Proximal humeral fractures are common in elderly, but despite the high incidence, optimal treatment is still discussed and remains a topic of controversy. Nonoperative treatment continuous to be the main modality. However, due to advancements in surgical technology with new techniques and implants, operative treatment could lead to better outcomes and less complications, even in older patients. Decision-making in elderly should incorporate comorbidities, activity level and patient expectations. This study was performed with the intention to find out, if there is a significant difference in treatment strategy and number of operations, in the last five years. Patients older than 65 years with proximal humeral fractures were included. Retrospective analysis of radiographic material and post-injury data was performed, from patients treated in 2015, 2019 and 2020. Last two years were also compared separately to exclude the effect of Coronavirus disease 2019 (COVID-19) pandemic. Epidemiological data assessment, fracture type and treatment strategy were analysed for corresponding years. Statistical analysis was focused on complex three-and four-part fractures. There were no statistically significant differences regarding incidence between the analysed years. Low energy fall was the mechanism of injury in majority of patients. Patients with tuberosity fractures were in average younger than patients in other groups. Although there were more computed tomography (CT) scans done in younger elderly patients, there was no significant difference in number of CTs compared to older patients (year 2015: p = 0.246; year 2019: p = 0.710, year 2020: p = 0.849). The number of operative interventions was the lowest in 2019 (p = 0.498) and the same was for the osteosynthesis using intramedullary nails (p = 0.014). Frequency of reversed shoulder arthroplasty surgeries is increasing, but the difference is not significant (p = 0.390). Both operative and nonoperative treatment result in similar range of motion (ROM) measurements (p = 0.164 for anteflexion. p = 0.163 for abduction), however the groups were not comparable regarding exact fracture types. In the analysed period of 5 years, epidemiology and treatment strategy of proximal humeral fractures did not change. Nonoperative approach remained the main treatment modality. No significant difference was noted in number of interventions or implants used, although there seemed to be an increased trend towards treatment with reverse shoulder arthroplasty (RSA) in complex fractures. A strong correlation was observed between radiographic indications for conservative treatment and actual implementation of it. However, when surgical treatment was indicated using the same radiological criteria, there were more than half of patients, who were not operated on. Radiologic indications are thus not enough for decision-making in treatment of three- and four-part fractures, and patient factors, such as comorbidities and pre-injury activity level, play a major role.

PURPOSE OF THE STUDY The increasing number of hip fractures puts enormous demand on our level 1 trauma centre. Because we have to synchronize hip fracture treatment with all other injuries delays to surgery can occur. In this study, we analysed the reasons for delay to surgery and how it impacts on mortality of hip fracture patients in our institution. MATERIAL AND METHODS We retrospectively studied 641 patients operated for hip fractures in one year period. Investigated characteristics were: age, gender, American Society of Anaesthesiologists score (ASA), time of hospital admission, time of surgery, type of surgery, anticoagulant therapy (ACT) and non-routine pre-operative tests (NRPT). Trochanteric (TF) and femoral neck fractures (FNF) were analysed separately. The surgery in first 48 hours was considered early. The time of death was obtained from the federal database. Univariate and multivariable analysis were performed. P-values <0.05 were considered statistically significant. RESULTS All tested characteristics were significantly different in both time groups. Delay to surgery was significantly influenced by the type of surgery - arthroplasty, odds ratio (OR) 17.2, ACT (OR 6.9) and NRPT (OR 4.0) in FNF group of patients and by ACT (OR 31,1) and ASA (OR 2.2) in TF. 30-day mortality rate was 5.1% and 1-year mortality was 18.4%. ASA (OR 1.9), preinjury residence (OR 1.4) and age (OR 1.1) had statistical influence on survival, but not delay to surgery. CONCLUSIONS The majority of delays are due to unavailability of operative capacities, after patient optimization. We see solution in dedicated operation rooms and teams for hip fracture treatment. Mortality is influenced by the patients' characteristics, but not by delay to surgery. A multidisciplinary approach and skilled surgical teams are, besides early operation, the most important assurance of a good outcome.

