Winston J. Warme

Commercially Funded and United States-Based Research Is More Likely to Be Published; Good-Quality Studies with Negative Outcomes Are Not

BACKGROUND Prior studies implying associations between receipt of commercial funding and positive (significant and/or pro-industry) research outcomes have analyzed only published papers, which is an insufficiently robust approach for assessing publication bias. In this study, we tested the following hypotheses regarding orthopaedic manuscripts submitted for review: (1) nonscientific variables, including receipt of commercial funding, affect the likelihood that a peer-reviewed submission will conclude with a report of a positive study outcome, and (2) positive outcomes and other, nonscientific variables are associated with acceptance for publication. METHODS All manuscripts about hip or knee arthroplasty that were submitted to The Journal of Bone and Joint Surgery, American Volume, over seventeen months were evaluated to determine the study design, quality, and outcome. Analyses were carried out to identify associations between scientific factors (sample size, study quality, and level of evidence) and study outcome as well as between non-scientific factors (funding source and country of origin) and study outcome. Analyses were also performed to determine whether outcome, scientific factors, or nonscientific variables were associated with acceptance for publication. RESULTS Two hundred and nine manuscripts were reviewed. Commercial funding was not found to be associated with a positive study outcome (p = 0.668). Studies with a positive outcome were no more likely to be published than were those with a negative outcome (p = 0.410). Studies with a negative outcome were of higher quality (p = 0.003) and included larger sample sizes (p = 0.05). Commercially funded (p = 0.027) and United States-based (p = 0.020) studies were more likely to be published, even though those studies were not associated with higher quality, larger sample sizes, or lower levels of evidence (p = 0.24 to 0.79). CONCLUSIONS Commercially funded studies submitted for review were not more likely to conclude with a positive outcome than were nonfunded studies, and studies with a positive outcome were no more likely to be published than were studies with a negative outcome. These findings contradict those of most previous analyses of published (rather than submitted) research. Commercial funding and the country of origin predict publication following peer review beyond what would be expected on the basis of study quality. Studies with a negative outcome, although seemingly superior in quality, fared no better than studies with a positive outcome in the peer-review process; this may result in inflation of apparent treatment effects when the published literature is subjected to meta-analysis.

Treatment of osseous defects associated with anterior shoulder instability.

Bone loss of the glenoid and/or humerus is a common consequence of traumatic anterior shoulder instability and can be a cause of recurrent instability after a Bankart repair. Accurate characterization of the size and location of osseous defects associated with traumatic instability is important when planning treatment. Open or arthroscopic soft tissue repairs are usually sufficient when less than 25% of the width of the glenoid bone has been lost. Bone replacement techniques may be necessary when glenoid bone loss is greater than 25% of the glenoid width. Glenoid bone restoration techniques include the use of a tricortical iliac crest graft or the transfer of the coracoid process to the area of glenoid deficiency. Bone grafting becomes a strong consideration when soft tissue repairs have failed to restore stability. Treatment of these severe defects may be followed by osteoarthritis. The destabilizing effects of anterior glenoid bone defects are compounded by concurrent defects of the posterior-lateral humeral head, commonly known as Hill-Sachs lesions, which can engage the glenoid defect. Large humeral head defects can be treated by transhumeral bone grafting techniques or osteoarticular allograft reconstruction. Prosthetic replacement of the proximal humerus is considered for humeral head defects involving more than 40% of the articular surface. Understanding the importance of humeral and glenoid bone deficiencies may help guide the treatment of recurrent anterior glenohumeral instability.

Prognostic Factors for Bacterial Cultures Positive for Propionibacterium acnes and Other Organisms in a Large Series of Revision Shoulder Arthroplasties Performed for Stiffness, Pain, or Loosening

