- Email: [email protected]
Recruitment rates in orthopaedic trauma trials: Zen or the art of riding dead horses
Injury, Int. J. Care Injured 48 (2017) 1719–1721
Contents lists available at ScienceDirect
Injury journal homepage: www.elsevier.com/locate/injury
Editorial
Recruitment rates in orthopaedic trauma trials: Zen or the art of riding dead horses
Editorials like this typically begin with ‘‘randomized controlled trials (RCT) provide the highest level of evidence (or similar)’’ which (apart from ‘‘p < 0.05 was considered statistically significant’’) probably belongs to one of the most frequently copy-pasted but misunderstood statements in the biomedical literature. At annual meetings of major international societies like the AAOS, OTA, and AAST, big, bigger and biggest RCT are praised as the last resort to solve conflicting clinical issues in times of ever decreasing effect sizes. We will not comment on this, as the debate about the sense and nonsense of both surgical and mega-trials already fill bookshelves. Yet, the sloppy notion ‘‘level I evidence’’ disrespects the complex scientific reasoning and history behind the RCT concept. From an editor’s perspective, most trials in our area are conservative (i.e., ‘‘compare A with B, randomize a certain number of patients between time points x and y, don’t care what happens in between, and do some sort of analysis’’) and stay behind recent methodological standards (like adaptive, Bayesian, bucket/basket, umbrella, platform approaches, just to name a few). There is a delicate trade-off between the anticipated gain in scientific and clinical knowledge and the vast resources needed for planning and conducting a solid trial, specifically in a multicenter environment. If operating costs of a trial outbalance its potential immediate or future implications, it probably is a dead horse. The well-known tribal wisdom of the Dakota Indians says that ‘‘when you discover that you are riding a dead horse, the best strategy is to dismount’’ (one of multiple references: https://www.theguardian. com/money/1999/nov/26/workandcareers). We all know the satirical modern alternative strategies (e.g., ‘‘changing riders’’, ‘‘appointing a committee to study the horse’’, ‘‘lowering the standards so dead horses can be included’’, etc.). However, when talking about patients and caregivers, ethical issues, hospital resources, research budgets and so on, there is little if any room for humor. Enrolling sufficient numbers of participants onto a trial to answer its primary and secondary objectives is key – in total, but also at individual centers and during a manageable time interval. The recently published Fixation using Alternative Implants for the Treatment of Hip Fractures (FAITH) trial, comparing sliding hip screw (SHS) with cancellous screws, included an impressive number of 1108 patients randomized to either treatment group – still, out of 7306 screened patients during six years at 81 centers [1]. This means that, on average, less than two patients were randomized per center annually. Altogether, the population included in the FAITH trial represents less than 10% of all hip http://dx.doi.org/10.1016/j.injury.2017.07.028 0020–1383/ß 2017 Published by Elsevier Ltd.
fracture cases in North America and Europe [2]. So, is FAITH really a success story or simply an example how to professionally ride a dead horse (or to tell the scientific community that dead horses can be ridden at all)? Inadequate recruitment with marginal numbers of patients identified and enrolled at single trial sites hampers the efficiency, integrity and validity of a trial and must alert investigators and sponsors alike. If the curves of observed to expected (O:E) recruitment rates diverge markedly at some point and show stagnation, stakeholders must responsibly decide whether substantial extra and unplanned efforts (e.g., organizing local investigator reminder and site training sessions, initiating additional centers, extending the recruitment period, or even modifying the clinical investigation plan) are justified to rescue the trial. This is anything but trivial and needs courage. The question is ‘‘If this horse was alive, do I want to ride it?’’ Recruitment behind expectation may indicate that eligibility criteria, interventions, outcomes, the frequency of measurements or the entire research plan do not fit into clinical practice. In this case, any trial result is unlikely to change health care in future, making the trial meaningless. In most cases, the decision to stop a trial prematurely is not made jointly between investigators and sponsors. The sponsor will decide in a top-down fashion. For example, the German ORCHID trial comparing volar locking plate fixation of distal radius fractures with cast stabilization was terminated prematurely by the public sponsor (the German Research Foundation, DFG) because of slow recruitment rates, against the clear vote of the steering committee [3]. There are, of course, exemptions beyond the rule like the DRAFFT trial (comparing volar locking plates with K-wires for fixing distal radius fractures) in which observed even exceeded expected recruitment rates [4]. While CONSORT flow-charts may allow for calculating ratios of screened:eligible:randomized:analyzed patients, readers need quick and simple information about trial efficiency to decide whether results are meaningful and suit their daily practice. We suggest the following recruitment indices: RRS
rate of randomized to screened patients
RAR
rate of analyzed to randomized patients
RPC
annual number of randomized patients per center
We surveyed 14 consecutive RCT published in Injury between 06/2016 and 06/2017 (Table 1). The median duration of recruitment
1720
Table 1 Characteristics of individual trials. Author
Year
Trial register
2017 NCT Bruntink MM [5] 00881088 Caiaffa V [6] 2016 Unclear
Entity
Intervention
Control
Recruitment
Nether lands Italy
Ankle or foot fractures immobilized 4 weeks Stable trochanteric fractures
Nadroparin
Fondaparinux
04/2009–12/2015 6.7
7
783
467
278
Yes
10
0.60 0.60
04/2012–10/2014 2.5
6
579
357
266
Yes
24
0.62 0.75
03/2008–09/2012 4.5
1
71
71
66
No
16
1.00 0.93
02/2010–04/2014 4.2
1
138
138
138
No
33
1.00 1.00
01/2009–01/2015 6.0
1
Unclear
87
73
No
14
NA
04/2013–04/2014 1.0
2
443
406
406
Yes
203 0.92 1.00
09/2005–06/2008 2.8
1
Unclear
28
28
No
10
07/2012–05/2014 1.8
2
1198
571
400
Yes
156 0.48 0.70
09/2014–03/2015 0.5
1
Unclear
84
77
Yes
169 NA
10/2013–09/2014 0.9
1
225
100
96
Yes
109 0.44 0.96
01/2014–11/2014 0.8
2
Unclear
72
64
No
43
01/2011–08/2014 3.6
1
412
380
353
Yes
106 0.92 0.93
08/2010–05/2014 3.8
1
139
107
90
Yes
29
04/2009–09/2011 2.4
1
472
274
266
Yes
113 0.58 0.97
Short IM nail with distal locking
Short IM nail without distal locking Crist BD [7] 2017 Unclear USA ORIF for acetabular VAC dressing Conventional fractures dressing Ducˇic´ S [8] 2016 Unclear Serbia/ Displaced supracondylar Dorgan’s K-wire Conventional Croatia fractures in children fixation K-wire fixation Georgiannos 2017 Unclear Greece Fragility fractures of Tibio-talo-calcaneal ORIF D [9] the ankle in the elderly nailing Ghafouri 2016 IRCT 20130 Iran Simple traumatic Povidone iodine Saline HB [10] 70610017N5 wounds in the ED cleansing irrigation IM nail Palmar Gradl 2016 Unclear Germany Intraarticular locking plate G [11] fractures of the distal radius (AO C2.1) Larsson 2016 Unclear Sweden Suspected hip fractures Pre-hospital fast Standard G [12] track care of care Cefuroxime/ Ondari 2016 Unclear Kenya Grade II open tibia Cefuroxime/ gentamycin JN [13] fractures gentamycin 24 h 5 days Qiu 2017 Unclear China Hemiarthroplasty IV Hemocoagulase Standard M [14] for hip fractures of care Sahin 2016 Unclear Turkey Unstable trochanteric IM nailing with IM nailing with E [15] fractures traction table manual traction IM nailing with Shin 2017 Unclear South Trochanteric fractures IM nailing Zimmer PFN II YS [16] Korea in elderly patients with Zimmer Natural Nail Sohn 2017 Unclear South Displaced proximal MIS plating Open plating HS [17] Korea humeral fractures Standard Unneby 2017 Unclear Sweden Hip fractures Pre-operative of care A [18] in elderly patients femoral nerve block
