Clinical research methods for treatment, diagnosis, prognosis, etiology, screening, and prevention: A narrative review.

This narrative review is an introduction for health professionals on how to conduct and report clinical research on six categories: treatment, diagnosis/differential diagnosis, prognosis, etiology, screening, and prevention. The importance of beginning with an appropriate clinical question and the exploration of how appropriate it is through a literature search are explained. There are three methodological directives that can assist clinicians in conducting their studies from a methodological perspective: (1) how to conduct an original study or a systematic review, (2) how to report an original study or a systematic review, and (3) how to assess the quality or risk of bias for a previous relevant original study or systematic review. This methodological overview article would provide readers with the key points and resources regarding how to perform high-quality research on the six main clinical categories.

What happens to intimate partner violence studies registered on clinicaltrials.gov? A systematic review of a clinical trials registry.

BACKGROUND: There is an increasing number of interventions aimed at reducing the incidence and improving the identification and management of intimate partner violence (IPV), which are being tested in randomized clinical trials. Publication bias, improper reporting, and selective reporting in clinical trials have led to widespread adoption of pre-registration of clinical trials. Non-publication of study results leads to inefficiency, ethical issues, and scientific issues with the IPV literature. When study results and methodology are not made available through publication or other public means, the results cannot be used to their full potential. The objective of this study was to determine the publication rates of IPV trials registered in a large clinical trial registry. METHODS: We conducted a systematic review of all IPV-related clinicaltrials.gov records and determined whether the studies that had been completed for ≥ 18 months have been published in a peer-reviewed journal or in the clinicaltrials.gov registry. Two authors extensively searched the literature and contacted study investigators to locate full-text publications for each included study. RESULTS: Of 83 completed IPV-related trials registered on clinicaltrials.gov, 64 (77.1%, 95% CI: 66.6-85.6) were subsequently published in full-text form. Of the 19 unpublished studies, authors confirmed that there was no publication for 11 studies; we were unable to contact the investigator or locate a publication for the remaining eight studies. Only four studies (all published) posted their results on clinicaltrials.gov upon completion. CONCLUSION: Approximately one in four IPV trials are not published 18 months after completion, indicating that clinicians, researchers, and other evidence users should consider whether publication bias might affect their interpretation of the IPV literature. Further research is warranted to understand reasons for non-publication of IPV research and methods to improve publication rates.

Orthopaedic Trainees Retain Knowledge After a Partner Abuse Course: An Education Study.

INTRODUCTION: Intimate partner violence (IPV) is a serious global issue that results in a large number of injuries and deaths among women. Educating clinicians about IPV can help providers identify, prevent, and treat victims, and, ultimately, improve care for victims of abuse. We sought to determine the effect of a half-day educational course on IPV for orthopaedic surgical trainees on knowledge and attitudes. QUESTIONS/PURPOSES: We asked (1) whether a half-day educational course on IPV can improve orthopaedic surgical trainees' knowledge and (2) attitudes regarding IPV; and (3) whether a course on IPV can be accepted and viewed as valuable by trainees? METHODS: Using published research on IPV in patients with musculoskeletal injuries, we developed a half-day educational course. The curriculum included lectures and discussion regarding the basics of IPV, the current state of IPV research, what to do when a patient is a victim or perpetrator, and the orthopaedic surgeon's role in recognizing, preventing, and assisting with IPV. All 33 course participants (30 men and three women), all orthopaedic surgical trainees, completed a questionnaire that included general true or false or agree or disagree statements regarding their knowledge, attitudes, and practices of IPV in the musculoskeletal setting; the questionnaire also included a knowledge test of 25 true or false statements. The questionnaire was administered immediately before, immediately after, and 3 months after the course; 76% (25 of 33) took the test immediately after the course and 82% (27 of 33) completed the test at 3 months. Participant knowledge scores were compared across the three different times to determine the effect of the course. RESULTS: Participants increased their knowledge after the course, and the increased knowledge was retained at retesting at 3 months; the mean percentage of correct answers before the course was 57%, which increased to 73% after the course, and was 68% 3 months later (F = 9.505; p = 0.001). Before the course, most of the course participants (30 of 32; 94%) agreed that IPV is an important issue; agreement increased to 100% immediately after the course. The largest change in attitude was in response to the statement: "I am skeptical that the health care system has the resources to screen for IPV." Before the course, 53% (17 of 32) of trainees endorsed this statement, but the percent decreased to 36% (nine of 25) after the course and remained low at 33% (nine of 27), at the 3-month test. CONCLUSIONS: Our findings show that a short course on IPV in patients with musculoskeletal injuries led to an improvement and retention of knowledge 3 months after the course. Based on our findings, we recommend that IPV education be integrated in training programs for orthopaedic surgeons. Future projects should focus on developing and implementing a sustainable education program that can affect practice for healthcare professionals and trainees in multiple clinical settings.

