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BT 47.475 638.825 Td /F3 13.5 Tf [(Quantum Leaps in Statistical Analyses of Measuring the Impact of time to Surgery)] TJ ET
BT 47.475 611.370 Td /F4 12.0 Tf [(Clary J. Foote, MD, MSc)] TJ ET
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BT 47.475 520.980 Td /F4 12.0 Tf [(Chad P. Coles, MD)] TJ ET
BT 47.475 485.124 Td /F2 12.0 Tf [(Division of Orthopaedics, Dalhousie University, Halifax, Canada )] TJ ET
BT 47.475 459.660 Td /F4 12.0 Tf [(Aleksi Reito, MD, PhD)] TJ ET
BT 47.475 423.804 Td /F2 12.0 Tf [(Tampere University Hospital \(TAUH\), Tampere, Finland)] TJ ET
BT 47.475 398.340 Td /F4 12.0 Tf [(Khalid Al-Hourani, MD)] TJ ET
BT 47.475 362.484 Td /F2 12.0 Tf [(Department of Orthopaedics, The Royal Infirmary of Edinburgh, Edinburgh, United Kingdom)] TJ ET
BT 47.475 337.020 Td /F4 12.0 Tf [(Michael Bosse, MD)] TJ ET
BT 47.475 301.164 Td /F2 12.0 Tf [(ATRIUM Musculoskeletal Institute, Carolinas Medical Center, Charlotte, USA)] TJ ET
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BT 47.475 135.240 Td /F4 12.0 Tf [(Ross Leighton, MD)] TJ ET
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BT 47.475 73.920 Td /F4 12.0 Tf [(Harmeeth Uppal MD)] TJ ET
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BT 48.000 754.800 Td /F2 8.0 Tf [(Tahir, Muhammad, MBBS, MRCS et al.)] TJ ET
BT 48.000 742.800 Td /F2 8.0 Tf [(Delay in Initial Debridement for Open Tibial Fractures and Its Possible Impact on Patient Outcomes. A Single-Center Prospective Cohort Study)] TJ ET
BT 48.000 730.800 Td /F2 8.0 Tf [(http://dx.doi.org/10.2106/JBJS.OA.20.00027)] TJ ET
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BT 47.475 662.280 Td /F4 12.0 Tf [(Jeffrey M. Smith, MD)] TJ ET
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BT 47.475 485.964 Td /F2 12.0 Tf [(Queen Mary University of London, UK)] TJ ET
BT 47.475 460.500 Td /F4 12.0 Tf [(Paul Tornetta III, MD)] TJ ET
BT 47.475 424.644 Td /F2 12.0 Tf [(Department of Orthopedics, Boston University Medical Center, Boston, USA)] TJ ET
BT 47.475 399.180 Td /F4 12.0 Tf [(GOLIATH Investigators Investigators)] TJ ET
BT 47.475 343.824 Td /F4 12.0 Tf [(Invited Commentary on )] TJ ET
BT 173.799 343.824 Td /F4 12.0 Tf [(Delay in Initial Debridement for Open Tibial Fractures and Its Possible )] TJ ET
BT 47.475 326.004 Td /F4 12.0 Tf [(Impact on Patient Outcomes: A Single-Center Prospective Cohort Study)] TJ ET
BT 47.475 290.184 Td /F2 12.0 Tf [(The investigators had two purposes for their prospective observational study of 1896 open tibial fractures. )] TJ ET
BT 47.475 272.364 Td /F2 12.0 Tf [(First, they sought to identify if there was an association between time to debridement and adverse events )] TJ ET
BT 47.475 254.544 Td /F2 12.0 Tf [(such as deep infection, amputation, nonunion, and mortality. They excluded patients that were debrided )] TJ ET
BT 47.475 236.724 Td /F2 12.0 Tf [(within 24 hours from injury, using a >24-48 hour group as the reference category and comparing outcome )] TJ ET
BT 47.475 218.904 Td /F2 12.0 Tf [(rates to those that were debrided >48-72 and >72-96 hours after injury. Second, they also investigated the )] TJ ET
BT 47.475 201.084 Td /F2 12.0 Tf [(association between time from injury to antibiotic prophylaxis using a dichotomous 12-hour cutoff from )] TJ ET
BT 47.475 183.264 Td /F2 12.0 Tf [(injury.)] TJ ET
BT 47.475 147.444 Td /F2 12.0 Tf [(Methodologically, they analyzed the delay to debridement groups using a standard chi-squared and )] TJ ET
BT 47.475 129.624 Td /F2 12.0 Tf [(presumably a univariate logistic regression, stratifying for Gustilo type \(grouped into Gustilo type I, II, )] TJ ET
