The cost-effectiveness of adding an ultrasound corticosteroid and local anaesthetic injection to advice and education for hip osteoarthritis.

OBJECTIVES: Evidence for the comparative cost-effectiveness of intra-articular corticosteroid injection in people with hip osteoarthritis (OA) remains unclear. This study investigated the cost-effectiveness of best current treatment (BCT) comprising advice and education plus a single ultrasound-guided intra-articular hip injection (USGI) of 40 mg triamcinolone acetonide and 4 ml 1% lidocaine hydrochloride (BCT+US-T) versus BCT alone. METHODS: A trial-based cost-utility analysis of BCT+US-T compared with BCT was undertaken over 6 months. Patient-level cost data were obtained, and effectiveness was measured in terms of quality-adjusted life years (QALYs), allowing the calculation of cost per QALY gained from a United Kingdom (UK) National Health Service (NHS) perspective. RESULTS: BCT+US-T was associated with lower mean NHS costs (BCT+US-T minus BCT: £-161.6, 95% CI: £-583.95 to £54.18) and small but significantly higher mean QALYs than BCT alone over 6 months (BCT+US-T minus BCT: 0.0487, 95% CI: 0.0091, 0.0886). In the base case, BCT+US-T was the most cost-effective and dominated BCT alone. Differences in total costs were driven by number of visits to NHS consultants, private physiotherapists, and chiropractors, and hip surgery, which were more common with BCT alone than BCT+US-T. CONCLUSION: Intra-articular corticosteroid injection plus BCT (BCT+US-T) for patients with hip OA results in lower costs and better outcomes, and is highly cost-effective, compared with BCT alone. TRIAL REGISTRATION: EudraCT: 2014-003412-37 (August 8, 2015) and registered with Current Controlled Trials: ISRCTN 50550256 (July 28, 2015). TRIAL PROTOCOL: Full details of the trial protocol can be found in the Supplementary Appendix, available with the full text of this article at https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-018-2153-0#citeas. DOI: doi.org/10.1186/s12891-018-2153-0.

Negative-pressure wound therapy versus standard dressings for adults with an open lower limb fracture: the WOLLF RCT.

BACKGROUND: Open fractures of the lower limb occur when a broken bone penetrates the skin and is exposed to the outside environment. These are life-changing injuries. The risk of deep infection may be as high as 27%. The type of dressing applied after surgical debridement could potentially reduce the risk of infection in the open-fracture wound. OBJECTIVES: To assess the disability, rate of deep infection, quality of life and resource use in patients with severe open fracture of the lower limb treated with negative-pressure wound therapy (NPWT) versus standard wound management after the first surgical debridement of the wound. DESIGN: A pragmatic, multicentre randomised controlled trial. SETTING: Twenty-four specialist trauma hospitals in the UK Major Trauma Network. PARTICIPANTS: A total of 460 patients aged ≥ 16 years with a severe open fracture of the lower limb were recruited from July 2012 through to December 2015. Patients were excluded if they presented more than 72 hours after their injury or were unable to complete questionnaires. INTERVENTIONS: Negative-pressure wound therapy (n = 226) where an 'open-cell' solid foam or gauze was placed over the surface of the wound and connected to a suction pump which created a partial vacuum over the dressing versus standard dressings not involving negative pressure (n = 234). MAIN OUTCOME MEASURES: Disability Rating Index (DRI) - a score of 0 (no disability) to 100 (completely disabled) at 12 months was the primary outcome measure, with a minimal clinically important difference of 8 points. The secondary outcomes were deep infection, quality of life and resource use collected at 3, 6, 9 and 12 months post randomisaton. RESULTS: There was no evidence of a difference in the patients' DRI at 12 months. The mean DRI in the NPWT group was 45.5 points [standard deviation (SD) 28.0 points] versus 42.4 points (SD 24.2 points) in the standard dressing group, giving a difference of -3.9 points (95% confidence interval -8.9 to 1.2 points) in favour of standard dressings (p = 0.132). There was no difference in HRQoL and no difference in the number of surgical site infections or other complications at any point in the 12 months after surgery. NPWT did not reduce the cost of treatment and it was associated with a low probability of cost-effectiveness. LIMITATIONS: Owing to the emergency nature of the interventions, we anticipated that some patients who were randomised into the trial would subsequently be unable or unwilling to take part. Such post-randomisation withdrawal of patients could have posed a risk to the external validity of the trial. However, the great majority of these patients (85%) were found to be ineligible after randomisation. Therefore, we can be confident that the patients who took part were representative of the population with severe open fractures of the lower limb. CONCLUSIONS: Contrary to the existing literature and current clinical guidelines, NPWT dressings do not provide a clinical or an economic benefit for patients with an open fracture of the lower limb. FUTURE WORK: Future work should investigate alternative strategies to reduce the incidence of infection and improve outcomes for patients with an open fracture of the lower limb. Two specific areas of potentially great benefit are (1) the use of topical antibiotic preparations in the open-fracture wound and (2) the role of orthopaedic implants with antimicrobial coatings when fixing the associated fracture. TRIAL REGISTRATION: Current Controlled Trials ISRCTN33756652 and UKCRN Portfolio ID 11783. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 73. See the NIHR Journals Library website for further project information.

