High-level Evidence Studies Research Articles

The Highest Level of Evidence in a High Impact Journal: Is This the Final Verdict?

Evidence-based medicine involves the deliberate integration of clinical research into therapeutic decision making.1 A prospective, randomized control trial (PRCT) is assumed to equally distribute unknown confounding variables and only manipulate the “treatment variable.” In medical PRCTs, this usually occurs in a well-defined population to determine efficacy; that is, does the intervention work on the participants in the study (internal validity)? In most medical (drug) studies, the greater challenge is determining whether the results can be extended to patients not in the study, so called external validity. Surgical or interventional studies face the same generalizabilty or external validity issues; however, one of the greatest challenges in surgical trials is patient recruitment, and the establishment of a valid study population to ensure internal validity. The recent history of medicine has been punctuated by PRCTs, which have established, reinforced, and challenged traditional clinical beliefs.2 One example of the astounding effect of level I trials is the recent literature on percutaneous vertebroplasty (PVP) compared with sham procedures3,4 and to conservative treatment5 for treatment of osteoporotic vertebral compression fractures. Many clinicians experience significant cognitive dissonance6 between the astounding early clinical improvement of many patients and the popular media perception of the results of these trials. An excellent review in this issue of the journal effectively dissects 2 of these studies and highlights strengths and weaknesses.5 However, the impact of these studies and others really distills down to the difficulties with establishing both internal and external validity. The major challenge of PRCTs is the requirement of equipoise by both patients and physicians regarding 2 apparently equally effective treatments. Clinicians may be biased to recommend direct interventions to some patients and only enroll patients in whom there is less severe intensity of symptoms, although this is controlled for once the study begins, the bias can be still appear through the inclusion-exclusion criteria developed by the clinicians. It is often the inclusion-exclusion measures that are adjusted based on expected recruitment. Patient consent to participate in interventional studies is by far the greatest challenge as systematic differences evolve between patients willing to participate in randomization. There may be significant differences in risk taking, expectations, and perseverance in people who are willing to relegate their treatment to chance versus patients who refused to participate. This volunteer bias would be akin to selection bias in observational studies. Most interventional studies have roughly 33% enrollment of those patients eligible. Patient preference is a big part of evidence-based medicine, and perhaps, the reason for the observational study advocates touting it as the best methodology for ensuring external validity. This dilemma was addressed in the Spine Patient Outcomes Research Trial by including an observational cohort to capture patients who were not enrolled in the prospective, randomized study.7,8 PRCTs are expected to have appropriate and accurate long term follow-up. However, in some situations long term follow-up may be less relevant than early functional results. For example, in the orthopedic literature, the natural history of most femur fractures is healing by 6 to 12 months regardless of treatment.9,10 The goal of internal fixation is early mobilization and pain control to avoid the sequelae of prolonged immobilization, possibly at the expense of soft tissue stripping and healing. Similarly, because the vertebral bodies have an excellent blood supply and soft tissue envelope, it is not surprising that the natural history of vertebral compression fractures is healing by 6 to 12 months. Is it fair to judge the long-term outcome of vertebroplasty compared with conservative treatment? Would anyone for go internal fixation of a femur fracture because of the equivocal long-term fracture healing? The real question is whether the “internal fixation” facilitates substantial early pain improvement and mobilization. Indeed, early pain relief after PVP has been observed in all of the PVP trials.11 An important overlooked result in the Rousing et al study was the significant (1.3 point, P < 0.02) improvement in Barthel functional score in the PVP group over the conservative group at 12 months. This functional improvement may be a reflection of earlier pain control and mobilization compared with conservatively treated patients. In practicing evidence-based medicine, we as clinicians and researchers must be wary of assigning truths to PRCTs, even if published in high impact journals. The so-called pinnacle of the research design hierarchy is not immune to methodological limitations often camouflaged by the unique and coveted PRCT design for evaluation of a surgical intervention. Common sense, continued investigation, and an appreciation of the principles around internal and external validity of high-level evidence studies will hopefully guide our practices in the future of spinal care.

