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The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1223 - 1230
1 Nov 2024
Dugdale EM Uvodich ME Pagnano MW Berry DJ Abdel MP Bedard NA

Aims

The prevalence of obesity is increasing substantially around the world. Elevated BMI increases the risk of complications following total hip arthroplasty (THA). We sought to evaluate trends in BMI and complication rates of obese patients undergoing primary THA over the last 30 years.

Methods

Through our institutional total joint registry, we identified 15,455 primary THAs performed for osteoarthritis from 1990 to 2019. Patients were categorized according to the World Health Organization (WHO) obesity classification and groups were trended over time. Cox proportional hazards regression analysis controlling for confounders was used to investigate the association between year of surgery and two-year risk of any reoperation, any revision, dislocation, periprosthetic joint infection (PJI), venous thromboembolism (VTE), and periprosthetic fracture. Regression was stratified by three separate groups: non-obese; WHO Class I and Class II (BMI 30 to 39 kg/m2); and WHO Class III patients (BMI ≥ 40 kg/m2).


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1050 - 1058
1 Oct 2024
Holleyman RJ Jameson SS Meek RMD Khanduja V Reed MR Judge A Board TN

Aims

This study evaluates the association between consultant and hospital volume and the risk of re-revision and 90-day mortality following first-time revision of primary hip arthroplasty for aseptic loosening.

Methods

We conducted a cohort study of first-time, single-stage revision hip arthroplasties (RHAs) performed for aseptic loosening and recorded in the National Joint Registry (NJR) data for England, Wales, Northern Ireland, and the Isle of Man between 2003 and 2019. Patient identifiers were used to link records to national mortality data, and to NJR data to identify subsequent re-revision procedures. Multivariable Cox proportional hazard models with restricted cubic splines were used to define associations between volume and outcome.


Bone & Joint Open
Vol. 5, Issue 8 | Pages 715 - 720
23 Aug 2024
Shen TS Cheng R Chiu Y McLawhorn AS Figgie MP Westrich GH

Aims

Implant waste during total hip arthroplasty (THA) represents a significant cost to the USA healthcare system. While studies have explored methods to improve THA cost-effectiveness, the literature comparing the proportions of implant waste by intraoperative technology used during THA is limited. The aims of this study were to: 1) examine whether the use of enabling technologies during THA results in a smaller proportion of wasted implants compared to navigation-guided and conventional manual THA; 2) determine the proportion of wasted implants by implant type; and 3) examine the effects of surgeon experience on rates of implant waste by technology used.

Methods

We identified 104,420 implants either implanted or wasted during 18,329 primary THAs performed on 16,724 patients between January 2018 and June 2022 at our institution. THAs were separated by technology used: robotic-assisted (n = 4,171), imageless navigation (n = 6,887), and manual (n = 7,721). The primary outcome of interest was the rate of implant waste during primary THA.


The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 359 - 364
1 Apr 2024
Özdemir E de Lange B Buckens CFM Rijnen WHC Visser J

Aims. To investigate the extent of bone development around the scaffold of custom triflange acetabular components (CTACs) over time. Methods. We performed a single-centre historical prospective cohort study, including all patients with revision THA using the aMace CTAC between January 2017 and March 2021. A total of 18 patients (18 CTACs) were included. Models of the hemipelvis and the scaffold component of the CTACs were created by segmentation of CT scans. The CT scans were performed immediately postoperatively and at least one year after surgery. The amount of bone in contact with the scaffold was analyzed at both times, and the difference was calculated. Results. The mean time between the implantation and the second CT scan was two years (1 to 5). The mean age of the patients during CTAC implantation was 75 years (60 to 92). The mean scaffold-bone contact area increased from 16% (SD 12.6) to 28% (SD 11.9). The mean scaffold-bone distance decreased from a mean of 6.5 mm (SD 2.0) to 5.5 mm (SD 1.6). None of the CTACs were revised or radiologically loose. Conclusion. There was a statistically significant increase of scaffold-bone contact area over time, but the total contact area of the scaffold in relation to the acetabular bone remained relatively low. As all implants remained well fixed, the question remains to what extend the scaffold contributes to the observed stability, in relation to the screws. A future design implication might be an elimination of the bulky scaffold component. This design modification would reduce production costs and may optimize the primary fit of the implant. Cite this article: Bone Joint J 2024;106-B(4):359–364


