Pitfalls and Important Issues in Testing Reliability Using Intraclass Correlation Coefficients in Orthopaedic Research

Background

Intra-class correlation coefficients (ICCs) provide a statistical means of testing the reliability. However, their interpretation is not well documented in the orthopedic field. The purpose of this study was to investigate the use of ICCs in the orthopedic literature and to demonstrate pitfalls regarding their use.

Methods

First, orthopedic articles that used ICCs were retrieved from the Pubmed database, and journal demography, ICC models and concurrent statistics used were evaluated. Second, reliability test was performed on three common physical examinations in cerebral palsy, namely, the Thomas test, the Staheli test, and popliteal angle measurement. Thirty patients were assessed by three orthopedic surgeons to explore the statistical methods testing reliability. Third, the factors affecting the ICC values were examined by simulating the data sets based on the physical examination data where the ranges, slopes, and interobserver variability were modified.

Results

Of the 92 orthopedic articles identified, 58 articles (63%) did not clarify the ICC model used, and only 5 articles (5%) described all models, types, and measures. In reliability testing, although the popliteal angle showed a larger mean absolute difference than the Thomas test and the Staheli test, the ICC of popliteal angle was higher, which was believed to be contrary to the context of measurement. In addition, the ICC values were affected by the model, type, and measures used. In simulated data sets, the ICC showed higher values when the range of data sets were larger, the slopes of the data sets were parallel, and the interobserver variability was smaller.

Conclusions

Care should be taken when interpreting the absolute ICC values, i.e., a higher ICC does not necessarily mean less variability because the ICC values can also be affected by various factors. The authors recommend that researchers clarify ICC models used and ICC values are interpreted in the context of measurement.     

The effects of age, physical activity level, and body anthropometry on calcaneal speed of sound value in men

Summary

The influences of age, physical activity, and body anthropometry on calcaneal speed of sound are different among young adults, middle-aged, and elderly men.

Introduction

Quantitative ultrasound assessment of bone health status is much needed for developing countries in the screening of osteoporosis, but further studies on the factors that influence the quantitative ultrasound indices are required.

Objectives

The present study examined the influence of age, lifestyle factors, and body anthropometry on calcaneal speed of sound (SOS) in a group of Malaysian men of diverse age range.

Subjects and methods

A cross-sectional study was conducted, and data from 687 eligible males were used for analysis. They answered a detailed questionnaire on their physical activity status, and their anthropometric measurements were taken. Their calcaneal SOS values were evaluated using the CM-200 sonometer (Furuno, Nishinomiya City, Japan).

Results

Subjects with higher body mass index (BMI) had higher calcaneal SOS values albeit significant difference was only found in the elderly subjects (p?<?0.05). Sedentary subjects had lower calcaneal SOS values than physically active subjects, but significant difference was only found in the middle-aged subjects (p?<?0.05). Calcaneal SOS was significantly (p?<?0.05) correlated with age in young men; height, BMI, and physical activity score in middle-aged men; height and physical activity score in elderly men; and age and physical activity score for overall subjects. In a multivariate regression model, significant (p?<?0.05) predictors for calcaneal SOS included age for young men; physical activity, BMI, body fat percentage, and height for middle-aged men; height for elderly men; and age, height, physical activity, weight, and body fat percentage for overall subjects.

Conclusion

Age, body anthropometry, and physical activity level have significant effects on the calcaneal SOS value in men.     

Management of skeletal-related events in patients with advanced prostate cancer and bone metastases: Incorporating new agents into clinical practice

Skeletal-related events (SREs) are a common complication of bone metastases, and have serious negative consequences for patients with castrate-resistant prostate cancer (CRPC). SREs can lead to severe pain, increased risk of death, increased health care costs and reduced quality of life. Until recently, zoledronic acid has been the sole standard of care for the prevention of SREs in men with CRPC with bone metastases. Denosumab, a receptor activator of nuclear factor kappa-B ligand (RANK-L) inhibitor, has been recently approved for use in Canada for this indication, thus presenting another option for these patients. Denosumab was shown to be superior to zoledronic acid in delaying the time to first or subsequent SREs in CRPC patients with bone metastases. This review discusses current and previous trials examining agents designed to prevent SREs in men with CRPC and bone metastases. It also discusses the practical aspects of administering a bone-targeted therapy, including choosing a bone-targeted therapy, monitoring at the onset and during therapy, switching from one therapy to another, and assessing potential complications.     

