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Bone & Joint Research
Vol. 5, Issue 5 | Pages 191 - 197
1 May 2016
Kienast B Kowald B Seide K Aljudaibi M Faschingbauer M Juergens C Gille J

Objectives. The monitoring of fracture healing is a complex process. Typically, successive radiographs are performed and an emerging calcification of the fracture area is evaluated. The aim of this study was to investigate whether different bone healing patterns can be distinguished using a telemetric instrumented femoral internal plate fixator. Materials and Methods. An electronic telemetric system was developed to assess bone healing mechanically. The system consists of a telemetry module which is applied to an internal locking plate fixator, an external reader device, a sensor for measuring externally applied load and a laptop computer with processing software. By correlation between externally applied load and load measured in the implant, the elasticity of the osteosynthesis is calculated. The elasticity decreases with ongoing consolidation of a fracture or nonunion and is an appropriate parameter for the course of bone healing. At our centre, clinical application has been performed in 56 patients suffering nonunion or fracture of the femur. Results. A total of 39 cases of clinical application were reviewed for this study. In total, four different types of healing curves were observed: fast healing; slow healing; plateau followed by healing; and non-healing. Conclusion. The electronically instrumented internal fixator proved to be valuable for the assessment of bone healing in difficult healing situations. Cost-effective manufacturing is possible because the used electronic components are derived from large-scale production. The incorporation of microelectronics into orthopaedic implants will be an important innovation in future clinical care. Cite this article: B. Kienast, B. Kowald, K. Seide, M. Aljudaibi, M. Faschingbauer, C. Juergens, J. Gille. An electronically instrumented internal fixator for the assessment of bone healing. Bone Joint Res 2016;5:191–197. DOI: 10.1302/2046-3758.55.2000611


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 3 | Pages 398 - 404
1 Mar 2012
Seide K Aljudaibi M Weinrich N Kowald B Jürgens C Müller J Faschingbauer M

In an interdisciplinary project involving electronic engineers and clinicians, a telemetric system was developed to measure the bending load in a titanium internal femoral fixator. As this was a new device, the main question posed was: what clinically relevant information could be drawn from its application? As a first clinical investigation, 27 patients (24 men, three women) with a mean age of 38.4 years (19 to 66) with femoral nonunions were treated using the system. The mean duration of the nonunion was 15.4 months (5 to 69). The elasticity of the plate-callus system was measured telemetrically until union. Conventional radiographs and a CT scan at 12 weeks were performed routinely, and healing was staged according to the CT scans. All nonunions healed at a mean of 21.5 weeks (13 to 37). Well before any radiological signs of healing could be detected, a substantial decrease in elasticity was recorded. The relative elasticity decreased to 50% at a mean of 7.8 weeks (3.5 to 13) and to 10% at a mean of 19.3 weeks (4.5 to 37). At 12 weeks the mean relative elasticity was 28.1% (0% to 56%). The relative elasticity was significantly different between the different healing stages as determined by the CT scans.

Incorporating load measuring electronics into implants is a promising option for the assessment of bone healing. Future application might lead to a reduction in the need for exposure to ionising radiation to monitor fracture healing.


Bone & Joint Open
Vol. 5, Issue 3 | Pages 218 - 226
15 Mar 2024
Voigt JD Potter BK Souza J Forsberg J Melton D Hsu JR Wilke B

