Maintaining the enterprisewide continuity and interoperability of patient allergy data.

PURPOSE: The efforts, results, and challenges of a large tertiary care, academic health care system to standardize and integrate allergy information across clinical information systems are discussed. SUMMARY: The University of Michigan Health System and its Information Technology Strategic Advisory Committee recognized the necessity for storing and maintaining allergy information in a single repository; therefore, the clinical data repository (CDR) was named as the central database for coded allergens and reactions for the University of Michigan Hospitals and Health Care Centers (UMHHC) electronic medical record. The Enterprise Allergy Project (EAP) began in June 2005 with the formation of a steering committee that included representatives from clinical departments with order-entry systems. The initial phase of the EAP consisted of several components. One component was a one-time conversion of existing free-text allergy information into coded allergens and reactions. Before the implementation of the EAP, the order-entry system only supported the entry of uncoded allergen and reaction information. An initial process of allergy matching reduced the list of un-coded allergens from 272,519 to 29,500 by using terms that indicated no allergies were present and trimming and modifying free-text strings that closely matched or easily translated to a coded allergen counterpart. Another component of the EAP consisted of the interface and technical build to support allergy information processing between the CDR and University of Michigan (UM)-Carelink. One goal of the EAP was to transfer data bidirectionally, but that goal could not safely be accomplished. CONCLUSION: Implementing a strategy for enterprise allergy integration at UMHHC has improved the quality of allergy information documented as measured by a significant decrease in the amount of uncoded allergens.

Prevalence, incidence, survival, and disease characteristics of systemic sclerosis in a large US population.

OBJECTIVE: To estimate the prevalence, incidence, survival, and disease characteristics of systemic sclerosis (SSc) in the Detroit tricounty area. METHODS: A census of SSc cases for the period 1989-1991 was conducted in the Detroit area, using multiple sources for case identification. Diagnoses were verified by medical record review. Capture-recapture analysis was used to estimate the total SSc population. Cases of localized scleroderma (morphea and linear disease) were excluded. RESULTS: Based on 706 verified cases of SSc, prevalence was initially estimated to be 242.0 cases per million adults (95% confidence interval [95% CI] 213-274), with an annual incidence of 19.3 new cases per million adults per year (95% CI 12.4-30.2). Capture-recapture analysis, based on the degree of overlap of verified cases among multiple sources, resulted in a revised prevalence estimate of 276 cases per million adults (95% CI 245-310). Sex- and race-specific prevalence estimates were significantly higher for women than for men, and for blacks than for whites. The average age at diagnosis was significantly younger for blacks than for whites. Compared with white patients, black patients were almost twice as likely to have diffuse disease (prevalence proportion ratio 1.86, 95% CI 1.48-2.35). Median survival was approximately 11 years. Factors negatively affecting survival included male sex (hazard ratio 1.81, 95% CI 1.29-2.55) and older age at diagnosis (hazard ratio 1.04, 95% CI 1.03-1.05). CONCLUSION: This study establishes baseline estimates of SSc occurrence and characteristics in a large US cohort consisting primarily of black adults and white adults. These data should facilitate research regarding the role of geographic, ethnic, racial, and environmental factors for this disease in comparison populations.

Scleroderma and solvent exposure among women.

Exposure to solvents has been reported to increase the risk of scleroderma. The authors investigated the relation between exposures to solvents in occupational and hobby settings and the development of scleroderma among women in a case-control study with population-based controls in Michigan (1980-1991) and Ohio (1980-1992). A total of 660 cases and 2,227 frequency-matched controls were interviewed by telephone. Diagnoses of scleroderma were verified by medical records review. Paint thinners and removers were significantly associated with scleroderma both by self-report (odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.4, 2.6) and after expert review (OR = 2.0, 95% CI: 1.5, 2.6). Other petroleum distillates (gasoline and mineral spirits) were not significantly associated with scleroderma after controlling for other correlated exposures in multivariable analyses. Trichloroethylene was associated with scleroderma both by self-report (OR = 2.0, 95% CI: 0.8, 4.8) and after expert review (OR = 1.9, 95% CI: 0.6, 6.6), but not significantly. Analyses by duration of exposure found that risk increased with the duration of use of any of the solvents (OR = 1.01/year of exposure, 95% CI: 1.01, 1.02), but there was no evidence of increasing risk with increasing duration of exposure for any specific solvent studied. In summary, exposures to paint thinners and removers were associated with scleroderma in women but showed no evidence of increasing risk with increasing duration. Exposures to other specific chlorinated and nonchlorinated hydrocarbon solvents were not clearly associated with scleroderma.