Surgical Management of Spondylolysis and Spondylolisthesis in Athletes

Symptomatic isthmic spondylolisthesis is a common problem in the competitive athlete. Presence of this disorder is recognized easily with imaging studies, although a certain index of suspicion is necessary in the face of normal x-rays. Bone scan, CT scan, and MRI may all play a role in diagnosis. Management of this condition, on the other hand, can be more challenging. There are no high level evidence studies with specific recommendations for bracing, rehab, or surgery. Most athletes successfully return to competition with nonoperative treatment. For those that fail, a pars repair or a fusion are potential options. There are a myriad of techniques advocated for both, and no head to head study has ever proven superiority. Even with fusion, many individuals can return to sports after several months of structured rehab, although a significant number of athletes will fail to resume their pre-injury level of activity.

Immediate loading of dental implants

The purpose of this review is to explore the concept of immediate loading as it pertains to dental implants and the indications for clinical practice. The definition of immediate loading will be considered together with a review of the relevant literature in an attempt to provide evidence-based guidelines for successful implementation into practice. A search of electronic databases including Medline, PubMed and the Cochrane Database of Systematic Reviews was undertaken using the terms "immediate loading'', "dental implants'', "immediate function'', "early loading'', "oral implants'', "immediate restoration'' and "systematic review''. This was supplemented by handsearching in peer-reviewed journals and cross-referenced with the articles accessed. Emphasis was given to systematic reviews and controlled clinical trials. A definition of immediate loading was suggested pertinent to the realities of logistics in clinical practice with respect to application and time frame. The literature was evaluated and shown to be limited with significant shortcomings. Guidelines and recommendations for clinical protocols were suggested and illustrated by examples of case types with a minimum of 1-3 years follow-up. A list of additional references for further reading was provided. Within the limitations of this review, there is evidence to suggest that immediate loading protocols have demonstrated high implant survival rates and may be cautiously recommended for certain clinical situations. However, more high level evidence studies, preferably randomized controlled trials (RCTs), over a long time frame are required to show a clear benefit over more conventional loading protocols.

Thromboembolism Following Foot and Ankle Surgery: A Case Series and Literature Review

Venous thromboembolism following major orthopedic procedures of the hip and knee is well documented and patients are therefore routinely prophylaxed following these proximal lower extremity procedures. In contrast, foot and ankle surgery is considered by most health care professionals to be a low-risk procedure for the development of venous thromboembolism. As a result, pharmacologic deep venous thrombosis prophylaxis is rarely administered. This postoperative practice is supported by the literature regarding deep venous thrombosis following foot and ankle surgery. In this article, we review the risk factors and explore the occurrence of thromboembolism after foot and ankle surgery in the literature. We also present our retrospective study of patients who developed venous thromboembolism after forefoot, midfoot, hindfoot, and ankle procedures. Over the course of 1.5 years, 4 of a consecutive series of 1000 patients (0.4%) developed a deep venous thrombolism and 3 of 1000 (0.3%) developed nonfatal pulmonary emboli. In our series, each of our patients who developed venous thromboembolism had at least 2 identifiable risk factors. The incidence of venous thromboembolism following foot and ankle surgery is rare (less than 1%), and the need for routine propylaxis postoperatively is not supported by any high level of evidence studies. 4.

