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Biomedical subjects

S E Gabriel

Publications and source records attributed to S E Gabriel.

At least 73 records · Page 4Linked to original sources

Indirect and nonmedical costs among people with rheumatoid arthritis and osteoarthritis compared with nonarthritic controls.

OBJECTIVE: Compared to rheumatoid arthritis (RA), osteoarthritis (OA) is considered much more benign and much less costly. We sought to describe the economic effects of RA and OA, in terms of the indirect and nonmedical expenditures, compared to nonarthritic controls. METHODS: Using our unique population based data resources, we developed a model for estimating and comparing disease specific costs among 2 randomly selected, community based samples of 200 patients each with RA and OA and a control group of 200 individuals from the same community who do not have arthritis. Data were collected using a pretested postal survey. Age and sex adjusted comparisons were conducted across the 3 groups, and predictors of cost and utilization were identified using logistic regression modeling. RESULTS: There were 123, 116, and 94 respondents among the RA, OA, and nonarthritis groups, respectively. The average age and the female-to-male ratios were higher in the OA and RA groups compared to the nonarthritis group. Patients with RA and OA required 3 times more days of care for their conditions compared to nonarthritics (p < 0.0001) and incurred significantly more expenditures for home or child care (p = 0.01) and other services (p = 0.001) (i.e., medical equipment, assistive devices, or home remodeling) compared to nonarthritics. In addition, patients with RA were significantly more likely to have lost their job or to have retired early due to their illness (p = 0.001); were the most likely to have reduced their work hours or stopped working entirely due to their illness (p = 0.003); and were 3 times more likely to have had a reduction in household family income than either individuals with OA or those without arthritis (p = 0.0001). Fifteen percent of respondents with RA were unable to get a job because of their illness, while 3% of respondents with OA and only 1% of nonarthritic respondents reported this experience (p = 0.001). Logistic regression analysis revealed that functional status and pain score, as well as the presence of either RA or OA, were significant predictors of cost and health services utilization. CONCLUSION: Disease specific indirect and nonmedical costs for OA are substantial and approach those for RA. This has important societal implications, given the high prevalence of OA.

Arthritis, Rheumatoid↗

The epidemiology of morphea (localized scleroderma) in Olmsted County 1960-1993.

OBJECTIVE: To determine the incidence, prevalence, survival rates, clinical manifestations, and longterm outcome of patients with morphea (localized scleroderma) and its subtypes over a 33 year period in Olmsted County, Minnesota. METHODS: We used the unique data resources of the Rochester Epidemiology Project to review all Olmsted County medical records with any potential diagnosis consistent with morphea (including plaque, generalized, bullous, linear, and deep entities) from 1960 through 1993. RESULTS: We screened 1030 medical records and identified 82 (59 female; 23 male) cases of morphea first diagnosed between 1960 and 1993. All cases were followed until death or migration from Olmsted County, a total of 754 person-years of observation. The annual age and sex adjusted incidence rate per 100,000 population was 2.7 (95% confidence interval 2.1, 3.3). The incidence rate increased significantly over the 33 years (p = 0.0037) on an average of 3.6% per year. The prevalence (estimated using cumulative incidence) at 80 years of age was about 2/1000. 50% of the patients had a cutaneous softening or evidence of disease resolution by 3.8 years' duration. The shortest active disease duration was found in the plaque group (50% resolution or skin softening by 2.7 years) compared to 5.5 years in the deep group. Arthralgias, synovitis, uveitis, and joint contractures were more frequent in the linear and deep categories. Although 9 patients (11%) developed some disease related disability over the followup period, this was common (44%) in the deep group. No case of morphea developed severe internal organ involvement and none progressed to systemic sclerosis. The survival rate was not significantly different from the general population (p = 0.409). CONCLUSION: Morphea, and its subtypes, are more common than previously recognized, and can lead to important disability.

Adolescent↗

Direct medical costs unique to people with arthritis.