Duration Centers, Screened, Randomized, Analyzed, CONSORT RPC RRS (years) n n n n
NA
NA
RAR
0.84
1.00
0.92
0.89
0.77 0.84
Editorial / Injury, Int. J. Care Injured 48 (2017) 1719–1721
Country
Editorial / Injury, Int. J. Care Injured 48 (2017) 1719–1721
was 2.7 years (interquartile range [IQR] 1.0–4.2 years). The median RRS was 0.69 (IQR 0.58–0.92). The median RAR was 0.93 (IQR 0.84– 0.97). The median RPC was 38 (IQR 16–113). Authors may consider providing these indices in addition to CONSORT recommendations. While there is currently no accepted benchmark, RRS and RAR around 1 suggest high acceptability of the trial by patients and clinicians, and transferability of results into clinical practice. We encourage authors to submit O:E cumulative recruitment curves as an adjunct to CONSORT diagrams. Readers of Injury deserve to know whether a trial was an energetic stallion or a nag under continuous resuscitation. If it was the latter – let us know. Tell us how you coped with this difficult situation, and why you continued riding an (almost) dead horse. This will generate truly novel data and help clinical researchers worldwide to make informed decisions about their projects. References [1] Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) Investigators. Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial. Lancet 2017;389:1519–27. [2] Kanis JA, Oden A, McCloskey EV, Johansson H, Wahl DA, Cooper C, et al. A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporos Int 2012;23:2239–56. [3] Bartl C, Stengel D, Bruckner T, Rossion I, Luntz S, Seiler C, et al. Open reduction and internal fixation versus casting for highly comminuted and intra-articular fractures of the distal radius (ORCHID): protocol for a randomized clinical multi-center trial. Trials 2011;12:84. [4] Costa ML, Achten J, Parsons NR, Rangan A, Griffin D, Tubeuf S, et al. Percutaneous fixation with Kirschner wires versus volar locking plate fixation in adults with dorsally displaced fracture of distal radius: randomised controlled trial. BMJ 2014;349:g4807. [5] Bruntink MM, Groutars YM, Schipper IB, Breederveld RS, Tuinebreijer WE, Derksen RJ. Nadroparin or fondaparinux versus no thromboprophylaxis in patients immobilised in a below-knee plaster cast (PROTECT): a randomised controlled trial. Injury 2017;48:936–40. [6] Caiaffa V, Vicenti G, Mori C, Panella A, Conserva V, Corina G, et al. Is distal locking with short intramedullary nails necessary in stable pertrochanteric fractures? A prospective, multicentre, randomised study. Injury 2016;47(Suppl. 4):S98–106. [7] Crist BD, Oladeji LO, Khazzam M, Della Rocca GJ, Murtha YM, Stannard JP. Role of acute negative pressure wound therapy over primarily closed surgical incisions in acetabular fracture ORIF: a prospective randomized trial. Injury 2017;48:1518–21. [8] Ducic S, Radlovic V, Bukva B, Radojicic Z, Vrgoc G, Brkic I, et al. A prospective randomised non-blinded comparison of conventional and Dorgan’s crossed pins for paediatric supracondylar humeral fractures. Injury 2016;47:2479–83. [9] Georgiannos D, Lampridis V, Bisbinas I. Fragility fractures of the ankle in the elderly: open reduction and internal fixation versus tibio-talo-calcaneal nailing: short-term results of a prospective randomized-controlled study. Injury 2017;48:519–24.
