>Delayed time from injury to surgery could also have contributed to the high infection rate. This could be due to delayed referral from primary health care facilities or seeking of professional help by the patients. Traditionally, 6 hours was considered the standard time for formal surgical irrigation and debridement following injury to minimize infection risk following an open fracture. However, a 2015 prospective observation study extended the time limit to 12 and even 24 hours with no significant effect on infection rates <xref ref-type="bibr" rid="scirp.138699-20">
     [20]
    </xref>. More recently, a meta-analysis of observational studies showed an increased infection risk in grade IIIa fractures and higher when irrigation and debridement were delayed more than 12 hours <xref ref-type="bibr" rid="scirp.138699-21">
     [21]
    </xref>. Based on these studies early surgical irrigation and debridement should be emphasized to minimize infection risk. Surgical treatment should be performed no later than 24 hours’ post-injury for grade I and II open fractures and within 12 hours for grade III open fractures, although earlier treatment may be preferable.</p>
   <p>However, recent studies have shown that the time from injury to debridement is not a significant prognostic factor in the management of open fractures <xref ref-type="bibr" rid="scirp.138699-22">
     [22]
    </xref> but rather the quality of the debridement and adequate stabilization of the fracture are helpful in improving outcomes in the management of open fractures.</p>
   <p>The relatively lower infection rate compared to that found by the systematic review could be attributed to the early wound closure i.e., 48.7% had primary would closure and also stabilization with the SIGN nail which has been shown to have better surgical outcomes compared to other fixation methods <xref ref-type="bibr" rid="scirp.138699-23">
     [23]
    </xref>.</p>
   <p>We also found a lower non-union rate (15.4%) compared to 27.9% found by a study in a level 1 trauma center in USA <xref ref-type="bibr" rid="scirp.138699-24">
     [24]
    </xref>. However, it is higher than the 9.7% found by a systematic review in the USA <xref ref-type="bibr" rid="scirp.138699-13">
     [13]
    </xref>. The lower non-union rate could be due to the stable fixation using the SIGN nail. SIGN nail requires reaming of the canal, which has the advantage of stimulating blood flow. The reaming gets deposited at the fracture site acting as a bone graft which has osteo-inductive and osteo-conductive properties. Reaming also provides for the use of a wide diameter nail which provides better stability required for healing <xref ref-type="bibr" rid="scirp.138699-25">
     [25]
    </xref>.</p>
   <p>The higher non-union rate could be associated with the higher energy of trauma among the patients managed at KOC which are known to be more prone to non-union <xref ref-type="bibr" rid="scirp.138699-26">
     [26]
    </xref>. The relatively high infection rate could also explain the high non-union rates as infections have been known to cause non-unions <xref ref-type="bibr" rid="scirp.138699-27">
     [27]
    </xref>.</p>
   <p>This study was limited by the fact that only data on long bones that were treated with SIGN nails was available. A prospective study looking at all open fractures of all bones treated using various methods would be needed to give a more wholesome picture of the treatment outcomes. This was a single center study and therefore subject to information bias. A multicenter study would help evaluate for variability and allow comparability of results, thus providing a better picture of current outcomes in most of the population.</p>
  </sec><sec id="s5">
   <title>5. Conclusion</title>
   <p>The management of open fractures is still a major challenge in low and middle income countries like Uganda, which still experiences relatively high complication rates i.e., infection and non-union rates which affect the quality of life of the patients. Policies that mitigate the occurrence of these high energy injuries from RTAs should be strengthened. Guidelines emphasizing the need for early antibiotic prophylaxis and faster access to surgical treatment need to be sensitized and enforced in an effort to better treatment outcomes among patients with open fractures.</p>
  </sec><sec id="s6">
   <title>
    <xref ref-type="bibr" rid="scirp.138699-"></xref>Funding</title>
   <p>This study did not receive any outside funding.</p>
  </sec><sec id="s7">
   <title>Acknowledgements</title>
   <p>We are sincerely grateful to the staff of Kumi Orthopaedic Center for the great support rendered during the data collection process.</p>
  </sec>
 </body><back>
  <ref-list>
   <title>References</title>
   <ref id="scirp.138699-ref1">
    <label>1</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Chalya, P.L., Mabula, J.B., Dass, R.M., Mbelenge, N., Ngayomela, I.H., Chandika, A.B., et al. (2012) Injury Characteristics and Outcome of Road Traffic Crash Victims at Bugando Medical Centre in Northwestern Tanzania. Journal of Trauma Management&amp;Outcomes, 6, Article No. 1. &gt;https://doi.org/10.1186/1752-2897-6-1 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref2">
