Trends in the occurrence of ischaemic heart disease over time in rheumatoid arthritis: 1821 patients from 1972 to 2017.

OBJECTIVE: To evaluate trends of acute myocardial infarction (AMI) and ischaemic heart disease (IHD) in rheumatoid arthritis (RA) patients compared with the general population over time. METHOD: We performed a retrospective cohort study of 1821 RA patients diagnosed from 1972 to 2013. Aggregated counts of the total population of the same county (Hordaland, Norway) and period were used for comparison. Information on AMI and IHD events was obtained from hospital patient administrative systems or cardiovascular registries. We estimated incidence rates and excess of events [standardized event ratio (SER) with 95% confidence interval (CI)] compared with the general population by Poisson regression. RESULTS: There was an average annual decline of 1.6% in age- and gender-adjusted AMI incidence rates from 1972 to 2017 (p < 0.035). The difference in events (excess events) in RA patients compared with the general population declined on average by 1.3% per year for AMI and by 2.3% for IHD from 1972 to 2014. There were no significant excess AMI (SER 1.05, 95% CI 0.82-1.35) or IHD events (SER 1.02, 95% CI 0.89-1.16) for RA patients diagnosed after 1998 compared with the general population. CONCLUSION: Incidence rates and excess events of AMI and IHD in RA patients declined from 1972 to 2017. There were no excess AMI or IHD events in RA patients diagnosed after 1998 compared with the general population.

Major differences in medical and surgical treatment of psoriatic arthritis and rheumatoid arthritis: a comparison of two historic cohorts.

OBJECTIVES: Substantial changes in the handling of patients with inflammatory arthritis have occurred during the past half century. Polyarticular psoriatic arthritis (PsA) has been treated with the same synthetic disease-modifying anti-rheumatic drugs (DMARDs) as rheumatoid arthritis (RA), but for PsA there is less documentation regarding their effect. For biologic DMARDs, evidence of effect is more convincing. We have previously investigated the risk of orthopaedic surgery in patients with RA and PsA to see whether the change in treatment over time has improved the long-term outcome of inflammatory arthritis. For RA, patients diagnosed from 1999 onwards had a lower risk of surgery than patients diagnosed in earlier years. For PsA, the risk of surgery did not change similarly. We wished to compare RA patients to PsA patients with regard to medical and surgical treatment. METHOD: We compared a historic cohort of 1010 RA patients diagnosed in 1972-2009 to a historic cohort of 590 PsA patients diagnosed in 1954-2011. RESULTS: PsA patients received significantly less medical treatment both in the first year of disease and during the disease course. Risk of surgery during the disease course was lower for PsA than for RA (20% vs 31%). The risk of surgery in RA patients diagnosed from 1999 onwards was similar to that of PsA patients. CONCLUSIONS: PsA patients received less intensive treatment than RA patients. Their prognosis, regarding orthopaedic surgery, was also less severe. Contrary to RA, the change in treatment did not have beneficial effects regarding the risk of orthopaedic surgery.

Peptidylarginine deiminase 4 (PAD4) activity in early rheumatoid arthritis.

Objectives: Peptidylarginine deiminases (PADs) are a family of calcium-dependent enzymes catalysing the conversion of arginine residues to citrulline, which may constitute a risk factor in rheumatoid arthritis (RA) pathogenesis. We investigated PAD activation by serum (PADAct) in early RA, and the associations between PAD activation and disease characteristics, treatment response, and progression of radiographic damage.Method: Sera from disease-modifying anti-rheumatic drug (DMARD)-naïve early RA patients (n = 225), classified according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria, and healthy controls (n = 63) were analysed for PAD4 activating capacity at 0, 3, 12, and 24 months using a high-performance liquid chromatography fluorometric method. Associations for PADAct were evaluated by Mann-Whitney U and chi-squared tests. Changes in PADAct levels were compared using the Wilcoxon signed-rank test.Results: PADAct positivity occurred in 42% (n = 95) of the patients and was more prevalent in anti-citrullinated protein antibody (ACPA)-positive vs ACPA-negative patients (47% vs 20%, p = 0.002), but not in rheumatoid factor (RF)-positive vs RF-negative patients (44% vs 38%, p = 0.49). PADAct-positive were younger than PADAct-negative patients [mean ± sd 48.7 ± 13.5 vs 53.2 ± 13.7 years, p = 0.011]. Median [25th, 75th percentile] PADAct levels were higher in patients than in controls (8768 [7491, 11 393] vs 7046 [6347, 7906], p < 0.0001) and decreased after initiation of DMARD treatment, but were not associated with treatment response or progression of radiographic damage after 2 years of follow-up.Conclusion: Serum capacity to activate PAD4 was associated with ACPA and RF positivity and earlier disease onset in early RA patients, and decreased after initiation of DMARD treatment, indicating that anti-PAD treatment could potentially be beneficial in RA.

Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial.

BACKGROUND AND OBJECTIVES: The 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures. METHODS: Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. RESULTS: Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. CONCLUSION: The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.

Predictors for orthopaedic surgery in patients with rheumatoid arthritis: results from a retrospective cohort study of 1010 patients diagnosed from 1972 to 2009 and followed up until 2015.

OBJECTIVES: To investigate how patient characteristics, time of diagnosis, and treatment affect the need for orthopaedic surgery in patients with rheumatoid arthritis (RA). METHOD: We reviewed the medical history of 1544 patients diagnosed with RA at Haukeland University Hospital in Bergen, Norway, from 1972 to 2009, of whom 1010 (mean age 57 years, 69% women) were included in the present study. Relevant orthopaedic procedures were obtained from the Norwegian Arthoplasty Register and the hospital's administrative patient records. In total, 693 procedures (joint synovectomies 22%, arthrodeses 21%, prostheses 41%, and forefoot procedures 12%) were performed in 315 patients. Survival analyses were completed to evaluate the impact of different factors such as age, gender, radiographic changes, and year of diagnosis, on the risk of undergoing surgery. RESULTS: Patients diagnosed in 1972-1985 and 1986-1998 had a relative risk of undergoing surgery of 2.4 and 2.2 (p < 0.001), respectively, compared to patients diagnosed in 1999-2009. Radiographic changes at diagnosis and female gender were also significant risk factors. Anti-rheumatic medication was significantly different in the three time periods. CONCLUSION: Patients with a diagnosis in the early years had a greatly increased risk of having orthopaedic surgery performed. This is probably due to the year of diagnosis being a proxy for the type and intensity of medical treatment.

Giant cell arteritis: incidence and phenotypic distribution in Western Norway 2013-2020.

Objectives: There is an increasing awareness of the spectrum of phenotypes in giant cell arteritis (GCA). However, there is sparse evidence concerning the phenotypic distribution which may be influenced by both genetic background and the environment. We established a cohort of all GCA-patients in the Bergen Health Area (Western Norway), to describe the phenotypic distribution and whether phenotypes differ with regards to incidence and clinical features. Methods: This is a retrospective cohort study including all GCA-patients in the Bergen Health Area from 2013-2020. Data were collected by reviewing patient records, and patients considered clinically likely GCA were included if they fulfilled at least one set of classification criteria. Temporal artery biopsy (TAB) and imaging results were used to classify the patients according to phenotype. The phenotype "cranial GCA" was used for patients with a positive TAB or halo sign on temporal artery ultrasound. "Non-cranial GCA" was used for patients with positive findings on FDG-PET/CT, MRI-, or CT angiography, or wall thickening indicative of vasculitis on ultrasound of axillary arteries. Patients with features of both these phenotypes were labeled "mixed." Patients that could not be classified due to negative or absent examination results were labeled "unclassifiable". Results: 257 patients were included. The overall incidence of GCA was 20.7 per 100,000 persons aged 50 years or older. Overall, the cranial phenotype was dominant, although more than half of the patients under 60 years of age had the non-cranial phenotype. The diagnostic delay was twice as long for patients of non-cranial and mixed phenotype compared to those of cranial phenotype. Headache was the most common clinical feature (78% of patients). Characteristic clinic features occurred less frequently in patients of non-cranial phenotype compared to cranial phenotype. Conclusion: The overall incidence for GCA was comparable to earlier reports from this region. The cranial phenotype dominated although the non-cranial phenotype was more common in patients under 60 years of age. The diagnostic delay was longer in patients with the non-cranial versus cranial phenotype, indicating a need for examination of non-cranial arteries when suspecting GCA.

