Publications

OBJECTIVE

We sought to develop a list of 5 tests, treatments, or services commonly used in rheumatology practice whose necessity or value should be questioned and discussed by physicians and patients.

METHODS

We used a multistage process combining consensus methodology and literature reviews to arrive at the American College of Rheumatology's (ACR) Top 5 list. Rheumatologists from diverse practice settings generated items using the Delphi method. Items with high content agreement and perceived high prevalence advanced to a survey of ACR members, who comprise >90% of the US rheumatology workforce. To increase the response rate, a nested random sample of 390 rheumatologists received more intensive survey followup. The samples were combined and weighting procedures were applied to ensure generalizability. Items with high ratings underwent literature review. Final items were then selected and formulated by the task force.

RESULTS

One hundred five unique items were proposed and narrowed down to 22 items during the Delphi rounds. A total of 1,052 rheumatologists (17% of those contacted) participated in the member-wide survey, whereas 33% of those in the nested random sample participated; respondent characteristics were similar in both samples. Based on survey results and available scientific evidence, 5 items (relating to antinuclear antibodies, Lyme disease, magnetic resonance imaging, bone absorptiometry, and biologic therapy for rheumatoid arthritis) were selected for inclusion.

CONCLUSION

The ACR Top 5 list is intended to promote discussions between physicians and patients about health care practices in rheumatology whose use should be questioned and to assist rheumatologists in providing high-value care.

BACKGROUND

Several studies have concluded that diabetes mellitus and heart disease carry similar risk for future cardiovascular disease (CVD). Most of these studies were too small to quantify independent risks specific to women. The purpose of this study was to determine whether diabetes mellitus is a coronary heart disease (CHD) risk equivalent for prediction of future CHD and CVD events in women.

METHODS AND RESULTS

The Raloxifene Use for the Heart (RUTH) trial was an international, multicenter, double-blind, randomized, placebo-controlled trial of raloxifene and CVD outcomes in 10 101 postmenopausal women selected for high CHD risk. Of these, 3672 had a history of diabetes mellitus without known CHD, and 3265 had a history of CHD without known diabetes mellitus. Cox proportional hazard models were used to compare cardiovascular outcomes in these 2 groups. Mean age at baseline was 67.5 years; median follow-up was 5.6 years. There were 725 deaths, including 450 cardiovascular deaths. In age-adjusted analyses, diabetic women had an increased risk of all-cause mortality compared with women with CHD. Although the overall risk of CHD and CVD was lower in diabetic women compared with women with CHD, the risk of fatal CHD, fatal CVD, and all-cause mortality was similar (hazard ratio [95% confidence interval]: 0.85 [0.65-1.12], 0.99 [0.78-1.25], and 1.18 [0.98-1.42], respectively, after adjusting for age, lifestyle factors, CHD risk factors, statin use, and treatment assignment).

CONCLUSIONS

In the RUTH trial, diabetes mellitus was a CHD risk equivalent in women for fatal, but not nonfatal, CHD and CVD.

BACKGROUND

Geriatric patients' (defined as those older than 65 years old) inherent comorbidities, functional limitations, and bone quality present obstacles to successful clinical outcomes for operatively treated supination external rotation (SER) ankle fractures. We retrospectively reviewed a prospectively collected series of SER injuries between 2004 and 2010. This is a comparison of the radiographic and clinical outcomes of our geriatric (27 patients) and nongeriatric (81 patients) populations. We hypothesized that geriatric patients would have worse outcomes when compared to nongeriatric patients.

METHODS

All SER ankle fractures (176) treated by a single surgeon were enrolled in a prospective database. All patients fulfilled inclusion criteria (108) consisting of 1 year of having clinical follow-up, postoperative radiographs, and Foot & Ankle Outcome Scores (FAOS). The primary outcome evaluated was functional outcome as exhibited by the FAOS. The secondary outcomes included adequacy of reduction, loss of reduction, postoperative complications (wound complications, infection, pain-driven hardware removal), and range of motion.

RESULTS

Despite significantly higher rates of diabetes (P < .001) and peripheral vascular disease (P < .001), there were statistically significantly better FAOS outcomes in the symptoms subcategory among the geriatric population. There was no significant difference in the articular reduction, syndesmotic reduction, wound complications, postoperative infections, or range of motion between these groups.

CONCLUSION

Geriatric patients exhibited equivalent complication rates, radiographic outcomes, and functional outcomes compared to nongeriatric patients in this series. Anatomic fixation and soft tissue management counter the inherent risks of operative intervention in geriatric populations that report higher rates of comorbidities. This study supports aggressive fracture- and ligament-specific operative intervention in geriatric patients presenting with unstable SER injuries.

Human and mouse marapsins (Prss27) are serine proteases preferentially expressed by stratified squamous epithelia. However, mouse marapsin contains a transmembrane anchor absent from the human enzyme. To gain insights into physical forms, activities, inhibition, and roles in epithelial differentiation, we traced tail loss in human marapsin to a nonsense mutation in an ancestral ape, compared substrate preferences of mouse and human marapsins with those of the epithelial peptidase prostasin, designed a selective substrate and inhibitor, and generated Prss27-null mice. Phylogenetic analysis predicts that most marapsins are transmembrane proteins. However, nonsense mutations caused membrane anchor loss in three clades: human/bonobo/chimpanzee, guinea pig/degu/tuco-tuco/mole rat, and cattle/yak. Most marapsin-related proteases, including prostasins, are type I transmembrane proteins, but the closest relatives (prosemins) are not. Soluble mouse and human marapsins are tryptic with subsite preferences distinct from those of prostasin, lack general proteinase activity, and unlike prostasins resist antiproteases, including leupeptin, aprotinin, serpins, and α2-macroglobulin, suggesting the presence of non-canonical active sites. Prss27-null mice develop normally in barrier conditions and are fertile without overt epithelial defects, indicating that marapsin does not play critical, non-redundant roles in development, reproduction, or epithelial differentiation. In conclusion, marapsins are conserved, inhibitor-resistant, tryptic peptidases. Although marapsins are type I transmembrane proteins in their typical form, they mutated independently into anchorless forms in several mammalian clades, including one involving humans. Similar pathways appear to have been traversed by prosemins and tryptases, suggesting that mutational tail loss is an important means of evolving new functions of tryptic serine proteases from transmembrane ancestors.