    <label>2</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Seid, M., Azazh, A., Enquselassie, F. and Yisma, E. (2015) Injury Characteristics and Outcome of Road Traffic Accident among Victims at Adult Emergency Department of Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia: A Prospective Hospital Based Study. BMC Emergency Medicine, 15, Article No. 10. &gt;https://doi.org/10.1186/s12873-015-0035-4 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref3">
    <label>3</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Elniel, A.R. and Giannoudis, P.V. (2018) Open Fractures of the Lower Extremity. EFORT Open Reviews, 3, 316-325. &gt;https://doi.org/10.1302/2058-5241.3.170072 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref4">
    <label>4</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Meara, J.G., Leather, A.J.M., Hagander, L., Alkire, B.C., Alonso, N., Ameh, E.A., et al. (2015) Global Surgery 2030: Evidence and Solutions for Achieving Health, Welfare, and Economic Development. The Lancet, 386, 569-624. &gt;https://doi.org/10.1016/s0140-6736(15)60160-x 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref5">
    <label>5</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Mathieu, L., Potier, L., Ndiaye, R., Mbaye, E., Sene, M., Faye, M., et al. (2019) Management of Gustilo Type IIIB Open Tibial Shaft Fractures with Limited Resources: Experience from an African Trauma Center. European Journal of Trauma and Emergency Surgery, 47, 217-223. &gt;https://doi.org/10.1007/s00068-019-01223-0 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref6">
    <label>6</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Callese, T.E., Richards, C.T., Shaw, P., Schuetz, S.J., Paladino, L., Issa, N., et al. (2015) Trauma System Development in Low and Middle-Income Countries: A Review. Journal of Surgical Research, 193, 300-307. &gt;https://doi.org/10.1016/j.jss.2014.09.040 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref7">
    <label>7</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Wong, E.G., Gupta, S., Deckelbaum, D.L., Razek, T. and Kushner, A.L. (2015) Prioritizing Injury Care: A Review of Trauma Capacity in Low and Middle-Income Countries. Journal of Surgical Research, 193, 217-222. &gt;https://doi.org/10.1016/j.jss.2014.08.055 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref8">
    <label>8</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     B Card, E., E Obayemi, J., Shirima, O., Rajaguru, P., Massawe, H., Premkumar, A., et al. (2021) Patient Patronage and Perspectives of Traditional Bone Setting at an Outpatient Orthopaedic Clinic in Northern Tanzania. African Health Sciences, 21, 418-26. &gt;https://doi.org/10.4314/ahs.v21i1.52 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref9">
    <label>9</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Nwachukwu, B.U. (2011) Traditional Bonesetters and Contemporary Orthopaedic Fracture Care in a Developing Nation: Historical Aspects, Contemporary Status and Future Directions. The Open Orthopaedics Journal, 5, 20-26. &gt;https://doi.org/10.2174/1874325001105010020 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref10">
    <label>10</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Gustilo, R.B., Mendoza, R.M. and Williams, D.N. (1984) Problems in the Management of Type III (Severe) Open Fractures. The Journal of Trauma: Injury, Infection, and Critical Care, 24, 742-746. &gt;https://doi.org/10.1097/00005373-198408000-00009 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref11">
    <label>11</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Kouassi, K.J., Manon, J., Fonkoue, L., Detrembleur, C. and Cornu, O. (2021) Treatment of Open Tibia Fractures in Sub-Saharan African Countries: A Systematic Review. Acta Orthopaedica Belgica, 87, 85-92. &gt;https://doi.org/10.52628/87.1.11 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref12">
    <label>12</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Fonkoue, L., Muluem, K.O., Nana, T., Kong, D., Ngongang, O., Ngo Yamben, M.A., et al. (2023) Outcome of a 2-Stage Management of Open Tibia Fracture in a Low-Income Country Lacking Plastic Surgeons: A Retrospective Cohort Study. Orthoplastic Surgery, 13, 25-30. &gt;https://doi.org/10.1016/j.orthop.2023.07.001 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref13">
    <label>13</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Turley, L., Barry, I. and Sheehan, E. (2023) Frequency of Complications in Intramedullary Nailing of Open Tibial Shaft Fractures: A Systematic Review. EFORT Open Reviews, 8, 90-99. &gt;https://doi.org/10.1530/eor-22-0076 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref14">
    <label>14</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Yang, Z., Xu, C., Zhu, Y., Li, J., Wu, Z., Zou, J., et al. (2021) Radical Treatment of Severe Open Fractures of Extremities by Orthoplastic Surgery: A 10-Year Retrospective Study. Journal of Orthopaedic Surgery and Research, 16, Article No. 340. &gt;https://doi.org/10.1186/s13018-021-02479-2 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref15">