Arthroscopic surgery for synovial chondromatosis of the hip: a systematic review of rates and predisposing factors for recurrence.

PURPOSE: Synovial chondromatosis of the hip is a benign condition whereby pain and functional limitations occur due to numerous intra-articular osteochondral fragments produced by a metaplastic synovium. Recurrence not only worsens morbidity but may lead to malignant transformation. With reported recurrence rates as high as 22% by open surgical approaches and given the increasing use of hip arthroscopy for the treatment of synovial chondromatosis, we sought to quantify the recurrence rate after arthroscopy, as well as identify predisposing factors for recurrence. METHODS: Using predetermined inclusion criteria, 3 electronic databases--Embase, Medline, and PubMed-were searched for relevant articles addressing arthroscopic surgery for synovial chondromatosis of the hip across all available dates up to and including February 16, 2014. A hand search of the reference sections of the included studies was also completed. Article screening was conducted in duplicate. Reviewer agreement statistics and descriptive statistics of the included studies are presented. RESULTS: From an initial retrieval of 2,542 studies, 14 studies satisfied the criteria for inclusion. A total of 197 patients (age range, 13 to 81 years) underwent hip arthroscopy for removal of intra-articular osteochondral fragments and synovectomy to alleviate both mechanical symptoms and pain. Follow-up periods ranged from 1 to 184 months, with approximately 7.6% of patients (15 of 197) lost to follow-up. The recurrence rate after hip arthroscopy was 7.1% (14 of 197), and the rate of minor complications, such as perineal and pedal neurapraxia, was 1%. CONCLUSIONS: For synovial chondromatosis of the hip, arthroscopic removal of osteochondral fragments with synovectomy is both safe and effective, with a mean recurrence rate of 7.1%. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.

Local control of extra-abdominal desmoid tumors: systematic review and meta-analysis.

The local control of desmoid tumors constitutes a continuing treatment dilemma due to its high recurrence rates. The purpose of this systematic review was to critically examine the current treatment of these rare tumors and to specifically evaluate the local failure and response rates of surgery, radiation and systemic therapy. We comprehensively searched the literature for relevant studies across Cinahl, Embase, Medline and the Cochrane databases. Articles were categorized as surgery, radiation, surgery + radiation and systemic therapy (including cytotoxic and non cytotoxic). Methodological quality of included studies was assessed using the Newcastle-Ottawa Scale. Pooled odd ratios (OR) for comparative studies and weighted proportions with 95% confidence intervals (CI) are reported. Thirty-five articles were included in the final analysis. Weighted mean local failure rates were 22% [95% CI (16-28%)], 35% [95% CI (26-44%)] and 28% [95% CI (18-39%)] for radiation alone, surgery alone and surgery + radiation respectively. In the analysis of comparative studies, surgery and radiation in combination had lower local failure rates than radiation alone [OR 0.7 (0.4, 1.2)] and surgery alone [OR 0.7 (0.4, 1.0)]. Weighted mean stable disease rates were 91% [95% CI (85-96%)] and 52% [95% CI (38-65%)] for non cytotoxic and cytotoxic chemotherapy respectively. The current evidence suggests that surgery alone has a consistently high rate of local recurrence in managing extra-abdominal desmoid tumors. Radiation therapy in combination with surgery improves local control rates. However, the limited data on systemic therapy for this rare tumor suggests the benefit of using both cytotoxic and non cytotoxic chemotherapy to achieve stable disease.

The surgical and functional outcome of limb-salvage surgery with vascular reconstruction for soft tissue sarcoma of the extremity.

