Effectiveness and cost-effectiveness of an individualised, progressive walking and education intervention for the prevention of low back pain recurrence in Australia (WalkBack): a randomised controlled trial.

BACKGROUND: Recurrence of low back pain is common and a substantial contributor to the disease and economic burden of low back pain. Exercise is recommended to prevent recurrence, but the effectiveness and cost-effectiveness of an accessible and low-cost intervention, such as walking, is yet to be established. We aimed to investigate the clinical effectiveness and cost-effectiveness of an individualised, progressive walking and education intervention to prevent the recurrence of low back pain. METHODS: WalkBack was a two-armed, randomised controlled trial, which recruited adults (aged 18 years or older) from across Australia who had recently recovered from an episode of non-specific low back pain that was not attributed to a specific diagnosis, and which lasted for at least 24 h. Participants were randomly assigned to an individualised, progressive walking and education intervention facilitated by six sessions with a physiotherapist across 6 months or to a no treatment control group (1:1). The randomisation schedule comprised randomly permuted blocks of 4, 6, and 8 and was stratified by history of more than two previous episodes of low back pain and referral method. Physiotherapists and participants were not masked to allocation. Participants were followed for a minimum of 12 months and a maximum of 36 months, depending on the date of enrolment. The primary outcome was days to the first recurrence of an activity-limiting episode of low back pain, collected in the intention-to-treat population via monthly self-report. Cost-effectiveness was evaluated from the societal perspective and expressed as incremental cost per quality-adjusted life-year (QALY) gained. The trial was prospectively registered (ACTRN12619001134112). FINDINGS: Between Sept 23, 2019, and June 10, 2022, 3206 potential participants were screened for eligibility, 2505 (78%) were excluded, and 701 were randomly assigned (351 to the intervention group and 350 to the no treatment control group). Most participants were female (565 [81%] of 701) and the mean age of participants was 54 years (SD 12). The intervention was effective in preventing an episode of activity-limiting low back pain (hazard ratio 0·72 [95% CI 0·60-0·85], p=0·0002). The median days to a recurrence was 208 days (95% CI 149-295) in the intervention group and 112 days (89-140) in the control group. The incremental cost per QALY gained was AU$7802, giving a 94% probability that the intervention was cost-effective at a willingness-to-pay threshold of $28 000. Although the total number of participants experiencing at least one adverse event over 12 months was similar between the intervention and control groups (183 [52%] of 351 and 190 [54%] of 350, respectively, p=0·60), there was a greater number of adverse events related to the lower extremities in the intervention group than in the control group (100 in the intervention group and 54 in the control group). INTERPRETATION: An individualised, progressive walking and education intervention significantly reduced low back pain recurrence. This accessible, scalable, and safe intervention could affect how low back pain is managed. FUNDING: National Health and Medical Research Council, Australia.

Productivity outcomes from chronic pain management interventions in the working age population; a systematic review.

ABSTRACT: Productivity loss because of chronic pain in the working age population is a widespread concern internationally. Interventions for chronic pain in working age adults might be expected to achieve enhanced productivity in terms of reduced costs of workers' compensation insurance, reduced disability support, and improved rates of return to work for injured workers. This would require the use of measures of productivity in the evaluation of chronic pain management interventions. The aim of this review was to identify and interpret the productivity outcomes of randomised controlled trials reported by studies that conducted economic evaluations (eg, cost-effectiveness and cost-utility) of chronic pain management interventions in the working age population published from database inception to March 2023. Econlit, Embase, and Pubmed electronic databases were searched, yielding 12 studies that met the selection criteria. All 12 studies used absenteeism to measure productivity, translating return to work measures into indirect costs. Only one study included return to work as a primary outcome. Ten studies found no statistically significant improvements in productivity-related costs. Despite evidence for reduced pain-related disability after pain management interventions, this review suggests that the use of measures for assessing productivity gains is lacking. Including such measures would greatly assist administrators and payers when considering the broader societal benefits of such interventions.

Effectiveness and cost-effectiveness of a progressive, individualised walking and education program for prevention of low back pain recurrence in adults: statistical analysis plan for the WalkBack randomised controlled trial.