Chemical stabilities and biological activities of thalidomide and its N-alkyl analogs.

UNLABELLED: PURPOSE. To determine whether the N-alkyl analogs of the thalidomide are active and stable, their stabilities in buffer and their abilities to inhibit tumor necrosis factor alpha (TNF-alpha) in vitro in human peripheral blood mononuclear cell cultures were investigated. METHODS: TNF-alpha concentrations were determined with the aid of ELISA kits. Chemical stabilities of the compounds were determined in three phosphate buffer solutions (pH 6, 6.4, and 7.4) at 25 and 32 degrees C by high-pressure liquid chromatography, and half-lives were calculated. RESULTS: The addition of N-alkyl groups to the glutarimide ring of the thalidomide molecule had little effect on the ability such compounds have to inhibit TNF-alpha production. There was no statistical difference between the activity of thalidomide and its N-alkyl analogs at a 95% confidence level. Like thalidomide, the N-alkyl analogs in this series inhibit an average of 60% of the TNF-alpha synthesis in lipopolysaccharide-stimulated peripheral blood mononuclear cell cultures. Thalidomide and its N-alkyl analogs are hydrolyzed at very similar rates, with half-lives ranging from 25 to 35 h at 32 degrees C at pH 6.4 and an average rate constant of 2.35 x 10(-2)/h. CONCLUSION: Alkylating thalidomide had little effect on its ability to inhibit the production of TNF-alpha in these cell cultures. All of the compounds tested seem to have some, perhaps comparable, therapeutic potential.

Percutaneous delivery of thalidomide and its N-alkyl analogs.

PURPOSE: The purpose of this study was to determine the permeation parameters of thalidomide and three of its N-alkyl analogs and to establish a correlation between the physicochemical properties of these compounds and their percutaneous rates of absorption. METHODS: In vitro permeation studies were performed from buffer, n-alkanols and various mixed components using vertical Franz diffusion cells fitted with human epidermal membranes. RESULTS: Measured steady-state fluxes indicate that N-methyl thalidomide is a far better penetrant of human skin than the "parent molecule". However, fluxes through skin drop off markedly from that of the methylated compound when the chain length is extended to propyl and pentyl. However, they remain well above the flux of thalidomide, which is less than 0.025 microg/cm2/h. CONCLUSIONS: The best skin permeant of this series was the N-methyl analog, which also exhibited the highest water (buffer) solubility compared to thalidomide, and the N-propyl and N-pentyl analogs. The N-propyl and N-pentyl analogs were more lipid soluble and exhibited higher partition coefficient values than the N-methyl analog. From all the permeability data using buffer, a series of n-alkanols and various combinations of solvents and enhancers as vehicles, the more water-soluble compound and not the more lipid soluble one was the best skin permeant.

Physicochemical characterization and solubility analysis of thalidomide and its N-alkyl analogs.

PURPOSE: The present study was primarily aimed at exploring the feasibility of improving percutaneous delivery via chemical manipulation of the thalidomide molecule to form analogs with improved physicochemical properties. N-Alkyl analogs were synthesized with the belief that these would be suitably hydrophobic and far less crystalline than the reference compound. This article presents their physicochemical properties. METHODS: Thalidomide and three of its N-alkyl analogs were synthesized. Identification and levels of purity (>96%) were assured through element analysis, fast atom-bombardment mass spectrometry, nuclear magnetic resonance spectroscopy, and high-performance liquid chromatography. N-Octanol/water partition coefficients were determined at pH 6.4. Solubilities in water and a series of n-alkanols were obtained. Best-fit solubility parameters were determined from the solubilities of the respective compounds in London solvents and were also calculated from respective hexane solubilities. melting points and heats of fusion. RESULTS: Methylation of the thalidomide molecule at its acidic nitrogen led to an aqueous solubility about 6-fold higher than thalidomide but, because the alkyl chain length was further extended from methyl to pentyl. aqueous solubilities decreased essentially exponentially. The destabilization of the crystalline structure with increasing alkyl chain length led to an increased solubility in nonpolar media. The log partition coefficient increased linearly with increasing alkyl chain length and the solubility parameters declined systematically through this series. By adding a methyl group to the thalidomide structure, the melting point dropped by more than 100 degrees C. Adding to the alkyl chain length led to further, more modest decreases. Heats of fusion decreased dramatically upon thalidomide's alkylation as well. CONCLUSION: Alkylation of the thalidomide molecule resulted in compounds with physicochemical properties that appear to be markedly better suited for percutaneous delivery.