BACKGROUND:Instrumentation of the pediatric spine is challenging due to anatomical constraints and the absence of specific instrumentation, which may result in iatrogenic injury and implant failure, especially in occipito-cervical constructs. Therefore, preoperative planning and in vitro testing of instrumentation may be necessary.METHODS:In this paper, we present a technical note on the use of 1:1 scale patient-specific 3D printed spinal models for preoperative assessment of feasibility of spinal instrumentation with conventional spinal implants in pediatric spinal pathologies.RESULTS:The printed 3D models fully matched the intraoperative anatomy and allowed a preoperative confirmation of the feasibility of the planned instrumentation with conventional screws for adult patients. In addition, the possibility of intraoperative model assessment resulted in better intraoperative sense of spinal anatomy and easier freehand screw insertion, thereby reducing the potential for iatrogenic injury. All 3D models were printed at the surgical department at a very low cost, and the direct communication between the surgeon and the dedicated specialist allowed for multiple models or special spinal segments to be printed for more detailed consideration.CONCLUSIONS:Our technical note highlights the critical steps for preoperative virtual planning and in vitro testing of spinal instrumentation on patient-specific 3D printed models at 1:1 scale. The simple and affordable method helps to better visualize pediatric spinal anatomy and confirm the suitability of preplanned conventional spinal instrumentation, thereby reducing X-ray exposure and intraoperative complications in freehand screw insertion without navigation.

PURPOSE:Hypoxia is a well-known complication in cemented arthroplasty; however, it is not known whether the level of hypoxia is related to the intramedullary pressure or to the age of the patient; therefore, we studied the intramedullary pressure and level of hypoxia in patients undergoing cemented arthroplasty.METHODS:A prospective study was performed during cemented arthroplasties in 25 patients with an average age of 66.2 ± 12.1 years old. The intramedullary pressure (IMP) was measured by placing a pressure transducer within the bone while simultaneously measuring the pulse oximetry arterial oxygen saturation (SpO2), pulse, and blood pressure. These variables were obtained immediately after spinal anaesthesia, five minutes after cementation, and 15 minutes after prosthesis insertion.RESULTS:One hundred percent of patients had hypoxia at some level, but 83% of elderly patients (older than 66.5 years) had hypoxia (SpO2 <94%) as compared to only 23% of younger patients (p = 0.006). In the group of young patients, IMP was roughly increased 32 times as compared with baseline level, with as consequences a decrease of 4% of SpO2 (from 98.3 to 94.15%); in the elderly group, the IMP was only increased 20 times, but a decrease of 6% of SpO2 (from 97.25 to 91%) was observed.CONCLUSIONS:This series demonstrated higher hypoxia in elderly healthy patients despite a paradoxical lower femoral increase of intramedullary pressure as compared with younger patients. This hypoxia is probably not only related to the cement but also to the patient's age with decline of maximum oxygen uptake capacity and increase bone porosity.CLINICAL TRIALS:ClinicalTrials.gov Identifier: NCT03930537 https://clinicaltrials.gov/ct2/show/NCT03930537.

Purpose To define factors influencing length of hospital stay (LOS) besides surgery delay. Methods We retrospectively analyzed 634 patients operated for hip fractures in 1-year period. Investigated characteristics were age, gender, American Society of Anesthesiologists score (ASA), time to surgery (first 48 h was considered early), type of surgery, anticoagulant therapy and non-routine pre-operative tests. Univariate and multivariable analysis were performed. p values < 0.05 were considered statistically significant. Results Median LOS was 12 days. Patients operated within 48 h had a LOS of 10 days, while patients operated after 48 h had 4 days longer LOS (p < 0.01). In multiple regression analyses, it was predicted that patients operated after 48 h with every 10 h delay to surgery had 7.3 h longer hospitalizations. All other factors did not influence the LOS. In early operation group, patients with hip arthroplasty had 3.3 days longer hospitalization compared to patients with osteosynthesis, every higher ASA score was associated with 1.4 days longer hospitalization, patients on anticoagulant therapy had 2.6 days longer LOS but surgery delay had no influence on LOS. Preinjury residence at a nursing home was associated with 4.4 days shorter hospitalizations compared to preinjury residence at home in both time frames. Conclusions In patients operated in first 48 h longer LOS is associated with ASA, anticoagulant therapy and operation type but not with delay to surgery. If patients are operated after 48 h, surgery delay is the only factor increasing LOS.