BACKGROUND: Exercise for the prevention of low back pain recurrences is recommended, but under-researched. The effectiveness and cost-effectiveness of a walking program for preventing low back pain recurrence remains unknown. This a priori statistical analysis plan describes the methods of analysis for the WalkBack trial. METHODS: WalkBack is a prospectively registered, pragmatic, randomised controlled trial. The aim is to investigate the effectiveness and cost-effectiveness of a 6-month progressive and individualised walking and education program (intervention) for the prevention of low back pain recurrences, compared to a no-treatment control group. The primary outcome is days to the first recurrence of an episode of activity-limiting low back pain. Key secondary outcomes include days to any recurrence of low back pain, days to a care-seeking recurrence of low back pain, disability level, health-related quality of life, costs associated with low back pain and adverse events. All participants will be followed for a minimum of 12 months. Analysis will follow the intention-to-treat principle. Cox regression is planned to assess the effects for the outcomes of time to activity-limiting, minimal and care-seeking recurrence. Hazard ratios and median survival times with 95% confidence intervals will be calculated. The effect of the intervention on continuous outcomes will be estimated with repeated-measure linear mixed models. An economic evaluation will be performed from the societal perspective for recurrence prevented (yes/no) and quality-adjusted life years. The proportion of adverse events between groups will be compared using Fisher's exact test. DISCUSSION: The WalkBack trial will provide evidence on the effectiveness and cost-effectiveness of a walking intervention to prevent low back pain recurrences. This statistical analysis plan provides transparency on the analysis of the trial. TRIAL REGISTRATION: WalkBack - Effectiveness and cost-effectiveness of a progressive individualised walking and education program for the prevention of a recurrence of low back pain. ACTRN12619001134112 . Date Registered: 14/08/2019.

Health, social and economic implications of adolescent risk behaviours/states: protocol for Raine Study Gen2 cohort data linkage study.

Background: Risk-taking behaviours are a major contributor to youth morbidity and mortality. Vulnerability to these negative outcomes is constructed from individual behaviour including risk-taking, and from social context, ecological determinants, early life experience, developmental capacity and mental health, contributing to a state of higher risk. However, although risk-taking is part of normal adolescent development, there is no systematic way to distinguish young people with a high probability of serious adverse outcomes, hindering the capacity to screen and intervene. This study aims to explore the association between risk behaviours/states in adolescence and negative health, social and economic outcomes through young adulthood. Methods: The Raine Study is a prospective cohort study which recruited pregnant women in 1989-91, in Perth, Western Australia. The offspring cohort (N = 2,868) was followed up at regular intervals from 1 to 27 years of age. These data will be linked to State government health and welfare administrative data. We will empirically examine relationships across multiple domains of risk (for example, substance use, sexual behaviour, driving) with health and social outcomes (for instance, road-crash injury, educational underachievement). Microsimulation models will measure the impact of risk-taking on educational attainment and labour force outcomes. Discussion: Comprehensive preventive child health programmes and policy prioritise a healthy start to life. This is the first linkage study focusing on adolescence to adopt a multi-domain approach, and to integrate health economic modelling. This approach captures a more complete picture of health and social impacts of risk behaviour/​states in adolescence and young adulthood.

Cost-effectiveness of Multidisciplinary Interventions for Chronic Low Back Pain: A Narrative Review.

OBJECTIVE: Chronic musculoskeletal pain in adults is a global health and economic problem. The aim of this paper was to systematically review and determine what proportion of multidisciplinary approaches to managing chronic musculoskeletal pain are cost-effective. MATERIALS AND METHODS: The EconLit, Embase, and PubMed electronic databases were searched for randomized and nonrandomized economic evaluation studies of nonpharmaceutical multidisciplinary chronic pain management interventions published from inception through to August 2019. RESULTS: Seven studies comprising 2095 patients were included. All studies involved diverse multidisciplinary teams in one or more of the study arms. All studies involved chronic (both chronic and subacute) low back pain and were economic evaluations from either a societal or health care perspective. Two of the 3 studies that reported on a multidisciplinary pain intervention compared with nonmultidisciplinary intervention concluded favorable cost-effectiveness based on cost per quality adjusted life years gained, 1 study was not found to be cost-effective. Cost-effectiveness of the multidisciplinary intervention of interest was also not established by another 3-arm study. Two studies compared 2 multidisciplinary interventions; neither of these could definitively declare cost-effectiveness. The remaining study indicated the intervention by a multidisciplinary team was more effective but at a higher cost. None of the included studies used decision models to estimate long-term health outcomes and cost-effectiveness of multidisciplinary programs. DISCUSSION: There are few studies on the cost-effectiveness of multidisciplinary chronic pain management interventions. This study encourages additional rigorous economic evaluations of multidisciplinary models for chronic pain management. Economic evaluations that enable extrapolating costs and effects of multidisciplinary programs beyond the time horizon of clinical trials may be more informative for clinicians and health administrators.