BACKGROUND Propionibacterium acnes has been grown on culture in half of the reported cases of chronic infection associated with shoulder arthroplasty. The presence of this organism can be overlooked because its subtle presentation may not suggest the need for culture or because, in contrast to many orthopaedic infections, multiple tissue samples and weeks of culture incubation are often necessary to recover this organism. Surgical decisions regarding implant revision and antibiotic therapy must be made before the results of intraoperative cultures are known. In the present study, we sought clinically relevant prognostic evidence that could help to guide treatment decisions. METHODS We statistically correlated preoperative and intraoperative observations on 193 shoulder arthroplasty revisions that were performed because of pain, loosening, or stiffness with the results of a Propionibacterium acnes-specific culture protocol. Regression models were used to identify factors predictive of a positive culture for Propionibacterium acnes. RESULTS One hundred and eight of the 193 revision arthroplasties were associated with positive cultures; 70% of the positive cultures demonstrated growth of Propionibacterium acnes. The rate of positive cultures per shoulder increased with the number of culture specimens obtained from each shoulder. Fifty-five percent of the positive cultures required observation for more than one week. Male sex, humeral osteolysis, and cloudy fluid were each associated with significant increases of ≥ 600% in the likelihood of obtaining a positive Propionibacterium acnes culture. Humeral loosening, glenoid wear, and membrane formation were associated with significant increases of >300% in the likelihood of obtaining a positive Propionibacterium acnes culture. CONCLUSIONS Preoperative and intraoperative factors can be used to help to predict the risk of a positive culture for Propionibacterium acnes. This evidence is clinically relevant to decisions regarding prosthesis removal or retention and the need for immediate antibiotic therapy at the time of revision shoulder arthroplasty before the culture results become available. LEVEL OF EVIDENCE Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Increased Frequency of Acute Local Reaction to Intra-Articular Hylan GF-20 (Synvisc) in Patients Receiving More Than One Course of Treatment

Background: Intra-articular knee injections with hylan GF-20 (Synvisc) have been shown to provide temporary relief of osteoarthritic symptoms. Several studies have suggested that repeated courses of treatment with this product may be administered without an increase in the likelihood of an adverse reaction. The present study was performed to test the hypothesis that the likelihood of a painful reaction to hylan GF-20 does not increase in patients who receive more than one course of treatment.Methods: The records of all patients who had received more than one course of treatment with hylan GF-20 were compared with a group of patients who had received only one course of treatment during the same fifteen-month period at a single center. The single-course group was prospectively enrolled and followed, as part of an ongoing randomized trial. The two groups were compared with respect to several demographic and clinical parameters as well as with respect to the frequency of painful acute local reactions following injections of hylan GF-20.Results: Local reactions to hylan GF-20 occurred significantly more often in patients who had received more than one course of treatment than they did in patients who had received only a single course of treatment; the reactions occurred in four (21%) of nineteen patients in the former group and in one (2%) of the forty-two patients in the latter (p = 0.029). All of the reactions were severe enough to cause the patient to seek unscheduled care. Following corticosteroid injection, the reactions abated without apparent sequelae. With the numbers available, no significant differences were detected between the multiple-course and single-course groups in terms of age, gender, body-mass index, or severity or bilaterality of the disease.Conclusions: The present study suggests that it may be reasonable to counsel patients who have been treated with a course of hylan GF-20 and who desire an additional course that the likelihood of a painful acute local reaction to the medication appears to be increased. Additional study of the frequency of acute local reactions following repeated courses of hylan GF-20 and investigation of the mechanisms of those reactions are warranted.

Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee a prospective, randomized trial

Background: Although both corticosteroid and hyaluronic acid injections are widely used to palliate the symptoms of knee osteoarthritis, little research involving a comparison of the two interventions has been done. We tested the hypothesis that there are no significant differences between Hylan G-F 20 (Synvisc) and the corticosteroid betamethasone sodium phosphate-betamethasone acetate (Celestone Soluspan) in terms of pain relief or improvement in function, as determined by validated scoring instruments. Methods: One hundred patients with knee osteoarthritis were randomized to receive intra-articular injection of either Hylan G-F 20 or the corticosteroid, and they were followed for six months. The patients treated with Hylan G-F 20 received one course of three weekly injections. The patients treated with the corticosteroid received one injection at the time of enrollment in the study, and they could request one more injection any time during the study. An independent, blinded evaluator assessed the patients with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), a modification of the Knee Society rating system, and the visual analog pain scale. Results: Both the group treated with the corticosteroid and the group treated with Hylan G-F 20 demonstrated improvements from baseline WOMAC scores (a median decrease from 55 to 40 points and from 54 to 44 points, respectively; p < 0.01 for both). The scores according to the Knee Society system did not significantly improve for the patients who received the corticosteroid (median, 58 to 70 points; p = 0.06) or for those who received Hylan G-F 20 (median, 58 to 68 points; p = 0.15). The scores on the visual analog scale improved for patients receiving Hylan G-F 20 (median, 70 to 52 mm; p < 0.01) but not for the patients who received the corticosteroid (median, 64 to 52 mm; p = 0.28). However, no significant differences between the two treatment groups were found with respect to the WOMAC, Knee Society system, or visual analog scale results. Women demonstrated a significant improvement in only one of the six possible outcome-treatment combinations (the WOMAC scale), whereas men demonstrated significant improvements in five of the six outcomes (all measures except the Knee Society rating system). Conclusions: No differences were detected between patients treated with intra-articular injections of Hylan G-F 20 and those treated with the corticosteroid with respect to pain relief or function at six months of follow-up. Women demonstrated significantly less response to treatment than men did for both treatments on all three outcome scales. Such significant gender-related differences warrant further investigation. Level of Evidence: Therapeutic study, Level I-1b (randomized controlled trial [no significant difference but narrow confidence intervals]). See Instructions to Authors for a complete description of levels of evidence.