Bone & Joint Open
Vol. 4, Issue 10 | Pages 801 - 807
23 Oct 2023
Walter N Szymski D Kurtz SM Lowenberg DW Alt V Lau EC Rupp M

Aims

This work aimed at answering the following research questions: 1) What is the rate of mechanical complications, nonunion and infection for head/neck femoral fractures, intertrochanteric fractures, and subtrochanteric fractures in the elderly USA population? and 2) Which factors influence adverse outcomes?

Methods

Proximal femoral fractures occurred between 1 January 2009 and 31 December 2019 were identified from the Medicare Physician Service Records Data Base. The Kaplan-Meier method with Fine and Gray sub-distribution adaptation was used to determine rates for nonunion, infection, and mechanical complications. Semiparametric Cox regression model was applied incorporating 23 measures as covariates to identify risk factors.


Bone & Joint Open
Vol. 4, Issue 10 | Pages 766 - 775
13 Oct 2023
Xiang L Singh M McNicoll L Moppett IK

Aims. To identify factors influencing clinicians’ decisions to undertake a nonoperative hip fracture management approach among older people, and to determine whether there is global heterogeneity regarding these factors between clinicians from high-income countries (HIC) and low- and middle-income countries (LMIC). Methods. A SurveyMonkey questionnaire was electronically distributed to clinicians around the world through the Fragility Fracture Network (FFN)’s Perioperative Special Interest Group and clinicians’ personal networks between 24 May and 25 July 2021. Analyses were performed using Excel and STATA v16.0. Between-group differences were determined using independent-samples t-tests and chi-squared tests. Results. A total of 406 respondents from 51 countries answered the questionnaire, of whom 225 came from HIC and 180 from LMIC. Clinicians from HIC reported a greater median and mean estimated proportion of admitted patients with hip fracture undergoing surgery (median 96% (interquartile range (IQR) 95% to 99%); mean 94% (SD 8%)) than those from LMIC (median 85% (IQR 75% to 95%); mean 81% (SD 16%); p < 0.001). Global heterogeneity seems to exist regarding factors such as anticipated life expectancy, insufficient resources, ability to pay, treatment costs, and perception of risk in hip fracture management decision-making. Conclusion. This study represents the first international sampling of clinician perspectives regarding nonoperative hip fracture management. Several factors seemed to influence the clinician decision-making process. Further research is needed to inform the development of best practice guidelines to improve decision-making and the quality of hip fracture care among older people. Cite this article: Bone Jt Open 2023;4(10):766–775


The Bone & Joint Journal
Vol. 105-B, Issue 10 | Pages 1060 - 1069
1 Oct 2023
Holleyman RJ Jameson SS Reed M Meek RMD Khanduja V Hamer A Judge A Board T

Aims

This study describes the variation in the annual volumes of revision hip arthroplasty (RHA) undertaken by consultant surgeons nationally, and the rate of accrual of RHA and corresponding primary hip arthroplasty (PHA) volume for new consultants entering practice.

Methods

National Joint Registry (NJR) data for England, Wales, Northern Ireland, and the Isle of Man were received for 84,816 RHAs and 818,979 PHAs recorded between April 2011 and December 2019. RHA data comprised all revision procedures, including first-time revisions of PHA and any subsequent re-revisions recorded in public and private healthcare organizations. Annual procedure volumes undertaken by the responsible consultant surgeon in the 12 months prior to every index procedure were determined. We identified a cohort of ‘new’ HA consultants who commenced practice from 2012 and describe their rate of accrual of PHA and RHA experience.