Multi-parametric magnetic resonance imaging assessment of whole tumour heterogeneity for chemoradiotherapy response prediction in rectal cancer.

BACKGROUND AND PURPOSE: Prediction of chemoradiotherapy response (CRT) in locally advanced rectal cancer would enable stratification of management. The purpose was to prospectively evaluate multi-parametric magnetic resonance imaging (MRI) assessment of tumour heterogeneity combining diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE) MRI for the prediction of CRT response in locally advanced rectal cancer. MATERIALS AND METHODS: Patients with Stage II or III rectal adenocarcinoma undergoing neoadjuvant CRT and surgery underwent MRI (DWI and DCE) before, during (week 3), and after CRT (1 week before surgery). Patients with histopathology tumour regression grade (TRG) 0-1 were classified as responders, and TRG 2-3 were classified as non-responders. A whole tumour voxel-wise technique was used to produce apparent diffusion coefficient (ADC) and Ktrans (Tofts model) histograms derived from DWI and DCE-MRI, respectively. Logistic regression was used to predict response status for ADC and Ktrans quantiles. RESULTS: Thirty-three patients were included in this analysis; 16 responders, and 17 non-responders. On heterogeneity analysis, odds of being a responder were significantly higher after CRT (before surgery) for higher ADC 75th (p = 0.049) and ADC 90th (p = 0.034) percentile values. The Ktrans quantiles were lower in non-responders than responders before and during CRT, and higher after CRT although no significant association with response status was observed (p ≥ 0.10). CONCLUSIONS: DWI-MRI after CRT (before surgery) incorporating a histogram analysis of whole tumour heterogeneity was predictive of CRT response in patients with locally advanced rectal cancer. DCE-MRI did not add value in response prediction. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12616001690448.

Daily Pad Usage Versus the International Consultation on Incontinence Questionnaire Short Form for Continence Assessment Following Radical Prostatectomy.

PURPOSE: Continence assessment is an essential component of follow-up after radical prostatectomy (RP). Several methods exist to assess the severity of urinary incontinence (UI). Our study examined the relationship and degree of agreement between International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) scores and the number of pads used in a 24-hour period in the assessment of UI following RP. METHODS: Continence was prospectively assessed in 746 men from a Spanish urology clinic 12 months after RP using the ICIQ-SF and pad usage. The relationship between ICIQ-SF scores and pad usage was assessed using Spearman rank correlation coefficients. The Jonckheere-Terpstra trend test was used to determine whether the ICIQ-SF score and the component question scores increased with increasing pad usage. The Bonferroni-corrected pairwise Wilcoxon rank-sum test was used to determine which pairs of pad usage levels differed. The weighted kappa was used to evaluate the agreement between pad usage levels and ICIQ-SF questions. RESULTS: The continence rate was 82% using the "no pad usage" definition of continence versus 78% using the definition of an ICIQ-SF score of 0 (P<0.001). Strong positive correlations were observed between the number of pads and the ICIQ-SF total and component question scores (rs>0.85, P<0.001). The ICIQ-SF total and component question scores increased significantly with increasing pad usage (P<0.001). The ICIQ-SF scores (P<0.018) for all pairs of pad usage levels (0, 1, 2, or 3 or more) differed significantly. The agreement between the ICIQ-SF leakage amount question and pad usage was very good (rs=0.861, P<0.001). CONCLUSION: At 12 months post-RP, 24-hour pad usage was closely correlated with ICIQ-SF, although the continence rate differed depending on the definition used. Higher levels of pad usage were associated with higher questionnaire scores, more leakage, and poor quality of life (interference with everyday life).

