The future of outcomes measurement: item banking,tailored short-forms,and computerized adaptive assessment

The use of item banks and computerized adaptive testing (CAT) begins with clear definitions of important outcomes, and references those definitions to specific questions gathered into large and well-studied pools, or “banks” of items. Items can be selected from the bank to form customized short scales, or can be administered in a sequence and length determined by a computer programmed for precision and clinical relevance. Although far from perfect, such item banks can form a common definition and understanding of human symptoms and functional problems such as fatigue, pain, depression, mobility, social function, sensory function, and many other health concepts that we can only measure by asking people directly. The support of the National Institutes of Health (NIH), as witnessed by its cooperative agreement with measurement experts through the NIH Roadmap Initiative known as PROMIS (www.nihpromis.org), is a big step in that direction. Our approach to item banking and CAT is practical; as focused on application as it is on science or theory. From a practical perspective, we frequently must decide whether to re-write and retest an item, add more items to fill gaps (often at the ceiling of the measure), re-test a bank after some modifications, or split up a bank into units that are more unidimensional, yet less clinically relevant or complete. These decisions are not easy, and yet they are rarely unforgiving. We encourage people to build practical tools that are capable of producing multiple short form measures and CAT administrations from common banks, and to further our understanding of these banks with various clinical populations and ages, so that with time the scores that emerge from these many activities begin to have not only a common metric and range, but a shared meaning and understanding across users. In this paper, we provide an overview of item banking and CAT, discuss our approach to item banking and its byproducts, describe testing options, discuss an example of CAT for fatigue, and discuss models for long term sustainability of an entity such as PROMIS. Some barriers to success include limitations in the methods themselves, controversies and disagreements across approaches, and end-user reluctance to move away from the familiar.     

Mortality among ferrous foundry workers

Mortality analyses were carried out for 278 male hourly workers who were employed for at least 10 years at a gray iron foundry and who died between January 1, 1970 and December 31, 1981. Statistically significant excess proportional mortality due to non-malignant respiratory disease (SPMR = 177), lung cancer (SPMR = 148), and leukemia (SPMR = 284) was found among the 221 white males. Among nonwhite males there was a significant excess in proportional mortality due to circulatory diseases (SPMR = 143). White males in the Finishing classification experienced a significant excess of proportional mortality due to nonmalignant respiratory disease (SPMR = 279) and lung cancer (SPMR = 179). White males in the Core Room classification experienced an excess of proportional mortality due to nonmalignant respiratory disease (SPMR = 321). Case-control studies demonstrated a significant association between nonmalignant respiratory disease and the Finishing classification after controlling for the effects of age, prior occupations in coal mining or foundries, and smoking. A positive but nonsignificant association between lung cancer and Finishing was also found after controlling for age, prior work history, and smoking in case control studies.     

Ultrasonographic measurement of shoulder subluxation in patients with post-stroke hemiplegia.

OBJECTIVE: To evaluate the ultrasonographic measurement of shoulder subluxation in patients with post-stroke hemiplegia. DESIGN: Prospective, single blind study. PATIENTS: A total of 41 patients with post-stroke hemiplegia were included (24 men and 17 women, mean age 56 years (standard deviation 11), age range 34-78 years). METHODS: Clinical evaluation of the affected shoulder was assessed using the Motricity Index scores and the Modified Ashworth Scale. Two ultrasonographic measurements were taken to check intra-rater reliability. The shoulder subluxation ratio was determined as the ratio of the radiographic vertical and horizontal distance, and the ultrasonographic lateral and anterior distances in the affected shoulder divided by that in the unaffected shoulder. RESULTS: Intraclass correlation coefficients of the repeated ultrasonographic lateral/anterior distance measurements in the unaffected and affected shoulders were 0.979/0.969 and 0.950/0.947, respectively. Ultrasonographic lateral/anterior distance ratios were negatively correlated with Motricity Index scores of the affected shoulder abduction (r = -0.490, p < 0.001/ r = -0.671, p < 0.001). Ultrasonographic anterior distance ratio was negatively correlated with Modified Ashworth Scale score of the affected shoulder (r = -0.374, p < 0.05). However, there was no correlation between radiographic distance ratios and clinical evaluation scores. CONCLUSION: We strongly recommend ultrasonography as a diagnostic tool to measure the degree of shoulder subluxation in patients with post-stroke hemiplegia.     

Polymorphism p53 codon-72 and invasive cervical cancer: a meta-analysis.