Ski injury statistics, 1982 to 1993, Jackson hole ski resort

A retrospective analysis was conducted on injury statistics compiled over 12 seasons, from 1982 to 1993 (2.55 million skier-days), at a Wyoming ski resort. The population at risk was determined by ticket sales per year. A total of 9749 skiing injuries was indexed by anatomic region and se verity according to diagnosis on initial evaluation. Injury rates were then analyzed as a function of time. The injury rate remained constant at 3.7 injuries per 1000 skier-days during the 12 seasons. The rate of lower extremity to up per extremity injury decreased from 4:1 to 2:1 during the study period (P < 0.03). The ankle injury rate also de creased with time (P < 0.04). Ulnar collateral ligament sprains make up 7% of all injuries. Knee sprains in general account for 30% of all injuries. The incidence of anterior cruciate ligament tears increased as a function of time (P < 0.04) and accounted for 16% of all skiing injuries during the study period. The medial collateral ligament sprain was the most common injury, making up 18% of skiing injuries. Forty-seven snowboard injuries from the 1992 to 1993 season are also presented. Our injury statistics mir ror those currently reported in North America, except our data reflect a higher incidence of knee sprains.

Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee

Background: Although both corticosteroid and hyaluronic acid injections are widely used to palliate the symptoms of knee osteoarthritis, little research involving a comparison of the two interventions has been done. We tested the hypothesis that there are no significant differences between Hylan G-F 20 (Synvisc) and the corticosteroid betamethasone sodium phosphate-betamethasone acetate (Celestone Soluspan) in terms of pain relief or improvement in function, as determined by validated scoring instruments. Methods: One hundred patients with knee osteoarthritis were randomized to receive intra-articular injection of either Hylan G-F 20 or the corticosteroid, and they were followed for six months. The patients treated with Hylan G-F 20 received one course of three weekly injections. The patients treated with the corticosteroid received one injection at the time of enrollment in the study, and they could request one more injection any time during the study. An independent, blinded evaluator assessed the patients with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), a modification of the Knee Society rating system, and the visual analog pain scale. Results: Both the group treated with the corticosteroid and the group treated with Hylan G-F 20 demonstrated improvements from baseline WOMAC scores (a median decrease from 55 to 40 points and from 54 to 44 points, respectively; p < 0.01 for both). The scores according to the Knee Society system did not significantly improve for the patients who received the corticosteroid (median, 58 to 70 points; p = 0.06) or for those who received Hylan G-F 20 (median, 58 to 68 points; p = 0.15). The scores on the visual analog scale improved for patients receiving Hylan G-F 20 (median, 70 to 52 mm; p < 0.01) but not for the patients who received the corticosteroid (median, 64 to 52 mm; p = 0.28). However, no significant differences between the two treatment groups were found with respect to the WOMAC, Knee Society system, or visual analog scale results. Women demonstrated a significant improvement in only one of the six possible outcome-treatment combinations (the WOMAC scale), whereas men demonstrated significant improvements in five of the six outcomes (all measures except the Knee Society rating system). Conclusions: No differences were detected between patients treated with intra-articular injections of Hylan G-F 20 and those treated with the corticosteroid with respect to pain relief or function at six months of follow-up. Women demonstrated significantly less response to treatment than men did for both treatments on all three outcome scales. Such significant gender-related differences warrant further investigation. Level of Evidence: Therapeutic study, Level I-1b (randomized controlled trial [no significant difference but narrow confidence intervals]). See Instructions to Authors for a complete description of levels of evidence.