OBJECTIVE: We report the results of a population based analysis of all health services used and charges incurred over a one-year period among a community based cohort of persons with a diagnosis of arthritis [including both osteoarthritis (OA) and rheumatoid arthritis (RA)] compared to a similar cohort of individuals from the same community who have never had a diagnosis of arthritis (NA), to examine the attributable costs of this chronic condition. METHODS: The unique resources of the Rochester Epidemiology Project were used to assemble the arthritis prevalence cohorts and the population based control cohort. The Olmsted County Health Care Utilization and Expenditures Database was used to collect information on health services utilization and charges. RESULTS: The average direct medical charges for the RA, OA, and NA cohorts were $3,802.05, $2,654.51, and $1,387.83, respectively (age and sex adjusted, p < 0.0001 for both the RA vs NA and OA vs NA comparisons). The median charges for these 3 groups were $1,050.00, $663.55, and $232.04 for the RA, OA, and NA groups, respectively (age and sex adjusted p < 0.0001 for both the RA vs NA and OA vs NA comparisons). These analyses indicated that, compared to the NA cohort both the OA and the RA prevalence cohorts incurred statistically significantly more charges, not only for the musculoskeletal disease care, but also for the care of numerous other conditions including respiratory, cardiovascular, gastrointestinal, neurological, and psychiatric conditions; and for general medical care. Individuals with arthritis (both OA and RA) also incurred statistically significantly more charges for diagnostic and therapeutic procedures, in-hospital care, imaging studies, physician services, equipment, and laboratory studies. Use of prescription medications was statistically significantly more common in the RA and OA groups compared to NA (96.3, 96, and 83%, respectively; age and sex adjusted p = 0.006 for the OA vs NA comparison and p = 0.015 for RA vs NA). CONCLUSION: These results emphasize the importance of considering all health services utilization (rather than only disease specific use) when estimating the economic effect of a chronic illness such as arthritis.

Adult↗

Deregulated expression and function of CFTR and Cl- secretion after activation of the Ras and Src/PyMT pathways in Caco-2 cells.

We evaluated the role of the activated Ras and Src/PyMT (Polyoma Middle T) signaling pathways on the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in human colonic Caco-2 cell lines. Control vector-transfected Caco-2 cell monolayer preparations (Caco-2-H) responded to forskolin with an increase in short circuit current (Isc) mediated by CFTR. Furthermore, Caco-2-H cells responded to ATP, a reported stimulator of intracellular Ca2+ (Cai2+), and a potential source of adenosine-mediated elevation of cAMP. In contrast, Caco-2 cells transfected with PyMT (Caco-2-MT), expressing high levels of PKC, showed no sustained Isc response to forskolin or ATP. Pretreatment of Caco-2-MT cells with 2.5 microM phorbol 12-myristate 13-acetate (PMA) for 24 hr. effectively down-regulated PKC activity and restored expression of CFTR mRNA but failed to re-establish functional CFTR. These data suggest that, stable up-regulation of PKC alpha, consequent to activation of the Ras or Src/PyMT pathways, leads to an absence of CFTR expression and Cl- secretion mediated by either cAMP or Cai2+. Moreover, Cl- secretion in the colonic Caco-2 epithelial cell line is mediated primarily by CFTR and an alternate Cai(2+)-activated Cl- channel is not functional in these cells.

Adenosine Triphosphate↗

Juvenile rheumatoid arthritis in Rochester, Minnesota 1960-1993. Is the epidemiology changing?

OBJECTIVE: To examine trends in the incidence and prevalence of juvenile rheumatoid arthritis (JRA) in Rochester, Minnesota, over 33 years. METHODS: The diagnostic retrieval system of the Rochester Epidemiology Project was utilized to screen medical records of all Rochester residents with any potential diagnoses of JRA from 1978 to 1993 (based on the American College of Rheumatology 1977 revised criteria). In addition, all cases of JRA from our previously identified cohort from 1960-1979 were verified, and the 2 data sets were combined, resulting in an incidence cohort spanning 33 years (1960-1993). RESULTS: Of the 1,240 medical records screened, we identified 65 cases of JRA diagnosed between 1960 and 1993 (48 females, 17 males). The average followup for cases was 12.7 years (range 0-34 years) for a total of 833 person-years of observation. A bimodal distribution of age at diagnosis was observed, with peaks between 0 and 4 years and 9 and 15 years. Seventy-two percent of patients had pauciarticular-onset, 17% had polyarticular-onset, and 11% had systemic-onset disease. Progression of pauciarticular to polyarticular disease occurred in 11% of the cases. The overall age- and sex-adjusted incidence rate was 11.7 per 100,000 population (95% confidence intervals 8.7, 14.8). The incidence rate per 100,000 population was 15.0, 14.1, and 7.8 for the time periods 1960-1969, 1970-1979, and 1980-1993, respectively (P = 0.024). A 3-year, centered, moving average, which was used to display time trends in incidence, suggested a cyclical pattern, with incidence peaks in 1967, 1975, and 1987. CONCLUSION: An overall decrease in the incidence rate over the last decade was observed, most marked in the pauciarticular- and systemic-onset subtypes. This decrease, along with the observed cyclical pattern, suggest that environmental factors may influence disease frequency.