Aims. Prior cost-effectiveness analyses on osseointegrated prosthesis for transfemoral unilateral amputees have analyzed outcomes in non-USA countries using generic quality of life instruments, which may not be appropriate when evaluating disease-specific quality of life. These prior analyses have also focused only on patients who had failed a socket-based prosthesis. The aim of the current study is to use a disease-specific quality of life instrument, which can more accurately reflect a patient’s quality of life with this condition in order to evaluate cost-effectiveness, examining both treatment-naïve and socket refractory patients. Methods. Lifetime Markov models were developed evaluating active healthy middle-aged male amputees. Costs of the prostheses, associated complications, use/non-use, and annual costs of arthroplasty parts and service for both a socket and osseointegrated (OPRA) prosthesis were included. Effectiveness was evaluated using the questionnaire for persons with a transfemoral amputation (Q-TFA) until death. All costs and Q-TFA were discounted at 3% annually. Sensitivity analyses on those cost variables which affected a change in treatment (OPRA to socket, or socket to OPRA) were evaluated to determine threshold values. Incremental cost-effectiveness ratios (ICERs) were calculated. Results. For treatment-naïve patients, the lifetime ICER for OPRA was $279/quality-adjusted life-year (QALY). For treatment-refractory patients the ICER was $273/QALY. In sensitivity analysis, the variable thresholds that would affect a change in the course of treatment based on cost (from socket to OPRA), included the following for the treatment-naïve group: yearly replacement components for socket > $8,511; cost yearly replacement parts OPRA < $1,758; and for treatment-refractory group: yearly replacement component for socket of > $12,467. Conclusion. The use of the OPRA prosthesis in physically active transfemoral amputees should be considered as a cost-effective alternative in both treatment-naïve and treatment-refractory socket prosthesis patients. Disease-specific quality of life assessments such as Q-TFA are more sensitive when evaluating cost-effectiveness. Cite this article: Bone Jt Open 2024;5(3):218–226


The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 394 - 400
1 Apr 2024
Kjærvik C Gjertsen J Stensland E Dybvik EH Soereide O

Aims. The aims of this study were to assess quality of life after hip fractures, to characterize respondents to patient-reported outcome measures (PROMs), and to describe the recovery trajectory of hip fracture patients. Methods. Data on 35,206 hip fractures (2014 to 2018; 67.2% female) in the Norwegian Hip Fracture Register were linked to data from the Norwegian Patient Registry and Statistics Norway. PROMs data were collected using the EuroQol five-dimension three-level questionnaire (EQ-5D-3L) scoring instrument and living patients were invited to respond at four, 12, and 36 months post fracture. Multiple imputation procedures were performed as a model to substitute missing PROM data. Differences in response rates between categories of covariates were analyzed using chi-squared test statistics. The association between patient and socioeconomic characteristics and the reported EQ-5D-3L scores was analyzed using linear regression. Results. The median age was 83 years (interquartile range 76 to 90), and 3,561 (10%) lived in a healthcare facility. Observed mean pre-fracture EQ-5D-3L index score was 0.81 (95% confidence interval 0.803 to 0.810), which decreased to 0.66 at four months, to 0.70 at 12 months, and to 0.73 at 36 months. In the imputed datasets, the reduction from pre-fracture was similar (0.15 points) but an improvement up to 36 months was modest (0.01 to 0.03 points). Patients with higher age, male sex, severe comorbidity, cognitive impairment, lower income, lower education, and those in residential care facilities had a lower proportion of respondents, and systematically reported a lower health-related quality of life (HRQoL). The response pattern of patients influenced scores significantly, and the highest scores are found in patients reporting scores at all observation times. Conclusion. Hip fracture leads to a persistent reduction in measured HRQoL, up to 36 months. The patients’ health and socioeconomic status were associated with the proportion of patients returning PROM data for analysis, and affected the results reported. Observed EQ-5D-3L scores are affected by attrition and selection bias mechanisms and motivate the use of statistical modelling for adjustment. Cite this article: Bone Joint J 2024;106-B(4):394–400


The Bone & Joint Journal
Vol. 104-B, Issue 8 | Pages 963 - 971
1 Aug 2022
Sun Z Liu W Liu H Li J Hu Y Tu B Wang W Fan C

