Transtibial osseointegration following unilateral traumatic amputation: An observational study of patients with at least two years follow-up.

IMPORTANCE: Most patients use a traditional socket prosthesis (TSP) to ambulate independently following transtibial amputation. However, these patients generally require prosthesis repairs more than twice annually and an entirely new prosthesis every two years. Furthermore, transtibial amputation patients have four times the skin ulceration rate of transfemoral patients, prompting more frequent prosthesis refitting and diminished use. Trans-Tibial osseointegration (TTOI) is a promising technique to address the limitations of TSP, but remains understudied with only four cohorts totaling 41 total procedures reported previously. Continued concerns regarding the risk of infection and questions as to functional capacity postoperatively have slowed adoption of TTOI worldwide. OBJECTIVE: This study reports the changes in mobility, quality of life (QOL), and the safety profile of the largest described cohort of patients with unilateral TTOI following traumatic amputation. DESIGN: Retrospective observational cohort study. The cohort consisted of patients with data outcomes collected before and after osseointegration intervention. SETTING: A large, tertiary referral, major metropolitan center. PARTICIPANTS: Twenty-one skeletally mature adults who had failed socket prosthesis rehabilitation, with at least two years of post-osseointegration follow-up. MAIN OUTCOMES AND MEASURES: Mobility was evaluated by K-level, Timed Up and Go (TUG), and Six Minute Walk Test (6MWT). QOL was assessed by survey: daily prosthesis wear hours, prosthesis problem experience, general contentment with prosthesis, and Short Form 36 (SF36). Adverse events included any relevant unplanned surgery such as for infection, fracture, implant loosening, or implant failure. RESULTS: All patients demonstrated statistically significant improvement post osseointegration surgery with respect to K-level, TUG, 6MWT, prosthesis wear hours, prosthesis problem experience, general prosthesis contentment score, and SF36 Physical Component Score (p < 0.01 for all). Three patients had four unplanned surgeries: two soft tissue refashionings, and one soft tissue debridement followed eventually by implant removal. No deaths, postoperative systemic complications, more proximal amputations, or periprosthetic fractures occurred. CONCLUSIONS AND RELEVANCE: TTOI is likely to confer mobility and QOL improvements to patients dissatisfied with TSP rehabilitation following unilateral traumatic transtibial amputation. Adverse events are relatively infrequent and not further disabling. Judicious use of TTOI seems reasonable for properly selected patients. LEVEL OF EVIDENCE: 2 (Therapeutic investigation, Observational study with dramatic effect).

Long-term Efficacy of Percutaneous Epidural Neurolysis of Adhesions in Chronic Lumbar Radicular Pain: 10 Year Follow-up of a Randomized Controlled Trial.