A statistical strategy to identify recombinant viral ribonucleoprotein of avian,human, and swine influenza A viruses with elevated polymerase activity

Objectives

Reassortment of influenza A viruses can give rise to viral ribonucleoproteins (vRNPs) with elevated polymerase activity and the previous three pandemic influenza viruses contained reassorted vRNPs of different origins. These suggest that reassorted vRNP may be one of the factors leading to a pandemic virus. In this study, we reconstituted chimeric vRNPs with three different viral strains isolated from avian, human and swine hosts. We applied a statistical strategy to identify the effect that the origin of a single vRNP protein subunit or the interactions between these subunits on polymerase activity.

Design

Eighty one chimeric vRNPs were reconstituted in 293T cells at different temperatures. Polymerase activity was determined by luciferase reporter assay and the results were analysed by multiway anova and other statistical methods.

Results

It was found that PB2, PB1, NP, PB2‐PB1 interaction, PB2‐PA interaction and PB1‐NP interaction had significant effect on polymerase activity at 37°C and several single subunits and interactions were identified to lead to elevation of polymerase activity. Furthermore, we studied 27 out of these 81 different chimieric vRNPs in different combinations via fractional factorial design approach. Our results suggested that the approach can identify the major single subunit or interaction factors that affect the polymerase activity without the need to experimentally reproduce all possible vRNP combinations.

Conclusions

Statistical approach and fractional factorial design are useful to identify the major single subunit or interaction factors that can modulate viral polymerase activity.     

Measurement of dyspnea in patients with obstructive sleep apnea

Purpose

Patients with obstructive sleep apnea (OSA) frequently complain of exertional dyspnea. We aimed to assess its related factors and the significance of its measurement in OSA.

Methods

We evaluated 301 subjects with suspected OSA for dyspnea during activities of daily living using the Medical Research Council (MRC) scale. We analyzed the relationships between MRC grades and various subjective and objective indices. Further, the relationship of disease severity based on the apnea/hypopnea index (AHI) with these indices was examined. Results were compared between those obtained using MRC grades and the AHI.

Results

Of 301 subjects, 265 were diagnosed with OSA. Their MRC scores were worse than in non-OSA patients. Among OSA patients, 125 had MRC grade 1 (mild), 121 had MRC grade 2 (moderate), and 19 had MRC grade 3 or more (severe) dyspnea. Various measurements differed significantly between groups categorized according to the MRC scale although determinants between mild and moderate groups and between moderate and severe groups differed. AHI categorizations were not significantly related to patient-reported measurements such as the Medical Outcomes Study 36-item short form, Pittsburgh Sleep Quality Index, and Hospital Anxiety and Depression Scale scores, unlike categorization based on the MRC scale.

Conclusions

Dyspnea is an important outcome in OSA although dyspnea in OSA patients is unrelated to the sleep disorder per se. Measurement of dyspnea in patients with OSA might provide further insights into the health of these patients and clinical manifestations of this disease.     

Effect of tyrosine kinase inhibitors,imatinib and nilotinib,in murine lipopolysaccharide-induced acute lung injury during neutropenia recovery

Introduction

Neutrophil recovery has been implicated in deterioration of oxygenation and exacerbation of preexisting acute lung injury (ALI). The aim of this study was to investigate whether imatinib or nilotinib was effective on lipopolysaccharide (LPS)-induced ALI during neutropenia recovery in mice.

Methods

Mice were rendered neutropenic with cyclophosphamide prior to the intratracheal instillation of LPS. Imatinib or nilotinib was administrated by oral gavage during neutropenia recovery. In order to study the effects of drugs, mice were killed on day 5 and blood, bronchoalveolar lavage (BAL) fluid and lung tissue samples were obtained. The lung wet/dry weight ratio and protein levels in the BAL fluid or lung tissue were determined.

Results

Treatment with imatinib or nilotinib significantly attenuated the LPS-induced pulmonary edema, and this result was supported by the histopathological examination. The concentrations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and myeloperoxidase in BAL fluid were significantly inhibited by imatinib or nilotinib in mice of ALI during neutropenia recovery. The mRNA expressions of platelet-derived growth factor receptor-β and c-KIT in imatinib or nilotinib group were significantly lower than LPS group.

Conclusions

Our data indicated that imatinib or nilotinib effectively attenuated LPS-induced ALI during neutropenia recovery. These results provide evidence for the therapeutic potential of imatinib and nilotinib in ALI during neutropenia recovery.