Bone & Joint Open
Vol. 4, Issue 8 | Pages 559 - 566
1 Aug 2023
Hillier DI Petrie MJ Harrison TP Salih S Gordon A Buckley SC Kerry RM Hamer A

Aims. The burden of revision total hip arthroplasty (rTHA) continues to grow. The surgery is complex and associated with significant costs. Regional rTHA networks have been proposed to improve outcomes and to reduce re-revisions, and therefore costs. The aim of this study was to accurately quantify the cost and reimbursement for a rTHA service, and to assess the financial impact of case complexity at a tertiary referral centre within the NHS. Methods. A retrospective analysis of all revision hip procedures was performed at this centre over two consecutive financial years (2018 to 2020). Cases were classified according to the Revision Hip Complexity Classification (RHCC) and whether they were infected or non-infected. Patients with an American Society of Anesthesiologists (ASA) grade ≥ III or BMI ≥ 40 kg/m. 2. are considered “high risk” by the RHCC. Costs were calculated using the Patient Level Information and Costing System (PLICS), and remuneration based on Healthcare Resource Groups (HRG) data. The primary outcome was the financial difference between tariff and cost per patient episode. Results. In all, 199 revision episodes were identified in 168 patients: 25 (13%) least complex revisions (H1); 110 (55%) complex revisions (H2); and 64 (32%) most complex revisions (H3). Of the 199, 76 cases (38%) were due to infection, and 78 patients (39%) were “high risk”. Median length of stay increased significantly with case complexity from four days to six to eight days (p = 0.006) and for revisions performed for infection (9 days vs 5 days; p < 0.001). Cost per episode increased significantly between complexity groups (p < 0.001) and for infected revisions (p < 0.001). All groups demonstrated a mean deficit but this significantly increased with revision complexity (£97, £1,050, and £2,887 per case; p = 0.006) and for infected failure (£2,629 vs £635; p = 0.032). The total deficit to the NHS Trust over two years was £512,202. Conclusion. Current NHS reimbursement for rTHA is inadequate and should be more closely aligned to complexity. An increase in the most complex rTHAs at major revision centres will likely place a greater financial burden on these units. Cite this article: Bone Jt Open 2023;4(8):559–566


The Bone & Joint Journal
Vol. 105-B, Issue 8 | Pages 864 - 871
1 Aug 2023
Tyas B Marsh M de Steiger R Lorimer M Petheram TG Inman DS Reed MR Jameson SS

Aims. Several different designs of hemiarthroplasty are used to treat intracapsular fractures of the proximal femur, with large variations in costs. No clinical benefit of modular over monoblock designs has been reported in the literature. Long-term data are lacking. The aim of this study was to report the ten-year implant survival of commonly used designs of hemiarthroplasty. Methods. Patients recorded by the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) between 1 September 1999 and 31 December 2020 who underwent hemiarthroplasty for the treatment of a hip fracture with the following implants were included: a cemented monoblock Exeter Trauma Stem (ETS), cemented Exeter V40 with a bipolar head, a monoblock Thompsons prosthesis (Cobalt/Chromium or Titanium), and an Exeter V40 with a Unitrax head. Overall and age-defined cumulative revision rates were compared over the ten years following surgery. Results. A total of 41,949 hemiarthroplasties were included. Exeter V40 with a Unitrax head was the most commonly used (n = 20,707, 49.4%). The overall rate of revision was small. A total of 28,201 patients (67.2%) were aged > 80 years. There were no significant differences in revision rates across all designs of hemiarthroplasty in patients of this age at any time. The revision rates for all designs were < 3.5%, three years postoperatively. At subsequent times the ETS and Exeter V40 with a bipolar head performed well in all age groups. The unadjusted ten-year mortality rate for the whole cohort was 82.2%. Conclusion. There was no difference in implant survival between all the designs of hemiarthroplasty in the first three years following surgery, supporting the selection of a cost-effective design of hemiarthroplasty for most patients with an intracapsular fracture of the hip, as determined by local availability and costs. Beyond this, the ETS and Exeter bipolar designs performed well in all age groups. Cite this article: Bone Joint J 2023;105-B(8):864–871


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 775 - 782
1 Jul 2023
Koper MC Spek RWA Reijman M van Es EM Baart SJ Verhaar JAN Bos PK

Aims

The aims of this study were to determine if an increasing serum cobalt (Co) and/or chromium (Cr) concentration is correlated with a decreasing Harris Hip Score (HHS) and Hip disability and Osteoarthritis Outcome Score (HOOS) in patients who received the Articular Surface Replacement (ASR) hip resurfacing arthroplasty (HRA), and to evaluate the ten-year revision rate and show if sex, inclination angle, and Co level influenced the revision rate.

