Development and Internal Validation of a Multivariable Prediction Model for Mortality After Hip Fracture with Machine Learning Techniques.

In order to estimate the likelihood of 1, 3, 6 and 12 month mortality in patients with hip fractures, we applied a variety of machine learning methods using readily available, preoperative data. We used prospectively collected data from a single university hospital in Copenhagen, Denmark for consecutive patients with hip fractures, aged 60 years and older, treated between September 2008 to September 2010 (n = 1186). Preoperative biochemical and anamnestic data were used as predictors and outcome was survival at 1, 3, 6 and 12 months after the fracture. After feature selection for each timepoint a stratified split was done (70/30) before training and validating Random Forest models, extreme gradient boosting (XGB) and Generalized Linear Models. We evaluated and compared each model using receiver operator characteristic (ROC), calibration slope and intercept, Spiegelhalter's z- test and Decision Curve Analysis. Using combinations of between 10 and 13 anamnestic and biochemical parameters we were able to successfully estimate the likelihood of mortality with an area under the curve on ROC curves of 0.79, 0.80, 0.79 and 0.81 for 1, 3, 6 and 12 month, respectively. The XGB was the overall best calibrated and most promising model. The XGB model most successfully estimated the likelihood of mortality postoperatively. An easy-to-use model could be helpful in perioperative decisions concerning level of care, focused research and information to patients. External validation is necessary before widespread use and is currently underway, an online tool has been developed for educational/experimental purposes ( https://hipfx.shinyapps.io/hipfx/ ).

Two novel prehabilitation apps to help patients stop smoking and risky drinking prior to hip and knee arthroplasty.

PURPOSE: Daily smoking or risky drinking increases the risk of complications after surgery by ~50%. Intensive prehabilitation aimed at complete cessation reduces the complication rate but is time-consuming. The purpose of this study was to carry out preoperative pilot tests (randomized design) of the feasibility (1A) and validation (1B) of two novel prehabilitation apps, habeat® (Ha-app) or rehaviour® (Re-app). METHODS: Patients scheduled for hip or knee arthroplasty with daily smoking, risky drinking, or both were randomised to one of the two apps. In part 1A, eight patients and their staff measured feasibility on a visual analog scale (VAS) and were interviewed about what worked well and the challenges requiring improvement. In part 1B, seven patients and their staff tested the improved apps for up to two weeks before validating the understanding, usability, coverage, and empowerment on a VAS and being interviewed. RESULTS: In 1A, all patients and staff returned scores of ≥5 for understanding the apps and mostly suggested technical improvements. In 1B, the scores varied widely for both apps, with no consensus achieved. Two of four patients (Ha-app) and one-third of the patients (Re-app) found the apps helpful for reducing smoking, but without successful quitting. The staff experienced low app competencies among patients and high time consumption. Specifically, patients most often needed help for the Ha-app, and the staff most often for Re-app; however, the staff reported the Re-app dashboard was more user-friendly. Support and follow-up from an addiction specialist staff member were suggested to complement the apps, thereby increasing the time consumption for staff. CONCLUSIONS: This pilot study to test prototype apps generated helpful feedback for the app developers. Based on the patient and staff comments, multiple improvements in functionality seem required before scaling up the evaluation for effect on prehabilitation and postoperative complications.

Operative versus non-operative treatment for 2-part proximal humerus fracture: A multicenter randomized controlled trial.

