The economic impact of the Coronavirus 2019 (Covid-2019): Implications for the mining industry.

The Coronavirus 2019 (Covid-19) global pandemic has not only caused infections and deaths, but it has also wreaked havoc with the global economy on a scale not seen since at least the Great Depression. Covid-19 has the potential to destroy individual livelihoods, businesses, industries and entire economies. The mining sector is not immune to these impacts, and the crisis has the potential to have severe consequences in the short, medium and long-term for the industry. Understanding these impacts, and analysing their significance for the industry, and the role it plays in wider economic development is a crucial task for academic research.

Establishing clinical severity for PROMIS® measures in adult patients with rheumatic diseases.

PURPOSE: Different patient-reported outcome (PRO) measures are used for rheumatic diseases (RD). The aims of this study are-(1) Identify PROMIS® domains most relevant to care of patients with RD, (2) Collect T-Score metrics in patients with RD, and (3) Identify clinically meaningful cut-points for these domains. METHODS: A convenience sample of RD patients was recruited consecutively during clinic visits, and asked to complete computer-adaptive tests on thirteen Patient-Reported Outcomes Measurement Information System (PROMIS®) instruments. Based on discussion with clinical providers, four measures were chosen to be relevant and actionable (from rheumatologists' perspective) in RD patients. Data from RD patients were used to develop clinical vignettes across a range of symptom severity. Vignettes were created based on most likely item responses at different levels on the T-score metric (mean = 50; SD = 10) and anchored at 5-point intervals (0.5 SDs). Patients with RD (N = 9) and clinical providers (N = 10) participated as expert panelists in separate one-day meetings using a modified educational standard setting method. RESULTS: Four domains (physical function, pain interferences, sleep disturbance, depression) that are actionable at the point-of-care were selected. For all domains, patients endorsed cut-points at lower levels of impairment than providers by 0.5 to 1 SD (e.g., severe impairment in physical function was defined as a T-score of 35 by patients and 25 by providers). CONCLUSIONS: We used a modified educational method to estimate clinically relevant cut-points to classify severity for PROMIS measures This allows for meaningful interpretation of PROMIS® measures in a clinical setting of RD population.

2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

OBJECTIVE: The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. METHODS: A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease--this being the appropriate current paradigm underlying the disease construct "rheumatoid arthritis." RESULTS: In the new criteria set, classification as "definite RA" is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0-5), serologic abnormality (score range 0-3), elevated acute-phase response (score range 0-1), and symptom duration (2 levels; range 0-1). CONCLUSION: This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimize the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct "rheumatoid arthritis."

The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis: Phase 2 methodological report.

OBJECTIVE: The American College of Rheumatology and the European League Against Rheumatism have developed new classification criteria for rheumatoid arthritis (RA). The aim of Phase 2 of the development process was to achieve expert consensus on the clinical and laboratory variables that should contribute to the final criteria set. METHODS: Twenty-four expert RA clinicians (12 from Europe and 12 from North America) participated in Phase 2. A consensus-based decision analysis approach was used to identify factors (and their relative weights) that influence the probability of "developing RA," complemented by data from the Phase 1 study. Patient case scenarios were used to identify and reach consensus on factors important in determining the probability of RA development. Decision analytic software was used to derive the relative weights for each of the factors and their categories, using choice-based conjoint analysis. RESULTS: The expert panel agreed that the new classification criteria should be applied to individuals with undifferentiated inflammatory arthritis in whom at least 1 joint is deemed by an expert assessor to be swollen, indicating definite synovitis. In this clinical setting, they identified 4 additional criteria as being important: number of joints involved and site of involvement, serologic abnormality, acute-phase response, and duration of symptoms in the involved joints. These criteria were consistent with those identified in the Phase 1 data-driven approach. CONCLUSION: The consensus-based, decision analysis approach used in Phase 2 complemented the Phase 1 efforts. The 4 criteria and their relative weights form the basis of the final criteria set.

2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

OBJECTIVE: The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. METHODS: A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease--this being the appropriate current paradigm underlying the disease construct 'RA'. RESULTS: In the new criteria set, classification as 'definite RA' is based on the confirmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0-5), serological abnormality (range 0-3), elevated acute-phase response (range 0-1) and symptom duration (two levels; range 0-1). CONCLUSION: This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct 'RA'.

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.