Sacroiliac Joint Dysfunction: Evaluation and Treatment

Sacroiliac joint (SIJ) dysfunction is once again garnering attention as a treatable diagnosis for the millions of individuals suffering from acute and chronic low back pain. Theoretically, excessive or restricted motion at the SIJ can alter the mechanics of the spine and pelvis causing pain. Often the clinician's history and physical examination are nonspecific in the evaluation of low back pain and a high index of suspicion is required to consider SIJ dysfunction as the cause for the patient's symptoms. Multiple physical examination maneuvers exist to detect SIJ dysfunction, but none are individually sensitive or specific enough to diagnose SIJ dysfunction alone. The clinician should learn 3 to 5 tests that can easily be performed and replicated for the evaluation of SIJ dysfunction and use them consistently in patients presenting with low back pain. Sacroiliac joint anesthetic blocks using computed tomography (CT) or fluoroscopic-guided injection are considered the gold standards for diagnosing SIJ dysfunction as the cause for nonspecific low back pain. Imaging studies and laboratory evaluations are generally unnecessary for the diagnosis of SIJ dysfunction unless specific elements of the history and physical suggest alternate etiologies. Interventions to treat the pain of SIJ dysfunction include nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, corticosteroid injections, osteopathic manipulation, radiofrequency denervation, SIJ belts, and surgery. While there are few high-level evidence studies evaluating and comparing these treatments in individuals with SIJ pain, patients may respond to one, or a combination of these treatments.

DNA Microarray-Based Gene Expression Profiling in Cancer: Aiding Cancer Diagnosis, Assessing Prognosis and Predicting Response to Therapy

A DNA microarray is a solid support such as a glass slide, silicon chip or nylon membrane on which DNA molecules are attached at precise locations. Using DNA microarrays, the expression of tens of thousands of genes in a biological sample can be detected in one experiment. Emerging data suggests that the use of DNA microarrays can aid the differentiation of tumors with similar morphological appearance, predict patient outcome independently of conventional prognostic factors and select for response or resistance to specific anti-cancer therapies. DNA microarray technology thus has the potential to supplement standard diagnostic procedures in oncology and permit a more individualized approach to patient management. Prior to clinical application, however, this methodology must be simplified, standardized, evaluated in external quality assessment schemes and made available at relatively low costs. Most importantly, the preliminary, but promising, early findings must be validated by high-level evidence studies, such as large prospective randomized trials or meta-analyses. Keywords: DNA microarrays, cancer, tumor markers, diagnosis, prognosis and prediction

Controversies in paraesophageal hernia repair; a review of literature

The surgical repair of paraesophageal hiatal hernias (PHH) can be performed by endoscopic means, but the procedure is not standardized and results have not been evaluated systematically so far. The aim of this review article was to clarify controversial subjects on the surgical approach and technique, i.e., recurrence rate after conventional versus laparoscopic PHH treatment, results of mesh reinforcement of the cruroplasty, the necessity for additional antireflux surgery, and indications for an esophageal lengthening procedure. An electronic Medline search was performed to identify all publications reporting on laparoscopic and conventional PHH surgery. The computer search was followed by additional hand searches in books, journals, and related articles. All types of publications were evaluated because of a lack of high-level evidence studies such as randomized controlled trials. Critical analysis followed for all articles describing a study population of >10 patients and those reporting postoperative outcome. A total of 32 publications were reviewed. Randomized controlled trials comparing laparoscopic and open techniques could not be identified. Nineteen of the publications described the results of retrospective series. Therefore, most of the studies retrieved were low in hierarchy of evidence (level II-c or lower). The overall median hospital time as published was 3 days for patients operated laparoscopically and 10 days in the conventional group. Postoperative complications, such as pneumonia, thrombosis, hemorrhage, and urinary and wound tract infections, appeared to be more frequent after conventional surgery. Follow-up was longer for conventional surgery (median 45 months versus 17.5 months after the laparoscopic technique). Recurrence rates reported were higher in patients operated conventionally (median 9.1% versus 7.0% for patients operated laparoscopically). Recurrences after PHH repair may decrease with usage of mesh in the hiatus, although uniform criteria for this procedure are lacking. No conclusions could be drawn regarding the necessity for an additional antireflux procedure. Furthermore, uniform specific indications for the need of an esophageal lengthening procedure or preoperative assessment methods for shortened esophagus could not be detected. Treatment based on standardized protocols for preoperative assessment and postoperative follow-up is required to clarify the current controversies.