Purpose The aim of this article is to present history, state of the art, and future trends in the treatment of acetabular fractures. Methods Review of recent and historical literature. Results Acetabular fractures are difficult to treat. The first descriptions of this injury already appeared in ancient Greek history, but intensive development started in the second half of the twentieth century after Judet and Letournel’s seminal work. Their classification is still the gold standard today. It is actually a pre-operative planning system and is used to determine the most appropriate surgical approach. The therapy of choice for dislocated fractures is open reduction and internal fixation. Recent modern techniques based on high-tech computerized planning systems and 3D printing have been successfully integrated into orthopaedic trauma practice. Conclusion There is no ideal surgical approach for acetabulum fracture treatment, so new approaches have been developed in recent decades. The best outcome series have shown good or excellent results, between 70 and 80%.

Pandemija virusa SARS-CoV-2 je popolnoma presenetila celotni svet. V zelo kratkem času je bilo potrebno reorganizirati zdravstveni sistem v celoti. Bolnišnice, ki sprejemajo bolnike s covidom-19, je bilo treba čez noč prestrukturirati v del bolnišnice za bolnike s covidom-19 in v del bolnišnice z ostalimi bolniki, ki nimajo covida-19. Pri delu s kirurškim bolnikom s covidom-19 je potrebna predvsem popolna in dosledna uporaba zaščitnih sredstev, da ne pride do okužbe zdravstvenega osebja. Prav tako je potrebna posebna klinična pot znotraj bolnišnic, da ne pride do kontaminacije v delu bolnišnice, ki je brez bolnikov s covidom-19. Začasno so bile odpovedane vse elektivne kirurške obravnave. Zdaj se pod posebnimi pogoji za zaščito zdravstvenih delavcev in bolnikov ponovno sproščajo. Pred elektivnimi kirurškimi posegi se priporoča jemanje brisov na covid-19, vendar to ni nujno. Brisi so namreč v 30 % negativni oz. nezanesljivi in se nanje ne moremo popolnoma zanesti. Predvsem je pomembno, da bolnik v zadnjih 14 dneh ni imel znakov prehladne bolezni in prav tako ne člani njegove družine. Znotraj ustanove se moramo vesti do vsakega sprejetega bolnika, kot da je lahko okužen z virusom SARS-CoV-2. Enako velja za osebje. Ravnati se je potrebno glede zaščitnih ukrepov tako, kot da je vsak od zaposlenih okužen z virusom SARS-CoV-2.

Purpose The aim of this article is to present history, state of the art, and future trends in the treatment of acetabular fractures. Methods Review of recent and historical literature. Results Acetabular fractures are difficult to treat. The first descriptions of this injury already appeared in ancient Greek history, but intensive development started in the second half of the twentieth century after Judet and Letournel’s seminal work. Their classification is still the gold standard today. It is actually a pre-operative planning system and is used to determine the most appropriate surgical approach. The therapy of choice for dislocated fractures is open reduction and internal fixation. Recent modern techniques based on high-tech computerized planning systems and 3D printing have been successfully integrated into orthopaedic trauma practice. Conclusion There is no ideal surgical approach for acetabulum fracture treatment, so new approaches have been developed in recent decades. The best outcome series have shown good or excellent results, between 70 and 80%.

Izhodišča: V razvitem svetu je pojavnost zlomov kolka med 400/100.000 do 1.000/100.000 prebivalcev, starejših od 64 let; število starajočega prebivalstva pa narašča. Kljub razvoju vsadkov za učvrstitev zlomov, napredku kirurške tehnike, anestezije in rehabilitacije rezultati pri mnogih poškodovancih ostajajo slabi. Smrtnost znaša v prvem letu do 35 %. Le približno polovica poškodovancev se vrne k prejšnjim dejavnostim. Na končni izid zdravljenja vpliva splošno stanje poškodovanca s pridruženimi boleznimi in način zdravljenja (čas operacija, tip operacije itd.). Z retrospektivno analizo smo ugotavljali rezultate zdravljenja zlomov kolka na Kliničnem oddelku za travmatologijo UKC Ljubljana. Metode: Observacijska retrospektivna kohortna študija upošteva vse poškodovance, ki so bili sprejeti na naš oddelek zaradi poškodbe kolka med 1. 1. 2016 in 31. 12. 2016. Obdelavo podatkov in statistično analizo smo napravili s programom Rstudio (verzija 1.1.463, 2018) in s knjižnicama Tidyverse in Survival. Rezultati: V enoletnem obdobju smo zdravili 717 poškodovancev z zlomom kolka. Mediana starost naših poškodovancev je bila 82 let. Večina poškodovancev je imela vrednost ASA 3 (56,5 %). V analizo preživetja smo vključili 695 oseb. Operirani poškodovanci so imeli enoletno preživetje 81,6 %, konzervativno zdravljeni 53,8 %. 79 % poškodovancev s pertrohanternim zlomom je bilo operiranih v okviru priporočenih 48 ur in le 33 % poškodovancev je imelo zlom vratu stegnenice. K prejšnjim dejavnostim glede pomičnosti se je vrnilo 52 % naših operiranih poškodovancev. Povprečna ležalna doba v bolnišnici je bila 12 dni. Zaključek: Rezultati oskrbe zlomov kolka pri nas so glede preživetja in pomičnosti po poškodbi vsaj primerljivi z rezultati v literaturi. Potrebno pa bo skrajšati čas pred operacijo, ki je potrebna za oskrbo zlomov vratu stegnenice tako, da se posebej organizirajo operacije, namenjene tem poškodovancem, ležalno dobo pa tako, da se omogoči oskrba in negovanje zunaj bolnišnice.