Methods

A total of 62 patients with an ASR-HRA were included and monitored yearly postoperatively. At follow-up, serum Co and Cr levels were measured and the HHS and the HOOS were scored. In addition, preoperative patient and implant variables and the need for revision surgery were recorded. We used a linear mixed model to relate the serum Co and Cr levels to different patient-reported outcome measures (PROMs). For the survival analyses we used the Kaplan-Meier and Cox regression model.


Bone & Joint Open
Vol. 4, Issue 5 | Pages 370 - 377
19 May 2023
Comeau-Gauthier M Bzovsky S Axelrod D Poolman RW Frihagen F Bhandari M Schemitsch E Sprague S

Aims

Using data from the Hip Fracture Evaluation with Alternatives of Total Hip Arthroplasty versus Hemiarthroplasty (HEALTH) trial, we sought to determine if a difference in functional outcomes exists between monopolar and bipolar hemiarthroplasty (HA).

Methods

This study is a secondary analysis of patients aged 50 years or older with a displaced femoral neck fracture who were enrolled in the HEALTH trial and underwent monopolar and bipolar HA. Scores from the Western Ontario and McMaster University Arthritis Index (WOMAC) and 12-Item Short Form Health Survey (SF-12) Physical Component Summary (PCS) and (MCS) were compared between the two HA groups using a propensity score-weighted analysis.


Bone & Joint Open
Vol. 4, Issue 5 | Pages 329 - 337
8 May 2023
Khan AQ Chowdhry M Sherwani MKA McPherson EJ

Aims

Total hip arthroplasty (THA) is considered the preferred treatment for displaced proximal femoral neck fractures. However, in many countries this option is economically unviable. To improve outcomes in financially disadvantaged populations, we studied the technique of concomitant valgus hip osteotomy and operative fixation (VOOF). This prospective serial study compares two treatment groups: VOOF versus operative fixation alone with cannulated compression screws (CCSs).

Methods

In the first series, 98 hip fixation procedures were performed using CCS. After fluoroscopic reduction of the fracture, three CCSs were placed. In the second series, 105 VOOF procedures were performed using a closing wedge intertrochanteric osteotomy with a compression lag screw and lateral femoral plate. The alignment goal was to create a modified Pauwel’s fracture angle of 30°. After fluoroscopic reduction of fracture, lag screw was placed to achieve the calculated correction angle, followed by inter-trochanteric osteotomy and placement of barrel plate. Patients were followed for a minimum of two years.


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 511 - 517
1 May 2023
Petrie MJ Panchani S Al-Einzy M Partridge D Harrison TP Stockley I

Aims. The duration of systemic antibiotic treatment following first-stage revision surgery for periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is contentious. Our philosophy is to perform an aggressive debridement, and to use a high local concentration of targeted antibiotics in cement beads and systemic prophylactic antibiotics alone. The aim of this study was to assess the success of this philosophy in the management of PJI of the hip using our two-stage protocol. Methods. The study involved a retrospective review of our prospectively collected database from which we identified all patients who underwent an intended two-stage revision for PJI of the hip. All patients had a diagnosis of PJI according to the major criteria of the Musculoskeletal Infection Society (MSIS) 2013, a minimum five-year follow-up, and were assessed using the MSIS working group outcome-reporting tool. The outcomes were grouped into ‘successful’ or ‘unsuccessful’. Results. A total of 299 two-stage revision THAs in 289 patients met the inclusion criteria, of whom 258 (86%) proceeded to second-stage surgery. Their mean age was 68.1 years (28 to 92). The median follow-up was 10.7 years (interquartile range (IQR) 6.3 to 15.0). A 91% success rate was seen in those patients who underwent reimplantation, decreasing to 86% when including those who did not proceed to reimplantation. The median duration of postoperative systemic antibiotics following the first stage was five days (IQR 5 to 9). There was no significant difference in outcome between those patients who were treated with antibiotics for ≤ 48 hours (p = 0.961) or ≤ five days (p = 0.376) compared with those who were treated with longer courses. Greater success rates were seen for Gram-positive PJIs (87%) than for Gram-negative (84%) and mixed-Gram PJIs (72%; p = 0.098). Conclusion. Aggressive surgical debridement with a high local concentration of targeted antibiotics at the time of first-stage revision surgery for PJI of the hip, without prolonged systemic antibiotics, provides a high rate of success, responsible antibiotic stewardship, and reduced hospital costs. Cite this article: Bone Joint J 2023;105-B(5):511–517


