Statistical fallacies in orthopedic research

Background:

A large number of statistical fallacies occur in medical research literature. These are mostly inadvertent and occur due to lack of understanding of the statistical concepts and terminologies. Many researchers do not fully appreciate the consequence of such fallacies on the credibility of their report.

Materials and Methods:

This article provides a general review of the issues that could give rise to statistical fallacies with focus on orthopedic research. Some of this is based on real-life literature and some is based on the actual experiences of the author in dealing with medical research over the past three decades. The text is in teaching mode rather than research mode.

Results:

Statistical fallacies occur due to inadequate sample that is used for generalized conclusion; incomparable groups presented as comparable; mixing of two or more distinct groups that in fact require separate consideration; misuse of percentages, means and graphs; incomplete reporting that suppresses facts; ignoring reality and depending instead on oversimplification; forgetting baseline values that affect the outcome; misuse of computer packages and use of black-box approach; misuse of P-values that compromises conclusions; confusing correlation with cause-effect; and interpreting statistical significance as medical significance.

Conclusion:

Mere awareness of the situations where statistical fallacies can occur may be adequate for researchers to sit up and take note while trying to provide a credible report.     

Single-cell RNA sequencing in orthopedic research

Although previous RNA sequencing methods have been widely used in orthopedic research and have provided ideas for therapeutic strategies, the specific mechanisms of some orthopedic disorders, including osteoarthritis, lumbar disc herniation,rheumatoid arthritis, fractures, tendon injuries, spinal cord injury, heterotopic ossification, and osteosarcoma, require further elucidation. The emergence of the single-cell RNA sequencing(sc RNA-seq) technique has introduced a new era of research on these ...     

Integrating computers into orthopedic research

The role of computers in orthopedic research and education is expanding rapidly. Its potential to manipulate large amounts of data and execute multiple complex assignments with great speed and accuracy indeed make the computer an awe-inspiring device. An important instrument in research is the computerized database, a collection of related data arranged so that useful information may be retrieved. Computer models derived from classical physics and fluid mechanics have been used to study motion of both extremities and spinal articulations. Computers also have found usefulness in clinical orthopedic research. The orthopedist of the future will use the computer directly in clinics and private practice for patient evaluation, computer-assisted preoperative planning, and financial recordkeeping.     

Molecular imaging promotes progress in orthopedic research

Modern orthopedic research is directed towards the understanding of molecular mechanisms that determine development, maintenance and health of musculoskeletal tissues. In recent years, many genetic and proteomic discoveries have been made which necessitate investigation under physiological conditions in intact, living tissues. Molecular imaging can meet this demand and is, in fact, the only strategy currently available for noninvasive, quantitative, real-time biology studies in living subjects. In this review, techniques of molecular imaging are summarized, and applications to bone and joint biology are presented. The imaging modality most frequently used in the past was optical imaging, particularly bioluminescence and near-infrared fluorescence imaging. Alternate technologies including nuclear and magnetic resonance imaging were also employed. Orthopedic researchers have applied molecular imaging to murine models including transgenic mice to monitor gene expression, protein degradation, cell migration and cell death. Within the bone compartment, osteoblasts and their stem cells have been investigated, and the organic and mineral bone phases have been assessed. These studies addressed malignancy and injury as well as repair, including fracture healing and cell/gene therapy for skeletal defects. In the joints, molecular imaging has focused on the inflammatory and tissue destructive processes that cause arthritis. As described in this review, the feasibility of applying molecular imaging to numerous areas of orthopedic research has been demonstrated and will likely result in an increase in research dedicated to this powerful strategy. Molecular imaging holds great promise in the future for preclinical orthopedic research as well as next-generation clinical musculoskeletal diagnostics.     

Basic surgical research

Introduction: Progress in surgery is critically dependent on better understanding of the pathophysiology of surgical patients and implementation of results derived from new disciplines such as biotechnology and molecular biology. Progress: Rapid development of novel technologies and methods requires mutual co-operation between basic scientists and clinicians. This collaborative effort can be fostered in institutions devoted to surgical research, where available methodological expertise is directed to the solving of surgical problems. Discussion: The quality of surgical research depends on expertise in the field of interest, knowledge on design of animal and clinical studies, familiarity with ethical issues and the rules of good laboratory practice. These abilities should be acquired at the earliest possible time, as medical or postgraduate student. Professional surgical research is a necessity for further improvement of treatments for surgical patients. It essentially needs an interdisciplinary work force in order to successfully compete with international development. Received: 4 August 1998 / Accepted: 24 August 1998     

Bioartificial pancreas research in Japan

The bioartificial pancreas (BAP), a medical device enclosing insulin-secreting cells in a semipermeable membrane, is expected to physiologically control glucose levels, and thus to be able to inhibit development of serious chronic complications in diabetic patients. In this brief review, we introduce research activities on the development of the BAP in Japan, including membrane preparation for the BAP, evaluation of in vitro and in vivo BAP functions, and challenges for production of insulin-secreting cells from stem cells.     

Basic research in kidney cancer

Context

Advances in basic research will enhance prognosis, diagnosis, and treatment of renal cancer patients.

Objective

To discuss advances in our understanding of the molecular basis of renal cancer, targeted therapies, renal cancer and immunity, and genetic factors and renal cell carcinoma (RCC).

Evidence acquisition

Data on recently published (2005-2011) basic science papers were reviewed.

Evidence synthesis

Advances in basic research have shown that renal cancers can be subdivided based on specific genetic profiles. Now that this molecular basis has been established, it is becoming clear that additional events play a major role in the development of renal cancer. For example, aberrant chromatin remodelling appears to be a main driving force behind tumour progression in clear cell RCC. A large number of potential biomarkers have emerged using various high-throughput platforms, but adequate biomarkers for RCC are still lacking. To bring the potential biomarkers and biomarker profiles to the clinical arena is a major challenge for the field.The introduction of tyrosine kinase inhibitors (TKIs) for therapy has shifted the interest away from immunologic approaches. Nevertheless, a wealth of evidence supports immunotherapy for RCC. Interestingly, studies are now appearing that suggest a combination of TKI and immunotherapy may be beneficial.Thus far, little attention has been paid to patient-specific differences. With high-throughput methods becoming cheaper and with the advances in sequencing possibilities, this situation is expected to change rapidly.

Conclusions

Great strides have been made in the understanding of molecular mechanisms of RCC. This has led this field to the enviable position of having a range of molecularly targeted therapies. Large sequencing efforts are now revealing more and more genes responsible for tumour development and progression, offering new targets for therapy. It is foreseen that through integration of high-throughput platforms, personalised cancer treatment for RCC patients will become possible.