Aims. Heterotopic ossification (HO) is a common complication after elbow trauma and can cause severe upper limb disability. Although multiple prognostic factors have been reported to be associated with the development of post-traumatic HO, no model has yet been able to combine these predictors more succinctly to convey prognostic information and medical measures to patients. Therefore, this study aimed to identify prognostic factors leading to the formation of HO after surgery for elbow trauma, and to establish and validate a nomogram to predict the probability of HO formation in such particular injuries. Methods. This multicentre case-control study comprised 200 patients with post-traumatic elbow HO and 229 patients who had elbow trauma but without HO formation between July 2019 and December 2020. Features possibly associated with HO formation were obtained. The least absolute shrinkage and selection operator regression model was used to optimize feature selection. Multivariable logistic regression analysis was applied to build the new nomogram: the Shanghai post-Traumatic Elbow Heterotopic Ossification Prediction model (STEHOP). STEHOP was validated by concordance index (C-index) and calibration plot. Internal validation was conducted using bootstrapping validation. Results. Male sex, obesity, open wound, dislocations, late definitive surgical treatment, and lack of use of non-steroidal anti-inflammatory drugs were identified as adverse predictors and incorporated to construct the STEHOP model. It displayed good discrimination with a C-index of 0.80 (95% confidence interval 0.75 to 0.84). A high C-index value of 0.77 could still be reached in the internal validation. The calibration plot showed good agreement between nomogram prediction and observed outcomes. Conclusion. The newly developed STEHOP model is a valid and convenient instrument to predict HO formation after surgery for elbow trauma. It could assist clinicians in counselling patients regarding treatment expectations and therapeutic choices. Cite this article: Bone Joint J 2022;104-B(8):963–971


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 4 | Pages 549 - 555
1 Apr 2012
Lefaivre KA Slobogean GP Valeriote J O’Brien PJ Macadam SA

We performed a systematic review of the literature to evaluate the use and interpretation of generic and disease-specific functional outcome instruments in the reporting of outcome after the surgical treatment of disruptions of the pelvic ring. A total of 28 papers met our inclusion criteria, with eight reporting only generic outcome instruments, 13 reporting only pelvis-specific outcome instruments, and six reporting both. The Short-Form 36 (SF-36) was by far the most commonly used generic outcome instrument, used in 12 papers, with widely variable reporting of scores. The pelvis-specific outcome instruments were used in 19 studies; the Majeed score in ten, Iowa pelvic score in six, Hannover pelvic score in two and the Orlando pelvic score in one. Four sets of authors, all testing construct validity based on correlation with the SF-36, performed psychometric testing of three pelvis-specific instruments (Majeed, IPS and Orlando scores). No testing of responsiveness, content validity, criterion validity, internal consistency or reproducibility was performed. The existing literature in this area is inadequate to inform surgeons or patients in a meaningful way about the functional outcomes of these fractures after fixation


The Bone & Joint Journal
Vol. 98-B, Issue 5 | Pages 690 - 695
1 May 2016
Dodd A Osterhoff G Guy P Lefaivre KA

We performed a systematic review of the literature pertaining to the functional outcomes of the surgical management of acetabular fractures. A total of 69 articles met our inclusion criteria, revealing that eight generic outcome instruments were used, along with five specific instruments. The majority of studies reported outcomes using a version of the d’Aubigne and Postel score, which has not been validated for use in acetabular fracture. Few validated outcome measures were reported. No psychometric testing of outcome instruments was performed. The current assessment of outcomes in surgery for acetabular fractures lacks scientific rigour, and does not give reliable outcome data for either scientific comparison or patient counselling. Take home message: The use of non-validated functional outcome measures is a major limitation of the current literature pertaining to surgical management of acetabular fractures; future studies should use validated outcome measures to ensure the legitimacy of the reported results. Cite this article: Bone Joint J 2016;98-B:690–5


The Bone & Joint Journal
Vol. 102-B, Issue 1 | Pages 42 - 47
1 Jan 2020
Jayakumar P Teunis T Vranceanu AM Williams M Lamb S Ring D Gwilym S