Bone & Joint Open
Vol. 4, Issue 4 | Pages 226 - 233
1 Apr 2023
Moore AJ Wylde V Whitehouse MR Beswick AD Walsh NE Jameson C Blom AW

Aims. Periprosthetic hip-joint infection is a multifaceted and highly detrimental outcome for patients and clinicians. The incidence of prosthetic joint infection reported within two years of primary hip arthroplasty ranges from 0.8% to 2.1%. Costs of treatment are over five-times greater in people with periprosthetic hip joint infection than in those with no infection. Currently, there are no national evidence-based guidelines for treatment and management of this condition to guide clinical practice or to inform clinical study design. The aim of this study is to develop guidelines based on evidence from the six-year INFection and ORthopaedic Management (INFORM) research programme. Methods. We used a consensus process consisting of an evidence review to generate items for the guidelines and online consensus questionnaire and virtual face-to-face consensus meeting to draft the guidelines. Results. The consensus panel comprised 21 clinical experts in orthopaedics, primary care, rehabilitation, and healthcare commissioning. The final output from the consensus process was a 14-item guideline. The guidelines make recommendations regarding increased vigilance and monitoring of those at increased risk of infection; diagnosis including strategies to ensure the early recognition of prosthetic infection and referral to orthopaedic teams; treatment, including early use of DAIR and revision strategies; and postoperative management including appropriate physical and psychological support and antibiotic strategies. Conclusion. We believe the implementation of the INFORM guidelines will inform treatment protocols and clinical pathways to improve the treatment and management of periprosthetic hip infection. Cite this article: Bone Jt Open 2023;4(4):226–233


The Bone & Joint Journal
Vol. 105-B, Issue 3 | Pages 254 - 260
1 Mar 2023
Bukowski BR Sandhu KP Bernatz JT Pickhardt PJ Binkley N Anderson PA Illgen R

Aims

Osteoporosis can determine surgical strategy for total hip arthroplasty (THA), and perioperative fracture risk. The aims of this study were to use hip CT to measure femoral bone mineral density (BMD) using CT X-ray absorptiometry (CTXA), determine if systematic evaluation of preoperative femoral BMD with CTXA would improve identification of osteopenia and osteoporosis compared with available preoperative dual-energy X-ray absorptiometry (DXA) analysis, and determine if improved recognition of low BMD would affect the use of cemented stem fixation.

Methods

Retrospective chart review of a single-surgeon database identified 78 patients with CTXA performed prior to robotic-assisted THA (raTHA) (Group 1). Group 1 was age- and sex-matched to 78 raTHAs that had a preoperative hip CT but did not have CTXA analysis (Group 2). Clinical demographics, femoral fixation method, CTXA, and DXA data were recorded. Demographic data were similar for both groups.


The Bone & Joint Journal
Vol. 105-B, Issue 2 | Pages 124 - 134
1 Feb 2023
Jain S Farook MZ Aslam-Pervez N Amer M Martin DH Unnithan A Middleton R Dunlop DG Scott CEH West R Pandit H

Aims

The aim of this study was to compare open reduction and internal fixation (ORIF) with revision surgery for the surgical management of Unified Classification System (UCS) type B periprosthetic femoral fractures around cemented polished taper-slip femoral components following primary total hip arthroplasty (THA).

Methods

Data were collected for patients admitted to five UK centres. The primary outcome measure was the two-year reoperation rate. Secondary outcomes were time to surgery, transfusion requirements, critical care requirements, length of stay, two-year local complication rates, six-month systemic complication rates, and mortality rates. Comparisons were made by the form of treatment (ORIF vs revision) and UCS type (B1 vs B2/B3). Kaplan-Meier survival analysis was performed with two-year reoperation for any reason as the endpoint.