The SARS-CoV-2 pandemic caught the world by complete surprise The whole healthcare system had to be reorganised in a very short time COVID-19 admitting hospitals had to be restructured overnight into parts with COVID-19 patients and parts with non-COVID-19 patients When working with surgical COVID-19 patients, a complete and consistent use of protective equipment is especially necessary to prevent infection of healthcare workers It is also important to organise special clinical pathways within hospitals to prevent contamination of non-COVID-19 parts of the hospital All elective surgeries have been temporarily cancelled We are beginning to rele-ase restrictions on elective surgery under special conditions to protect healthcare workers and patients COVID-19 swabs are recommended, but not strictly necessary, before elective surgery Swabs can be either negative or inconclusive in 30% of cases, and therefore cannot be comple-tely relied upon It is especially important that patients or their families did not have signs of a respiratory infection in the previous 14 days We must consider each patient as potentially infected with SARS-CoV-2 in the hospital The same is true for healthcare workers – when using protective equipment we must act as if each worker is potentially infected with SARS-CoV-2

OBJECTIVE:The objective of this prospective study was to determine the optimal timing for surgical decompression (SD) in patients with acute traumatic cervical spinal cord injury (tSCI) within the first 24 hours of injury. METHODS:In successive patients with fracture and/or dislocation of the subaxial cervical spine and American Spinal Injury Association Impairment Scale (AIS) grades A-C, receiver operating characteristic curve analysis was used to determine the optimal timing for SD within the first 24 hours of cervical tSCI to obtain a neurological recovery of at least two AIS grades. Multivariate logistic regression was used to model significant neurological recovery with time to SD, degree of spinal canal compromise (SCC), and severity of injury. RESULTS:In this cohort of 64 patients, the optimal timing for SD to obtain a significant neurological improvement was within 4 hours of injury (95% confidence interval 4-9 hours). Increasing the delay from injury to SD or the degree of SCC significantly reduced the likelihood of significant neurological improvement. Due to the strong correlation with SCC, the severity of injury was a marginally significant predictor of neurological recovery. CONCLUSIONS:These findings indicate that in patients with acute cervical tSCI and AIS grades A-C, the optimal timing for SD is within the first 4-9 hours of injury, depending on the degree of SCC and the severity of injury. Further studies are required to better understand the interrelationships among the timing of SD, injury severity, and degree of SCC in these patients.

Intraosseous lipomas are rare benign bone neoplasms with an incidence of less than 0.1%; origin in the calcaneus has been reported in only a few patients. First-line treatment remains conservative, but several surgical techniques have also been described. We describe a 44-year-old woman with increasing pain in her left heel for a year and a half, who noticed swelling on the lateral side of the calcaneus. The patient underwent radiography, magnetic resonance imaging, and computed tomography of her left foot, which was suspicious for an intraosseous lipoma with a threatening calcaneal fracture. We performed a surgical procedure, curettage of the tumor, spongioplastics (by autologous bone transplant and β-tricalcium phosphate), and internal stabilization with a calcaneal plate considering the goal of immediate postoperative weightbearing. Histologic examination confirmed an intraosseous lipoma of the calcaneus. The patient's pain was relieved immediately after surgery. Internal stabilization of the calcaneus allowed the patient to immediately fully weightbear and to return to usual daily activities. Although a benign bone tumor, intraosseous lipoma can cause many complications, such as persistent pain, decreased function, or even pathologic fracture as a result of calcaneal bone weakening. Choosing an appropriate treatment is still controversial. Conservative treatment is the first option, but for patients with severe problems and threatening fracture, surgery is necessary. Internal fixation for stabilization enables immediate postoperative weightbearing and shortens recovery time.