BACKGROUND: Although increasingly used, the benefit of surgical treatment of displaced 2-part proximal humerus fractures has not been proven. This trial evaluates the clinical effectiveness of surgery with locking plate compared with non-operative treatment for these fractures. METHODS AND FINDINGS: The NITEP group conducted a superiority, assessor-blinded, multicenter randomized trial in 6 hospitals in Finland, Estonia, Sweden, and Denmark. Eighty-eight patients aged 60 years or older with displaced (more than 1 cm or 45 degrees) 2-part surgical or anatomical neck proximal humerus fracture were randomly assigned in a 1:1 ratio to undergo either operative treatment with a locking plate or non-operative treatment. The mean age of patients was 72 years in the non-operative group and 73 years in the operative group, with a female sex distribution of 95% and 87%, respectively. Patients were recruited between February 2011 and April 2016. The primary outcome measure was Disabilities of Arm, Shoulder, and Hand (DASH) score at 2-year follow-up. Secondary outcomes included Constant-Murley score, the visual analogue scale for pain, the quality of life questionnaire 15D, EuroQol Group's 5-dimension self-reported questionnaire EQ-5D, the Oxford Shoulder Score, and complications. The mean DASH score (0 best, 100 worst) at 2 years was 18.5 points for the operative treatment group and 17.4 points for the non-operative group (mean difference 1.1 [95% CI -7.8 to 9.4], p = 0.81). At 2 years, there were no statistically or clinically significant between-group differences in any of the outcome measures. All 3 complications resulting in secondary surgery occurred in the operative group. The lack of blinding in patient-reported outcome assessment is a limitation of the study. Our assessor physiotherapists were, however, blinded. CONCLUSIONS: This trial found no significant difference in clinical outcomes at 2 years between surgery and non-operative treatment in patients 60 years of age or older with displaced 2-part fractures of the proximal humerus. These results suggest that the current practice of performing surgery on the majority of displaced proximal 2-part fractures of the humerus in older adults may not be beneficial. TRIAL REGISTRATION: ClinicalTrials.gov NCT01246167.

No signs of dose escalations of potent opioids prescribed after tibial shaft fractures: a study of Swedish National Registries.

BACKGROUND: The pattern of opioid use after skeletal trauma is a neglected topic in pain medicine. The purpose of this study was to analyse the long-term prescriptions of potent opioids among patients with tibial shaft fractures. METHODS: Data were extracted from the Swedish National Hospital Discharge Register, the National Pharmacy Register, and the Total Population Register, and analysed accordingly. The study period was 2005-2008. RESULTS: We identified 2,571 patients with isolated tibial shaft fractures. Of these, 639 (25%) collected a prescription for opioids after the fracture. The median follow-up time was 17 (interquartile range [IQR] 7-27) months. Most patients with opioid prescriptions after fracture were male (61%) and the median age was 45 (16-97) years. The leading mechanism of injury was fall on the same level (41%). At 6 and 12 months after fracture, 21% (95% CI 17-24) and 14% (11-17) were still being treated with opioids. Multiple Cox regression-analysis (adjusted for age, sex, type of treatment, and mechanism of injury) revealed that older patients (age >50 years) were more likely to end opioid prescriptions (Hazard ratio 1.5 [95% CI 1.3-1.9]). During follow-up, the frequency of patients on moderate and high doses declined. Comparison of the daily morphine equivalent dose among individuals who both had prescriptions during the first 3 months and the 6th month indicated that the majority of these patients (11/14) did not have dose escalations. CONCLUSIONS: We did not see any signs in registry-data of major dose escalations over time in patients on potent opioids after tibial shaft fractures.

Lower extremity soft tissue reconstruction and amputation rates in patients with open tibial fractures in Sweden during 1998-2010.

BACKGROUND: The rates of soft tissue reconstruction and amputation after open tibial fractures have not been studied on a national perspective. We aimed to determine the frequency of soft tissue coverage after open tibial fracture as well as primary and secondary amputation rates. METHODS: Data on all patients (> = 15 years) admitted to hospital with open tibial fractures were extracted from the Swedish National Patient Register (1998-2010). All surgical procedures, re-admissions, and mechanisms of injury were analysed accordingly. The risk of amputation was calculated using logistic regression (adjusted for age, sex, mechanism of injury, reconstructive surgery and fixation method). The mean follow-up time was 6 (SD 3.8) years. RESULTS: Of 3,777 patients, 342 patients underwent soft tissue reconstructive surgery. In total, there were 125 amputations. Among patients with no reconstructive surgery, 2% (n = 68 patients) underwent amputation. In an adjusted analysis, patients older than 70 years (OR = 2.7, 95%, CI = 1.1-6) and those who underwent reconstructive surgery (OR = 3.1, 95% CI = 1.6-5.8) showed higher risk for amputation. Fixations other than intramedullary nailing (plate, external fixation, closed reduction and combination) as the only method were associated with a significant higher risk for amputation (OR 5.1-14.4). Reconstruction within 72 hours (3 days) showed better results than reconstruction between 4-90 days (p = 0.04). CONCLUSIONS: The rate of amputations after open tibial fractures is low (3.6%). There is a higher risk for amputations with age above 70 (in contrast: male sex and tissue reconstruction are rather indicators for more severe soft tissue injuries). Only a small proportion of open tibial fractures need soft tissue reconstructive surgery. Reconstruction with free or pedicled flap should be performed within 72 hours whenever possible.