Arthritis, Juvenile↗

Clusters of Cl- channels in CFTR-expressing Sf9 cells switch spontaneously between slow and fast gating modes.

The Sf9 insect Spodoptora frugiperda cell line was used for heterologous expression of the cloned human cystic fibrosis transmembrane conductance regulator (CFTR) cDNA, or the cloned beta-galactosidase gene, using the baculovirus Autographa califonica as the infection vector. Using application of the patch-clamp technique, evidence for functional expression of CFTR was obtained according to the following three criteria. Firstly, whole-cell currents recorded 2 days after infection with CFTR revealed a statistically significant increase of membrane conductance, approximately 25 times above that of mock-infected control cells, with the reversal potential of the major current component being governed by the chloride equilibrium potential (ECl). Secondly, in contrast to uninfected cells and cells infected with beta-galactosidase, the membrane conductance to chloride of CFTR-injected cells was stimulated by cytosolic adenosine 3',5'-cyclic monophosphate (cAMP), which was raised by exposing the cells to 10 microM forskolin. Thirdly, recordings of currents through single channels in excised outside-out membrane patches of CFTR-infected cells revealed channels which were clearly different from the native insect chloride channel. Excised outside-out patches of CFTR-infected and forskolin-stimulated cells exhibited wave-like gating kinetics of well-resolved current transitions. All-point Gaussian distributions revealed contributions from several (five to nine) identical channels. Such channels, in excised outside-out patches, studied with a pipette [Cl-] = 40 mM and a bath [Cl-] = 150 mM, rectified the current in agreement with simple electrodiffusion and with a single-channel Goldman-Hodgkin-Katz permeability, PCl = 1. 34 x 10(-14) +/- 0.23 x 10(-14 )cm3/s (n = 5), corresponding to a physiological single-channel conductance of 2.8 +/- 0.5 pS (VM = ECl) and a limiting conductance, gamma150/150, = 7.7 +/- 1.3 pS ([Cl-]Bath = [Cl-]Cell = 150 mM). Currents recorded from multichannel excised outside-out patches could shift from the above mode of resolvable unitary conductance transitions to one which was too fast to reveal the dwell-times of closed and open states. During periods characterized by noisy currents, the variance (sigma2) of current fluctuations about their stationary mean value depicted a U-shaped function of membrane potential, with a minimum value at a pipette potential where the chloride current was shown to be zero. Thus, it can be concluded that the current fluctuations are caused by fast gating of channels specific for chloride ions. Switching back and forth between the two gating modes of clusters of chloride channels occurred from moment to moment in excised patches when the membrane potential was held at a constant value indicating cooperative gating as a result of interaction between neighbouring chloride channels.

Animals↗

A mathematical model that improves the validity of osteoarthritis diagnoses obtained from a computerized diagnostic database.

We developed an algorithm, using recursive partitioning, that utilized information from a computerized, diagnostic database to predict the diagnosis of osteoarthritis as determined by medical record review. The complete (inpatient and outpatient) medical records for a random sample of 400 Olmsted County, Minnesota residents with a database diagnosis consistent with osteoarthritis were reviewed, and confirmation or rejection of the diagnosis was accomplished. Of the 387 patients in our sample, only 232 (a positive predictive value of 60%) fulfilled diagnostic criteria for osteoarthritis following medical record review. A classification tree was created that used information from the diagnostic database to partition the study population according to the proportion of individuals with a "true" diagnosis of osteoarthritis (based on medical record review). The receiver-operating characteristic curve generated from these data illustrated that the algorithm substantially improved the validity of the database diagnosis, yielding a positive predictive value of 89% and a negative predictive value of 70% (sensitivity of 75% and specificity of 86%) at a selected cutoff point. This model also provides the capability of selecting the cutoff point to favor either specificity or sensitivity. These data demonstrate that a mathematical model can substantially improve the validity of computerized diagnostic databases in osteoarthritis.