Purpose To test the effect of 3D printed implants, designed according to surgeon's individual plan, on the accuracy of reduction of an acetabular fracture model. Methods Seven identical standardized plastic bone models of an anterior column/posterior hemi-transverse acetabular fracture were used. A CT of one plastic fracture model was made. Using preoperative planning software, three surgeons independently planned the reduction and fixation procedure and designed implants and drill guides. The designed implants and guides were then 3D printed. Each surgeon first executed his plan using his 3D printed plates and guides on one fracture model and then performed another procedure on an identical model with standard implants and instrumentation. Displacement of the fragments at the weight-bearing fracture lines in the acetabulum was measured after fixation. Linear mixed effect models were used to evaluate the effect of different solutions to the same fracture pattern. Results Mean (SD) displacement of the fracture line between the ischium and stable fragment was 1.1 (0.9) mm for the standard implant and 0.8 (0.6) mm for the 3D printed implant, while the displacements of the fracture line between the stable fragment and anterior column were 0.6 (0.6) and 0.3 (0.3) for the standard and 3D printed methods, respectively (p < 0.001). Mean (SD) fracture line step-off at any fracture line for the standard implant was 1.2 (0.9) mm and 0.4 (0.4) mm for the 3D printed implant (p = 0.022). Conclusions Patient-specific 3D printed plates and drill guides may facilitate retaining accurate reduction and fixation of select acetabular fracture patterns.

BACKGROUND:Early diagnosis of acute posttraumatic osteomyelitis (POM) is of vital importance for avoiding devastating complications. Diagnosing POM is difficult due to the lack of a highly specific and sensitive test, such as in myocardial infarct, stroke and intracranial bleeding. Serum inflammatory markers, C-reactive protein (CRP), procalcitonin (PCT), white blood cells (WBC) can support clinical findings but they are not able to differentiate between inflammatory response to infection and the host response to non-infection insult with high specificity and sensitivity.AIM:The objectives of the study were to investigate whether the biochemical and immunoinflammatory patient profile could facilitate postoperative monitoring, guide the antibiotic treatment and timing of revision surgery.PATIENTS AND METHODS:This prospective nonrandomised cohort study included 86 patients after high-energy injury to the shin requiring primary surgical treatment (open or closed reduction and internal fixation of tibial fracture). Values of the biochemical and immunoinflammatory profile were measured on admission (ADD), first postoperative day (POD1) and fourth-postoperative day (POD4).RESULTS:We discovered on our sample that the development of POM is associated with increased CRP on ADD, POD1 and decreased albumins on POD4. Further studies are needed to prove that these differences can be useful in diagnosing the risk of infection. The assessment of other important risk factors such as: the extent of soft tissue damage, multiple fractures, transfusion rate, need for conversion primary external fixation to intramedullary (IM) nailing or locking plate fixation can empower our clinical judgment of POM.CONCLUSIONS:We can improve prediction of posttraumatic osteomyelitis by using the perioperative inflammatory biomarker CRP in combination with postoperative albumins levels and other associated independent risk factors.

Dislocation after hip arthroplasty is still a major concern. Recent study of the volumetric wear of the cup has suggested that stresses studied in a one-legged stance model could predispose arthroplasty dislocation. The aim of this work was to study whether biomechanical parameters of contact stress distribution in total hip arthroplasty during a neutral hip position can predict a higher possibility of the arthroplasty dislocating. Biomechanical parameters were determined using 3-dimensional mathematical models of the one-legged stance within the HIPSTRESS method. Geometrical parameters were measured from standard anteroposterior X-ray images of the pelvis and proximal femora. Fifty-five patients subjected to total hip arthroplasty that later suffered dislocation of the head and, for comparison, ninety-four total hip arthroplasties that were functional at least 10 years after the implantation, were included in the study. Arthroplasties that suffered dislocation had on average a 6% higher resultant hip force than the control group (p = 0.004), 11% higher peak stress on the load-bearing area (p = 0.001) and a 50% more laterally positioned stress pole (p = 0.026), all parameters being less favorable in the group of unstable arthroplasties. There was no statistically significant difference in the gradient index or in the functional angle of the weight bearing. Our study showed that arthroplasties that show a tendency to push the head out of the cup in the representative body position—the one-legged stance—are prone to dislocation. An unfavorable resultant hip force, peak stress on the load bearing and laterally positioned stress pole are predictors of arthroplasty dislocation.