1721
[10] Ghafouri HB, Zare M, Bazrafshan A, Abazarian N, Ramim T. Randomized, controlled trial of povidone-iodine to reduce simple traumatic wound infections in the emergency department. Injury 2016;47:1913–8. [11] Gradl G, Falk S, Mittlmeier T, Wendt M, Mielsch N, Gradl G. Fixation of intraarticular fractures of the distal radius using intramedullary nailing: a randomized trial versus palmar locking plates. Injury 2016;47(Suppl. 7):S25–30. [12] Larsson G, Stromberg RU, Rogmark C, Nilsdotter A. Prehospital fast track care for patients with hip fracture: impact on time to surgery, hospital stay, postoperative complications and mortality a randomised, controlled trial. Injury 2016;47:881–6. [13] Ondari JN, Masika MM, Ombachi RB, Ating’a JE. Unblinded randomized control trial on prophylactic antibiotic use in gustilo II open tibia fractures at Kenyatta National Hospital, Kenya. Injury 2016;47:2288–93. [14] Qiu M, Zhang X, Cai H, Xu Z, Lin H. The impact of hemocoagulase for improvement of coagulation and reduction of bleeding in fracture-related hip hemiarthroplasty geriatric patients: a prospective, single-blinded, randomized, controlled study. Injury 2017;48:914–9. [15] Sahin E, Songur M, Kalem M, Zehir S, Aksekili MA, Keser S, et al. Traction table versus manual traction in the intramedullary nailing of unstable intertrochanteric fractures: a prospective randomized trial. Injury 2016;47:1547–54. [16] Shin YS, Chae JE, Kang TW, Han SB. Prospective randomized study comparing two cephalomedullary nails for elderly intertrochanteric fractures: Zimmer natural nail versus proximal femoral nail antirotation II. Injury 2017;48:1550– 7. [17] Sohn HS, Jeon YS, Lee J, Shin SJ. Clinical comparison between open plating and minimally invasive plate osteosynthesis for displaced proximal humeral fractures: a prospective randomized controlled trial. Injury 2017;48:1175–82. [18] Unneby A, Svensson O, Gustafson Y, Olofsson B. Femoral nerve block in a representative sample of elderly people with hip fracture: a randomised controlled trial. Injury 2017;48:1542–9.
Dirk Stengel* Cyril Mauffrey Ian Civil A.C. Gray C. Roberts Hans-Christoph Pape C. Evans Bridget Kool O.J. Mauffrey Peter Giannoudis BG Kliniken Group of Hospitals, BG Klinikum Unfallkrankenhaus Berlin gGmH, Warener Str. 7, 12683 Berlin, Germany *Corresponding author E-mail address: [email protected] (D. Stengel).
Contents lists available at ScienceDirect
Injury journal homepage: www.elsevier.com/locate/injury
Editorial
Recruitment rates in orthopaedic trauma trials: Zen or the art of riding dead horses
Editorials like this typically begin with ‘‘randomized controlled trials (RCT) provide the highest level of evidence (or similar)’’ which (apart from ‘‘p < 0.05 was considered statistically significant’’) probably belongs to one of the most frequently copy-pasted but misunderstood statements in the biomedical literature. At annual meetings of major international societies like the AAOS, OTA, and AAST, big, bigger and biggest RCT are praised as the last resort to solve conflicting clinical issues in times of ever decreasing effect sizes. We will not comment on this, as the debate about the sense and nonsense of both surgical and mega-trials already fill bookshelves. Yet, the sloppy notion ‘‘level I evidence’’ disrespects the complex scientific reasoning and history behind the RCT concept. From an editor’s perspective, most trials in our area are conservative (i.e., ‘‘compare A with B, randomize a certain number of patients between time points x and y, don’t care what happens in between, and do some sort of analysis’’) and stay behind recent methodological standards (like adaptive, Bayesian, bucket/basket, umbrella, platform approaches, just to name a few). There is a delicate trade-off between the anticipated gain in scientific and clinical knowledge and the vast resources needed for planning and conducting a solid trial, specifically in a multicenter environment. If operating costs of a trial outbalance its potential immediate or future implications, it probably is a dead horse. The well-known tribal wisdom of the Dakota Indians says that ‘‘when you discover that you are riding a dead horse, the best strategy is to dismount’’ (one of multiple references: https://www.theguardian. com/money/1999/nov/26/workandcareers). We all know the satirical modern alternative strategies (e.g., ‘‘changing riders’’, ‘‘appointing a committee to study the horse’’, ‘‘lowering the standards so dead horses can be included’’, etc.). However, when talking about patients and caregivers, ethical issues, hospital resources, research budgets and so on, there is little if any room for humor. Enrolling sufficient numbers of participants onto a trial to answer its primary and secondary objectives is key – in total, but also at individual centers and during a manageable time interval. The recently published Fixation using Alternative Implants for the Treatment of Hip Fractures (FAITH) trial, comparing sliding hip screw (SHS) with cancellous screws, included an impressive number of 1108 patients randomized to either treatment group – still, out of 7306 screened patients during six years at 81 centers [1]. This means that, on average, less than two patients were randomized per center annually. Altogether, the population included in the FAITH trial represents less than 10% of all hip http://dx.doi.org/10.1016/j.injury.2017.07.028 0020–1383/ß 2017 Published by Elsevier Ltd.