The value of preoperative grade of radiographic and histological changes in predicting pain relief after total knee arthroplasty for osteoarthritis.

PURPOSE: Many attempts with contradictory results have been made to correlate different features of OA with pain. One reason may be that pain at rest and pain with movement are seldom considered separately although the mechanisms may be quite different. Furthermore, pain ratings are subject to individual interpretation making an inter-individual comparison questionable. By instead calculating the absolute and relative changes in pain on an intra-individual level after total knee arthroplasty (TKA), we aimed at exploring a relationship between pain and radiological and histological changes. METHODS: In 69 patients undergoing TKA, preoperative radiographs and perioperative histological samples of the synovial membrane were graded for severity of osteoarthritic and inflammatory changes. The findings were related to the intensity of pain at rest and with movement both preoperatively and 18 months postoperatively according to the visual analogue scale (VAS). RESULTS: The radiographic and histological findings showed no significant correlation with the mean pre- or postoperative pain scores. Instead, change in pain with movement from pre- to postoperative was significantly related to the grade of radiographic osteoarthritis. Best pain relief by TKA was achieved in patients with severe radiographic changes. This, however, only applied to pain with movement. CONCLUSIONS: Pain at rest and pain with movement may have different mechanisms. We believe that assessing the intensity of pain at rest and pain with movement separately and considering changes in pain on an individual level will be helpful strategies in future follow-up studies and efforts aimed at explaining the mechanisms of pain in OA.

Epidemiology of adult ankle fractures in Sweden between 1987 and 2004: a population-based study of 91,410 Swedish inpatients.

BACKGROUND AND PURPOSE: Previous national epidemiological data on the characteristics and trends of patients with ankle fractures have been limited. We therefore analyzed data on Swedish inpatients with ankle fractures in this nationwide population study, based on data from 1987 through 2004. PATIENTS AND METHODS: Data on all inpatients aged 15 years and older with ankle fracture were extracted from the Swedish National Patient Register for the period 1987-2004. RESULTS: We identified 91,410 hospital admissions with ankle fracture, corresponding to an annual incidence rate of 71 per 10(5) person-years. During the study period, the number of hospital admissions increased by 0.2% annually, mainly from increase in fracture incidence in the elderly women. Mean age at admission was 45 (SD 19) years for men and 58 (18) for women. The major mechanism of injury was falling at the same level (64%). INTERPRETATION: This nationwide study of inpatients with ankle fractures showed an increase in fracture incidence, particularly in elderly women.

Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multi-centre randomised clinical trial.