OBJECTIVES: Although some studies have reported that the arginine isoform on codon 72 of p53 increases the susceptibility to invasive cervical cancer, such data remain controversial. The objective of this study was to quantitatively summarize the evidence for such a relationship. METHODS: Our data sources consisted of a MEDLINE search of the literature published before December 2002, bibliography review, and expert consultation. Thirty-seven studies met the inclusion criteria. Information on sample size, study design, Hardy-Weinberg equilibrium, and method of genotype determination was abstracted by two reviewers using a standardized protocol. The overall odds ratio (OR) of the p53 gene on invasive cervical cancer was estimated using the Mantel-Haenzel method. RESULTS: The overall OR (95% confidence interval) for cervical cancer among those with the homozygous mutant (Arg/Arg) was 1.2 (1.1-1.3, P=0.001) compared with those with the heterozygous mutant (Arg/Pro). By a cellular type of cervical cancer, the overall OR among those with Arg/Arg was statistically significant in adenocarcinomas (1.7, 1.1-2.6, P=0.024), but not in squamous cell carcinomas (1.1, 0.9-1.2, P=0.960), compared with Pro/Pro. Compared with Arg/Pro, the OR among those with Arg/Arg was statistically significant in HPV types 16 (1,5, 1.2-2.0, P=0.002). CONCLUSIONS: Overall, the p53 gene was associated with increased risk for invasive cervical cancer. However, the risk varied by country, cellular, and HPV type.     

Interactions between membrane IgM and the cytoskeleton involve the cytoplasmic domain of the immunoglobulin receptor

Cross-linking induced interactions between the membrane form of immunoglobulin (mIg) and the cytoskeletal matrix have been described by several groups. To date, the function of mIgM association with the cytoskeleton is not yet understood. Delineation of the molecular basis of these interactions will be instrumental in elucidating their function. We have previously shown that the Igα/β heterodimer is not required for ligand-induced mIgM binding to the cytoskeleton. In this study, we have investigated the role of other B cell-specific proteins in mediating these interactions. For this, we expressed mIgM in the non-hematopoietic human cervical carcinoma cell line HeLa S3 and verified the capacity of the surface-expressed IgM to interact with the cytoskeletal matrix upon cross-linking with anti-μ chain antibodies. We show here that only the mIgM molecule itself and no other B cell-specific protein(s) is required in mediating mIgM interactions with actin filaments. In an attempt to determine the cytoskeleton-binding site of mIgM we investigated the role of the cytoplasmic tail of mIgM (KVK) in binding the receptor to actin-based microfilaments. Using mutated forms of mIgM expressed in J558L cells, we show here that KVK plays a role in mediating these interactions. The absence of KVK did not, however, completely abrogate mIgM-cytoskeletal interactions, suggesting that there are additional molecular requirements for the ligand-induced mIgM binding to the cytoskeletal matrix.     

The biomechanical and morphological changes in the medial collateral ligament of the rabbit after immobilization and remobilization

The effects of immobilization and remobilization on the biomechanical and morphological properties of the femur-medial collateral ligament-tibia complex and each of its components were investigated in the rabbit. Specimens that had been obtained after periods of unilateral immobilization of the knee and remobilization were evaluated for structural properties. In addition, the mechanical properties of the substance of the medial collateral ligament and the histological characteristics of both the substance of the ligament and its sites of insertion were evaluated. After immobilization, there were significant reductions in the ultimate load and energy-absorbing capabilities of the bone-ligament complex, and an increased number of failures occurred by tibial avulsion. The tissue of the medial collateral ligament also became less stiff as a result of immobilization. Histologically, the femoral and tibial insertion sites showed increased osteoclastic activity, resorption of bone, and disruption of the normal attachment of the bone to the ligament. With remobilization, the ultimate load and energy-absorbing capabilities of the bone-ligament complex improved but did not return to normal. Failure by tibial avulsion became less frequent, and the stress-strain characteristics of the medial collateral ligament returned to normal. Histologically, the sites of insertion of the ligament also showed evidence of recovery.     