fracture cases in North America and Europe [2]. So, is FAITH really a success story or simply an example how to professionally ride a dead horse (or to tell the scientific community that dead horses can be ridden at all)? Inadequate recruitment with marginal numbers of patients identified and enrolled at single trial sites hampers the efficiency, integrity and validity of a trial and must alert investigators and sponsors alike. If the curves of observed to expected (O:E) recruitment rates diverge markedly at some point and show stagnation, stakeholders must responsibly decide whether substantial extra and unplanned efforts (e.g., organizing local investigator reminder and site training sessions, initiating additional centers, extending the recruitment period, or even modifying the clinical investigation plan) are justified to rescue the trial. This is anything but trivial and needs courage. The question is ‘‘If this horse was alive, do I want to ride it?’’ Recruitment behind expectation may indicate that eligibility criteria, interventions, outcomes, the frequency of measurements or the entire research plan do not fit into clinical practice. In this case, any trial result is unlikely to change health care in future, making the trial meaningless. In most cases, the decision to stop a trial prematurely is not made jointly between investigators and sponsors. The sponsor will decide in a top-down fashion. For example, the German ORCHID trial comparing volar locking plate fixation of distal radius fractures with cast stabilization was terminated prematurely by the public sponsor (the German Research Foundation, DFG) because of slow recruitment rates, against the clear vote of the steering committee [3]. There are, of course, exemptions beyond the rule like the DRAFFT trial (comparing volar locking plates with K-wires for fixing distal radius fractures) in which observed even exceeded expected recruitment rates [4]. While CONSORT flow-charts may allow for calculating ratios of screened:eligible:randomized:analyzed patients, readers need quick and simple information about trial efficiency to decide whether results are meaningful and suit their daily practice. We suggest the following recruitment indices: RRS
rate of randomized to screened patients
RAR
rate of analyzed to randomized patients
RPC
annual number of randomized patients per center
We surveyed 14 consecutive RCT published in Injury between 06/2016 and 06/2017 (Table 1). The median duration of recruitment
1720
Table 1 Characteristics of individual trials. Author
Year
Trial register
2017 NCT Bruntink MM [5] 00881088 Caiaffa V [6] 2016 Unclear
Entity
Intervention
Control
Recruitment
Nether lands Italy
Ankle or foot fractures immobilized 4 weeks Stable trochanteric fractures
Nadroparin
Fondaparinux
04/2009–12/2015 6.7
7
783
467
278
Yes
10
0.60 0.60
04/2012–10/2014 2.5
6
579
357
266
Yes
24
0.62 0.75
03/2008–09/2012 4.5
1
71
71
66
No
16
1.00 0.93
02/2010–04/2014 4.2
1
138
138
138
No
33
1.00 1.00
01/2009–01/2015 6.0
1
Unclear
87
73
No
14
NA
04/2013–04/2014 1.0
2
443
406
406
Yes
203 0.92 1.00
09/2005–06/2008 2.8
1
Unclear
28
28
No
10
07/2012–05/2014 1.8
2
1198
571
400
Yes
156 0.48 0.70
09/2014–03/2015 0.5
1
Unclear
84
77
Yes
169 NA
10/2013–09/2014 0.9
1
225
100
96
Yes
109 0.44 0.96
01/2014–11/2014 0.8
2
Unclear
72
64
No
43
01/2011–08/2014 3.6
1
412
380
353
Yes
106 0.92 0.93
08/2010–05/2014 3.8
1
139
107
90
Yes
29
04/2009–09/2011 2.4
1
472
274
266
Yes
113 0.58 0.97
Short IM nail with distal locking