BT 47.475 111.804 Td /F2 12.0 Tf [(and III without substratification among Gustilo type IIIs\). They did not identify an association between )] TJ ET
BT 47.475 93.984 Td /F2 12.0 Tf [(Gustilo type III fractures and very late debridement although was a 3% \(Odds ratio 1.03\) increase in the )] TJ ET
BT 47.475 76.164 Td /F2 12.0 Tf [(deep infection rate between the >24-48 hour and the >48-72 hour cohorts \(p=0.48\). There were also trends )] TJ ET
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BT 48.000 742.800 Td /F2 8.0 Tf [(Delay in Initial Debridement for Open Tibial Fractures and Its Possible Impact on Patient Outcomes. A Single-Center Prospective Cohort Study)] TJ ET
BT 48.000 730.800 Td /F2 8.0 Tf [(http://dx.doi.org/10.2106/JBJS.OA.20.00027)] TJ ET
BT 48.000 718.800 Td /F2 8.0 Tf [(2 of 6)] TJ ET
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BT 47.475 687.744 Td /F2 12.0 Tf [(for increased odds for delay for Gustilo type I fractures.)] TJ ET
BT 47.475 651.924 Td /F2 12.0 Tf [(We performed an independent analysis across Gustilo types and there was a clear increase in the odds of )] TJ ET
BT 47.475 634.104 Td /F2 12.0 Tf [(infection associated with surgery >48 hours \(OR 1.44, 95% CI 1.11 to 1.86, p=0.006\). However, when we )] TJ ET
BT 47.475 616.284 Td /F2 12.0 Tf [(used aggregated their estimates across the Gustilo subgroups, it resulted in a much smaller estimate from )] TJ ET
BT 47.475 598.464 Td /F2 12.0 Tf [(the data they provided across the Gustilo types estimates which resulted in a much smaller estimate \(OR )] TJ ET
BT 47.475 580.644 Td /F2 12.0 Tf [(1.10, 95% CI 0.78 to 1.55, p=0.57\). We require data from the original authors to investigate this )] TJ ET
BT 47.475 562.824 Td /F2 12.0 Tf [(discrepancy.)] TJ ET
BT 47.475 527.004 Td /F2 12.0 Tf [(For those that were debrided >48 hours after injury, compared to >24-48 hours, the odds of amputation )] TJ ET
BT 47.475 509.184 Td /F2 12.0 Tf [(increased 3-fold \(OR 3.15, 95% CI 1.69 to 5.89, p<0.001\). It is unclear from the paper when the )] TJ ET
BT 47.475 491.364 Td /F2 12.0 Tf [(amputations took place. Because there is a greater amputation rate in the delayed debridement groups, it is )] TJ ET
BT 47.475 473.544 Td /F2 12.0 Tf [(unclear if this impacted the infection rates. Specifically, if having more delayed amputations in the >48 )] TJ ET
BT 47.475 455.724 Td /F2 12.0 Tf [(hours debridement groups resulted in a reduced number of at risk of infection and therefore artificially )] TJ ET
BT 47.475 437.904 Td /F2 12.0 Tf [(reduced the deep infection rates in these cohorts.)] TJ ET
BT 47.475 402.084 Td /F2 12.0 Tf [(We performed three analyses based on assumptions that, 1\) amputations occurred early \(prior to any risk )] TJ ET
BT 47.475 384.264 Td /F2 12.0 Tf [(of infection\), 2\) amputations were incurred as a result of deep infection and were not accounted for in the )] TJ ET
BT 47.475 366.444 Td /F2 12.0 Tf [(analyses, and 3\) amputations occurred secondarily due to the occurrence of infection and were accounted )] TJ ET
BT 47.475 348.624 Td /F2 12.0 Tf [(for in the analyses.)] TJ ET
BT 47.475 312.804 Td /F2 12.0 Tf [(One, we removed the amputations from the total count of patients in each time window \(and also those )] TJ ET
BT 47.475 294.984 Td /F2 12.0 Tf [(that died\) as they may have incurred the amputation early \(assumption one=competing risk\). When this )] TJ ET
BT 47.475 277.164 Td /F2 12.0 Tf [(was conducted, it raised the odds of infection for Gustilo type III fractures that were delayed >48 hours )] TJ ET
BT 47.475 259.344 Td /F2 12.0 Tf [(from injury \(OR 1.51, 95% CI 1.03 to 2.23, p=0.04; ~8.7% increase in the deep infection rate\). In scenario )] TJ ET
