Justin Paoloni

Topical glyceryl trinitrate treatment of chronic noninsertional achilles tendinopathy: A randomized, double-blind, placebo-controlled trial

BACKGROUND Noninsertional Achilles tendinopathy is a degenerative overuse disorder. No method has been universally successful in treating this condition. Topically applied nitric oxide has been shown, in animal models, to be effective for the treatment of fractures and cutaneous wounds through mechanisms that may include stimulation of collagen synthesis in fibroblasts. The goal of the present study was to determine if topical glyceryl trinitrate improves clinical outcome measures in patients with Achilles tendinopathy. METHODS A prospective, randomized, double-blind, placebo-controlled trial involving a total of sixty-five patients (eighty-four Achilles tendons) was performed to compare continuous application of topical glyceryl trinitrate (at a dosage of 1.25 mg per twenty-four hours) with rehabilitation alone for the treatment of noninsertional Achilles tendinopathy. RESULTS Compared with the control group, the glyceryl trinitrate group showed reduced pain with activity at twelve weeks (p = 0.02) and twenty-four weeks (p = 0.03), reduced night pain at twelve weeks (p = 0.04), reduced tenderness at twelve weeks (p = 0.02), decreased pain scores after the hop test at twenty-four weeks (p = 0.005), and increased ankle plantar flexor mean total work compared with the baseline level at twenty-four weeks (p = 0.04). Twenty-eight (78%) of thirty-six tendons in the glyceryl trinitrate group were asymptomatic with activities of daily living at six months, compared with twenty (49%) of forty-one tendons in the placebo group (p = 0.001, chi-square analysis). The mean effect size for all outcome measures was 0.14. CONCLUSIONS Topical glyceryl trinitrate significantly reduced pain with activity and at night, improved functional measures, and improved outcomes in patients with Achilles tendinopathy.

Topical Nitric Oxide Application in the Treatment of Chronic Extensor Tendinosis at the Elbow A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial

Background: Extensor tendinosis (“tennis elbow”) is a degenerative overuse tendinopathy of the wrist extensors at their attachment to the lateral humeral epicondyle. No treatment has been universally successful. Topical application of nitric oxide has been used effectively to treat fractures and cutaneous wounds in animal models, presumably by stimulation of collagen synthesis in fibroblasts. Purpose: To determine whether topical nitric oxide can improve outcome of patients with extensor tendinosis. Study Design: Prospective, randomized, double-blinded clinical trial. Methods: Eighty-six patients with extensor tendinosis were randomized into two equal groups; both were instructed to perform a standard tendon rehabilitation program. One group received an active glyceryl trinitrate transdermal patch, and the other group received a placebo patch. Results: Patients in the glyceryl trinitrate group had significantly reduced elbow pain with activity at 2 weeks, reduced epicondylar tenderness at 6 and 12 weeks, and an increase in wrist extensor mean peak force and total work at 24 weeks. At 6 months, 81% of treated patients were asymptomatic during activities of daily living, compared with 60% of patients who had tendon rehabilitation alone. Conclusions: Application of topical nitric oxide improved early pain with activity, late functional measures, and outcomes of patients with extensor tendinosis.

Topical Glyceryl Trinitrate Application in the Treatment of Chronic Supraspinatus Tendinopathy A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial

Background Topical glyceryl trinitrate therapy has previously demonstrated short-term pain reduction in patients with supraspinatus tendinopathy. Hypothesis Topical glyceryl trinitrate improves outcome measures in patients with supraspinatus tendinopathy. Study Design Randomized controlled clinical trial; Level of evidence, 1. Methods Fifty-three patients (57 shoulders) were recruited, and the authors completed a prospective, randomized, double-blinded, placebo-controlled clinical trial of continuous topical glyceryl trinitrate treatment (1.25 mg/24-h glyceryl trinitrate). Results The glyceryl trinitrate group had significantly reduced shoulder pain with activity, at night, and at rest at week 24 (P =. 03); reduced internal rotation impingement at week 24 (P =. 02); increased range of motion in abduction and internal rotation at week 24 (P =. 04); and increased force at weeks 12 and 24 with supraspinatus muscle testing (P =. 001), external rotation (P =. 04), internal rotation (P =. 01), adduction (P =. 04), and subscapularis pushoff (P =. 01). Forty-six percent of patients on glyceryl trinitrate patches were asymptomatic with activities of daily living at 6 months compared with 24% of patients with tendon rehabilitation alone (P =. 007, χ2 analysis). Mean effect size for all outcome measures was 0.26. Discussion Topical glyceryl trinitrate treatment significantly improved pain scores, range of motion, internal rotation impingement, muscular force, and patient outcomes in patients with supraspinatus tendinopathy. Topical glyceryl trinitrate should be included as part of nonsurgical management of chronic tendinopathies.

Platelet-rich plasma treatment for ligament and tendon injuries.