Aims. Patient engagement in adaptive health behaviours and interactions with their healthcare ecosystem can be measured using self-reported instruments, such as the Patient Activation Measure (PAM-13) and the Effective Consumer Scale (ECS-17). Few studies have investigated the influence of patient engagement on limitations (patient-reported outcome measures (PROMs)) and patient-reported experience measures (PREMs). First, we assessed whether patient engagement (PAM-13, ECS-17) within two to four weeks of an upper limb fracture was associated with limitations (the Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH), and Patient-Reported Outcome Measurement Information System Upper Extremity Physical Function computer adaptive test (PROMIS UE PF) scores) measured six to nine months after fracture, accounting for demographic, clinical, and psychosocial factors. Secondly, we assessed the association between patient engagement and experience (numerical rating scale for satisfaction with care (NRS-C) and satisfaction with services (NRS-S) six to nine months after fracture. Methods. A total of 744 adults with an isolated fracture of the proximal humerus, elbow, or distal radius completed PROMs. Due to multicollinearity of patient engagement and psychosocial variables, we generated a single variable combining measures of engagement and psychosocial factors using factor analysis. We then performed multivariable analysis with p < 0.10 on bivariate analysis. Results. Patient engagement and psychosocial factors combined to form a single factor (factor 1) accounting for 20% (QuickDASH, semi-partial R. 2. = 0.20) and 14% (PROMIS UE PF, semi-partial R. 2. = 0.14) of the variation in limitations six to nine months after fracture. Factor 1 also accounted for 17% (NRS-C, semi-partial R. 2. = 0.17) of variation in satisfaction with care, and 21% (NRS-S, semi-partial R. 2. = 0.21) of variation in satisfaction with services. Demographic factors (age, sex, work status) and measures of greater pathophysiology (type of fracture, high-energy injury, post-surgical complications), accounted for much less variation. Conclusion. Patients who actively manage their health and demonstrate effective emotional and social functioning share a common underlying trait. They have fewer limitations and greater satisfaction with care during recovery from upper limb fractures. Future efforts should focus on evaluating initiatives that optimize patient engagement, such as patient education, coaching, and a communication strategy for healthcare professionals. Cite this article: Bone Joint J 2020;102-B(1):42–47


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 603 - 612
1 Jun 2024
Ahmad A Egeland EH Dybvik EH Gjertsen J Lie SA Fenstad AM Matre K Furnes O

Aims

This study aimed to compare mortality in trochanteric AO/OTA A1 and A2 fractures treated with an intramedullary nail (IMN) or sliding hip screw (SHS). The primary endpoint was 30-day mortality, with secondary endpoints at 0 to 1, 2 to 7, 8 to 30, 90, and 365 days.

Methods

We analyzed data from 26,393 patients with trochanteric AO/OTA A1 and A2 fractures treated with IMNs (n = 9,095) or SHSs (n = 17,298) in the Norwegian Hip Fracture Register (January 2008 to December 2020). Exclusions were made for patients aged < 60 years, pathological fractures, pre-2008 operations, contralateral hip fractures, fractures other than trochanteric A1/A2, and treatments other than IMNs or SHSs. Kaplan-Meier and Cox regression analyses adjusted for type of fracture, age, sex, cognitive impairment, American Society of Anesthesiologists (ASA) grade, and time period were conducted, along with calculations for number needed to harm (NNH).


Bone & Joint Open
Vol. 4, Issue 8 | Pages 602 - 611
21 Aug 2023
James HK Pattison GTR Griffin J Fisher JD Griffin DR

Aims

To evaluate if, for orthopaedic trainees, additional cadaveric simulation training or standard training alone yields superior radiological and clinical outcomes in patients undergoing dynamic hip screw (DHS) fixation or hemiarthroplasty for hip fracture.

Methods

This was a preliminary, pragmatic, multicentre, parallel group randomized controlled trial in nine secondary and tertiary NHS hospitals in England. Researchers were blinded to group allocation. Overall, 40 trainees in the West Midlands were eligible: 33 agreed to take part and were randomized, five withdrew after randomization, 13 were allocated cadaveric training, and 15 were allocated standard training. The intervention was an additional two-day cadaveric simulation course. The control group received standard on-the-job training. Primary outcome was implant position on the postoperative radiograph: tip-apex distance (mm) (DHS) and leg length discrepancy (mm) (hemiarthroplasty). Secondary clinical outcomes were procedure time, length of hospital stay, acute postoperative complication rate, and 12-month mortality. Procedure-specific secondary outcomes were intraoperative radiation dose (for DHS) and postoperative blood transfusion requirement (hemiarthroplasty).


Bone & Joint Open
Vol. 5, Issue 8 | Pages 621 - 627
1 Aug 2024
Walter N Loew T Hinterberger T Alt V Rupp M

Aims

Fracture-related infections (FRIs) are a devastating complication of fracture management. However, the impact of FRIs on mental health remains understudied. The aim of this study was a longitudinal evaluation of patients’ psychological state, and expectations for recovery comparing patients with recurrent FRI to those with primary FRI.