BT 47.475 241.524 Td /F2 12.0 Tf [(two, the amputation cases may not have been accounted for as infections. If we assume the amputations )] TJ ET
BT 47.475 223.704 Td /F2 12.0 Tf [(were all due to deep infection \(a strong assumption\), it raises the estimate to OR=2.19 \(95% CI 1.55 to )] TJ ET
BT 47.475 205.884 Td /F2 12.0 Tf [(3.09, p<0.001; ~16.7% increase in the deep infection rate\) for >24-48 versus >48 hours. The last possible )] TJ ET
BT 47.475 188.064 Td /F2 12.0 Tf [(scenario is that those that incurred infection and were amputated were accounted for in both outcomes. )] TJ ET
BT 47.475 170.244 Td /F2 12.0 Tf [(The problem with this scenario is it would suggest that the deep infections associated with greater delays )] TJ ET
BT 47.475 152.424 Td /F2 12.0 Tf [(to initial debridement may be more aggressive \(i.e. superinfections\), leading to a 3-fold odds increase in )] TJ ET
BT 47.475 134.604 Td /F2 12.0 Tf [(the amputation rate with debridement >48 hours. Therefore, reporting that there is not an increase in an )] TJ ET
BT 47.475 116.784 Td /F2 12.0 Tf [(infection problem with delayed debridement would be neglecting this very crucial fact. Specifically, )] TJ ET
BT 47.475 98.964 Td /F2 12.0 Tf [(even though the infection rate may have remained stable over time the severity of the infections \(and their )] TJ ET
BT 47.475 81.144 Td /F2 12.0 Tf [(consequences\) increased progressively.)] TJ ET
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BT 48.000 754.800 Td /F2 8.0 Tf [(Tahir, Muhammad, MBBS, MRCS et al.)] TJ ET
BT 48.000 742.800 Td /F2 8.0 Tf [(Delay in Initial Debridement for Open Tibial Fractures and Its Possible Impact on Patient Outcomes. A Single-Center Prospective Cohort Study)] TJ ET
BT 48.000 730.800 Td /F2 8.0 Tf [(http://dx.doi.org/10.2106/JBJS.OA.20.00027)] TJ ET
BT 48.000 718.800 Td /F2 8.0 Tf [(3 of 6)] TJ ET
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BT 47.475 687.744 Td /F2 12.0 Tf [(To give some quantification around the potential disparity in the severity of the infection outcome, one )] TJ ET
BT 47.475 669.924 Td /F2 12.0 Tf [(could consider the amputation rate among the total infections for those debrided >24-48 versus >48 hours. )] TJ ET
BT 47.475 652.104 Td /F2 12.0 Tf [(Compared with the >24-48 group, the odds of amputation among the deep infected is 2.7-fold higher for )] TJ ET
BT 47.475 634.284 Td /F2 12.0 Tf [(those debrided >48 hours \(95% CI 1.38 to 5.29, p=0.004\). So this metric would suggest the infections )] TJ ET
BT 47.475 616.464 Td /F2 12.0 Tf [(incurred after very late debridement may be 3-times more aggressive. Among those infected that were )] TJ ET
BT 47.475 598.644 Td /F2 12.0 Tf [(debrided >24-48 hours, only 12.1% got an amputation in contrast to 27.2% for those infected debrided >48 )] TJ ET
BT 47.475 580.824 Td /F2 12.0 Tf [(hours \(ARI 15.1%, 95% CI 6.4 to 23.7%, p=0.006\). Therefore, all of the sensitivity analyses suggest )] TJ ET
BT 47.475 563.004 Td /F2 12.0 Tf [(inferior outcomes with delay to debridement >48 hours from injury compared to >24-48 hours from )] TJ ET
BT 47.475 545.184 Td /F2 12.0 Tf [(injury, mediated through either a higher deep infection rate and/or more severe infections leading to a )] TJ ET
BT 47.475 527.364 Td /F2 12.0 Tf [(substantial increase in the odds of amputation. The authors made note of the increased risk of amputation )] TJ ET
BT 47.475 509.544 Td /F2 12.0 Tf [(qualitatively in the results.)] TJ ET
BT 47.475 473.724 Td /F2 12.0 Tf [(From the TIIME Study Registry Gustilo type III open fractures, we conducted analyses looking at the )] TJ ET
BT 47.475 455.904 Td /F2 12.0 Tf [(impact of time to debridement on the amputation rate. The was higher early likely related to injury severity )] TJ ET