BACKGROUND: This study compared the surgical, oncological, and functional outcomes of patients undergoing limb-salvage surgery for extremity soft tissue sarcoma with vascular resection and reconstruction with the outcomes of those undergoing limb-salvage without vascular reconstruction. METHODS: Nineteen patients were identified from a prospective soft-tissue sarcoma database who underwent vascular resection and reconstruction as part of their limb-salvage surgery and who were followed up for at least 1 year or until death. Each of these 19 patients was case-matched to 2 additional patients on the basis of tumor location, size, and depth; patient age; and timing of radiation. To compare functional outcome, a subset of patients was case-matched with additional criteria including wound-complication status, motor nerve sacrifice, similar preoperative function as determined by the Toronto Extremity Salvage Score, and no metastases at diagnosis or the 1-year follow-up. RESULTS: Patients in the vascular reconstruction group were more likely to require a muscle transfer (53% vs. 18%; P = .008), experience a wound complication (68% vs. 32%; P = .03), experience deep venous thrombosis (26% vs. 0; P = .003), experience significant limb edema (87% vs. 20%; P = .001), and ultimately require an amputation (16% vs. 3%; P = .07). Patients who underwent vascular reconstruction had only slightly lower Toronto Extremity Salvage Score scores 1 year after surgery (78.5 vs. 84.2; P = .35). There were no significant differences in local or systemic tumor relapse between the two groups. CONCLUSIONS: Vascular reconstruction is a feasible option in limb-salvage surgery for soft tissue sarcoma but is associated with an increased risk for postoperative complications, including amputation. Although function is not significantly worse after vascular reconstruction, the results are less predictable.

The indications for and the prognostic significance of amputation as the primary surgical procedure for localized soft tissue sarcoma of the extremity.

BACKGROUND: The indications for primary amputation of a localized soft tissue sarcoma (STS) of the extremity are not well defined in the literature. However, it has been suggested that patients who require an amputation to treat an STS are at increased risk for developing metastases. We categorized the main indications for primary amputation in our patient population and compared their oncological outcome with the outcome of patients who underwent limb-sparing surgery. METHODS: 413 consecutive patients treated surgically at a single center for primary, nonmetastatic, deep, intermediate-, or high-grade STS of the extremity were reviewed. Indications for primary amputation were identified. Demographics and outcomes were compared between the amputation and limb-salvage groups. Multivariate Cox model analysis was used to identify independent risk factors for systemic relapse. RESULTS: Twenty-five (6%) of 413 patients with STS underwent primary amputation: they were older (P = .05), had larger tumors (P = .001), and had a significantly greater risk of developing metastatic disease than patients who underwent limb-sparing procedures (P = .008). However, multivariate analysis demonstrated that the only independent predictors of systemic relapse were tumor size (P = .0001) and tumor grade (P = .0001). Primary amputation was not an independent risk factor for metastatic disease. CONCLUSIONS: The decision to perform a primary amputation for an STS of the extremity is based on the location and local extent of the tumor, and the expected function of the extremity after tumor resection. The higher risk of metastases for patients who require primary amputation is accounted for by independent risk factors associated with their tumors--predominantly large tumor size.

Treatment of osseous metastases in patients with renal cell carcinoma.

The records of 99 patients treated at one institution for osseous metastases secondary to renal cell carcinoma were reviewed. Patients were followed up for at least 24 months or until death. Survival was analyzed with respect to age, gender, disease-free interval, location of osseous metastases, number of osseous metastatic sites, resection of osseous metastases, and primary tumor resection. The mean age of the 72 men and 27 women was 60 years (range, 34-82 years) and the mean followup was 20 months (range, 2-81 months). Twenty-six patients (26%) had a solitary osseous metastasis, 47 patients (48%) had multiple osseous metastases, and 26 patients (26%) had additional visceral involvement such as the lung and brain at the time of diagnosis. In 49 patients (49%), the renal cell carcinoma was diagnosed concurrently with detection of the osseous metastasis. The presence of one osseous renal carcinoma metastasis, wide resection of the lesion, and a history of nephrectomy were identified as independent predictors of survival in patients with renal cell carcinoma. The eight patients who had wide resection of a solitary osseous metastasis in combination with a nephrectomy had a disease-specific survival rate of 100% (mean followup, 69 months; range, 24-76 months). Patients who present with these characteristics are candidates for aggressive surgical treatment with curative intent.

Tenascin-C expression and distribution in cultured human chondrocytes and chondrosarcoma cells.