    <label>15</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Craig, J., Fuchs, T., Jenks, M., Fleetwood, K., Franz, D., Iff, J., et al. (2014) Systematic Review and Meta-Analysis of the Additional Benefit of Local Prophylactic Antibiotic Therapy for Infection Rates in Open Tibia Fractures Treated with Intramedullary Nailing. International Orthopaedics, 38, 1025-1030. &gt;https://doi.org/10.1007/s00264-014-2293-2 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref16">
    <label>16</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Lack, W.D., Karunakar, M.A., Angerame, M.R., Seymour, R.B., Sims, S., Kellam, J.F., et al. (2015) Type III Open Tibia Fractures. Journal of Orthopaedic Trauma, 29, 1-6. &gt;https://doi.org/10.1097/bot.0000000000000262 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref17">
    <label>17</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Rodriguez, L., Jung, H.S., Goulet, J.A., Cicalo, A., Machado-Aranda, D.A. and Napolitano, L.M. (2014) Evidence-Based Protocol for Prophylactic Antibiotics in Open Fractures. Journal of Trauma and Acute Care Surgery, 77, 400-408. &gt;https://doi.org/10.1097/ta.0000000000000398 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref18">
    <label>18</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Chang, Y., Kennedy, S.A., Bhandari, M., Lopes, L.C., Bergamaschi, C.D.C., Carolina de Oliveira e Silva, M., et al. (2015) Effects of Antibiotic Prophylaxis in Patients with Open Fracture of the Extremities. JBJS Reviews, 3, e2. &gt;https://doi.org/10.2106/jbjs.rvw.n.00088 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref19">
    <label>19</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Chang, Y., Bhandari, M., Zhu, K.L., Mirza, R.D., Ren, M., Kennedy, S.A., et al. (2019) Antibiotic Prophylaxis in the Management of Open Fractures. JBJS Reviews, 7, e1. &gt;https://doi.org/10.2106/jbjs.rvw.17.00197 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref20">
    <label>20</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Srour, M., Inaba, K., Okoye, O., Chan, C., Skiada, D., Schnüriger, B., et al. (2015) Prospective Evaluation of Treatment of Open Fractures. JAMA Surgery, 150, 332-336. &gt;https://doi.org/10.1001/jamasurg.2014.2022 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref21">
    <label>21</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Foote, C.J., Tornetta, P., Reito, A., Al-Hourani, K., Schenker, M., Bosse, M., et al. (2020) A Reevaluation of the Risk of Infection Based on Time to Debridement in Open Fractures. Journal of Bone and Joint Surgery, 103, 265-273. &gt;https://doi.org/10.2106/jbjs.20.01103 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref22">
    <label>22</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Singh, A., Agarwal, A., Mohan, R., Singh, S., Tewari, P. and Srivastava, S. (2023) The Effect of Timing of Debridement and Surgical Intervention in Open Fractures on the Rate of Infection and Surgical Outcomes: A Prospective Study in a Tertiary Care Setup. Cureus, 15, e37204. &gt;https://doi.org/10.7759/cureus.37204 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref23">
    <label>23</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Guo, C., Ma, J., Ma, x., Wang, Y., Sun, L., Lu, B., et al. (2018) Comparing Intramedullary Nailing and Plate Fixation for Treating Distal Tibail Fractures: A Meta-Analysis of Randomized Controlled Trials. International Journal of Surgery, 53, 5-11. &gt;https://doi.org/10.1016/j.ijsu.2018.03.026 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref24">
    <label>24</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Ford, A.N., Harkin, E.A., Lyons, M.M., Summers, H.D., Hecht, G.G., Lack, W.D., et al. (2021) Clinical and Radiographic Predictors of Nonunion in Open Tibial Shaft Fractures. Orthopedics, 44, 142-147. &gt;https://doi.org/10.3928/01477447-20210416-04 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref25">
    <label>25</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Penzkofer, R., Maier, M., Nolte, A., von Oldenburg, G., Püschel, K., Bühren, V., et al. (2008) Influence of Intramedullary Nail Diameter and Locking Mode on the Stability of Tibial Shaft Fracture Fixation. Archives of Orthopaedic and Trauma Surgery, 129, 525-531. &gt;https://doi.org/10.1007/s00402-008-0700-0 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref26">
    <label>26</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Tian, R., Zheng, F., Zhao, W., Zhang, Y., Yuan, J., Zhang, B., et al. (2020) Prevalence and Influencing Factors of Nonunion in Patients with Tibial Fracture: Systematic Review and Meta-Analysis. Journal of Orthopaedic Surgery and Research, 15, Article No. 377. &gt;https://doi.org/10.1186/s13018-020-01904-2 
    </mixed-citation>
   </ref>
   <ref id="scirp.138699-ref27">
    <label>27</label>
    <mixed-citation publication-type="other" xlink:type="simple">
     Mills, L., Tsang, J., Hopper, G., Keenan, G. and Simpson, A.H.R.W. (2016) The Multifactorial Aetiology of Fracture Nonunion and the Importance of Searching for Latent Infection. Bone&amp;Joint Research, 5, 512-519. &gt;https://doi.org/10.1302/2046-3758.510.bjr-2016-0138
    </mixed-citation>
   </ref>
  </ref-list>
 </back>
</article>