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Gene G Hunder

Publications and source records attributed to Gene G Hunder.

At least 19 recordsLinked to original sources
PubMed2006

Treatment of giant cell arteritis using induction therapy with high-dose glucocorticoids: a double-blind, placebo-controlled, randomized prospective clinical trial.

OBJECTIVE: Glucocorticoid (GC) therapy for giant cell arteritis (GCA) is effective but requires prolonged administration, resulting in adverse side effects. The goal of the current study was to test the hypothesis that induction treatment with high-dose pulse intravenous (IV) methylprednisolone permits a shorter course of therapy. METHODS: Twenty-seven patients with biopsy-proven GCA were enrolled in a randomized, double-blind, placebo-controlled study to receive IV methylprednisolone (15 mg/kg of ideal body weight/day) or IV saline for 3 consecutive days. All patients were started on 40 mg/day prednisone and followed the same tapering schedule as long as disease activity was controlled. The numbers of patients with disease in remission after 36, 52, and 78 weeks of treatment and taking <or=5 mg/day prednisone were compared. Cumulative prednisone dose, number of relapses, and development of adverse GC effects were assessed. RESULTS: Ten of the 14 IV GC-treated patients, but only 2 of 13 control patients, were taking <or=5 mg/day prednisone at 36 weeks (P = 0.003). This difference was maintained; there was a higher number of sustained remissions after discontinuation of treatment in the IV GC-treated group and a lower median daily dose of prednisone at 78 weeks (P = 0.0004). The median cumulative dose of oral prednisone, excluding the IV GC dose, was 5,636 mg in the IV GC-treated group compared with 7,860 mg in the IV saline-treated group (P = 0.001). CONCLUSION: Initial treatment of GCA with IV GC pulses allowed for more rapid tapering of oral GCs and had long-term benefits, with a higher frequency of patients experiencing sustained remission of their disease after discontinuation of treatment.

Administration, Oral↗
PubMed2006

The early history of giant cell arteritis and polymyalgia rheumatica: first descriptions to 1970.

Giant cell arteritis and polymyalgia rheumatica were described separately more than 100 years ago. However, the original reports of both conditions were neglected for many years. After the article by Horton et al on giant cell arteritis in the 1930s and studies published by others in the 1940s, giant cell arteritis began to be recognized as a specific disease. In the 1950s and 1960s, many of the numerous presentations and complications of giant cell arteritis were recorded. In a somewhat similar fashion, physicians became cognizant of polymyalgia rheumatica only after several independent descriptions in the 1940s and 1950s. The rapid response of both syndromes to glucocorticoid therapy was discovered shortly after cortisone's effect on rheumatoid arthritis was described. The origin of the proximal aching and stiffness in polymyalgia rheumatica was more difficult to understand. The relatively minor findings in the joints on physical examination seemed insufficient to account for the severe discomfort. As the link between polymyalgia rheumatica and giant cell arteritis became apparent, some thought the aching in polymyalgia rheumatica was related to vasculitis. The debate about whether proximal synovitis or vasculitis was the cause of the symptoms continued after 1970. Although the reason these 2 conditions were associated was not considered by 1970, the establishment of the syndromes as clinically linked entities provided the groundwork for further progress in the next decades.

Denmark↗
PubMed2005

Direct medical costs of polymyalgia rheumatica.