Methods

A prospective longitudinal study was conducted at a level 1 trauma centre from January 2020 to December 2022. In total, 56 patients treated for FRI were enrolled. The ICD-10 symptom rating (ISR) and an expectation questionnaire were assessed at five timepoints: preoperatively, one month postoperatively, and at three, six, and 12 months.


The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 412 - 418
1 Apr 2024
Alqarni AG Nightingale J Norrish A Gladman JRF Ollivere B

Aims

Frailty greatly increases the risk of adverse outcome of trauma in older people. Frailty detection tools appear to be unsuitable for use in traumatically injured older patients. We therefore aimed to develop a method for detecting frailty in older people sustaining trauma using routinely collected clinical data.

Methods

We analyzed prospectively collected registry data from 2,108 patients aged ≥ 65 years who were admitted to a single major trauma centre over five years (1 October 2015 to 31 July 2020). We divided the sample equally into two, creating derivation and validation samples. In the derivation sample, we performed univariate analyses followed by multivariate regression, starting with 27 clinical variables in the registry to predict Clinical Frailty Scale (CFS; range 1 to 9) scores. Bland-Altman analyses were performed in the validation cohort to evaluate any biases between the Nottingham Trauma Frailty Index (NTFI) and the CFS.


Bone & Joint Open
Vol. 5, Issue 2 | Pages 147 - 153
19 Feb 2024
Hazra S Saha N Mallick SK Saraf A Kumar S Ghosh S Chandra M

Aims

Posterior column plating through the single anterior approach reduces the morbidity in acetabular fractures that require stabilization of both the columns. The aim of this study is to assess the effectiveness of posterior column plating through the anterior intrapelvic approach (AIP) in the management of acetabular fractures.

Methods

We retrospectively reviewed the data from R G Kar Medical College, Kolkata, India, from June 2018 to April 2023. Overall, there were 34 acetabulum fractures involving both columns managed by medial buttress plating of posterior column. The posterior column of the acetabular fracture was fixed through the AIP approach with buttress plate on medial surface of posterior column. Mean follow-up was 25 months (13 to 58). Accuracy of reduction and effectiveness of this technique were measured by assessing the Merle d’Aubigné score and Matta’s radiological grading at one year and at latest follow-up.


Aims

Ankle fracture fixation is commonly performed by junior trainees. Simulation training using cadavers may shorten the learning curve and result in a technically superior surgical performance.

Methods

We undertook a preliminary, pragmatic, single-blinded, multicentre, randomized controlled trial of cadaveric simulation versus standard training. Primary outcome was fracture reduction on postoperative radiographs.


Bone & Joint Open
Vol. 5, Issue 1 | Pages 37 - 45
19 Jan 2024
Alm CE Karlsten A Madsen JE Nordsletten L Brattgjerd JE Pripp AH Frihagen F Röhrl SM

Aims

Despite limited clinical scientific backing, an additional trochanteric stabilizing plate (TSP) has been advocated when treating unstable trochanteric fractures with a sliding hip screw (SHS). We aimed to explore whether the TSP would result in less post operative fracture motion, compared to SHS alone.

Methods

Overall, 31 patients with AO/OTA 31-A2 trochanteric fractures were randomized to either a SHS alone or a SHS with an additional TSP. To compare postoperative fracture motion, radiostereometric analysis (RSA) was performed before and after weightbearing, and then at four, eight, 12, 26, and 52 weeks. With the “after weightbearing” images as baseline, we calculated translations and rotations, including shortening and medialization of the femoral shaft.


Bone & Joint Open
Vol. 4, Issue 4 | Pages 273 - 282
20 Apr 2023
Gupta S Yapp LZ Sadczuk D MacDonald DJ Clement ND White TO Keating JF Scott CEH

Aims

To investigate health-related quality of life (HRQoL) of older adults (aged ≥ 60 years) after tibial plateau fracture (TPF) compared to preinjury and population matched values, and what aspects of treatment were most important to patients.