BT 47.475 438.084 Td /F2 12.0 Tf [(and decreased for the first nine-hour \(OR 0.76, 95% CI 0.58 to 1.00, p=0.049, Figure 1\). In the stratified )] TJ ET
BT 47.475 420.264 Td /F2 12.0 Tf [(spline model, the amputation rate stayed slow and stable from nine to 12 hours, increasing thereafter. )] TJ ET
BT 47.475 402.444 Td /F2 12.0 Tf [(When comparing amputation rates around 10 hours to those at 24 hours from injury to debridement the )] TJ ET
BT 47.475 384.624 Td /F2 12.0 Tf [(amputation rate increased by 2.05-fold \(95% CI 1.00 to 4.21, p=0.05, Figure 1\).)] TJ ET
BT 47.475 348.804 Td /F2 12.0 Tf [()] TJ ET
BT 47.475 312.984 Td /F2 12.0 Tf [()] TJ ET
BT 47.475 277.164 Td /F2 12.0 Tf [()] TJ ET
BT 47.475 241.344 Td /F2 12.0 Tf [()] TJ ET
BT 47.475 205.524 Td /F2 12.0 Tf [()] TJ ET
BT 47.475 169.704 Td /F2 12.0 Tf [()] TJ ET
BT 47.475 133.884 Td /F2 12.0 Tf [()] TJ ET
BT 47.475 98.064 Td /F2 12.0 Tf [(Figure 1: Stratified spline model of the amputation rates across times from injury to debridement.)] TJ ET
BT 47.475 62.244 Td /F2 12.0 Tf [(Figure 2 shows data from the TIIME Registry that shows the impact of further delays to flap coverage )] TJ ET
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BT 48.000 754.800 Td /F2 8.0 Tf [(Tahir, Muhammad, MBBS, MRCS et al.)] TJ ET
BT 48.000 742.800 Td /F2 8.0 Tf [(Delay in Initial Debridement for Open Tibial Fractures and Its Possible Impact on Patient Outcomes. A Single-Center Prospective Cohort Study)] TJ ET
BT 48.000 730.800 Td /F2 8.0 Tf [(http://dx.doi.org/10.2106/JBJS.OA.20.00027)] TJ ET
BT 48.000 718.800 Td /F2 8.0 Tf [(4 of 6)] TJ ET
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BT 47.475 687.744 Td /F2 12.0 Tf [(from the timing of nailing in Gustilo type III fractures requiring flap coverage. It leads to an increased )] TJ ET
BT 47.475 669.924 Td /F2 12.0 Tf [(amputation rate. Compared with nailed and flapped early, coverage at 6 days had a 1.72-fold higher )] TJ ET
BT 47.475 652.104 Td /F2 12.0 Tf [(amputation rate \(95% CI 0.86 to 3.43, p=0.13\). Compared with the total time to surgery of 10 hours, the )] TJ ET
BT 47.475 634.284 Td /F2 12.0 Tf [(total time to debridement and flap coverage >72 hours increased the amputation rate by 2.19-fold \(95% CI )] TJ ET
BT 47.475 616.464 Td /F2 12.0 Tf [(1.11 to 4.35, p=0.03\). Those that become infected with definitive surgery late that get infected have a 2.17-)] TJ ET
BT 47.475 598.644 Td /F2 12.0 Tf [(fold higher amputation rate than those that received definitive surgery early and get infected \(95% CI 0.44 )] TJ ET
BT 47.475 580.824 Td /F2 12.0 Tf [(to 10.7, p=0.34\). From our work, this suggests that a rising infection rate is not the only concern with )] TJ ET
BT 47.475 563.004 Td /F2 12.0 Tf [(delayed surgery but also more impactful nosocomial infections that carry with it a greater likelihood of )] TJ ET
BT 47.475 545.184 Td /F2 12.0 Tf [(delayed amputation due to infection. This suggests that accounting for the amputation rate in analyses is )] TJ ET
BT 47.475 527.364 Td /F2 12.0 Tf [(critical for 1\) adjusting the infection rates appropriately, 2\) gauging the severity of infections.)] TJ ET
BT 47.475 491.544 Td /F2 12.0 Tf [()] TJ ET
BT 47.475 455.724 Td /F2 12.0 Tf [()] TJ ET
BT 47.475 419.904 Td /F2 12.0 Tf [()] TJ ET
BT 47.475 384.084 Td /F2 12.0 Tf [()] TJ ET
BT 47.475 348.264 Td /F2 12.0 Tf [()] TJ ET
BT 47.475 312.444 Td /F2 12.0 Tf [()] TJ ET
BT 47.475 276.624 Td /F2 12.0 Tf [()] TJ ET
BT 47.475 240.804 Td /F2 12.0 Tf [(Figure 2: Spline analyses showing the association between time to flap coverage and the secondary )] TJ ET
BT 47.475 222.984 Td /F2 12.0 Tf [(amputation rate.)] TJ ET