Platelet-rich plasma (PRP) is derived from centrifuging whole blood, has a platelet concentration higher than that of the whole blood, is the cellular component of plasma that settles after centrifugation, and contains numerous growth factors. There is increasing interest in the sports medicine and athletic community about providing endogenous growth factors directly to the injury site, using autologous blood products such as PRP, to potentially facilitate healing and earlier return to sport after musculoskeletal injury. Despite this interest, and apparent widespread use, there is a lack of high-level evidence regarding randomized clinical trials assessing the efficacy of PRP in treating ligament and tendon injuries. Basic science and animal studies and small case series reports on PRP injections for ligament or tendon injuries, but few randomized controlled clinical trials have assessed the efficacy of PRP injections and none have demonstrated scientific evidence of efficacy. Scientific studies should be performed to assess clinical indications, efficacy, and safety of PRP, and this will require appropriately powered randomized controlled trials with adequate and validated clinical and functional outcome measures and sound statistical analysis. Other aspects of PRP use that need to be determined are (1) volume of injection/application, (2) most effective preparation, (3) buffering/activation, (4) injection technique (1 depot vs multiple depots), (5) timing of injection to injury, (6) single application versus series of injections, and (7) the most effective rehabilitation protocol to use after PRP injection. With all proposed treatments, the doctor and the patient should weigh up potential benefits of treatment, potential risks, and costs. Based on the limited publications to date and theoretical considerations, the potential risks involved with PRP are fortunately very low. However, benefits remain unproven to date, particularly when comparing PRP with other injections for ligament and tendon injuries.

Three-year Followup Study of Topical Glyceryl Trinitrate Treatment of Chronic Noninsertional Achilles Tendinopathy

Background: Topical glyceryl trinitrate treatment has demonstrated short-term efficacy in chronic noninsertional Achilles tendinopathy. No long-term followup is reported. We aimed to assess if the demonstrated efficacy of this treatment persisted 3 years after discontinuation of therapy. Methods: A followup study of 52 patients (68 tendons) treated with 6 months of glyceryl trinitrate therapy or placebo was performed 3 years after cessation of therapy. Assessment included pain scores, return to previous activity, the Victorian Institute of Sport Achilles tendon scale (VISA-A), asymptomatic patient outcomes, clinical assessment of tendon tenderness, and functional hop test. Results: Patients treated with topical glyceryl trinitrate had significantly less Achilles tendon tenderness (p = 0.03), and improved VISA-A scores (p = 0.04) than those in the placebo group; 88% (28 of 32 tendons) of patients were completely asymptomatic at 3 years (VISA-A score of 100) compared to 67% (24 of 36 tendons) of patients treated with rehabilitation alone (p = 0.03 with Chi square analysis). Other outcome measures showed nonsignificant trends towards improvement in the glyceryl trinitrate group (pain scores p = 0.07, functional hop test p = 0.07, and return to sport p = 0.16). The mean estimated effect size for all outcome measures was 0.21. Conclusions: Topical glyceryl trinitrate treatment has demonstrated efficacy in treating chronic noninsertional Achilles tendinopathy, and the treatment benefits continue at 3 years. Significant differences in asymptomatic patient outcomes for the glyceryl trinitrate group continue at 3 years, and this is confirmed by the effect size estimate. This suggests that the mechanism of action of topical glyceryl trinitrate on chronic tendinopathies is more than an analgesic effect.

Randomised, double-blind, placebo-controlled clinical trial of a new topical glyceryl trinitrate patch for chronic lateral epicondylosis

Objective: This study aimed to determine whether a new glyceryl trinitrate patch preparation is effective in treating chronic lateral epicondylosis. Design: Randomised double-blind controlled clinical trial. Setting: Private practice patients: 154 adult patients with chronic lateral epicondylosis were recruited, with 136 patients completing the trial. Interventions: 8 weeks of glyceryl trinitrate patch application (dosages of 72 mg/24 h, 1.44 mg/24 h, and 3.6 mg/24 h), or placebo patch application. Main outcome measures: Subjective global assessment of change in elbow symptoms, patient-rated tennis elbow evaluation, visual analogue pain at rest, visual analogue pain with activity, visual analogue pain intensity, grip strength, and strength testing using the Orthopaedic Research Institute-Tennis Elbow Testing System. Results: At 8 weeks there was a significant decrease in elbow pain with activity in the glyceryl trinitrate 0.72 mg/24 h group compared with placebo (p = 0.04). There were no other significant differences. Conclusions: Continuous 1.25 mg/24 h topical glyceryl trinitrate treatment, when combined with daily exercise rehabilitation, has previously demonstrated efficacy in treating chronic lateral epicondylosis. There was significantly decreased elbow pain with activity at 8 weeks in the glyceryl trinitrate 0.72 mg/24 h group (p = 0.04). This short-term dose-ranging study did not demonstrate a treatment effect of a new topical glyceryl trinitrate patch in dosages of 1.44 mg/24 h or 3.6 mg/24 h, which conflicts with previous studies on topical glyceryl trinitrate treatment. Trial registration number: NCT00447928.