OBJECTIVE: To describe the patterns of care and direct medical costs of polymyalgia rheumatica (PMR) to test the hypothesis that the direct medical costs incurred by patients with PMR are higher than costs incurred by age- and sex-matched population-based controls from the same community. METHODS: The study population comprised 193 Olmsted County, Minnesota residents who were first diagnosed with PMR between January 1, 1987 and December 31, 1999. Inclusion criteria were as follows: age > or = 50 years; bilateral aching and morning stiffness (lasting > or = 30 minutes) persisting for at least 1 month and involving the neck, shoulders, or hip girdle regions; and an erythrocyte sedimentation rate (ESR) > or = 40 mm/hour. In patients who fulfilled the first 2 criteria, but had a normal ESR, a rapid response to low-dose corticosteroids served as the third criterion. A total of 695 age- and sex-matched subjects without PMR served as control subjects. Billing data from the Olmsted County Healthcare Expenditure and Utilization Database (OCHEUD) were used to provide estimates of nationally representative unit costs in the year 2002 inflation-adjusted dollars. All subjects were followed using the OCHEUD records until December 31, 2002 to assess the total direct medical costs. Generalized quantile regression modeling was used to estimate the effect of PMR on direct medical costs, after adjusting for age, sex, Charlson comorbidity score, number of hospital days, and number of radiographs. RESULTS: During the first year following diagnosis, subjects with PMR used a substantially higher number of outpatient services and laboratory tests compared with controls, but during the subsequent 4 years, there were no differences between the 2 groups. In age- and sex-adjusted analysis, PMR was associated with a significant incremental cost of 2,233 dollars at the 10th percentile of costs and 27,712 dollars at the 90th percentile of costs. However, further adjustments for comorbidities, number of hospital days, radiographs, and imaging eliminated the incremental cost difference between the subjects with PMR and control subjects. PMR subjects were significantly more likely to have a history of myocardial infarction (odds ratio [OR] 1.78, 95% confidence interval [95% CI] 1.13, 2.82), peripheral vascular diseases (OR 2.21, 95% CI 1.37, 3.60), and cerebrovascular diseases (OR 1.60, 95% CI 1.08, 2.39) compared with the controls. CONCLUSION: Incremental direct medical costs associated with the management of PMR can be substantial, especially early in the disease course. These incremental costs appear to originate mainly from comorbid cardiovascular conditions that were shown to be more prevalent among subjects with PMR.

Aged↗
PubMed2005

Use of physician services in a population-based cohort of patients with polymyalgia rheumatica over the course of their disease.

OBJECTIVE: To describe the use of generalist and rheumatologist services in a population-based cohort of patients with polymyalgia rheumatica (PMR) and to identify predictors of rheumatology care. METHODS: We identified all incident cases of PMR among residents of Olmsted County, Minnesota between 1970 and 1999. Patients were followed for a maximum of 5 years after their incidence date. Logistic regression and zero-inflated Poisson regression models were used to assess the association between rheumatology care and age, sex, giant cell arteritis (GCA), PMR relapses, corticosteroid complications, comorbidity, and various laboratory findings, adjusting for the total number of visits. RESULTS: Of the 364 incident cases of PMR eligible for this analysis, 67% were women and the mean age at incidence was 73 years. Over a mean followup of 4.1 years, individuals in this cohort utilized a total of 5,108 physician office visits and 2,015 telephone calls. The mean number of generalist and rheumatologist visits per person-years of follow-up during the first year of PMR was 7.02 and 2.15, respectively. Thereafter, there was a steady decline in both generalist and rheumatologist visits. One hundred forty-four (40%) patients had no rheumatologist visits and 102 (28%) had only 1 rheumatologist visit, mostly for diagnostic confirmation. Men and patients with several comorbid conditions were significantly more likely to be seen by rheumatologists (P < 0.001). However, once referred, women, older patients, and those with GCA, PMR relapses, and corticosteroid complications had significantly more rheumatologist visits (P < 0.001). CONCLUSION: The use of physician services in PMR is considerable. Generalists provide the large majority of care. Rheumatologist involvement is generally limited to diagnostic confirmation and management of complications. The relative paucity of rheumatology care following the period of diagnosis may represent an opportunity for improving the care of patients with PMR.

Aged↗
PubMed2005

Relapse in a population based cohort of patients with polymyalgia rheumatica.