Adult↗

Update on the epidemiology of the rheumatic diseases.

Epidemiologic studies continue to enhance our understanding of the rheumatic diseases. Such studies now indicate that 26 million American women are at risk for osteoporotic fractures. Contrary to previous recommendations, the identification and treatment of patients at risk for osteoporosis may be valuable even among very elderly people. Other epidemiologic studies suggest that the incidence of rheumatoid arthritis is decreasing and that it is a more benign disease than previously recognized. Osteoarthritis remains a leading cause of physical and work disability in North America. The roles of occupational physical activity, obesity, and highly competitive (though not low-impact) exercise as risk factors for osteoarthritis continue to be explored. Pharmacoepidemiologic research has recently demonstrated that a policy of prior authorization for prescription of nonsteroidal anti-inflammatory drugs may be highly cost effective. Finally, controlled epidemiologic studies have not confirmed an association between silicone breast implants and connective tissue diseases, a conclusion recently endorsed by the American College of Rheumatology.

Anti-Inflammatory Agents, Non-Steroidal↗

Monoclonal antibody against conductive chloride transport in pig ileal apical membrane vesicles.

Conductive chloride transport in the small intestine is an important factor controlling fluid movement from the blood to the lumen of the gut. Several proteins with potential conductive chloride ion channel activity are expressed in the enterocyte cell population. However, it is not clear whether one or more than one protein species is normally responsible for mediating conductive chloride transport. We have raised monoclonal antibodies that inhibit conductive chloride transport in apical membrane vesicles prepared from porcine ileal enterocytes. These monoclonal antibodies have been used to identify a unique protein involved with this conductive chloride transport. Here, we report that anti-chloride conductance monoclonal antibodies did not detect any antigen in Western blots of enterocyte apical membrane protein. Dot blotting and immunoprecipitation experiments indicated that the antigen recognized by these monoclonal antibodies was not the cystic fibrosis transmembrane conductance regulator. The antigen was localized to both villus and crypt regions of ileum on immunohistochemistry. A 90-kDa protein species was immunoprecipitated from a primary enterocyte cell line by these monoclonal antibodies. This 90-kDa protein may be a chloride ion channel or may play some regulatory role in conductive chloride transport in enterocyte apical membrane vesicles.

Animals↗

Primary care: specialists or generalists.

A critical appraisal of the literature on the cost and quality trade-offs of primary care provided by specialists in comparison with that provided by generalists is presented.

Continuity of Patient Care↗

A diagnostic algorithm for distinguishing the eosinophilia-myalgia syndrome from fibromyalgia and chronic myofascial pain.

OBJECTIVE: To develop a diagnostic algorithm for the eosinophilia-myalgia syndrome (EMS) that complements the existing case definition. METHODS: We conducted a retrospective study using data on 59 clinical and laboratory variables from a consecutive referral cohort of 91 patients with EMS meeting the Centers for Disease Control and Prevention case definition. Age and sex matched controls included 93 patients with fibromyalgia and 99 patients with chronic myofascial pain. The study period was March 1989 to April 1992. Recursive partitioning was used to create a diagnostic algorithm. RESULTS: In the 283 case patients and controls with disabling myalgias, 4 differentiating variables identified patients with EMS: extremity edema, leukocyte count > 12.5 x 10(9)/l, dyspnea, and absence of arthralgias. These 4 variables form a diagnostic algorithm that has a sensitivity of 95.6%, a specificity of 96.9%, and positive and negative predictive values of 93.5 and 97.9%, respectively. CONCLUSION: This algorithm is practical and can be easily applied in any medical setting. It also readily distinguishes EMS from other common myalgia syndromes.

