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.

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.

Low-intensity pulsed ultrasound (LIPUS) can decrease the economic burden of fracture non-union.

OBJECTIVES: Few studies have evaluated the economic burden of surgical and conservative treatment of fracture non-union. An analysis was undertaken of aggregated payer data to determine economic costs of non-unions treated with surgery only vs non-unions treated conservatively with low-intensity pulsed ultrasound (LIPUS) only. METHODS: This study used administrative claims from a health plan database including nearly 80 million people. Patients with a claim for non-union surgery or LIPUS for non-union were identified, from April 2007 until April 2010. A retrospective cohort was formed by pairwise demographic matching among patients who received 'Surgery Only' or 'LIPUS Only'. Date of the first non-union intervention (surgery or LIPUS) was defined as the index date. All medical costs were assessed over 12 months following the index date for the 'Surgery Only' and 'LIPUS Only' cohorts. RESULTS: A total of 1158 matched patients were identified. 'Surgery Only' patients used significantly more healthcare services. In the year following intervention, 'Surgery Only' patients had total medical costs $6289 higher than 'LIPUS Only' patients (Mean = $11,276 vs $4986; p < 0.0001). Outpatient costs accounted for >68% of overall costs in both cohorts, and outpatient costs were significantly higher among the 'Surgery Only' cohort (Mean = $7682 vs $4196; p < 0.0001). Total inpatient costs were also significantly higher among the 'Surgery Only' cohort (Mean = $3302 vs $381; p < 0.0001). LIMITATIONS: Limitations of this work are typical of all studies based on administrative claims data: errors in the database are assumed to distribute randomly between cohorts, and some patients may have been miscoded as to treatment received or costs billed. CONCLUSIONS: 'Surgery Only' patients used significantly and substantially more healthcare services in treatment of fracture non-union. Conservative treatment with 'LIPUS only' for fracture non-union could potentially result in cost savings projected to roughly $1 billion dollars [corrected].

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 $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 $392,582 in direct costs (SD $423,256). Researchers experienced a median 91.8% decrease in publication output and large declines in funding after censure by the ORI.

Retractions in the medical literature: how can patients be protected from risk?

BACKGROUND: Medical research so flawed as to be retracted may put patients at risk by influencing treatments. OBJECTIVE: To explore hypotheses that more patients are put at risk if a retracted paper appears in a journal with a high impact factor (IF) so that the paper is widely read; is written by a 'repeat offender' author who has produced other retracted research; or is a clinical trial. METHODS: English language papers (n=788) retracted from the PubMed database between 2000 and 2010 were evaluated. Only those papers retracting research with humans or freshly derived human material were included; 180 retracted primary papers (22.8%) met inclusion criteria. Subjects enrolled and patients treated were tallied, both in the retracted primary studies and in 851 secondary studies that cited a retracted primary paper. RESULTS: Retracted papers published in high-IF journals were cited more often (p=0.0004) than those in low-IF journals, but there was no difference between high- and low-IF papers in subjects enrolled or patients treated. Retracted papers published by 'repeat offender' authors did not enrol more subjects or treat more patients than papers by one-time offenders, nor was there a difference in number of citations. However, retracted clinical trials treated more patients (p=0.0002) and inspired secondary studies that put more patients at risk (p=0.0019) than did other kinds of medical research. CONCLUSIONS: If the goal is to minimise risk to patients, the appropriate focus is on clinical trials. Clinical trials form the foundation of evidence-based medicine; hence, the integrity of clinical trials must be protected.

DAILY BUDGETS OF PHOTOSYNTHETICALLY FIXED CARBON IN SYMBIOTIC ZOANTHIDS.

We tested the hypothesis that some zoanthids are able to meet a portion of their daily respiratory carbon requirement with photosynthetic carbon from symbiotic algal cells (= zooxanthellae). A daily budget was constructed for carbon (C) photosynthetically fixed by zooxanthellae of the Bermuda zoanthids Zoanthus sociatus and Palythoa variabilis. Zooxanthellae have an average net photosynthetic C fixation of 7.48 and 15.56 µgC·polyp-1·day-1 for Z. sociatus and P. variabilis respectively. The C-specific growth rate (µc) was 0.215·day-1 for Z. sociatus and 0.152·day-1 for P. variabilis. The specific growth rate (µ) of zooxanthellae in the zoanthids was measured to be 0.011 and 0.017·day-1 for Z. sociatus and P. variabilis zooxanthellae respectively. Z. sociatus zooxanthellae translocated 95.1% of the C assimilated in photosynthesis, while P. variabilis zooxanthellae translocated 88.8% of their fixed C. As the animal tissue of a polyp of Z. sociatus required 14.75 µgC·day-1 for respiration, and one of P. variabiis required 105.54 µgC·day-1, the contribution of zooxanthellae to animal respiration (CZAR) was 48.2% for Z. sociatus and 13.1% for P. variabilis.