Survival and death causes of patients with giant cell arteritis in Western Norway 1972-2012: a retrospective cohort study.

BACKGROUND: Our objective was to determine the survival and causes of death in a large and well-characterized cohort of patients with giant cell arteritis (GCA). METHODS: This is a hospital-based, retrospective, observational cohort study including patients diagnosed with GCA in Western Norway during 1972-2012. Patients were identified through computerized hospital records using the International Classification of Diseases (ICD)-coding system. Medical records were reviewed. Patients were randomly assigned population controls matched on age, sex, and geography from the Central Population Registry of Norway (CPRN). Date and cause of death were obtained from the Norwegian Cause of Death Registry (NCoDR). The survival was analyzed using Kaplan-Meier methods with the Gehan-Breslow test and the causes of death using cumulative incidence and Cox models for competing risks. RESULTS: We identified 881 cases with a clinical diagnosis of GCA of which 792 fulfilled the American College of Rheumatology (ACR) 1990 classification criteria. Among those fulfilling the ACR criteria, 528 were also biopsy-verified. Cases were matched with 2577 population controls. A total of 490 (56%) GCA patients and 1517 (59%) controls died during the study period. We found no difference in the overall survival of GCA patients compared to controls, p = 0.413. The most frequent underlying causes of death in both groups were diseases of the circulatory system followed by cancer. GCA patients had increased risk of dying of circulatory disease (HR 1.31, 95% CI 1.13-1.51, p < 0.001) but lower risk of dying of cancer (HR 0.56, 95% CI 0.42-0.73, p < 0.001) compared to population controls. CONCLUSIONS: We found no difference in the overall survival of GCA patients compared to matched controls, but there were differences in the distribution of underlying death causes.

Correction to: Incidence of giant cell arteritis in Western Norway 1972-2012: a retrospective cohort study.

Following publication of the original article [1], the authors reported an error.

Incidence of giant cell arteritis in Western Norway 1972-2012: a retrospective cohort study.

BACKGROUND: Giant cell arteritis (GCA) is the most common systemic vasculitis in persons older than 50 years. The highest incidence rates of the disease have been reported in Scandinavian countries. Our objective was to determine the epidemiology of GCA in an expected high-incidence region during a 41-year period. METHODS: This is a hospital-based, retrospective, cohort study. Patients diagnosed with GCA in Bergen health area during 1972-2012 were identified through computerized hospital records (n = 1341). Clinical information was extracted from patients' medical journals, which were reviewed by a standardized method. We excluded patients if data were unavailable (n = 253), if the reviewing rheumatologist found GCA to be an implausible diagnosis (n = 207) or if the American College of Rheumatology (ACR) 1990 classification criteria for GCA were not fulfilled (n = 89). Descriptive methods were used to characterize the sample. Incidence was analyzed by graphical methods and Poisson regression. RESULTS: A total of 792 patients were included. The average annual cumulative incidence of GCA was 16.7 (95% CI 15.5-18.0) per 100,000 of the population ≥ 50 years old. The corresponding incidence for biopsy-verified GCA was 11.2 (95% CI 10.2-12.3). The annual cumulative incidence increased with time in the period 1972-1992 (relative risk (RR) 1.1, p < 0.001) but not in 1993-2012 (RR 1.0, p = 0.543). The incidence was higher in women compared to men (average annual incidence 37.7 (95% CI 35.8-39.6) vs. 14.3 (95% CI 13.2-15.5), p < 0.001) with women having a twofold to threefold higher incidence rate throughout the study period. Average annual incidence increased with age until the 7th decade of life in both sexes throughout the study period (2.8 (95% CI 2.3-3.3) for age <60, 15.5 (95% CI 14.4-16.8) for age 60-69, 34.5 (95% CI 32.8-36.4) for age 70-79 and 26.8 (95% CI 25.3-28.4) for age ≥80 years, p < 0.001 for all age adjustments). CONCLUSIONS: Our study confirms an incidence of GCA comparable to previous reports on Scandinavian populations. Our results show increasing incidence from 1972 through 1992, after which the incidence has levelled out.