Resorption rate and biocompatibility characteristics of two polyester ventilation tubes in a guinea pig model

OBJECTIVES: Determine the resorption rate and biocompatibility characteristics of 2 polyester ventilation tubes, and to determine whether soap and water exposure accelerates polyester tube degradation. STUDY DESIGN AND SETTING: 50/50 poly (D, L-lactide-co-glycolide; PLGA-50) and poly (L-lactide; PLA) polymers were placed into the tympanic membranes of Hartley pigmented guinea pigs. Integrity of the tubes was determined by weekly otoscopic examination. Biocompatibility was assessed by comparing auditory brainstem response (ABR) thresholds and by examining tympanic membrane changes following tube resorption. Shah minigrommet ventilation tubes were used as controls. In the second portion of this study, implanted PLGA-50 and PLA tubes were exposed weekly to a mixture of soap and water (1:5) until complete resorption was observed. Biocompatibility was assessed by periodic ABR testing and tympanic membrane examination. RESULTS: The PLA tubes remained in the tympanic membrane for a longer period (63.2 +/- 19.3 days) than the PLGA-50 (18.8 +/- 8.1 days). The tympanic membrane and resorbable tube interface demonstrated equivalent findings for auditory thresholds and tissue histopathology at the implant site compared to nonresorbable controls. The resorption behavior was not altered by exposure to soap and water. Tympanic membranes of all animals following tube degradation and soap water exposure were intact with minimal scarring and no signs of persistent foreign body response. The histological analysis showed that implantation of resorbable tubes was not accompanied by secondary infection with otorrhea through the tube, did not result in a permanent perforation or dislocation of the tube into the middle ear cavity, and was not followed by excess tympanosclerosis or localized or diffuse membrane atrophy. CONCLUSIONS AND SIGNIFICANCE: Resorbable polyester pressure equalization tubes demonstrate predictable resorption behavior and similar biocompatibility characteristics when compared with nonresorbable Shah minigrommet ventilation tubes. Exposure to soap water does not accelerate polyester tube degradation nor change the host tissue response during the indwelling period or after complete resorption. The data suggests that resorbable ventilation tubes are substantially equivalent to other FDA-approved tympanostomy devices with regard to safety and biocompatibility in the guinea pig model examined and may provide improved clinical performance by combining this approach with sustained release technology. EBM RATING: B-2.     

A learned odor decreases the number of Fos-immunopositive granule cells in the olfactory bulb of young rats

Olfactory stimulation evokes a column of activity within the olfactory bulb extending from the glomerular layer to the granule cell layer that can be visualized with 2-deoxyglucose autoradiography, optical imaging, Fos protein immunohistochemistry and c-fos mRNA in situ hybridization. The Fos response to odors is typified by the activity of relatively few juxtaglomerular cells, which often occur in foci, and a large number of granule cells extending through much of the bulb. In this study, we characterized the granule cell response to an odor for which young rats had acquired a preference. Fos-like immunoreactive granule cells were quantified by image analysis, and densely stained cells were counted in a region previously shown to be responsive to peppermint odor. We found that odor-trained pups have about half the number of Fos-immunopositive superficial granule cells which respond to a learned odor than do control pups. We then determined whether there was a correlation between the juxtaglomerular cell response and the response of the superficial granule cells deep to those glomerular layer cells. We found a positive correlation between the number of juxtaglomerular cells and the number of granule cells demonstrating Fos immunoreactivity in both control and trained pups, a relationship that changed with early olfactory training.     

VESICO-URETERIC REFLUX AND SURGICALLY TREATED PELVI-URETERIC JUNCTION OBSTRUCTION IN INFANTS UNDER THE AGE OF 12 MONTHS

Background : Pelvi-ureteric junction obstruction has been increasingly diagnosed in infants, mostly as a consequence of antenatal ultrasound examinations. Methods : Of 55 infants below the age of 12 months who underwent dismembered pyeloplasty over a 7-year period, we aimed to determine the patterns and outcome of associated vesico-ureteric reflux that was present in 15 (28%) of the 53 infants in whom follow-up was available. Results : A total of eight infants had resolution of their reflux with conservative management and the median time to resolution was 15 months. Five infants proceeded to ureteroneocystotomy. Conclusions : Given the association of vesico-ureteric reflux and pelvi-ureteric junction obstruction, routine cystography is recommended when the diagnosis of pelvi-ureteric junction obstruction is made.     

Extensive Aberrant Mongolian Spot

A 9-month-old male infant had generalized diffuse blue-gray pigmentation over most of his body, sparing the scalp, face, neck, palms, soles, periumbilical area, genital area, and nipples. Within the lesion, there were several conspicuous macules of considerably darker hue. Histologic examination revealed numerous dermal melanocytes. By 16 months of age, the child's blue-gray pigmentation had decreased substantially.