OBJECTIVE: To determine the incidence and the clinical, laboratory, and treatment related predictors of relapse in polymyalgia rheumatica (PMR). METHODS: Using the population based resources of the Rochester Epidemiology Project, we assembled an incidence cohort of subjects with PMR first diagnosed between January 1, 1970, and December 31, 1999. For inclusion, subjects were required to fulfill 3 criteria: (1) age > or = 50 years; (2) bilateral aching and morning stiffness in neck, shoulders, or hip girdle regions; and (3) erythrocyte sedimentation rate (ESR) > or = 40 mm/h. In subjects who fulfilled the first 2 criteria but had a normal ESR, a rapid response to low dose corticosteroids (CS) served as the third criterion. Patients were followed until permanent remission, migration, or a maximum of 5 years after their incidence date. Relapse was defined as an exacerbation of PMR symptoms requiring an adjustment of CS dose (> or = 5 mg) occurring at least 30 days after the incidence date. Time to relapse was modeled using the Kaplan-Meier method. CS treatment patterns were modeled using linear and nonlinear models. Cox regression models were used to evaluate predictors of time to first and subsequent relapses. RESULTS: The study population included 364 patients with a mean age of 73.4 years and 244 (67%) were women. Among the 284 patients treated with CS, a higher initial CS dose and faster CS tapering rate were significant predictors of future relapses, after adjusting for age, sex, ESR, giant cell arteritis at PMR diagnosis, and the intensity of rheumatologist care. Every 5 mg/day increase in initial CS dose was associated with a 7% increase in the risk of relapse [hazard ratio (HR) 1.07, 95% CI 1.02, 1.13]. The hazard of having a relapse was 4-fold higher when the CS tapering rate was fast (HR 4.27, 95% CI 2.84, 6.44), and 2-fold higher when the CS tapering rate was medium (HR 2.19, 95% CI 1.54, 3.11) compared to slow tapering. CONCLUSION: Higher initial CS doses and faster tapering are significant predictors of future relapses. Our results suggest that efforts should be made to minimize initial CS dose and taper CS slowly in order to avoid disease relapses.

Aged↗
PubMed2004

Reappraisal of the epidemiology of giant cell arteritis in Olmsted County, Minnesota, over a fifty-year period.

OBJECTIVE: To investigate time trends in the incidence and survival of giant cell arteritis (GCA) over a 50-year period in Olmsted County, Minnesota. METHODS: Using the unified record system at the Mayo Clinic, we identified all incident cases of GCA first diagnosed between 1950 and 1999. Incidence rates were estimated and adjusted to the 1980 United States white population for age and sex. The annual incidence rates were graphically illustrated using a 3-year centered moving average. Survival rates were computed and compared with the expected rates in the population. RESULTS: There were 173 incident cases of GCA during the 50-year study period. Of these, 79% were women and the mean age at diagnosis was 74.8 years. The overall age- and sex-adjusted incidence per 100,000 persons 50 years of age or older was 18.8 (95% confidence interval [95% CI] 15.9-21.6). Incidence was higher in women (24.4; 95% CI 20.3-28.6) than in men (10.3; 95% CI 6.9-13.6). Incidence rates increased significantly over the study period (P = 0.017); in particular, a progressive increase was observed from 1950 to 1979; subsequently, no substantial increases in incidence rates were observed. A cyclic pattern of annual incidence rates was apparent, with evidence of 6 peak periods. Survival among individuals with GCA was not significantly different from that expected in the population (P = 0.80). CONCLUSIONS: The incidence of GCA increased over the first 3 decades of the study, then remained stable over the last 20 years. The previously observed cyclic pattern of annual incidence rates was still apparent over a 50-year period. Overall survival in GCA was similar to that in the population.

Age Distribution↗
PubMed2004

Prognostic markers of radiographic progression in early rheumatoid arthritis.

OBJECTIVE: To identify prognostic markers that are predictive of progressive erosive disease in patients with early rheumatoid arthritis (RA). METHODS: The study involved an inception cohort of 111 consecutive patients with RA and a disease duration of <1 year. Patients were treated according to an algorithm designed to avoid overtreatment of mild disease and to accelerate treatment in patients who had continuous disease activity. Patients were evaluated for the presence of clinical and laboratory disease activity markers. We determined the frequency of CD4+,CD28(null) T cells by flow cytometry, HLA-DRB1 gene polymorphisms by polymerase chain reaction (PCR)/sequencing, and 26 single-nucleotide polymorphisms in 19 candidate genes by multiplex PCR and hybridization to an immobilized probe array. Data were analyzed using proportional odds models to identify prognostic markers predictive of erosive progression over 2 years on serial hand/wrist radiographs. RESULTS: After 2 years, disease activity in 52% of the cohort was controlled by treatment with hydroxychloroquine and nonsteroidal agents. Forty-eight percent of the patients did not develop erosions. Older age, presence of erosions at baseline, presence of rheumatoid factor, rheumatoid factor titer, and HLA-DRB1*04 alleles, particularly homozygosity for HLA-DRB1*04, were univariate predictors of radiographic progression. Promising novel markers were the frequency of CD4+,CD28(null) T cells as an immunosenescence indicator, and a polymorphism in the uteroglobin gene. CONCLUSION: Clinical disease activity in patients with early RA can frequently be controlled with nonaggressive treatment, but this is not always sufficient to prevent new erosions. Rheumatoid factor titer, HLA-DRB1 polymorphisms, age, and immunosenescence markers are predictors of poor radiographic outcome. A polymorphism in the uteroglobin gene may identify patients who have a low risk of erosive disease.