Intramedullary nail fixation versus locking plate fixation for adults with a fracture of the distal tibia: the UK FixDT RCT.

BACKGROUND: The best treatment for fractures of the distal tibia remains controversial. Most of these fractures require surgical fixation, but the outcomes are unpredictable and complications are common. OBJECTIVES: To assess disability, quality of life, complications and resource use in patients treated with intramedullary (IM) nail fixation versus locking plate fixation in the 12 months following a fracture of the distal tibia. DESIGN: This was a multicentre randomised trial. SETTING: The trial was conducted in 28 UK acute trauma centres from April 2013 to final follow-up in February 2017. PARTICIPANTS: In total, 321 adult patients were recruited. Participants were excluded if they had open fractures, fractures involving the ankle joint, contraindication to nailing or inability to complete questionnaires. INTERVENTIONS: IM nail fixation (n = 161), in which a metal rod is inserted into the hollow centre of the tibia, versus locking plate fixation (n = 160), in which a plate is attached to the surface of the tibia with fixed-angle screws. MAIN OUTCOME MEASURES: The primary outcome measure was the Disability Rating Index (DRI) score, which ranges from 0 points (no disability) to 100 points (complete disability), at 6 months with a minimum clinically important difference of 8 points. The DRI score was also collected at 3 and 12 months. The secondary outcomes were the Olerud-Molander Ankle Score (OMAS), quality of life as measured using EuroQol-5 Dimensions (EQ-5D), complications such as infection, and further surgery. Resource use was collected to inform the health economic evaluation. RESULTS: Participants had a mean age of 45 years (standard deviation 16.2 years), were predominantly male (61%, 197/321) and had experienced traumatic injury after a fall (69%, 223/321). There was no statistically significant difference in DRI score at 6 months [IM nail fixation group, mean 29.8 points, 95% confidence interval (CI) 26.1 to 33.7 points; locking plate group, mean 33.8 points, 95% CI 29.7 to 37.9 points; adjusted difference, 4.0 points, 95% CI -1.0 to 9.0 points; p = 0.11]. There was a statistically significant difference in DRI score at 3 months in favour of IM nail fixation (IM nail fixation group, mean 44.2 points, 95% CI 40.8 to 47.6 points; locking plate group, mean 52.6 points, 95% CI 49.3 to 55.9 points; adjusted difference 8.8 points, 95% CI 4.3 to 13.2 points; p < 0.001), but not at 12 months (IM nail fixation group, mean 23.1 points, 95% CI 18.9 to 27.2 points; locking plate group, 24.0 points, 95% CI 19.7 to 28.3 points; adjusted difference 1.9 points, 95% CI -3.2 to 6.9 points; p = 0.47). Secondary outcomes showed the same pattern, including a statistically significant difference in mean OMAS and EQ-5D scores at 3 and 6 months in favour of IM nail fixation. There were no statistically significant differences in complications, including the number of postoperative infections (13% in the locking plate group and 9% in the IM nail fixation group). Further surgery was more common in the locking plate group (12% in locking plate group and 8% in IM nail fixation group at 12 months). The economic evaluation showed that IM nail fixation provided a slightly higher quality of life in the 12 months after injury and at lower cost and, therefore, it was cost-effective compared with locking plate fixation. The probability of cost-effectiveness for IM nail fixation exceeded 90%, regardless of the value of the cost-effectiveness threshold. LIMITATIONS: As wound dressings after surgery are clearly visible, it was not possible to blind the patients to their treatment allocation. This evidence does not apply to intra-articular (pilon) fractures of the distal tibia. CONCLUSIONS: Among adults with an acute fracture of the distal tibia who were randomised to IM nail fixation or locking plate fixation, there were similar disability ratings at 6 months. However, recovery across all outcomes was faster in the IM nail fixation group and costs were lower. FUTURE WORK: The potential benefit of IM nail fixation in several other fractures requires investigation. Research is also required into the role of adjuvant treatment and different rehabilitation strategies to accelerate recovery following a fracture of the tibia and other long-bone fractures in the lower limb. The patients in this trial will remain in longer-term follow-up. TRIAL REGISTRATION: Current Controlled Trials ISRCTN99771224 and UKCRN 13761. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 25. See the NIHR Journals Library website for further project information.

