Latent variable mixture models: a promising approach for the validation of patient reported outcomes

Purpose

A fundamental assumption of patient-reported outcomes (PRO) measurement is that all individuals interpret questions about their health status in a consistent manner, such that a measurement model can be constructed that is equivalently applicable to all people in the target population. The related assumption of sample homogeneity has been assessed in various ways, including the many approaches to differential item functioning analysis.

Methods

This expository paper describes the use of latent variable mixture modeling (LVMM), in conjunction with item response theory (IRT), to examine: (a) whether a sample is homogeneous with respect to a unidimensional measurement model, (b) implications of sample heterogeneity with respect to model-predicted scores (theta), and (c) sources of sample heterogeneity. An example is provided using the 10 items of the Short-Form Health Status (SF-36^®) physical functioning subscale with data from the Canadian Community Health Survey (2003) (N = 7,030 adults in Manitoba).

Results

The sample was not homogeneous with respect to a unidimensional measurement structure. Specification of three latent classes, to account for sample heterogeneity, resulted in significantly improved model fit. The latent classes were partially explained by demographic and health-related variables.

Conclusion

The illustrative analyses demonstrate the value of LVMM in revealing the potential implications of sample heterogeneity in the measurement of PROs.

     

Direct-to-participant feedback and awareness of bone mineral density testing results in a population-based sample of mid-aged Canadians

Summary  

This population-based study of mid-aged Canadians assessed awareness of diagnosis by bone mineral density (BMD) following dual-energy X-ray absorptiometry (DXA) testing and compared the effects of feedback only to the physician with direct-to-participant feedback. Poor recall of osteoporosis results was observed irrespective of the feedback destination, but direct-to-participant feedback improved recall of borderline or normal results.     

Melt electrospinning of biodegradable polyurethane scaffolds

Electrospinning from a melt, in contrast to from a solution, is an attractive tissue engineering scaffold manufacturing process as it allows for the formation of small diameter fibers while eliminating potentially cytotoxic solvents. Despite this, there is a dearth of literature on scaffold formation via melt electrospinning. This is likely due to the technical challenges related to the need for a well-controlled high-temperature setup and the difficulty in developing an appropriate polymer. In this paper, a biodegradable and thermally stable polyurethane (PU) is described specifically for use in melt electrospinning. Polymer formulations of aliphatic PUs based on (CH(2))(4)-content diisocyanates, polycaprolactone (PCL), 1,4-butanediamine and 1,4-butanediol (BD) were evaluated for utility in the melt electrospinning process. The final polymer formulation, a catalyst-purified PU based on 1,4-butane diisocyanate, PCL and BD in a 4/1/3M ratio with a weight-average molecular weight of about 40kDa, yielded a nontoxic polymer that could be readily electrospun from the melt. Scaffolds electrospun from this polymer contained point bonds between fibers and mechanical properties analogous to many in vivo soft tissues.     

Quantifying the effect of pore size and surface treatment on epidermal incorporation into percutaneously implanted sphere-templated porous biomaterials in mice

The sinus between skin and a percutaneous medical device is often a portal for infection. Epidermal integration into an optimized porous biomaterial could seal this sinus. In this study, we measured epithelial ingrowth into rods of sphere-templated porous poly(2-hydroxyethyl methacrylate) implanted percutaneously in mice. The rods contained spherical 20-, 40-, or 60-μm pores with and without surface modification. Epithelial migration was measured 3, 7, and 14 days post-implantation utilizing immunohistochemistry for pankeratins and image analysis. Our global results showed average keratinocyte migration distances of 81 ± 16.85 μm (SD). Migration was shorter through 20-μm pores (69.32 ± 21.73) compared with 40 and 60 μm (87.04 ± 13.38 μm and 86.63 ± 8.31 μm, respectively). Migration was unaffected by 1,1' carbonyldiimidazole surface modification without considering factors of pore size and healing duration. Epithelial integration occurred quickly showing an average migration distance of 74.13 ± 12.54 μm after 3 days without significant progression over time. These data show that the epidermis closes the sinus within 3 days, migrates into the biomaterial (an average of 11% of total rod diameter), and stops. This process forms an integrated epithelial collar without evidence of marsupialization or permigration.     

2010 Panel on the biomaterials grand challenges

In 2009, the National Academy for Engineering issued the Grand Challenges for Engineering in the 21st Century comprised of 14 technical challenges that must be addressed to build a healthy, profitable, sustainable, and secure global community (http://www.engineeringchallenges.org). Although crucial, none of the NEA Grand Challenges adequately addressed the challenges that face the biomaterials community. In response to the NAE Grand Challenges, Monty Reichert of Duke University organized a panel entitled Grand Challenges in Biomaterials at the at the 2010 Society for Biomaterials Annual Meeting in Seattle. Six members of the National Academies-Buddy Ratner, James Anderson, Allan Hoffman, Art Coury, Cato Laurencin, and David Tirrell-were asked to propose a grand challenge to the audience that, if met, would significantly impact the future of biomaterials and medical devices. Successfully meeting these challenges will speed the 60-plus year transition from commodity, off-the-shelf biomaterials to bioengineered chemistries, and biomaterial devices that will significantly advance our ability to address patient needs and also to create new market opportunities.     

Congenital anomalies in the offspring of nurses: association with area of employment during pregnancy

The purpose of this study was to determine whether registered nurses in specific areas of employment during pregnancy had a higher risk for congenital anomalies in their offspring. An offspring cohort (n = 22,611) was created through linkage of the British Columbia Vital Statistics Agency live and stillbirth records from 1986 to 2000, to a female cohort database of registered nurses. Of these, 16,005 (70.8%) were registered in a specific area of employment when pregnant. Odds ratios were calculated using generalized estimating equations (GEE), binary logistic regression with adjustment for sex, mother's age, and year of birth. Elevated risks of congenital anomalies were found for the singleton offspring of nurses employed in the following areas: operating rooms and pediatric nursing units (heart anomalies); maternal newborn units (integument); emergency room (respiratory system); and psychiatry (upper alimentary tract). Further research is needed to determine whether these are chance or consistent findings and whether exposure patterns might provide biological plausibility.