Bone & Joint Open
Vol. 3, Issue 12 | Pages 991 - 997
23 Dec 2022
McPherson EJ Stavrakis AI Chowdhry M Curtin NL Dipane MV Crawford BM

Aims

Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects.

Methods

We performed a retrospective review at a single institution of patients undergoing revision THA by a single surgeon. We identified 49 consecutive patients with large acetabular defects where the biphasic BGS was applied, with no other products added to the BGS. After placement of metallic acetabular implants, the BGS was injected into the remaining bone defects surrounding the new implants. Patients were followed and monitored for functional outcome scores, implant fixation, radiological graft site remodelling, and revision failures.


Bone & Joint Open
Vol. 3, Issue 11 | Pages 877 - 884
14 Nov 2022
Archer H Reine S Alshaikhsalama A Wells J Kohli A Vazquez L Hummer A DiFranco MD Ljuhar R Xi Y Chhabra A

Aims

Hip dysplasia (HD) leads to premature osteoarthritis. Timely detection and correction of HD has been shown to improve pain, functional status, and hip longevity. Several time-consuming radiological measurements are currently used to confirm HD. An artificial intelligence (AI) software named HIPPO automatically locates anatomical landmarks on anteroposterior pelvis radiographs and performs the needed measurements. The primary aim of this study was to assess the reliability of this tool as compared to multi-reader evaluation in clinically proven cases of adult HD. The secondary aims were to assess the time savings achieved and evaluate inter-reader assessment.

Methods

A consecutive preoperative sample of 130 HD patients (256 hips) was used. This cohort included 82.3% females (n = 107) and 17.7% males (n = 23) with median patient age of 28.6 years (interquartile range (IQR) 22.5 to 37.2). Three trained readers’ measurements were compared to AI outputs of lateral centre-edge angle (LCEA), caput-collum-diaphyseal (CCD) angle, pelvic obliquity, Tönnis angle, Sharp’s angle, and femoral head coverage. Intraclass correlation coefficients (ICC) and Bland-Altman analyses were obtained.


Bone & Joint Open
Vol. 3, Issue 9 | Pages 684 - 691
1 Sep 2022
Rodriguez S Shen TS Lebrun DG Della Valle AG Ast MP Rodriguez JA

Aims

The volume of ambulatory total hip arthroplasty (THA) procedures is increasing due to the emphasis on value-based care. The purpose of the study is to identify the causes for failed same-day discharge (SDD) and perioperative factors leading to failed SDD.

Methods

This retrospective cohort study followed pre-selected patients for SDD THA from 1 August 2018 to 31 December 2020. Inclusion criteria were patients undergoing unilateral THA with appropriate social support, age 18 to 75 years, and BMI < 37 kg/m2. Patients with opioid dependence, coronary artery disease, and valvular heart disease were excluded. Demographics, comorbidities, and perioperative data were collected from the electronic medical records. Possible risk factors for failed SDD were identified using multivariate logistic regression.


The Bone & Joint Journal
Vol. 104-B, Issue 8 | Pages 922 - 928
1 Aug 2022
Png ME Petrou S Fernandez MA Achten J Parsons N McGibbon A Gould J Griffin XL Costa ML

Aims

The aim of this study was to compare the cost-effectiveness of cemented hemiarthroplasty (HA) versus hydroxyapatite-coated uncemented HA for the treatment of displaced intracapsular hip fractures in older adults.

Methods

A within-trial economic evaluation was conducted based on data collected from the World Hip Trauma Evaluation 5 (WHiTE 5) multicentre randomized controlled trial in the UK. Resource use was measured over 12 months post-randomization using trial case report forms and participant-completed questionnaires. Cost-effectiveness was reported in terms of incremental cost per quality-adjusted life year (QALY) gained from the NHS and personal social service perspective. Methodological uncertainty was addressed using sensitivity analysis, while decision uncertainty was represented graphically using confidence ellipses and cost-effectiveness acceptability curves.