Short IM nail without distal locking Crist BD [7] 2017 Unclear USA ORIF for acetabular VAC dressing Conventional fractures dressing Ducˇic´ S [8] 2016 Unclear Serbia/ Displaced supracondylar Dorgan’s K-wire Conventional Croatia fractures in children fixation K-wire fixation Georgiannos 2017 Unclear Greece Fragility fractures of Tibio-talo-calcaneal ORIF D [9] the ankle in the elderly nailing Ghafouri 2016 IRCT 20130 Iran Simple traumatic Povidone iodine Saline HB [10] 70610017N5 wounds in the ED cleansing irrigation IM nail Palmar Gradl 2016 Unclear Germany Intraarticular locking plate G [11] fractures of the distal radius (AO C2.1) Larsson 2016 Unclear Sweden Suspected hip fractures Pre-hospital fast Standard G [12] track care of care Cefuroxime/ Ondari 2016 Unclear Kenya Grade II open tibia Cefuroxime/ gentamycin JN [13] fractures gentamycin 24 h 5 days Qiu 2017 Unclear China Hemiarthroplasty IV Hemocoagulase Standard M [14] for hip fractures of care Sahin 2016 Unclear Turkey Unstable trochanteric IM nailing with IM nailing with E [15] fractures traction table manual traction IM nailing with Shin 2017 Unclear South Trochanteric fractures IM nailing Zimmer PFN II YS [16] Korea in elderly patients with Zimmer Natural Nail Sohn 2017 Unclear South Displaced proximal MIS plating Open plating HS [17] Korea humeral fractures Standard Unneby 2017 Unclear Sweden Hip fractures Pre-operative of care A [18] in elderly patients femoral nerve block
Duration Centers, Screened, Randomized, Analyzed, CONSORT RPC RRS (years) n n n n
NA
NA
RAR
0.84
1.00
0.92
0.89
0.77 0.84
Editorial / Injury, Int. J. Care Injured 48 (2017) 1719–1721
Country
Editorial / Injury, Int. J. Care Injured 48 (2017) 1719–1721
was 2.7 years (interquartile range [IQR] 1.0–4.2 years). The median RRS was 0.69 (IQR 0.58–0.92). The median RAR was 0.93 (IQR 0.84– 0.97). The median RPC was 38 (IQR 16–113). Authors may consider providing these indices in addition to CONSORT recommendations. While there is currently no accepted benchmark, RRS and RAR around 1 suggest high acceptability of the trial by patients and clinicians, and transferability of results into clinical practice. We encourage authors to submit O:E cumulative recruitment curves as an adjunct to CONSORT diagrams. Readers of Injury deserve to know whether a trial was an energetic stallion or a nag under continuous resuscitation. If it was the latter – let us know. Tell us how you coped with this difficult situation, and why you continued riding an (almost) dead horse. This will generate truly novel data and help clinical researchers worldwide to make informed decisions about their projects. References [1] Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) Investigators. Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial. Lancet 2017;389:1519–27. [2] Kanis JA, Oden A, McCloskey EV, Johansson H, Wahl DA, Cooper C, et al. A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporos Int 2012;23:2239–56. [3] Bartl C, Stengel D, Bruckner T, Rossion I, Luntz S, Seiler C, et al. Open reduction and internal fixation versus casting for highly comminuted and intra-articular fractures of the distal radius (ORCHID): protocol for a randomized clinical multi-center trial. Trials 2011;12:84. [4] Costa ML, Achten J, Parsons NR, Rangan A, Griffin D, Tubeuf S, et al. Percutaneous fixation with Kirschner wires versus volar locking plate fixation in adults with dorsally displaced fracture of distal radius: randomised controlled trial. BMJ 2014;349:g4807. [5] Bruntink MM, Groutars YM, Schipper IB, Breederveld RS, Tuinebreijer WE, Derksen RJ. Nadroparin or fondaparinux versus no thromboprophylaxis in patients immobilised in a below-knee plaster cast (PROTECT): a randomised controlled trial. Injury 2017;48:936–40. [6] Caiaffa V, Vicenti G, Mori C, Panella A, Conserva V, Corina G, et al. Is distal locking with short intramedullary nails necessary in stable pertrochanteric fractures? A prospective, multicentre, randomised study. Injury 2016;47(Suppl. 