R. Grant Steen

Misconduct accounts for the majority of retracted scientific publications

A detailed review of all 2,047 biomedical and life-science research articles indexed by PubMed as retracted on May 3, 2012 revealed that only 21.3% of retractions were attributable to error. In contrast, 67.4% of retractions were attributable to misconduct, including fraud or suspected fraud (43.4%), duplicate publication (14.2%), and plagiarism (9.8%). Incomplete, uninformative or misleading retraction announcements have led to a previous underestimation of the role of fraud in the ongoing retraction epidemic. The percentage of scientific articles retracted because of fraud has increased ∼10-fold since 1975. Retractions exhibit distinctive temporal and geographic patterns that may reveal underlying causes.

Why has the number of scientific retractions increased

Background The number of retracted scientific publications has risen sharply, but it is unclear whether this reflects an increase in publication of flawed articles or an increase in the rate at which flawed articles are withdrawn. Methods and Findings We examined the interval between publication and retraction for 2,047 retracted articles indexed in PubMed. Time-to-retraction (from publication of article to publication of retraction) averaged 32.91 months. Among 714 retracted articles published in or before 2002, retraction required 49.82 months; among 1,333 retracted articles published after 2002, retraction required 23.82 months (p<0.0001). This suggests that journals are retracting papers more quickly than in the past, although recent articles requiring retraction may not have been recognized yet. To test the hypothesis that time-to-retraction is shorter for articles that receive careful scrutiny, time-to-retraction was correlated with journal impact factor (IF). Time-to-retraction was significantly shorter for high-IF journals, but only ∼1% of the variance in time-to-retraction was explained by increased scrutiny. The first article retracted for plagiarism was published in 1979 and the first for duplicate publication in 1990, showing that articles are now retracted for reasons not cited in the past. The proportional impact of authors with multiple retractions was greater in 1972–1992 than in the current era (p<0.001). From 1972–1992, 46.0% of retracted papers were written by authors with a single retraction; from 1993 to 2012, 63.1% of retracted papers were written by single-retraction authors (p<0.001). Conclusions The increase in retracted articles appears to reflect changes in the behavior of both authors and institutions. Lower barriers to publication of flawed articles are seen in the increase in number and proportion of retractions by authors with a single retraction. Lower barriers to retraction are apparent in an increase in retraction for “new” offenses such as plagiarism and a decrease in the time-to-retraction of flawed work.

Financial costs and personal consequences of research misconduct resulting in retracted publications

The number of retracted scientific articles has been increasing. Most retractions are associated with research misconduct, entailing financial costs to funding sources and damage to the careers of those committing misconduct. We sought to calculate the magnitude of these effects. Data relating to retracted manuscripts and authors found by the Office of Research Integrity (ORI) to have committed misconduct were reviewed from public databases. Attributable costs of retracted manuscripts, and publication output and funding of researchers found to have committed misconduct were determined. We found that papers retracted due to misconduct accounted for approximately

Epidemiology of Fracture Nonunion in 18 Human Bones.

58 million in direct funding by the NIH between 1992 and 2012, less than 1% of the NIH budget over this period. Each of these articles accounted for a mean of

Sources of error in the retracted scientific literature

392,582 in direct costs (SD

Treatment of chronic (>1 year) fracture nonunion: Heal rate in a cohort of 767 patients treated with low-intensity pulsed ultrasound (LIPUS)

423,256). Researchers experienced a median 91.8% decrease in publication output and large declines in funding after censure by the ORI. DOI: http://dx.doi.org/10.7554/eLife.02956.001

Hyaluronic Acid Injections Are Associated with Delay of Total Knee Replacement Surgery in Patients with Knee Osteoarthritis: Evidence from a Large U.S. Health Claims Database