Adolescent↗
PubMed2004

Polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology characterized by aching and stiffness in the shoulder and in the pelvic girdles and neck. In the past, PMR was considered a manifestation of giant cell arteritis (GCA) or a variant of elderly-onset rheumatoid arthritis (EORA). The current diagnostic criteria for PMR were empirically formulated by clinical experts who had studied the disease extensively. Arthroscopic, radioisotopic and magnetic resonance imaging studies all have indicated the presence of a synovitis in proximal joints and periarticular structures. The synovitis is probably responsible for the musculoskeletal symptoms in PMR. The prominence assigned to the proximal symptoms has probably overshadowed the less well recognized and more variable distal musculoskeletal manifestations which are present in about half of the cases. A normal erythrocyte sedimentation rate does not exclude a diagnosis of PMR. C-reactive protein and interleukin-6 seem to be more sensitive indicators of disease activity both at diagnosis and during relapse/recurrence. Corticosteroids are the drugs of choice for treating PMR. A course of treatment of 1-2 years is often required. However, some patients have a chronic, relapsing course and require low doses of corticosteroids for several years. Large, multicenter, double-blind, placebo-controlled studies are required to define the role of methotrexate and anti-TNF-alpha agents as corticosteroid-sparing drugs in PMR.

Aged↗
PubMed2004

Aortic aneurysm and dissection in patients with biopsy-proven giant cell arteritis from northwestern Spain: a population-based study.

Most classical manifestations of giant cell arteritis (GCA) are the result of occlusive vascular involvement. However, unlike ischemic manifestations, aortic aneurysmal disease in patients with GCA has been less well described. We assessed the incidence and predictors of aortic aneurysm and dissection in patients with biopsy-proven GCA from the Lugo region of northwestern Spain and compared the results with those in a 2003 report from Olmsted County, MN. We performed a retrospective study of biopsy-proven GCA patients diagnosed from 1981 to 2001 at the single hospital for a well-defined population of almost 250,000 people. Twenty (9.5%) of the 210 biopsy-proven GCA patients diagnosed during the study period developed aortic aneurysmal disease. Sixteen of the 20 patients had thoracic aneurysms and 6 had abdominal aneurysms. The incidence of aortic aneurysm and/or dissection in Lugo (18.9 per 1000 person years at risk) was similar to that reported in Olmsted County (18.7 per 1000 person years at risk). Hypertension (hazard ratio: 4.73) and polymyalgia rheumatica with a marked acute inflammatory response at the time of diagnosis of GCA (hazard ratio: 3.71) were the best predictors of aortic aneurysmal disease. Our present observations suggest that a severe inflammatory response associated with hypertension at the time of diagnosis of GCA may promote the development of aortic aneurysmal disease. GCA patients having these features should be monitored for the existence of aortic aneurysm and dissection.

Aged↗
PubMed2004

Initiation of glucocorticoid therapy: before or after temporal artery biopsy?