INTRODUCTION: Hyperbaric oxygen treatment (HBOT) is sometimes used in the management of open fractures and severe soft tissue crush injury, aiming to reduce complications and improve outcomes. METHODS: Patients with open tibial fractures were randomly assigned within 48 hours of injury to receive standard trauma care or standard care plus 12 sessions of HBOT. The primary outcome was the incidence of necrosis or infection or both occurring within 14 days of injury. RESULTS: One-hundred and twenty patients were enrolled. Intention to treat primary outcome occurred in 25/58 HBOT assigned patients and 34/59 controls (43% vs 58%, odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25 to 1.18, P = 0.12). Tissue necrosis occurred in 29% of HBOT patients and 53% of controls (OR 0.35, 95% CI 0.16 to 0.78, P = 0.01). There were fewer late complications in patients receiving HBOT (6/53 vs 18/52, OR 0.22, 95% CI 0.08 to 0.64, P = 0.007) including delayed fracture union (5/53 vs 13/52, OR 0.31, 95% CI 0.10 to 0.95, P = 0.04). Quality of life measures at one and two years were superior in HBOT patients. The mean score difference in short form 36 was 2.90, 95% CI 1.03 to 4.77, P = 0.002, in the short musculoskeletal function assessment (SMFA) was 2.54, 95% CI 0.62 to 4.46, P = 0.01; and in SMFA daily activities was 19.51, 95% CI 0.06 to 21.08, P = 0.05. CONCLUSIONS: In severe lower limb trauma, early HBOT reduces tissue necrosis and the likelihood of long-term complications, and improves functional outcomes. Future research should focus on optimal dosage and whether HBOT has benefits for other injury types.

Health-related quality of life (EQ-5D) before and after orthopedic surgery.

BACKGROUND AND PURPOSE: Population data on mortality and life expectancy are generally available for most countries. However, no longitudinal data based on the health-related quality of life outcome from the EQ-5D instrument have been reported for orthopedic patients. We assessed the effect of orthopedic surgery as measured by EQ-5D. METHODS: We analyzed EQ-5D data from 2,444 patients who were operated at the Department of Orthopedic Surgery at Karolinska University Hospital, 2001-2005. We also made a comparison between results from this cohort and those from a Swedish EQ-5D population survey. RESULTS: The mean EQ-5D (index) score improved from 0.54 to 0.72. Hip and knee arthroplasty, operations related to previous surgery, trauma-related procedures, and rheumatoid arthritis surgeries had preoperative EQ-5D (index) scores of 0.48 to 0.52. All of these groups showed substantial improvement in scores (0.63 to 0.80). Patients with tumors or diseases of the elbow/hand showed higher preoperative scores (0.66 to 0.77), which were similar postoperatively. In most patients, the EQ-5D (index) score improved but did not reach the level reported for an age- and sex-matched population sample (mean difference = 0.11). INTERPRETATION: Our results can be used as part of the preoperative patient information to increase the level of patient awareness and cooperation, and to facilitate rehabilitation. In future it will be possible-but not easy-to use the EQ-5D instrument as a complementary consideration in clinical priority assessment.

Thoracolumbar vertebral fractures in Sweden: an analysis of 13,496 patients admitted to hospital.

National Longitudinal data of thoracolumbar fracture incidence, trends or mortality rates are lacking. The correlation between admissions and operations of thoracolumbar vertebral fractures has not been investigated. The aim of our nationwide population-based epidemiological study was to analyse the incidence, admissions, operations, and case fatality rate among patients with thoracolumbar vertebral fractures admitted to hospital in Sweden. The Swedish Hospital Discharge Register (SHDR) and the Cause of Death Register (CDR) were linked to determine the incidence of surgical interventions, trends, characteristics of the patients, and case fatality rate for thoracolumbar vertebral fractures based on comprehensive national data. The annual incidence of thoracolumbar fractures was on average 30 per 100,000 inhabitants and did not change considerably during the study period. Among patients younger than 60 years of age the annual incidence was 13 per 100,000 and was twice as high in men compared to women. The proportion operated on was 15%. In the age-group 60 years and older the majority were women. In this group two percent were operated on. However, males were operated on twice as often as women. The 90-day case-fatality rate after surgery was 1.4%. This information may assist health care providers in health care planning. Moreover, these data can also be used for power calculations when planning future clinical studies.

Diagnosis of Open Tibial Fracture Showed High Positive Predictive Value in the Swedish National Patient Register.