Physical activity energy expenditure predicts changes in body composition in middle-aged healthy whites: effect modification by age.

BACKGROUND: It is unclear whether physical activity energy expenditure (PAEE) predicts changes in body composition. OBJECTIVE: The objective was to describe the independent associations between PAEE and changes in body composition in a population-based cohort. DESIGN: This was a prospective population-based study conducted in 739 (311 men and 428 women) healthy middle-aged (median age: 53.8 y) whites. The median follow-up was 5.6 y. PAEE (MJ/d) was assessed by heart rate monitoring, individually calibrated by using the FLEX heart rate method. Fat mass (FM) and fat-free mass (FFM) were assessed by bioimpedance. RESULTS: Body weight (BW) at follow-up was significantly related to baseline PAEE (P < 0.05) after adjustment for sex, baseline age, FM, FFM, and follow-up time. A significant interaction between PAEE and age (P = 0.023) was observed. After the subjects were stratified (above and below the median for age), BW increased by a mean (+/-SD) of 1.7 +/- 5.9 kg (P < 0.0001) in the younger cohort. In this group, follow-up FM was significantly associated with baseline PAEE (P = 0.036) after adjustment for confounders. In the older cohort, BW did not change between baseline and follow-up. In this group, in contrast with the younger population, follow-up BW, FM, and FFM were all significantly and positively associated with baseline PAEE (P < 0.01 for all). CONCLUSIONS: Baseline PAEE predicts a change in FM in younger adults, who as a group gained weight in this study. In contrast, baseline PAEE in older adults--who were on average weight stable--is associated with a gain in BW, which was explained by an increase in FM and FFM.

Physical activity energy expenditure predicts progression toward the metabolic syndrome independently of aerobic fitness in middle-aged healthy Caucasians: the Medical Research Council Ely Study.

OBJECTIVE: To examine over a period of 5.6 years the prospective associations between physical activity energy expenditure (PAEE), aerobic fitness (Vo(2max)), obesity, and the progression toward the metabolic syndrome in a population-based cohort of middle-aged men and women (n = 605) who were free of the metabolic syndrome at baseline. RESEARCH DESIGN AND METHODS: PAEE was measured objectively by individually calibrated heart rate against energy expenditure. Vo(2max) was predicted from a submaximal exercise stress test. Fat mass and fat-free mass were assessed by bio-impedance. A metabolic syndrome score was computed by summing the standardized values for obesity, hypertension, hyperglycemia, insulin resistance, hypertriglyceridemia, and the inverse level of HDL cholesterol and expressed as a continuously distributed outcome. Generalized linear models were used to examine the independent prospective associations between PAEE and Vo(2max) and the metabolic syndrome score after adjusting for sex, baseline age, smoking, socioeconomic status, follow-up time, and baseline phenotypes. RESULTS: PAEE predicted progression toward the metabolic syndrome, independent of baseline metabolic syndrome, body fat, Vo(2max), and other confounding factors (standardized beta = -0.00085, P = 0.046). This association was stronger when excluding the adiposity component from the metabolic syndrome (standardized beta = -0.0011, P = 0.035). Vo(2max) was not an independent predictor of the metabolic syndrome after adjusting for physical activity (standardized beta = 0.00011, P = 0.93). CONCLUSIONS: PAEE predicts progression toward the metabolic syndrome independent of aerobic fitness, obesity, and other confounding factors. This finding underscores the importance of physical activity for metabolic disease prevention even when an improvement in aerobic fitness is absent.

Adjusting for energy intake--what measure to use in nutritional epidemiological studies?