Importance Failure of bone fracture healing occurs in 5% to 10% of all patients. Nonunion risk is associated with the severity of injury and with the surgical treatment technique, yet progression to nonunion is not fully explained by these risk factors. Objective To test a hypothesis that fracture characteristics and patient-related risk factors assessable by the clinician at patient presentation can indicate the probability of fracture nonunion. Design, Setting, and Participants An inception cohort study in a large payer database of patients with fracture in the United States was conducted using patient-level health claims for medical and drug expenses compiled for approximately 90.1 million patients in calendar year 2011. The final database collated demographic descriptors, treatment procedures as per Current Procedural Terminology codes; comorbidities as per International Classification of Diseases, Ninth Revision codes; and drug prescriptions as per National Drug Code Directory codes. Logistic regression was used to calculate odds ratios (ORs) for variables associated with nonunion. Data analysis was performed from January 1, 2011, to December 31, 2012. Exposures Continuous enrollment in the database was required for 12 months after fracture to allow sufficient time to capture a nonunion diagnosis. Results The final analysis of 309 330 fractures in 18 bones included 178 952 women (57.9%); mean (SD) age was 44.48 (13.68) years. The nonunion rate was 4.9%. Elevated nonunion risk was associated with severe fracture (eg, open fracture, multiple fractures), high body mass index, smoking, and alcoholism. Women experienced more fractures, but men were more prone to nonunion. The nonunion rate also varied with fracture location: scaphoid, tibia plus fibula, and femur were most likely to be nonunion. The ORs for nonunion fractures were significantly increased for risk factors, including number of fractures (OR, 2.65; 95% CI, 2.34-2.99), use of nonsteroidal anti-inflammatory drugs plus opioids (OR, 1.84; 95% CI, 1.73-1.95), operative treatment (OR, 1.78; 95% CI, 1.69-1.86), open fracture (OR, 1.66; 95% CI, 1.55-1.77), anticoagulant use (OR, 1.58; 95% CI, 1.51-1.66), osteoarthritis with rheumatoid arthritis (OR, 1.58; 95% CI, 1.38-1.82), anticonvulsant use with benzodiazepines (OR, 1.49; 95% CI, 1.36-1.62), opioid use (OR, 1.43; 95% CI, 1.34-1.52), diabetes (OR, 1.40; 95% CI, 1.21-1.61), high-energy injury (OR, 1.38; 95% CI, 1.27-1.49), anticonvulsant use (OR, 1.37; 95% CI, 1.31-1.43), osteoporosis (OR, 1.24; 95% CI, 1.14-1.34), male gender (OR, 1.21; 95% CI, 1.16-1.25), insulin use (OR, 1.21; 95% CI, 1.10-1.31), smoking (OR, 1.20; 95% CI, 1.14-1.26), benzodiazepine use (OR, 1.20; 95% CI, 1.10-1.31), obesity (OR, 1.19; 95% CI, 1.12-1.25), antibiotic use (OR, 1.17; 95% CI, 1.13-1.21), osteoporosis medication use (OR, 1.17; 95% CI, 1.08-1.26), vitamin D deficiency (OR, 1.14; 95% CI, 1.05-1.22), diuretic use (OR, 1.13; 95% CI, 1.07-1.18), and renal insufficiency (OR, 1.11; 95% CI, 1.04-1.17) (multivariate P < .001 for all). Conclusions and Relevance The probability of fracture nonunion can be based on patient-specific risk factors at presentation. Risk of nonunion is a function of fracture severity, fracture location, disease comorbidity, and medication use.

Bone fracture nonunion rate decreases with increasing age: A prospective inception cohort study

Retraction of flawed articles is an important mechanism for correction of the scientific literature. We recently reported that the majority of retractions are associated with scientific misconduct. In the current study, we focused on the subset of retractions for which no misconduct was identified, in order to identify the major causes of error. Analysis of the retraction notices for 423 articles indexed in PubMed revealed that the most common causes of error‐related retraction are laboratory errors, analytical errors, and irreproducible results. The most common laboratory errors are contamination and problems relating to molecular biology procedures (e.g., sequencing, cloning). Retractions due to contamination were more common in the past, whereas analytical errors are now increasing in frequency. A number of publications that have not been retracted despite being shown to contain significant errors suggest that barriers to retraction may impede correction of the literature. In particular, few cases of retraction due to cell line contamination were found despite recognition that this problem has affected numerous publications. An understanding of the errors leading to retraction can guide practices to improve laboratory research and the integrity of the scientific literature. Perhaps most important, our analysis has identified major problems in the mechanisms used to rectify the scientific literature and suggests a need for action by the scientific community to adopt protocols that ensure the integrity of the publication process.—Casadevall, A., Steen, R. G., Fang, F. C. Sources of error in the retracted scientific literature. FASEB J. 28, 3847‐3855 (2014). www.fasebj.org

Biological Risk Factors for Nonunion of Bone Fracture.