OBJECTIVE: To identify clinical findings in patients with suspected giant cell arteritis (GCA) that may help clinicians decide when to initiate glucocorticoid therapy. PATIENTS AND METHODS: Medical diagnostic codes and surgical indexing were used to identify all patients who had temporal artery biopsy at the Mayo Clinic in Rochester, Minn, between January 1, 1988, and December 31, 1997. Patient medical records were abstracted for pertinent clinical data, glucocorticoid use, and final diagnoses. Sensitivities, specificities, predictive values, and likelihood ratios were calculated for the association of the various clinical findings and the presence of a positive biopsy result. Graphic and arithmetic models were constructed to predict positive temporal artery biopsy results. RESULTS: During the 10-year interval, 1113 patients had temporal artery biopsy. The results were positive for GCA in 373 patients (33.5%) and negative in 740 (665%). Twenty percent of all patients were taking glucocorticoids at the time of biopsy. The presence of jaw claudication had a positive predictive value of 78. Combinations of jaw claudication with new headache, scalp tenderness, and decreased vision had still higher values. Positive likelihood ratios in patients with these combinations and in those with diplopia were greater than 3. A normal erythrocyte sedi-mentation rate in patients not taking corticosteroids provided a high negative likelihood ratio of 40. An arithmetic equation provided the probability of a positive biopsy result on a continuous scale using 6 variables identified by logistic regression. Patients with a greater than 80% chance of a positive biopsy result and those with less than a 10% chance were identified. CONCLUSION: Positive predictive values, likelihood ratios, and an arithmetic formula identify patients who have an increased or decreased chance of a positive temporal artery biopsy result. Use of these methods to determine early initiation of glucocorticoid therapy before temporal artery biopsy or deferral until after biopsy may help reduce both vascular complications of GCA and adverse effects of corticosteroids.

Administration, Oral↗
PubMed2003

Glucocorticoid therapy in giant cell arteritis: duration and adverse outcomes.

OBJECTIVE: To evaluate the course of glucocorticoid (GC) therapy and associated adverse events in a population-based cohort of patients with giant cell arteritis (GCA). METHODS: We identified 125 Olmsted County residents with GCA diagnosed between 1950 and 1991 and obtained followup information on the 120 patients who were diagnosed antemortem and agreed to participate in this study. Clinical variables, GC doses, and GC adverse events on each patient were recorded. The relationship between GC therapy and the development of adverse events was studied by the Cox and Anderson-Gill proportional hazards models. RESULTS: All patients were treated with GCs and responded rapidly (median initial dosage 60 mg prednisone/day). The dosage was later reduced according to the treating physicians' judgment. The median duration required to reach 7.5 mg/day was 6.5 months and the median duration required to reach 5 mg/day was 7.5 months. Relapses or recurrences occurred in 57 patients. For the 87 patients followed to discontinuation of GC therapy and permanent remission of GCA (median of 22 months), the total median dose of prednisone was 6.47 gm. Adverse events associated with GCs were recorded in 103 (86%) patients and 2 or more events occurred in 70 patients (58%). Age and higher cumulative dose of GCs were associated with the development of adverse GC side effects. CONCLUSION: GCs are therapeutically effective in GCA and the prednisone dosage was reduced to physiologic levels in three-fourths of the patients within 1 year. However, most patients developed serious adverse side effects related to GCs, indicating that less toxic therapeutic measures are needed.

Adrenocortical Hyperfunction↗
PubMed2003

Incidence and predictors of large-artery complication (aortic aneurysm, aortic dissection, and/or large-artery stenosis) in patients with giant cell arteritis: a population-based study over 50 years.

OBJECTIVE: To determine the incidence and predictors of large-artery complication (aortic aneurysm, aortic dissection, and/or large-artery stenosis) in patients with giant cell arteritis (GCA). METHODS: The cohort of all residents of Olmsted County, Minnesota, in whom GCA was diagnosed between January 1, 1950, and December 31, 1999, was followed up. The incidence of aortic aneurysm, aortic dissection, and large-artery stenosis was determined. Possible predictors and correlates of large-artery complication were assessed. RESULTS: Forty-six incident cases of large-artery complication (representing 27% of the 168 patients in the cohort) were identified. These included 30 incident cases (18%) of aortic aneurysm and/or aortic dissection. Of these cases, 18 (11%) involved the thoracic aorta, with aortic dissection developing in 9 (5%). There were 21 incident cases (13%) of large-artery stenosis. Fifteen patients (9%) had incident cervical artery stenosis, and 6 (4%) had incident subclavian/axillary/brachial artery stenosis. One patient (0.6%) had incident iliac/femoral artery stenosis attributable to GCA. Hyperlipidemia and coronary artery disease were associated with aortic aneurysm and/or dissection (P < 0.05 for both). Cranial symptoms (headache, scalp tenderness, abnormal temporal arteries) were negatively associated with large-artery stenosis (hazard ratio [HR] 0.10 [95% confidence interval (95% CI) 0.03-0.35, P < 0.0005]), as was a higher erythrocyte sedimentation rate (HR 0.80 [95% CI 0.67-0.95, P < 0.05] per 10 mm/hour). CONCLUSION: Large-artery complication is common in GCA. Increased awareness of large-artery complication in GCA, particularly early-occurring aortic dissection, may decrease associated mortality.