Association between funding source and study outcome in orthopaedic research.

The current report tests the hypotheses that commercial funding, country of origin, and presence of a coinvestigator with training in statistics are related to the likelihood of a published orthopaedic study arriving at a positive conclusion. All articles from the Journal of Bone and Joint Surgery (American), the Journal of Arthroplasty, and the American Journal of Sports Medicine published in 1 year were reviewed. The blinded review process classified each article as to study design and outcome (positive or negative), according to previously published definitions. Commercial funding was significantly associated with a positive outcome; 78.9% of commercially funded studies concluded with a positive outcome, compared with 63.3% of nonfunded studies. The presence of a statistician or epidemiologist as a coinvestigator, and the place of origin of the study were not associated with outcome. Only 21% of published studies were prospective, 3.5% were randomized, and 10.5% stated an experimental hypothesis; these factors were not associated with study outcome. Published studies that received funding from commercial parties were significantly more likely to report a positive outcome than studies that received no such funding. This does not imply the presence of a corrupting or causative influence of industry sponsorship on research outcomes; additional research is needed to determine whether such nonscientific factors actually affect study outcome or likelihood of publication.

Nonabsorbable Versus Absorbable Suture Anchors for Open Bankart Repair A Prospective, Randomized Comparison

Suture anchors facilitate the surgical repair of capsuloligamentous structures to bone. Bioabsorbable suture anchors, which obviate potential pitfalls in the periarticular use of permanent implants, have recently become available. We randomly assigned 40 patients to undergo modified Bankart shoulder repairs with either nonabsorbable or absorbable suture anchors. The patients had a history of recurrent traumatic anterior instability that had not improved with nonoperative management. The average patient age was 22 years (range, 17 to 46), and the average preoperative Rowe score was 47 points in the nonabsorbable anchor group and 47 points in the absorbable anchor group. Average postoperative Rowe scores were 96 and 93 points, respectively. There was one failed result in the nonabsorbable anchor group and two in the absorbable anchor group. No statistically significant subjective or objective differences were found at an average of 25 months postoperatively. Our results reveal that, in this application, bioabsorbable suture anchors are a viable option for the repair of soft tissue to bone.

Published Evidence Relevant to the Diagnosis of Impingement Syndrome of the Shoulder

BACKGROUND Acromioplasty for impingement syndrome of the shoulder is one of the most common orthopaedic surgical procedures. The rate with which this procedure is performed has increased dramatically. This investigation sought high levels of evidence in the published literature related to five hypotheses pertinent to the concept of the impingement syndrome and the rationale supporting acromioplasty in its treatment. METHODS We conducted a systematic review of articles relevant to the following hypotheses: (1) clinical signs and tests can reliably differentiate the so-called impingement syndrome from other conditions, (2) clinically common forms of rotator cuff abnormality are caused by contact with the coracoacromial arch, (3) contact between the coracoacromial arch and the rotator cuff does not occur in normal shoulders, (4) spurs seen on the anterior aspect of the acromion extend beyond the coracoacromial ligament and encroach on the underlying rotator cuff, and (5) successful treatment of the impingement syndrome requires surgical alteration of the acromion and/or coracoacromial arch. Three of the authors independently reviewed each article and determined the type of study, the level of evidence, and whether it supported the concept of the impingement syndrome. Articles with level-III or IV evidence were excluded from the final analysis. RESULTS These hypotheses were not supported by high levels of evidence. CONCLUSIONS The concept of impingement syndrome was originally introduced to cover the full range of rotator cuff disorders, as it was recognized that rotator cuff tendinosis, partial tears, and complete tears could not be reliably differentiated by clinical signs alone. The current availability of sonography, magnetic resonance imaging, and arthroscopy now enable these conditions to be accurately differentiated. Nonoperative and operative treatments are currently being used for the different rotator cuff abnormalities. Future clinical investigations can now focus on the indications for and the outcome of treatments for the specific rotator cuff diagnoses. It may be time to replace the nonspecific diagnosis of so-called impingement syndrome by using modern methods to differentiate tendinosis, partial tears, and complete tears of the rotator cuff.