BACKGROUND Established fracture nonunions rarely heal without secondary intervention. Revision surgery is the most common intervention, though non-surgical options for nonunion would be useful if they could overcome nonunion risk factors. Our hypothesis is that low-intensity pulsed ultrasound (LIPUS) can enhance heal rate (HR) in fractures that remain nonunion after one year, relative to the expected HR in the absence of treatment, which is expected to be negligible. METHODS We collated outcomes from a prospective patient registry required by the U.S. Food & Drug Administration. Patient data were collected over a 4-year period beginning in 1994 and were individually reviewed and validated by a registered nurse. Patients were only included if they had four data points available: date when fracture occurred; date when LIPUS treatment began; date when LIPUS treatment ended; and a dichotomous outcome of healed vs. failed, assessed by clinical and radiological criteria. Data were used to calculate two derived variables: days to treatment (DTT) with LIPUS, and days on treatment (DOT) with LIPUS. Every validated chronic nonunion patient (DTT>365 days) with complete data is reported. RESULTS Heal rate for chronic nonunion patients (N=767) treated with LIPUS was 86.2%. Heal rate was 82.7% among 98 patients with chronic nonunion ≥5 years duration, and 12 patients healed after chronic nonunion >10 years (HR=63.2%). There was more patient loss to follow-up, non-compliance, and withdrawal, comparing chronic nonunion patients to all other patients (p<0.0001). Patient age was the only factor associated with failure to heal among chronic nonunions (p<0.004). Chronic nonunion patients averaged 3.1 surgical procedures prior to LIPUS, but some LIPUS-treated patients were able to heal without revision surgery. Among 91 patients who received LIPUS ≥90 days after their last surgery, HR averaged 85.7%, and the time from last surgery to index use of LIPUS averaged 449.6 days. CONCLUSIONS Low-intensity pulsed ultrasound enhanced HR among fractures that had been nonunion for at least 1 year, and even healed fractures that had been nonunion >10 years. LIPUS resulted in successful healing in the majority of nonunions without further surgical intervention.

Comparison of two hyaluronic acid formulations for safety and efficacy (CHASE) study in knee osteoarthritis: a multicenter, randomized, double-blind, 26-week non-inferiority trial comparing Durolane to Artz

Background The growing prevalence of osteoarthritis (OA) and the medical costs associated with total knee replacement (TKR) surgery for end-stage OA motivate a search for agents that can delay OA progression. We test a hypothesis that hyaluronic acid (HA) injection is associated with delay of TKR in a dose-dependent manner. Methods and Findings We retrospectively evaluated records in an administrative claims database of ~79 million patients, to identify all patients with knee OA who received TKR during a 6-year period. Only patients with continuous plan enrollment from diagnosis until TKR were included, so that complete medical records were available. OA diagnosis was the index event and we evaluated time-to-TKR as a function of the number of HA injections. The database included 182,022 patients with knee OA who had TKR; 50,349 (27.7%) of these patients were classified as HA Users, receiving ≥1 courses of HA prior to TKR, while 131,673 patients (72.3%) were HA Non-users prior to TKR, receiving no HA. Cox proportional hazards modelling shows that TKR risk decreases as a function of the number of HA injection courses, if patient age, gender, and disease comorbidity are used as background covariates. Multiple HA injections are therefore associated with delay of TKR (all, P < 0.0001). Half of HA Non-users had a TKR by 114 days post-diagnosis of knee OA, whereas half of HA Users had a TKR by 484 days post-diagnosis (χ2 = 19,769; p < 0.0001). Patients who received no HA had a mean time-to-TKR of 0.7 years; with one course of HA, the mean time to TKR was 1.4 years (χ2 = 13,725; p < 0.0001); patients who received ≥5 courses delayed TKR by 3.6 years (χ2 = 19,935; p < 0.0001). Conclusions HA injection in patients with knee OA is associated with a dose-dependent increase in time-to-TKR.