ECMO, ARDS and meta-analyses: Bayes to the rescue?

PURPOSE: A recent meta-analysis by Munshi et al. (Lancet Respiratory Medicine, 2019) claimed mortality treatment efficacy for extra corporeal membrane oxygenation (ECMO) in the acute respitratory syndrome (ARDS) despite very low meta-analytic study numbers (n = 2 (RCTs), risk-ratio (RR) 0·73 (95%CI: 0·58-0·92); n = 5 (2 RCT, 3 observational), RR 0·69 (95%CI: 0·50-0·95)). We explore this efficacy claim by a comprehensive re-analysis of the data. METHODS: Data were sourced from the two- and five-study meta-analyses, conducted using the Der-Simonian & Laird (DSL) method. A variety of frequentist (DSL, restricted maximum likelihood (REML), Paul-Mandel (PM), with/without Hartung-Knapp-Sidik-Jonkman variance correction), a beta-binomial model (BBN)) and Bayesian models (2 finite-mixture and several Markov-Chain-Monte-Carlo) were used to estimate treatment effects. Fragility-indices, the minimum patients changing mortality outcome needed to induce a conclusion change were also applied. RESULTS: For the 2-study and 5-study meta-analysis only the uncorrected frequentist estimators (DSL, REML, PM) demonstrated significant RR. Except for the BBN model, which was significant for the 2-study meta-analysis, intervals for all other models included the null. Both meta-analyses demonstrated fragility. CONCLUSIONS: Having canvassed the conduct of both meta-analyses presented by Munshi et al. and proffered alternative methods, we find no certainty regarding the efficacy of ECMO in ARDS.

Self-assessment of daily hearing function for implant recipients: A comparison of mean total scores for the Speech Spatial Qualities of Hearing Scale (SSQ49) with the SSQ12.

OBJECTIVE: To assess the relationship and agreement between mean total scores for the Speech Spatial Qualities of Hearing Scale (SSQ49) and the shorter SSQ12 to measure daily hearing function for a large group of auditory implant recipients. METHODS: Prospective, longitudinal self-assessment by 1013 implant recipients using the SSQ49 at preimplant and at annual post-implant intervals (one, two and three-years) via an international registry. Mean total scores were calculated for the SSQ49 and the extracted SSQ12 responses. Pearson correlation and Bland-Altman agreement were examined between the SSQ49, SSQ12 and transformed SSQ12 versions. Longitudinal mixed-effects models were used to compare changes over time. RESULTS: Very high correlation was shown between mean total scores for all versions while perfect agreement was not reached. Clinically acceptable agreement (<1.0 unit) between all versions was obtained with the transformed SSQ12 being least biased. All versions showed statistically significant improvement at one-year post-implant (>2.2 units; p < 0.001). CONCLUSIONS: All scale-versions showed comparable sensitivity to changes in self-reported hearing function over time. TheSSQ12 may be considered as a potential time-efficient self-assessment of hearing function for implant recipients in routine practice. Further research may involve independent repeated administration of each scale version.

Updating the evidence for the role of corticosteroids in severe sepsis and septic shock: a Bayesian meta-analytic perspective.