BACKGROUND: The measurement of energy intake in epidemiological studies is difficult. However, it is important that energy intake is assessed if epidemiological analyses are to correspond to isocaloric experiments. The aim of this study was to compare self-reported energy intake, physical activity, and body weight with energy expenditure measured by 4 days of heart rate monitoring with individual calibration of the relationship between heart rate and oxygen consumption. METHODS: Volunteer sub-study of 97 men and women (mean ages 54 and 51 years respectively) within the European Investigation into Cancer (EPIC) study in Norfolk (UK). Dietary assessment of energy intake and physical activity was by self-report and weight was measured using standard techniques. Energy expenditure was assessed objectively by recording heart rate for 4 days following a calibration of the relationship between heart rate and oxygen consumption. RESULTS: Self-reported energy intake by 7-day diary (mean 8.5 MJ/day) and food frequency questionnaire (FFQ) (mean 8.8 MJ/day) were significantly lower than objectively measured total energy expenditure (mean 11.2 MJ/day). The deattenuated partial correlations between total energy expenditure were 0.33 (7-day diary), 0.34 (FFQ), 0.50 (physical activity), and 0.56 (weight). Weight accounted for 31% (deattenuated) of the sum of squares about the mean of true energy intake after adjusting for age and sex. With the addition of self-reported physical activity, the model was significantly improved (R2 = 0.57). Adding energy either assessed by the diary or FFQ did not improve the model. CONCLUSIONS: The results presented here indicate that to adjust for energy intake, for the purpose of replicating an isocaloric experiment in an observational epidemiological study, one would do considerably better adjusting for weight and physical activity, than adjusting for energy intake estimated from an FFQ.

Validity and repeatability of a simple index derived from the short physical activity questionnaire used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

OBJECTIVE: To assess the validity and repeatability of a simple index designed to rank participants according to their energy expenditure estimated by self-report, by comparison with objectively measured energy expenditure assessed by heart-rate monitoring with individual calibration. DESIGN: Energy expenditure was assessed over one year by four separate episodes of 4-day heart-rate monitoring, a method previously validated against whole-body calorimetry and doubly labelled water. Cardio-respiratory fitness was assessed by four repeated measures of sub-maximum oxygen uptake. At the end of the 12-month period, participants completed a physical activity questionnaire that assessed past-year activity. A simple four-level physical activity index was derived by combining occupational physical activity together with time participating in cycling and other physical exercise (such as keep fit, aerobics, swimming and jogging). SUBJECTS: One hundred and seventy-three randomly selected men and women aged 40 to 65 years. RESULTS: The repeatability of the physical activity index was high (weighted kappa=0.6, ). There were positive associations between the physical activity index from the questionnaire and the objective measures of the ratio of daytime energy expenditure to resting metabolic rate and cardio-respiratory fitness As an indirect test of validity, there was a positive association between the physical activity index and the ratio of energy intake, assessed by 7-day food diaries, to predicted basal metabolic rate. CONCLUSIONS: The summary index of physical activity derived from the questions used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study suggest it is useful for ranking participants in terms of their physical activity in large epidemiological studies. The index is simple and easy to comprehend, which may make it suitable for situations that require a concise, global index of activity.

Validity and repeatability of the EPIC-Norfolk Physical Activity Questionnaire.

BACKGROUND: Physical activity is an important lifestyle which is often poorly assessed in epidemiological studies. The European Prospective Investigation into Cancer Study-Norfolk cohort (EPIC-Norfolk), a large population-based cohort study, has developed a comprehensive questionnaire to assess activity in different domains of life aimed at assessing total energy expenditure. We report the repeatability of this instrument and its validity against repeated objective measures of fitness and energy expenditure undertaken throughout the time frame of reference of the questionnaire. METHODS: The validity of the instrument was measured in 173 individuals randomly selected from a continuing population-based cohort study. Energy expenditure was assessed by four separate episodes of 4-day heart-rate monitoring, a method previously validated against whole body calorimetry and doubly-labelled water. Cardio-respiratory fitness was assessed by four repeated measures of sub-maximum oxygen uptake. At the end of the 12-month period, participants completed the physical activity questionnaire that assesses past-year activity at home, work and in recreation. Repeatability was assessed in a separate group of 399 randomly selected participants in EPIC who completed the physical activity questionnaire twice with a 3-month interval. RESULTS: The age- and sex-adjusted correlation between the objective measure of daytime energy expenditure and the sum of recreational and occupational reported physical activity (in MET h per week) was 0.28 (P < 0.001). The reported time spent in vigorous activity was correlated with cardio-respiratory fitness (0.16, P < 0.05) and with the proportion of time when energy expenditure was more than five times basal (0.17, P < 0.05). The repeatability of the sum of recreational and occupational reported activity was high, r = 0.73. CONCLUSIONS: The indices of physical activity derived from this questionnaire have levels of validity and repeatability comparable to other physical activity instruments that are used in large epidemiological studies and which have undergone such intense development and testing.