Cricket fast bowling workload patterns as risk factors for tendon, muscle, bone and joint injuries

Objective To assess workload-related risk factors for injuries to particular tissue types in cricket fast bowlers. Design 235 fast bowlers who bowled in 14600 player innings over a period of 15 years were followed in a prospective cohort risk factor study to compare overs bowled in each match (including preceding workload patterns) and injury risk in the 3–4 weeks subsequent to the match. Injuries were categorised according to the affected tissue type as either: bone stress, tendon injuries, muscle strain or joint injuries. Workload risk factors were examined using binomial logistic regression multivariate analysis, with a forward stepwise procedure requiring a significance of <0.05. Results High acute match workload and high previous season workload were risk factors for tendon injuries, but high medium term (3-month workload) was protective. For bone stress injuries, high medium term workload and low career workload were risk factors. For joint injuries, high previous season and career workload were risk factors. There was little relationship between muscle injury and workload although high previous season workload was slightly protective. Conclusions The level of injury risk for some tissue types varies in response to preceding fast bowling workload, with tendon injuries most affected by workload patterns. Workload planning may need to be individualised, depending on individual susceptibility to various injury types. This study supports the theory that tendons are at lowest risk with consistent workloads and susceptible to injury with sudden upgrades in workload. Gradual upgrades are recommended, particularly at the start of a bowlers career to reduce the risk of bone stress injury.

Five-year prospective comparison study of topical glyceryl trinitrate treatment of chronic lateral epicondylosis at the elbow

Background Topical glyceryl trinitrate (GTN) treatment has previously demonstrated short-term efficacy in the treatment of lateral epicondylosis. No long-term follow-up has been performed. Hypothesis Benefits from topical GTN persist 5 years after the cessation of therapy. Study design A prospective comparative study. Methods A follow-up study of 58 patients treated with 6 months of topical GTN or placebo, combined with a tendon rehabilitation programme, was performed 5 years after discontinuation of therapy. Assessment included patient-rated pain scores, clinically assessed lateral epicondylar and proximal common extensor tendon tenderness, hand-held dynamometer measurement of resisted third finger metacarpophalangeal extension with a fully extended elbow (Maudsleys test) and wrist extensor tendon mean peak force using a modified chair pick-up test (the Orthopaedic Research Institute—tennis elbow testing system). Results Patients in both the GTN group and those in the placebo group had significant improvements in symptoms, clinical signs and provocative functional tests compared with baseline week 0 measures. GTN did not offer any additional clinical benefit over a standard tendon rehabilitation programme at 5 years. Conclusion While GTN appears to offer short-term benefits up to 6 months in the treatment of lateral epicondylosis, at 5 years there does not appear to be significant clinical benefits when compared with patients undertaking a standard tendon rehabilitation programme alone. This is in contrast to findings of continued benefits at long-term follow-up described in the literature for patients with Achilles tendinopathy treated with GTN.

Fast bowling match workloads over 5-26 days and risk of injury in the following month

OBJECTIVES This study examined whether high match fast bowling workloads in the short to medium term were associated with increased bowling injury rates. DESIGN Prospective cohort study. METHODS Over a 15 year period, workload patterns for 235 individual fast bowlers during time periods from 5 to 26 days were examined to consider whether there was an increased injury rate during the month (28 days) subsequent to the workload. RESULTS Fast bowlers who bowled more than 50 match overs in a 5 day period had a significant increase in injury over the next month compared to bowlers who bowled 50 overs or less RR 1.54 (95% CI 1.04-2.29). For periods ranging from 12 to 26 days, there was no statistically-significant increase in injury over the next month from exceeding thresholds of certain amounts of overs, although bowlers who bowled more than 100 overs in 17 days had a non-significant increase in injury over the next month RR 1.78 (95% CI 0.90-3.50). CONCLUSION There were no statistically-significant increases in subsequent injury risk for high workloads for periods of 12-26 days, although exceeding 100 overs in 17 days (or less) was associated with higher injury rates. Compression of cricket fixtures is likely to have only a minimal contribution to increased fast bowling injury rates being seen in the T20 era (along with sudden workload increases due to transferring between forms of the game, which has been previously established as a major contributor).

Identification of prognostic indicators for patient outcomes in extensor tendinopathy at the elbow

Extensor tendinopathy is a degenerative overuse condition involving the common extensor tendon at the lateral humeral epicondyle. The diagnosis and management of this condition are clinically based. Our aims were to determine if through patient history and clinical examination we could ascertain prognostic factors affecting time to symptom resolution in extensor tendinopathy. Symptomatic patients (N=28) had a thorough history and examination, and rehabilitation monitored regularly for 6 months. Patient outcomes at 6 months were then correlated with specific factors on initial presentation. Factors implicated as having prognostic significance regarding patient outcomes were a current history of manual work (P=0.04, effect size −0.29), and a current history of weekly participation in racquet sports (P=0.01, effect size −0.41). These individual factors had a significantly decreased chance of symptom resolution at the 6‐month stage, and when combined had an effect size of −0.6 (P=0.001). Negative patient outcomes may be related to current high and repetitive levels of tendon stress, and rest from recreational and occupational use of wrist extensor tendons may be necessary to enhance the chances of complete symptom resolution. Enforced rest has monetary and quality‐of‐life implications, but is probably preferable to an incomplete recovery and prolonged tendon pain and dysfunction.