Adult↗

The incidence of giant cell arteritis in Olmsted County, Minnesota: apparent fluctuations in a cyclic pattern.

OBJECTIVE: To investigate trends in the incidence of giant cell arteritis over a 42-year period in Olmsted County, Minnesota. DESIGN: Population-based incidence study. SETTING: Olmsted County, Minnesota. METHODS: All incidence cases of giant cell arteritis first diagnosed between 1950 and 1991 were identified using the unified record system at Mayo Clinic. Age- and sex-specific incidence rates were calculated using the number of incidence cases as the numerator and population estimates as the denominator. Overall rates were age- and sex-adjusted to the 1980 United States white population. The annual incidence rates were graphically illustrated using a 3-year centered moving average. RESULTS: Between 1950 and 1991, 125 Olmsted County residents (103 women and 22 men) were diagnosed with giant cell arteritis. The age- and sex-adjusted incidence per 100,000 persons 50 years of age or older was 17.8 (95% CI, 14.7 to 21.0); incidence was significantly higher in women (24.2 [CI, 19.5 to 28.9]) than in men (8.2 [CI, 4.8 to 11.6]). Age-specific incidence rates increased with age (P < 0.0001). The annual incidence rates increased significantly over the study period (P = 0.002) and appear to have clustered in five peak periods, which occurred about every 7 years. A significant calendar-time effect was identified; it predicted an increase in incidence of 2.6% (CI, 0.9% to 4.3%) every 5 years. CONCLUSIONS: Our observation of a regular cyclic pattern in incidence rates over time supports the hypothesis of an infectious cause for giant cell arteritis. Similar studies in other populations are needed to confirm our findings.

Age Distribution↗

Epidemiology of polymyalgia rheumatica in Olmsted County, Minnesota, 1970-1991.

OBJECTIVE: To determine the incidence, prevalence, and survival of polymyalgia rheumatica (PMR) over a 22-year period in Olmsted County, Minnesota. METHODS: Using the unified record system at the Mayo Clinic for the Olmsted County population, we reviewed all medical records with a diagnosis of PMR from 1970 through 1991. RESULTS: There were 245 (173 female; 72 male) incidence cases of PMR between 1970 and 1991. The average annual age- and sex-adjusted incidence of PMR per 100,000 population > or = 50 years was 52.5 (95% confidence interval [CI] 45.9-59.2), with a significantly higher incidence in females (61.7; 95% CI 52.3-71.2) than in males (39.9; 95% CI 30.7-49.2). The incidence varied over the period of observation, but no significant trends were found. The prevalence of PMR among persons > or = 50 years on January 1, 1992 was 6/1,000. There was a small but significantly increased survival rate among male PMR patients compared with the general population. CONCLUSION: Our data demonstrate that PMR is a common nonfatal disease in the elderly, the incidence and clinical manifestations of which have varied but remained relatively stable over the last 2 decades.

Age Distribution↗

Medical costs in community subjects with irritable bowel syndrome.

BACKGROUND & AIMS: Costs of management of irritable bowel syndrome (IBS) are unknown. The direct medical charges in community subjects with IBS were estimated. METHODS: An age- and sex-stratified random sample of residents of Olmsted County, Minnesota, ranging in age from 20 to 95 years, was mailed a valid self-report questionnaire. Subjects were categorized as having IBS, having some symptoms but inadequate criteria for IBS, and controls. All charges (in 1992 U.S. dollars) for health services rendered in the year before completing the survey were obtained (except outpatient medications). RESULTS: A total of 88% of subjects with IBS, 86% of subjects with some symptoms of IBS, and 83% of controls incurred direct medical charges during the study year. The odds of incurring charges were 1.6 times greater in subjects with IBS relative to those without symptoms (P < 0.01) adjusting for age, sex, education, marital status, and employment. Overall median charges incurred by subjects with IBS were $742 compared with $429 for controls and $614 for subjects with some symptoms. Among those subjects with nonzero charges, there were significant positive associations with age, higher education, and symptom groups (all P < 0.01) but not sex. CONCLUSIONS: The economic impact of IBS is significant. A better understanding of the determinants of these costs is needed so that cost-saving strategies can be implemented.

Adult↗