BACKGROUND: No long-term follow-up data exist in any treatment for chronic radicular pain occurring with disc pathology and after failed back surgery. A previous randomized controlled trial (RCT) has proven efficacy in short-term follow-up as an evidence-based effective therapeutic option. OBJECTIVES: Long term data is needed to determine the efficacy and cost- effectiveness of minimal invasive procedures. The present study reports 10 year follow-up results from the randomized trial. STUDY DESIGN: A prospective, randomized, placebo-controlled, interventional clinical trial. A power calculation was based on a previous feasibility trial. SETTING: University medical centers. METHODS: After a 4 year enrollment phase, 381 patients with chronic radicular pain persisting beyond 4 months, who failed conservative treatments, were screened. Ninety patients were enrolled. Patients were randomly assigned to receive percutaneous epidural lysis of adhesions or placebo with concealed allocation in permuted blocks of 4 to 8 patients each, and stratified by treatment center. The primary outcomes were a mean change of the Oswestry Disability Index (ODI) scores and Visual Analog Scale (VAS), one and 10 years after intervention. For each rating scale an analysis of variance with the within-patient factor time (baseline, one year follow-up, 10 year follow-up) and the between-patient factor treatment (lysis, placebo) was used. RESULTS: Homogeneity was shown at baseline between the groups. The ODI and VAS scores were significantly better one and 10 years in the lysis group vs the control group. The ODI in the lysis group improved from 55.3 ± 11.6 to 9.6 ± 9.3 after one year and to 11.7 ± 14.2 after 10 years. The placebo group also improved from 55.4 ± 11.5 to 30.7 ± 14.2 after one year and to 24.8 ± 12.0 after 10 years. The VAS improved from 6.7 ± 1.1 to 1.2 ± 1.1 after one year and to 1.5 ± 1.4 after 10 years in the lysis group and from 6.7 ± 1.1 to 2.8 ± 1.5 after one year and to 2.9 ± 1.3 after 10 years after placebo intervention. The statistical difference of the ODI and VAS between the treatment and control groups remain significant up to 10 years. No treatment-related severe adverse effects occurred within the 10 years, but minor transient neurological effects were seen directly after the intervention. LIMITATIONS: The long-term effects of single treatment components cannot be specified as no imaging examination was performed at 10 year follow-up. A large variety of unanalyzed noninvasive treatments were done within the 10 years. Some patients did not clearly remember the intervention after 10 years. Uncontrolled effects such as higher inhomogeneity of biometric properties, concomitant therapies, pain tolerance level, or just social effects could occur, but were not analyzed in the trial. CONCLUSION: This is the first 10 year follow-up report of a placebo-controlled RCT showing efficacy of the minimally invasive percutaneous adhesiolysis procedure for patients with chronic lumbosacral radicular pain. No alternative evidence-based treatment modality with 10 year follow-up is available to be recommended. This procedure should be considered as the first treatment option for patients with chronic lumbosacral radicular pain.

Two-Stage Osseointegrated Reconstruction of Post-traumatic Unilateral Transfemoral Amputees.

A new technique called osseointegration was introduced recently by intimately connecting the artificial limb prosthesis to the residual bone, eliminating the problematic socket-residuum interface. The objective here is to describe the two-stage strategy for the osseointegrated reconstruction of amputated limbs and discuss the clinical outcomes of the procedure. This is a prospective case series of 37 post-traumatic unilateral transfemoral amputees with a minimum 2-yr follow-up. Outcome measures included the Questionnaire for persons with a Transfemoral Amputation (Q-TFA), the Short Form Health Survey 36 (SF-36), the 6 Minute Walk Test (6MWT), and Timed Up and Go (TUG) tests. Adverse events including infection, revision surgery, fractures, and implant failures were reported. Clinical outcomes for all outcome measures were significantly improved at follow-up. Twelve participants were wheelchair bound pre-operatively; however, all 12 were able to ambulate after osseointegrated reconstruction. Sixteen patients experienced infection episodes but were managed successfully without the need for implant removal. One periprosthetic fracture occurred due to increased activity, which was revised successfully. These results confirm that the procedure is a suitable alternative for post-traumatic unilateral transfemoral amputees experiencing socket-related discomfort, with the potential to reduce recovery time compared with other treatment protocols.

Randomized Placebo-Controlled Placebo Trial to Determine the Placebo Effect Size.