INTRODUCTION: The Swedish National Patient Register was validated only for a few diagnoses in the field of trauma. In this study, we calculated the positive predictive values (PPV) of the diagnosis of open tibial fracture and corresponding E-codes (cause of injury). PATIENTS AND METHODS: Out of 2845 cases from a 10-year period (2007-2016), a random sample of 300 cases was selected for review of medical records. The accuracy of the diagnosis and cause of injury was calculated and presented as PPV. We divided the study population into two subgroups (moderate and severe injury) that were analyzed separately. Severe injury was defined as when a patient had an amputation and/or reconstructive surgical procedures, indicated by corresponding ICD-codes. RESULTS: The PPV of the diagnosis of open tibial fracture was 87% (95% CI: 86-88%) overall, 86% (95% CI: 79-91%) for moderate injuries and 96% (95% CI: 91-98%) for severe injuries. The PPV for E-codes was 74% (95% CI: 65-81%). The majority of injuries were caused by falls (47%) or transport accidents (38%). Most of these injuries were caused by high-energy trauma (60%). CONCLUSION: The PPV of the diagnosis of open tibial fracture in the Swedish National Patient Register is high (87%). The PPV of E-codes was lower (79%). The results imply that the register is well suited for healthcare evaluation and research purposes regarding trauma diagnoses. Most open tibial fractures are high-energy injuries.

[Patient blood management - to transfuse blood on appropriate indications]. / Transfusionsstrategi ­ att ge blod på rätt indikation - I Sverige ges fler blodtransfusioner än i jämförbara länder ­ restriktiv policy ger inte sämre vårdresultat.

During the last decade, the varying use and the lack of consistent indications for blood transfusions have been questioned. Comparisons of liberal and restrictive transfusion policies, most often support a restrictive policy. This has led to an evidence-based approach to optimizing the care of patients who might need transfusion, Patient Blood Management (PBM). There is evidence that both anemia and allogeneic blood transfusions are independently associated with increased morbidity and mortality. In elective surgery it is possible to adapt the three pillars of PBM in a structured way; i.e. optimization of red blood cell mass, reduction of blood loss and bleeding, and optimization of the patient's physiological tolerance towards anemia. These activities should be included in the pre-peri- and postoperative routines, in all surgical units.

Decreasing incidence of tibial shaft fractures between 1998 and 2004: information based on 10,627 Swedish inpatients.

BACKGROUND AND PURPOSE: There is a lack of national epidemiological data on the characteristics of patients with tibial shaft fractures. We therefore analyzed data on Swedish patients with tibial shaft fractures in this nationwide population study based on data from 1998 through 2004. METHODS: Data on all patients with tibial shaft fractures were extracted from the Swedish National Hospital Discharge Register. RESULTS: We identified 10,627 hospital admissions for tibial shaft fractures, corresponding to an annual incidence rate of 17 per 100,000 person-years (pyr). The number of hospital admissions decreased by 12% during the period 1998-2004, mostly from a reduction in male incidence. The median (SD) age at admission was 28 (22) years for men and 51 (26) years for women. The two major mechanisms of injury were falls on the same level (48%) and transport accidents (21%). Surgical procedures were dominated by osteosynthesis with nail (48%), followed by closed reduction and plaster cast (27%), and external fixation (12%). 12% of all tibial shaft fractures were classified as open, corresponding to an incidence rate of 2.3 per 100,000 pyr, which declined during 1998-2004. INTERPRETATION: This nationwide study of tibial shaft fractures shows a falling off of fracture incidence, a finding that can be used to advantage by healthcare providers.

Mortality, risk factors and causes of death in Swedish patients with open tibial fractures - a nationwide study of 3, 777 patients.