Methods

We undertook a retrospective, case-control study of 67 patients at mean 3.5 years (SD 1.3; 1.3 to 6.1) after TPF (47 patients underwent fixation, and 20 nonoperative management). Patients completed EuroQol five-dimension three-level (EQ-5D-3L) questionnaire, Lower Limb Function Scale (LEFS), and Oxford Knee Scores (OKS) for current and recalled prefracture status. Propensity score matching for age, sex, and deprivation in a 1:5 ratio was performed using patient level data from the Health Survey for England to obtain a control group for HRQoL comparison. The primary outcome was the difference in actual (TPF cohort) and expected (matched control) EQ-5D-3L score after TPF.


The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 401 - 411
1 Apr 2024
Carrothers A O'Leary R Hull P Chou D Alsousou J Queally J Bond SJ Costa ML

Aims

To assess the feasibility of a randomized controlled trial (RCT) that compares three treatments for acetabular fractures in older patients: surgical fixation, surgical fixation and hip arthroplasty (fix-and-replace), and non-surgical treatment.

Methods

Patients were recruited from seven UK NHS centres and randomized to a three-arm pilot trial if aged older than 60 years and had a displaced acetabular fracture. Feasibility outcomes included patients’ willingness to participate, clinicians’ capability to recruit, and dropout rates. The primary clinical outcome measure was the EuroQol five-dimension questionnaire (EQ-5D) at six months. Secondary outcomes were Oxford Hip Score, Disability Rating Index, blood loss, and radiological and mobility assessments.


The Bone & Joint Journal
Vol. 104-B, Issue 11 | Pages 1256 - 1265
1 Nov 2022
Keene DJ Alsousou J Harrison P O’Connor HM Wagland S Dutton SJ Hulley P Lamb SE Willett K

Aims

To determine whether platelet-rich plasma (PRP) injection improves outcomes two years after acute Achilles tendon rupture.

Methods

A randomized multicentre two-arm parallel-group, participant- and assessor-blinded superiority trial was undertaken. Recruitment commenced on 28 July 2015 and two-year follow-up was completed in 21 October 2019. Participants were 230 adults aged 18 years and over, with acute Achilles tendon rupture managed with non-surgical treatment from 19 UK hospitals. Exclusions were insertion or musculotendinous junction injuries, major leg injury or deformity, diabetes, platelet or haematological disorder, medication with systemic corticosteroids, anticoagulation therapy treatment, and other contraindicating conditions. Participants were randomized via a central online system 1:1 to PRP or placebo injection. The main outcome measure was Achilles Tendon Rupture Score (ATRS) at two years via postal questionnaire. Other outcomes were pain, recovery goal attainment, and quality of life. Analysis was by intention-to-treat.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 4 | Pages 524 - 527
1 Apr 2006
Dowrick AS Gabbe BJ Williamson OD Cameron PA

Although the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire was designed, and has been validated, as a measure of disability in patients with disorders of the upper limb, the influence of those of the lower limb on disability as measured by the DASH score has not been assessed. The aim of this study was to investigate whether it exclusively measures disability associated with injuries to the upper limb. The Short Musculoskeletal Functional Assessment, a general musculoskeletal assessment instrument, was also completed by participants. Disability was compared in 206 participants, 84 with an injury to the upper limb, 73 with injury to the lower limb and 49 controls. We found that the DASH score also measured disability in patients with injuries to the lower limb. Care must therefore be taken when attributing disability measured by the DASH score to injuries of the upper limb when problems are also present in the lower limb. Its inability to discriminate clearly between disability due to problems at these separate sites must be taken into account when using this instrument in clinical practice or research


Bone & Joint Open
Vol. 3, Issue 5 | Pages 398 - 403
9 May 2022
Png ME Petrou S Knight R Masters J Achten J Costa ML

Aims

This study aims to estimate economic outcomes associated with 30-day deep surgical site infection (SSI) from closed surgical wounds in patients with lower limb fractures following major trauma.

Methods

Data from the Wound Healing in Surgery for Trauma (WHiST) trial, which collected outcomes from 1,547 adult participants using self-completed questionnaires over a six-month period following major trauma, was used as the basis of this empirical investigation. Associations between deep SSI and NHS and personal social services (PSS) costs (£, 2017 to 2018 prices), and between deep SSI and quality-adjusted life years (QALYs), were estimated using descriptive and multivariable analyses. Sensitivity analyses assessed the impact of uncertainty surrounding components of the economic analyses.