INTRODUCTION: Current low (stress) dose corticosteroid regimens may have therapeutic advantage in severe sepsis and septic shock despite conflicting results from two landmark randomised controlled trials (RCT). We systematically reviewed the efficacy of corticosteroid therapy in severe sepsis and septic shock. METHODS: RCTs were identified (1950-September 2008) by multiple data-base electronic search (MEDLINE via OVID, OVID PreMedline, OVID Embase, Cochrane Central Register of Controlled trials, Cochrane database of systematic reviews, Health Technology Assessment Database and Database of Abstracts of Reviews of Effects) and hand search of references, reviews and scientific society proceedings. Three investigators independently assessed trial inclusion and data extraction into standardised forms; differences resolved by consensus. RESULTS: Corticosteroid efficacy, compared with control, for hospital-mortality, proportion of patients experiencing shock-resolution, and infective and non-infective complications was assessed using Bayesian random-effects models; expressed as odds ratio (OR, (95% credible-interval)). Bayesian outcome probabilities were calculated as the probability (P) that OR ≥1. Fourteen RCTs were identified. High-dose (>1000 mg hydrocortisone (equivalent) per day) corticosteroid trials were associated with a null (n = 5; OR 0.91(0.31-1.25)) or higher (n = 4, OR 1.46(0.73-2.16), outlier excluded) mortality probability (P = 42.0% and 89.3%, respectively). Low-dose trials (<1000 mg hydrocortisone per day) were associated with a lower (n = 9, OR 0.80(0.40-1.39); n = 8 OR 0.71(0.37-1.10), outlier excluded) mortality probability (20.4% and 5.8%, respectively). OR for shock-resolution was increased in the low dose trials (n = 7; OR 1.20(1.07-4.55); P = 98.2%). Patient responsiveness to corticotrophin stimulation was non-determinant. A high probability of risk-related treatment efficacy (decrease in log-odds mortality with increased control arm risk) was identified by metaregression in the low dose trials (n = 9, slope coefficient -0.49(-1.14, 0.27); P = 92.2%). Odds of complications were not increased with corticosteroids. CONCLUSIONS: Although a null effect for mortality treatment efficacy of low dose corticosteroid therapy in severe sepsis and septic shock was not excluded, there remained a high probability of treatment efficacy, more so with outlier exclusion. Similarly, although a null effect was not excluded, advantageous effects of low dose steroids had a high probability of dependence upon patient underlying risk. Low dose steroid efficacy was not demonstrated in corticotrophin non-responders. Further large-scale trials appear mandated.

Extracorporeal membrane oxygenation (ECMO) reconsidered.

The role of extracorporeal membrane oxygenation (ECMO) in the treatment of the acute respiratory distress syndrome (ARDS) is controversial, notwithstanding the recent publication of the results of the CESAR (Conventional Ventilation or ECMO for Severe Adult Respiratory Failure) trial. Using Bayesian meta-analytic methods from three randomised controlled trials (RCTs) of ECMO in ARDS, we estimate the mortality odds ratio to be 0.78 (95% credible interval, 0.25-3.04), P (OR > 1) = 30%. Thus, a null effect of ECMO is not excluded and there appears only weak evidence of efficacy. We survey particular problems associated with the conduct of the "pragmatic" CESAR trial: composite endpoints, sample size estimation under uncertainty of baseline mortality rates, the generation of unbiased treatment comparisons, the impact of treatment non-compliance, and the uncertainty associated with cost-effectiveness and cost-utility analysis. We conclude that the CESAR trial is problematic in terms of both the clinical and economic outcomes, although observational series suggest plausible efficacy. We suggest that ECMO finds rationale as rescue therapy and that the current uncertainty of its role mandates a further RCT.

Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis.

OBJECTIVE: To systematically review the efficacy of steroids in the prevention of acute respiratory distress syndrome (ARDS) in critically ill adults, and treatment for established ARDS. DATA SOURCES: Search of randomised controlled trials (1966-April 2007) of PubMed, Cochrane central register of controlled trials, Cochrane database of systematic reviews, American College of Physicians Journal Club, health technology assessment database, and database of abstracts of reviews of effects. DATA EXTRACTION: Two investigators independently assessed trials for inclusion and extracted data into standardised forms; differences were resolved by consensus. DATA SYNTHESIS: Steroid efficacy was assessed through a Bayesian hierarchical model for comparing the odds of developing ARDS and mortality (both expressed as odds ratio with 95% credible interval) and duration of ventilator free days, assessed as mean difference. Bayesian outcome probabilities were calculated as the probability that the odds ratio would be > or =1 or the probability that the mean difference would be > or =0. Nine randomised trials using variable dose and duration of steroids were identified. Preventive steroids (four studies) were associated with a trend to increase both the odds of patients developing ARDS (odds ratio 1.55, 95% credible interval 0.58 to 4.05; P(odds ratio > or =1)=86.6%), and the risk of mortality in those who subsequently developed ARDS (three studies, odds ratio 1.52, 95% credible interval 0.30 to 5.94; P(odds ratio > or =1)=72.8%). Steroid administration after onset of ARDS (five studies) was associated with a trend towards reduction in mortality (odds ratio 0.62, 95% credible interval 0.23 to 1.26; P(odds ratio > or =1)=6.8%). Steroid therapy increased the number of ventilator free days compared with controls (three studies, mean difference 4.05 days, 95% credible interval 0.22 to 8.71; P(mean difference > or =0)=97.9%). Steroids were not associated with increase in risk of infection. CONCLUSIONS: A definitive role of corticosteroids in the treatment of ARDS in adults is not established. A possibility of reduced mortality and increased ventilator free days with steroids started after the onset of ARDS was suggested. Preventive steroids possibly increase the incidence of ARDS in critically ill adults.