Introduction. A ganglion cyst is a common benign tumor, mainly found in the wrist and ankle. The ones originating from a tendon, such as in our case, are the most rare. The ganglion cyst presents with a variety of symptoms, offering a wide range of possible differential diagnoses. Physical examination is crucial to make an accurate diagnosis, but magnetic resonance imaging (MRI) can help in identifying the ganglion cyst. The treatment is mostly conservative, but in cases when the ganglion cyst disables the patient's ability for normal life functioning, due to pain and decreased mobility, surgery is necessary. Case report. A 38-year-old female with persistent ankle pain and edema was clinically diagnosed with luxation of peroneal tendons. Further investigation with MRI showed tenosynovitis of peroneal tendons and rupture of the superior peroneal retinaculum with an intratendinous ganglion cyst of peroneus brevis tendon. Surgical treatment with the reconstruction of peroneus brevis and peroneal retinaculum was performed with semitendinosus graft and anchor sutures. Histology confirmed the diagnosis of the intratendinous ganglion. After four months of rehabilitation, the patient returned to normal daily and sports activities and was pain-free on the follow-up. No recurrence of the ganglion cyst was acknowledged. Conclusion. Surgery is crucial for patients with intratendinous ganglion cyst and symptomatic instability of the peroneal tendons with chronic subluxation.

The aim of this study was to predict ongoing acute posttraumatic osteomyelitis with markers of postoperative infections in in patients with high-energy tibial fractures. Understanding the posttraumatic and postoperative kinetics of inflammation markers may improve our ability to use them as an early diagnostic tool and treat the infections early. A novelty in this study is improved prediction of posttraumatic osteomyelitis development by using perioperative inflammatory biomarkers PCT and CRP in combination with postoperative albumins.

Because of the ageing crisis in western world the fragility fractures of the pelvic ring joint the big four group of typical fractures in osteoporotic elderly patients: fractures of the proximal femur, fractures of the proximal humerus, fractures of the distal radius and thoracic and lumbar low energy spinal fractures. All these fractures are the result of low energy with the typical fall of the patient from the standing height. The Slovenian recommendations include Rommens classification for non-displaced and displaced fractures of the anterial and posterial pelvic ring with the operative indications. The recommendations were launched at the Slovenian society of trauma surgeons meeting in November 7 th , 2015.

PURPOSE OF THE STUDYInterspinous dynamic stabilisation devices (IDSDs) are used for stabilisation and indirect decompression of the spinal motion segment in minimally invasive treatment of degenerative conditions of lumbar spine. Good methodological quality studies on biomechanical effects of IDSDs are lacking in scientific literature. The purpose of this study was to evaluate the biomechanical effect of dynamic IDSD implantation on a spinal motion segment.MATERIAL AND METHODSWe conducted a parallel group randomised trial (RT) on twelve patients, comparing radiological stabilisation and indirect decompression outcome measures between groups of patients with an isolated degenerative condition of L4-L5 motion segment and unilateral L5 nerve root radiculopathy. One group of six patients was operated by decompression and dynamic IDSD implantation and the other group of six patients by decompression alone. The radiological assessment was performed 6 months postoperatively in all patients.RESULTSDynamic IDSD implantation significantly decreased segmental intervertebral angle (IA) and significantly increased segmental foraminal height (FH) and foraminal width (FW). The implantation had no effect on segmental range of motion (ROM) and posterior disc height (PDH).CONCLUSIONSThe studied dynamic IDSD improved radiological indirect decompression outcome measures while only partially improved radiological stabilisation outcome measures.Oxford Centre for Evidence-Based Medicine 2011 Level 3: randomised trial with small effect size.