4):S98–106. [7] Crist BD, Oladeji LO, Khazzam M, Della Rocca GJ, Murtha YM, Stannard JP. Role of acute negative pressure wound therapy over primarily closed surgical incisions in acetabular fracture ORIF: a prospective randomized trial. Injury 2017;48:1518–21. [8] Ducic S, Radlovic V, Bukva B, Radojicic Z, Vrgoc G, Brkic I, et al. A prospective randomised non-blinded comparison of conventional and Dorgan’s crossed pins for paediatric supracondylar humeral fractures. Injury 2016;47:2479–83. [9] Georgiannos D, Lampridis V, Bisbinas I. Fragility fractures of the ankle in the elderly: open reduction and internal fixation versus tibio-talo-calcaneal nailing: short-term results of a prospective randomized-controlled study. Injury 2017;48:519–24.
1721
[10] Ghafouri HB, Zare M, Bazrafshan A, Abazarian N, Ramim T. Randomized, controlled trial of povidone-iodine to reduce simple traumatic wound infections in the emergency department. Injury 2016;47:1913–8. [11] Gradl G, Falk S, Mittlmeier T, Wendt M, Mielsch N, Gradl G. Fixation of intraarticular fractures of the distal radius using intramedullary nailing: a randomized trial versus palmar locking plates. Injury 2016;47(Suppl. 7):S25–30. [12] Larsson G, Stromberg RU, Rogmark C, Nilsdotter A. Prehospital fast track care for patients with hip fracture: impact on time to surgery, hospital stay, postoperative complications and mortality a randomised, controlled trial. Injury 2016;47:881–6. [13] Ondari JN, Masika MM, Ombachi RB, Ating’a JE. Unblinded randomized control trial on prophylactic antibiotic use in gustilo II open tibia fractures at Kenyatta National Hospital, Kenya. Injury 2016;47:2288–93. [14] Qiu M, Zhang X, Cai H, Xu Z, Lin H. The impact of hemocoagulase for improvement of coagulation and reduction of bleeding in fracture-related hip hemiarthroplasty geriatric patients: a prospective, single-blinded, randomized, controlled study. Injury 2017;48:914–9. [15] Sahin E, Songur M, Kalem M, Zehir S, Aksekili MA, Keser S, et al. Traction table versus manual traction in the intramedullary nailing of unstable intertrochanteric fractures: a prospective randomized trial. Injury 2016;47:1547–54. [16] Shin YS, Chae JE, Kang TW, Han SB. Prospective randomized study comparing two cephalomedullary nails for elderly intertrochanteric fractures: Zimmer natural nail versus proximal femoral nail antirotation II. Injury 2017;48:1550– 7. [17] Sohn HS, Jeon YS, Lee J, Shin SJ. Clinical comparison between open plating and minimally invasive plate osteosynthesis for displaced proximal humeral fractures: a prospective randomized controlled trial. Injury 2017;48:1175–82. [18] Unneby A, Svensson O, Gustafson Y, Olofsson B. Femoral nerve block in a representative sample of elderly people with hip fracture: a randomised controlled trial. Injury 2017;48:1542–9.
Dirk Stengel* Cyril Mauffrey Ian Civil A.C. Gray C. Roberts Hans-Christoph Pape C. Evans Bridget Kool O.J. Mauffrey Peter Giannoudis BG Kliniken Group of Hospitals, BG Klinikum Unfallkrankenhaus Berlin gGmH, Warener Str. 7, 12683 Berlin, Germany *Corresponding author E-mail address: [email protected] (D. Stengel).