The relationship between the outcome of studies of autologous chondrocyte implantation and the presence of commercial funding
ABSTRACT Autologous chondrocyte implantation (ACI) is an expensive treatment option for focal cartilage defects, and commercial funding of research is associated with a study reaching a positive conclusion. The purpose of this analysis is to compare outcomes (and levels of evidence) between published ACI outcome studies that were commercially funded and studies that were not commercially funded.
Commercially funded ACI literature could be commercially biased.
MEDLINE was searched for human, knee, ACI, nonmembrane, English language, and clinical outcome studies. Studies were evaluated with regard to funding status (commercially funded or not commercially funded), outcomes, and levels of evidence. Outcomes and levels of evidence were evaluated and compared for commercially funded studies versus those that were not commercially funded.
Twenty-three studies were included; 16 (70%) were commercially funded. Pooled clinical outcome measures data were not significantly different (Lysholm, Modified Cincinnati, patient-reported Cincinnati, Tegner, pain Visual Analog Scale) when comparing commercially funded studies with those that were not commercially funded. However, distribution of levels of evidence was significantly lower (P = .045) for commercially funded studies.
Reassuringly, commercial funding of ACI studies did not result in a difference in published clinical outcomes versus those that were not commercially funded. However, the lower levels of evidence of commercially funded studies suggests that commercially funded ACI studies may be of less value to surgeons desiring to practice evidence-based medicine, and, in the future, commercial entities funding medical research could selectively fund studies of the highest levels of evidence.
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ABSTRACT: Biochemical analysis of the components of the mRNA decay machinery is crucial to understand the mechanisms of mRNA decay. The Lsm1p‐7p‐Pat1p complex is a key activator of decapping in the 5′ to 3′‐mRNA decay pathway that is highly conserved in all eukaryotes. The first step in this pathway is poly(A) shortening that is followed by the selective decapping and subsequent 5′ to 3′‐exonucleolytic degradation of the oligoadenylated mRNAs. Earlier studies suggested that the Lsm1p‐7p‐Pat1p complex preferentially associates with oligoadenylated mRNAs and facilitates their decapping in vivo (Tharun and Parker, 2001a; Tharun et al., 2000). They also showed that the Lsm1p through Lsm7p and Pat1p are involved in protecting the 3′‐ends of mRNAs in vivo from trimming (He and Parker, 2001). Therefore, to gain better insight into the biologic function of the Lsm1p‐7p‐Pat1p complex, it is important to determine its in vitro RNA binding properties. Here I describe the methods we use in my laboratory for the purification and in vitro RNA binding analysis of this complex from the budding yeast Saccharomyces cerevisiae. Purification was achieved with tandem affinity chromatography using a split‐tag strategy. This involved use of a strain expressing FLAG‐tagged Lsm1p and 6×His‐tagged Lsm5p and purification by a two‐step procedure with an anti‐FLAG antibody matrix followed by a Ni–NTA matrix. The purified complex was analyzed for its RNA binding properties with gel mobility shift assays. Such analyses showed that this complex has the intrinsic ability to distinguish between oligoadenylated and polyadenylated RNAs and that it binds near the 3′‐ends of RNAs (Chowdhury et al., 2007). These observations, therefore, highlighted the importance of the intrinsic RNA binding properties of this complex as key determinants of its in vivo functions.
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ABSTRACT: The purpose of this systematic review was to determine the effectiveness of cell-based therapy for articular cartilage defects of the knee. We performed a literature search in Medline (1994 to 2009) regarding cell-based therapies for chondral lesions. We identified 10 Level I or II randomized controlled trials and 3 Level II prospective comparative studies. Although many of these studies had substantial flaws, which could introduce bias, we overall found no difference between the cell-based studies and other interventions. In addition, we identified 26 Level III and IV studies of cell-based therapy. There is insufficient evidence from the studies included in this review to say whether cell-based therapy is superior to other treatment strategies in articular cartilage lesions of the knee.Arthroscopy The Journal of Arthroscopic and Related Surgery 06/2009; 25(5):531-52. DOI:10.1016/j.arthro.2009.02.007 · 3.19 Impact Factor
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ABSTRACT: Anterior cruciate ligament graft fixation has become one of the most investigated topics in the sports traumatology literature. With over 400 publications within the past decade, a plausible explanation for the popularity of the topic would be that anterior cruciate ligament graft fixation represents an obvious clinical problem. Yet this does not seem to be the case. We set out to analyze the veracity of the notion that the fixation site is the weak link in a reconstructed knee in the early postoperative period. A mere temporal association is found between the first clinical reports on increased anterior tibial translation relative to the femur with soft-tissue grafts and the first pullout studies reporting lower ultimate failure loads with such grafts. This association was sufficient to convince the orthopaedic community at large that actual causality exists between soft-tissue graft fixation failure and increased knee laxity during healing. Thus the concept of "graft slippage" was born. Even with the imminent risk of being misconstrued as contentious, we submit that the entire concept of graft slippage is a myth, founded on poor scientific practice and affected by commercial bias. As a way forward, clinically important phenomena should be demonstrated through experiments with clear and sound clinical endpoints. As for preclinical studies, although they are indisputably helpful in the elaboration of such phenomena, serious hazards lie in declaring them a sufficient scientific basis for new research or, worse, for clinical standards of care. More importantly, no matter how sophisticated or fascinating their methodology, preclinical studies do not relieve us from the necessity and duty of proving our theories, whenever possible, with randomized controlled trials.Arthroscopy The Journal of Arthroscopic and Related Surgery 05/2010; 26(5):681-4. DOI:10.1016/j.arthro.2009.11.023 · 3.19 Impact Factor