BT 47.475 187.164 Td /F2 12.0 Tf [(The GOLIATH Collaboration has limited access to some datasets involving patients with lengthy delays )] TJ ET
BT 47.475 169.344 Td /F2 12.0 Tf [(\(1-4\). When we aggregate this data across all Gustilo types, it suggests an increase in the infection rate of )] TJ ET
BT 47.475 151.524 Td /F2 12.0 Tf [(1.37-fold with surgery >48 hours \(95% CI 1.09 to 1.73, p=0.006, very low confidence\) versus >24-48 )] TJ ET
BT 47.475 133.704 Td /F2 12.0 Tf [(hours. However, compared with surgery ?12 hours, delays >48 hours carry with it a 2.63-fold \(95% CI )] TJ ET
BT 47.475 115.884 Td /F2 12.0 Tf [(1.48 to 4.68, p=0.001, moderate confidence\) higher risk of infection. In Gustilo type III fractures the 1.37 )] TJ ET
BT 47.475 98.064 Td /F2 12.0 Tf [(estimate increases to 1.55 \(95% CI 1.06 to 2.26, p=0.02, low confidence\) of >48 versus >24-48 hours. )] TJ ET
BT 47.475 80.244 Td /F2 12.0 Tf [(Compared to timing to surgery of ?12 hours, >48 hours carries with a 2.98-fold increase in the infection )] TJ ET
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BT 104.475 291.363 Td /F2 9.0 Tf [(Alliance Reducing Trauma Adverse Events\). AAOS; San Deigo2021.)] TJ ET
BT 92.575 279.465 Td /F2 9.0 Tf [(2.)] TJ ET
BT 104.475 277.998 Td /F2 9.0 Tf [(Duyos OA, Beaton-Comulada D, Davila-Parrilla A, Perez-Lopez JC, Ortiz K, Foy-Parrilla C, et al. Management of Open )] TJ ET
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BT 92.575 239.370 Td /F2 9.0 Tf [(3.)] TJ ET
BT 104.475 237.903 Td /F2 9.0 Tf [(Marecek GP, J.T.; Heckmann, N. Delayed Debridement of Open Tibia Fractures Beyond 24 and 48 Hours Does Not Appear to )] TJ ET
BT 104.475 224.538 Td /F2 9.0 Tf [(Increase Infection and Reoperation Risk. 2021.)] TJ ET
BT 92.575 212.640 Td /F2 9.0 Tf [(4.)] TJ ET
BT 104.475 211.173 Td /F2 9.0 Tf [(Tahir MA, N; Shaikh, S.A.; Jamali, A.R.; Choudry, U.K.; Khan, S. . Delay in Initial Debridement for Open Tibial Fractures )] TJ ET
BT 104.475 197.808 Td /F2 9.0 Tf [(and Its Possible Impact on Patient Outcomes: A Single-Center Prospective Cohort Study. JBJS [Internet]. 2021. Available )] TJ ET
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(from the timing of nailing in Gustilo type III fractures requiring flap \
coverage. It leads to an increased )Tj
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(amputation rate. Compared with nailed and flapped early, coverage at 6 d\
ays had a 1.72-fold higher )Tj
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(amputation rate \(95% CI 0.86 to 3.43, p=0.13\). Compared with the total\
time to surgery of 10 hours, the )Tj
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(total time to debridement and flap coverage >72 hours increased the ampu\
tation rate by 2.19-fold \(95% CI )Tj
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(1.11 to 4.35, p=0.03\). Those that become infected with definitive surge\
ry late that get infected have a 2.17-)Tj
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(fold higher amputation rate than those that received definitive surgery \
early and get infected \(95% CI 0.44 )Tj
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(to 10.7, p=0.34\). From our work, this suggests that a rising infection \
rate is not the only concern with )Tj
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with it a greater likelihood of )Tj
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(Figure 2: Spline analyses showing the association between time to flap c\
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(\(1-4\). When we aggregate this data across all Gustilo types, it sugges\
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