BACKGROUND: Open tibial fractures are serious, complicated injuries. Previous studies suggested an increased risk of death, however, this has not been studied in large population-based settings. We aimed to analyze mortality including causes of death in all patients with open tibial fractures in Sweden. Moreover, we wanted to compare mortality rates with the Swedish population and determine whether treatment-related or demographic variables were independently associated with death. METHOD: We searched the Swedish National Hospital Discharge Register for all patients with open tibial fracture between 1998 and 2010. We collected the following variables: age, gender, length of stay, mechanism of injury and treatment rendered. We then cross-referenced the Swedish Cause of Death Register to determine the cause of death, if applicable. We compared mortality in the study population with population-based mortality data from Statistics Sweden and determined whether variables were independently associated with death using regression analysis. RESULTS: Of the 3777 open tibial fractures, 425 (11.3%) patients died. The most common causes of death for elderly patients were cardiovascular and respiratory disease. Patients aged 15-39 years succumbed to external causes (accidents, suicides or poisoning). Increasing age (OR 25.7 (95% CI 11.8-64.8) p < 0.001), length of hospital stay (HR 1.01, (95% CI 1.01-1.02,) p < 0.001), limb amputation (OR 4.8 (95% CI 1.86-11.1) p < 0.001) and cause of the accident were independently associated with an increased mortality. CONCLUSION: Patients with open tibial fractures have an increased risk of death compared with the general population in all age- and gender-groups. External causes of death are over-represented and indicate a subgroup with a risky behaviour among younger males. Elderly patients have an increased risk of dying comparable to hip fracture patients. They are at risk for cardiovascular and respiratory failure and should be treated with urgency, emphasizing the need for specialized geriatric trauma units.

Effects of a formalized collaboration between plastic and orthopedic surgeons in severe extremity trauma patients; a retrospective study.

BACKGROUND: Severe trauma to the extremities often includes a combination of fractures and soft tissue injuries. Several publications support that the patient outcome is better when skeletal stabilization is followed by early soft-tissue coverage. In an effort to optimize the treatment of these patients, we established a formalized collaboration in 2008 between the Departments of reconstructive plastic surgery and orthopedics at the Karolinska University Hospital. METHODS: A retrospective review was conducted for all patients who had suffered severe extremity trauma and received either a free or a pedicled flap for extremity reconstruction. We compared the management of patients 0-4 years before and 0-4 years after the collaboration started especially with respect to; choice of flap, time to flap coverage, number of operations/revisions, total in-hospital stay. RESULTS: After initiation of the collaboration, the number of flaps increased from 13 flaps (5 free and 8 pedicled) to 44 flaps (21 free and 23 pedicled). Fewer postoperative revisions was seen, as well as shorter in-hospital stay. CONCLUSIONS: The present study highlights the importance of formalized collaboration between orthopedic and plastic surgeons in severe extremity trauma patients. The concept of an interdisciplinary approach has led to an increased number of trauma patients referred for plastic surgical consultation, an increased number of flaps, fewer postoperative revisions and shorter hospital stay.

Hyperbaric Oxygen in Lower Limb Trauma (HOLLT); protocol for a randomised controlled trial.

INTRODUCTION: Open fractures with significant soft tissue injury are associated with high rates of complications, such as non-union, infection, chronic pain and disability. Complications often require further inpatient care, and in many cases, multiple operations and prolonged rehabilitation. Use of hyperbaric oxygen therapy as an adjunct to standard orthopaedic trauma care has the potential to reduce the complications of musculoskeletal injury and thus improve outcomes. Two previous randomised trials have suggested some positive effect, but neither functional measures nor long-term outcomes were reported. METHODS AND ANALYSIS: An international, multicentre, randomised, open-label, clinical trial. Patients with trauma with an acute open fracture of the tibia with severe soft tissue injury (Gustilo grade 3) and high risk of injury-related complications were recruited from participating major trauma hospitals with hyperbaric facilities. Patients were enrolled with the expectation of commencing 12 sessions of hyperbaric oxygen therapy within 48 h of injury. The primary outcome measure is the incidence of acute complications of the open fracture wound at 14 days. Other short-term outcome measures include amputation, need for fasciotomy, time until wound closure, breakdown of closed wounds, time until definitive orthopaedic fixation, number of operative procedures, intensive care stay and hospital stay. Long-term follow-up will continue for 2 years postinjury. ETHICS AND DISSEMINATION: Ethics approval was given by The Alfred Health Human Ethics Committee (206/04) and the Monash University Human Research Ethics Committee (CF07/4208). Approval was also obtained from the institutional research ethics committee at each participating site. This study will make a significant contribution to the trauma literature and should answer the question of whether hyperbaric oxygen therapy can significantly improve outcomes in severe lower limb trauma. Collective study results will be published in international journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT00264511; Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12607000559415.