BACKGROUND: It is the gold standard to use a placebo treatment as the control group in prospective randomized controlled trials (RCTs). Although placebo-controlled trials can reveal an effect of an active treatment, the pure effect of a placebo treatment alone has never been presented or evaluated. No evidence-based, placebo-therapeutic options are currently available, and no placebo-controlled trials have been performed to elucidate the pure placebo effect. OBJECTIVES: To analyze the pure placebo effect on clinical, chronic pain through a blinded RCT. STUDY DESIGN: A prospective, randomized, placebo-controlled trial. SETTING: Medical University centers. METHODS: One-hundred eighty-two patients suffering from chronic plantar heel pain for over 6 months,who failed to respond to conservative treatments, were screened and 106 of these patients were enrolled into this study. The patients were randomly assigned to receive either a blinded placebo shockwave treatment or an unblinded placebo shockwave treatment. The primary outcome measure was the differences in percentage change of visual analogue scale (VAS) scores 6 weeks after the intervention. The secondary outcome measure was the differences in Roles and Maudsley pain score (RMS) 6 weeks after intervention. As an exploratory outcome, 2-sided group comparisons for baseline characteristics between active treatment and controls were done using the Mann-Whitney-U tests for group comparisons; treatment efficiency was calculated by the effect size coefficient and benchmarks for the Mann-Whitney estimator according to the t-test of 2 independent samples for quantitative data, as well as the Fisher's exact test for binary data. RESULTS: Patients from both groups did not differ with respect to heel pain ratings at baseline, for both the VAS (P = .476) and RMS (P = .810) scores. After 6 weeks, patients receiving the blinded placebo treatment reported less heel pain on both scales (VAS: P = .031; RMS: P = .004). Change scores of pain ratings were significantly higher in the blinded placebo group than in the un-blinded placebo group (VAS: P = .002; RMS: P = .002). LIMITATIONS: As the study represents the first to use an inverse placebo RCT (IPRCT), further conceptual and methodological issues need to be addressed to describe detailed, underlying mechanisms. Specific contextual, intrapersonal, and interpersonal factors modulating the placebo effects should be addressed in future IPRCTs. CONCLUSIONS: The present study indicated that true placebo effect sizes can be analyzed through a proper IPRCT design. Instead of treating high numbers of patients with placebos in a RCT, which increases the risk for subjects not receiving the active treatment, the IPRCT technique seems to be much more appropriate to analyze the effect sizes of any active treatment, in accordance with the Good Clinical Practice guidelines and Declarations of Helsinki. KEY WORDS: Pain, randomized controlled trial, RCT, placebo, effect size, inverse placebo, study, pain therapy.

Percutaneous epidural lysis of adhesions in chronic lumbar radicular pain: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Chronic radicular pain can occur after disc pathology and failed back surgery. An evidence-based effective therapeutic option is not available nor does a gold standard exist. OBJECTIVES: A randomized controlled trial to analyze the clinical efficacy of percutaneous epidural lysis of adhesions in chronic radicular pain. STUDY DESIGN: Prospective randomized placebo controlled interventional trial. Power calculation based on a feasibility trial. SETTING: Medical university centers. METHODS: Within 4 years a total of 381 patients with chronic radicular pain lasting longer than 4 months which failed to respond to conservative treatments were screened and 90 patients were enrolled. They were randomly assigned to receive either percutaneous neurolysis or placebo with concealed allocation in permuted blocks of 4 to 8, stratified by treatment center. The primary outcome measure was the differences in percent change of Oswestry Disability Index (ODI) scores 3 months after intervention. Secondary outcome measures were difference in percent change of ODI scores and Visual Analog Scale (VAS) 6 and 12 months after intervention and success rates defined as at least 50% reduction in ODI scores and VAS scores (mean change from baseline) at 3, 6, and 12 months after treatment. Explorative, 2-sided group comparisons for baseline characteristics between active treatment and controls were done using the t-test for 2 independent samples for quantitative data and Fisher's exact test for binary data. RESULTS: The ODI and VAS scores as well as the success rates for ODI vs VAS were significantly better 3, 6, and 12 months in the lysis group vs the control group. The ODI in the lysis group improved from 55.3 ± 11.6 to 26.4 ± 10.8 after 3 months. The placebo group improved from 55.4 ± 11.5 to 41.8 ± 14.6 (P < 0.01). VAS improved from 6.7 ± 1.1 to 2.9 ± 1.9 in the active group and from 6.7 ± 1.1 to 4.8 ± 2.2 (P < 0.01) after placebo. Twelve month follow-up shows further improvement, the differences remain significant. In multiple linear regression, forward and backward variable selection methods resulted in the same covariate model confirming the univariate result for group comparison in the primary analysis. No severe side effects occurred but minor transient neurological effects such as partial sensomotoric deficits did. One dura puncture and one catheter displacement were found. LIMITATIONS: Specific effects of single treatment components cannot be specified because there was no imaging examination after treatment. CONCLUSION: Based on the findings of our study as well as other studies, we believe the minimally invasive percutaneous adhesiolysis procedure should be the first choice treatment option for patients with chronic lumbosacral radicular pain who present with clinical history and findings similar to those of the patients enrolled in our study.