Aged↗
PubMed2003

Mortality of large-artery complication (aortic aneurysm, aortic dissection, and/or large-artery stenosis) in patients with giant cell arteritis: a population-based study over 50 years.

OBJECTIVE: To determine the mortality of giant cell arteritis (GCA) with large-artery complication compared with that of GCA without large-artery complication. METHODS: An inception cohort of 168 residents of Olmsted County, Minnesota, in whom GCA was diagnosed between January 1, 1950, and December 31, 1999, was followed up. Mortality in patients with incident large-artery complication (aortic aneurysm, aortic dissection, and large-artery stenosis) was determined and compared with that in patients in whom large-artery complication did not develop. RESULTS: No difference in survival was observed between the total group of patients with any type of large-artery complication and patients without large-artery complication or the general population. However, mortality was markedly increased in the 9 patients in whom thoracic aortic dissection developed (median survival 1.1 years [interquartile range 0.2-7.8 years]) compared with that in all other patients with GCA (P < 0.001). No difference in survival was observed between the group of patients with either aortic aneurysm and/or dissection (thoracic and/or abdominal aorta) and the group with GCA without large-artery complication. Survival of patients with GCA and large-artery stenosis was not different from that of patients with GCA without large-artery complication. CONCLUSION: Thoracic aortic dissection in GCA is associated with markedly increased mortality. Overall, mortality in the whole group of patients with GCA with large-artery complication was similar to that in patients with GCA without large-artery complication.

Aortic Dissection↗
PubMed2002

A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis.

OBJECTIVE: To evaluate treatment with methotrexate (MTX) in patients with newly diagnosed giant cell arteritis (GCA) to determine if MTX reduces GCA relapses and cumulative corticosteroid (CS) requirements and diminishes disease- and treatment-related morbidity. METHODS: This was a multicenter, randomized, double-blind study. Over 4 years, 16 centers from the International Network for the Study of Systemic Vasculitides enrolled patients with unequivocal GCA. The initial treatment was 1 mg/kg/day (<or=60 mg every day) prednisone, plus either 0.15 mg/kg/week MTX (increased to 0.25 mg/kg/week, for a maximum weekly dosage of 15 mg) or placebo. Two physicians, both blinded to treatment allocation, evaluated each patient at every trial visit. One physician was responsible for providing global medical care. The other assessed GCA status according to a standard protocol. Treatment failure was defined as 2 distinct relapses or persistence of disease activity after the first relapse, in spite of increased CS therapy. RESULTS: Ninety-eight patients were enrolled. No significant differences between treatment groups were noted with regard to age, frequency of positive findings on temporal artery biopsy (placebo 87%, MTX 79%), or comorbidities at the time of enrollment. The median dosage of MTX was 15 mg/week. The incidence of treatment failure was comparable between groups after 12 months: 57.5% in the MTX group failed treatment (95% confidence interval [95% CI] 41.6-73.4%) compared with 77.3% in the placebo group (95% CI 61.9-92.8%) (P = 0.26). In a Cox regression analysis, MTX was not associated with a reduced risk of treatment failure (relative risk 0.72; 95% CI 0.41-1.28). There were no significant differences between groups with regard to abnormal elevations of the erythrocyte sedimentation rate following initial remissions, serious morbidity due to GCA, cumulative CS dose, or treatment toxicity. In the MTX group, there were fewer cases of GCA relapse heralded by symptoms of isolated polymyalgia rheumatica (1 case versus 5 in the placebo group; P = 0.05). CONCLUSION: The results of this randomized, multicenter trial do not support the adjunctive use of MTX to control disease activity or to decrease the cumulative dose and toxicity of CS in patients with GCA.

Aged↗