Tenascin-C (TNC) is an oligomeric glycoprotein of the extracellular matrix with several distinct isoforms variably expressed during embryogenesis, tumorogenesis, angiogenesis and wound healing. In the normal human adult, TNC is found in large concentrations in articular cartilage, suggesting tissue-specific function. The purpose of this study was to determine the specific in vitro TNC splicing patterns of articular chondrocytes and a human chondrosarcoma cell line. Cells were cultured in a three-dimensional bead system and TNC splice variant expression and distribution were examined with the use of Western blotting techniques, semi-quantitative reverse-transcription polymerase chain reaction and immunohistochemistry. At both the transcriptional and post-translational levels, the chondrocytes were found to express significantly higher levels of the smaller 220 kDa isoform (P < 0.01), which was predominantly incorporated into the matrix. The splicing pattern of the malignant cells was characterized by a higher proportion of the larger 320 kDa isoform which was extruded into the media. In vivo studies are necessary to verify the expression of the large TNC isoform in chondrosarcoma and the production and integration of the smaller isoform in normal chondroid matrix. In addition, elucidation of the biologic functions of the two major TNC isoforms may lead to the development of novel diagnostic and therapeutic approaches to chondrosarcoma.

Giant-cell tumor of the appendicular skeleton.

The common objective of all surgical procedures in the treatment of giant-cell tumor of bone is to minimize the incidence of local recurrence. The purpose of this study was to determine what, if any, patient factors, tumor characteristics, or surgical practices correlate with local recurrence. Seventy-five patients treated for a giant-cell tumor of the appendicular skeleton were followed up for at least 2 years. The mean duration of followup was 62 months (range, 24-224 months). The highest proportion of patients had intralesional curettage, high-speed burring, and adjuvant treatment. Ten patients (13%) had a local recurrence. Bivariate analysis revealed that, with the numbers available, none of the patient variables, tumor variables, or surgical approaches correlated with local recurrence. Post hoc power analysis revealed the power of the study to be 33% to detect a clinically significant difference between treatment groups. The data presented here potentially could contribute to a metaanalysis, which would have the statistical power to determine which tumor-related factors and surgical techniques are most important in predicting recurrence in giant-cell tumor of bone.

Pathologic fracture in osteosarcoma : prognostic importance and treatment implications.

BACKGROUND: The presence of a pathologic fracture in an osteosarcoma has been considered a poor prognostic factor and an indication for immediate amputation. The purpose of the present study was to determine, in the current era of neoadjuvant chemotherapy, whether a pathologic fracture in an osteosarcoma has prognostic importance and whether limb salvage can be safely performed in such patients without compromising clinical outcome. METHODS: In a cooperative effort of the Musculoskeletal Tumor Society, members from eight institutions provided retrospective data on fifty-two patients with osteosarcoma who had a pathologic fracture and on fifty-five patients with osteosarcoma who had not had a pathologic fracture and had been followed for at least two years or until disease recurrence, metastasis, or death. The two groups were matched for patient age and tumor location. Outcomes examined were survival and local recurrence. A subgroup analysis was performed to assess differences in outcome within the group with the pathologic fracture. RESULTS: The five-year estimated survival rates were 55% for the group with a pathologic fracture and 77% for the group without a fracture (p = 0.02). The rate of survival without a local recurrence at five years was 75% for the group with a fracture and 96% for the group without a fracture (p = 0.007). In the group with a fracture, seven (23%) of the thirty patients managed with limb salvage and four (18%) of the twenty-two managed with an amputation had a local recurrence (p = 0.75). Eleven (37%) of the thirty patients with a fracture who were managed with limb salvage and ten (45%) of the twenty-two patients with a fracture who were managed with an amputation died of the disease (p = 0.50). Five patients underwent open reduction and internal fixation followed by limb-salvage surgery. Two of them had a local recurrence and died at an average of eight months postoperatively. The remaining three patients were alive at an average of 6.1 years postoperatively. Local disease control and the survival of these patients were not significantly different from those for the thirty-three patients who were treated with nonoperative immobilization of the fracture followed by limb-salvage surgery. CONCLUSIONS: Patients with osteosarcoma who present with a pathologic fracture or sustain one during preoperative chemotherapy have an increased risk of local recurrence and a decreased rate of survival compared with patients who have not sustained a pathologic fracture. The performance of a limb-salvage procedure in carefully selected patients with a pathologic fracture does not significantly increase the risk of local recurrence or death. Factors predictive of improved outcome, such as the response to chemotherapy and union of the fracture, should be taken into account when limb salvage is being considered.