The efficacy of loop diuretics in acute renal failure: assessment using Bayesian evidence synthesis techniques.

OBJECTIVE: To quantify the therapeutic efficacy of loop diuretics in acute renal failure using Bayesian evidence synthesis, because despite widespread use, the role of diuretics is controversial. DATA SOURCE: Randomized controlled trials or nonrandomized studies, 1966 to January 2007, identified from MEDLINE and EMBASE databases and manual bibliographic search. STUDY SELECTION: Studies with assessable predefined end points, exclusive of those pertaining to acute renal failure prophylaxis or chronic renal failure. DATA EXTRACTION: Data extraction was performed jointly by the first two authors; independent study assessment was via standard checklist, unblinded. DATA SYNTHESIS: The primary outcome was mortality; secondary outcomes were time to renal function normalization and total number of dialyses. Bayesian hierarchical random effects estimates of treatment effects were determined as risk ratio for mortality, incidence rate ratio for dialysis number, and mean difference for continuous measures. Bayesian outcome probabilities were calculated as probability (P) that risk ratio or incidence rate ratio of loop diuretics >1 and probability that mean difference >0. Five randomized controlled trials and eight nonrandomized studies were identified. Loop diuretics were not associated with decreased mortality in either randomized controlled trials or nonrandomized studies: overall risk ratio 1.10; 95% credible interval 0.85, 1.42; P(risk ratio >1) > 83.8%. The oliguric period was decreased by loop diuretics: overall mean difference -7.70 days; 95% credible interval -12.51, -2.08; P (mean difference >0) = 0.7%. Although the dialysis rate credible interval, loop diuretics vs. control, spanned unity (incidence rate ratio 0.71; 95% credible interval 0.47, 1.06), the probability that the incidence rate ratio exceeded unity indicated a substantial benefit: P (incidence rate ratio >1 = 4.1%. Uremic duration was not substantially different, loop diuretics vs. control: overall mean difference -1.54 days; 95% credible interval -5.62, 2.46; P [mean difference >0] = 17.8%). CONCLUSIONS: Loop diuretics were not associated with improved survival benefit in acute renal failure, despite reduction in oliguric period and high probability of a significant reduction in dialysis numbers. Further studies to clarify this dichotomy appear mandated.

Prediction of risk of death using 30-day outcome: a practical end point for quality auditing in intensive care.

STUDY OBJECTIVE: To validate the APACHE (acute physiology and chronic health evaluation) III unadjusted and similar hospital mortality estimate models on 30-day mortality, and to propose a simple approach to modeling local 30-day in-hospital mortality of critically ill hospitalized adults for quality management and risk-adjusted monitoring. DESIGN: Noninterventional, observational study. PATIENTS: A total of 5,278 consecutive eligible hospital admissions between January 1, 1995, and December 31, 1999. MEASUREMENTS: Prospective collection of demographic, diagnostic, physiologic, laboratory, and hospital admission and discharge data. RESULTS: The APACHE III mortality predictions exhibited excellent discrimination (receiver operating characteristic [ROC] curve area) for 30-day outcome (ROC area, 0.89) and hospital outcome (ROC area, 0.89). Calibration curves and Hosmer-Lemeshow statistics demonstrated good calibration of all models on 30-day outcome, except for the unadjusted APACHE III model. New, simplified risk adjustment models showed good discrimination and calibration on development and test data. ROC areas were 0.88 (developmental data) and 0.87 (test data), and the new model calibration was equivalent to the APACHE III model. CONCLUSION: For quality audit, 30-day in-hospital mortality can be used as an alternative outcome to survival to hospital discharge. New logistic regression models provide evidence that local models, possessing good calibration and discrimination, may be built from a few explanatory variables.