Delay in operative treatment among patients with small bowel obstruction.

BACKGROUND AND AIMS: Delay in operative treatment for small bowel obstruction (SBO) has been shown to affect outcome adversely. The objective of this study was to detect time trends in treatment delay for patients with SBO during the study period 1961 to 1995 and to investigate factors influencing and factors affected by delay. MATERIALS AND METHODS: The records of 815 patients with 921 operations for SBO from 1961-1995 were studied. Patients with large bowel obstruction, paralytic ileus and SBO caused by abdominal cancer or intussusception were excluded. Data were analysed with descriptive statistics and multiple linear regression analyses. RESULTS: Old age and female sex were associated with increased treatment delay. Delay in hospital increased from 5 hours (median) in the 1960'ies to 16 hours (median) in the 1990'ies. Treatment delay correlated significantly with postoperative morbidity and hospital stay. Mortality increased after prolonged treatment delay in SBO caused by hernias whereas no significant increase in mortality was observed among adhesive obstructions. CONCLUSIONS: Hospital delay increased throughout the study period. Old patients and women had a longer median treatment delay than did young ones and men. Treatment delay led to an increase in postoperative morbidity and hospital stay after surgery for SBO.

Bacterial findings in infected hip joint replacements in patients with rheumatoid arthritis and osteoarthritis: a study of 318 revisions for infection reported to the norwegian arthroplasty register.

High rates of Staphylococcus aureus are reported in prosthetic joint infection (PJI) in rheumatoid arthritis (RA). RA patients are considered to have a high risk of infection with bacteria of potentially oral or dental origin. One thousand four hundred forty-three revisions for infection were reported to the Norwegian Arthroplasty Register (NAR) from 1987 to 2007. For this study 269 infection episodes in 255 OA patients served as control group. In the NAR we identified 49 infection episodes in 37 RA patients from 1987 to 2009. The RA patients were, on average, 10 years younger than the OA patients and there were more females (70% versus 54%). We found no differences in the bacterial findings in RA and OA. A tendency towards a higher frequency of Staphylococcus aureus (18% versus 11%) causing PJI was found in the RA patients compared to OA. There were no bacteria of potential odontogenic origin found in the RA patients, while we found 4% in OA. The bacteria identified in revisions for infection in THRs in patients with RA did not significantly differ from those in OA. Bacteria of oral or dental origin were not found in infected hip joint replacements in RA.

Hemodynamic changes associated with strangulation obstruction in cats.

While changes in blood flow associated with simple intestinal obstruction have been studied extensively, little is known about blood flow changes associated with strangulation obstruction. Closed loop strangulation was produced in anesthetized cats by means of a baby pressure gasket. Intestinal blood flow was measured by transit time flowmetry. Blood pressure was measured in a carotid artery and in veins of a closed loop of small intestine. The gasket pressure was increased stepwise in 10 mm Hg increments after which the intestinal venous pressure was kept constant at 50 mm Hg for 5 h. Increasing gasket pressure was followed by a corresponding increase in venous pressure in the closed bowel loop. Blood flow in the closed loop decreased with increasing venous pressure and was closely related to the arteriovenous perfusion pressure under stepwise increase of the gasket pressure and during prolonged periods with increased venous pressure. At constant elevated venous pressure the intestinal blood flow was determined by the arterial pressure. The vascular resistance in the closed loop increased exponentially with increasing venous pressure and especially at very low blood flow. In conclusion, we have found that strangulation obstruction is associated with increased venous pressure in the closed loop which contributes to maintaining intestinal blood flow during the obstruction.

Early operation or conservative management of patients with small bowel obstruction?

OBJECTIVE: To evaluate the outcome after initial non-operative treatment in patients with small bowel obstruction (SBO). DESIGN: Prospective study. SETTING: University hospital, Norway. PATIENTS: One hundred and fifty-four patients with 166 episodes of SBO admitted during the period (1994-1995). Patients younger than 10 years as well as patients with large bowel obstruction, paralytic ileus, incarcerated hernia or SBO caused by cancer were excluded from the study. INTERVENTIONS: Patients with signs of strangulation were operated on early. The rest were given a trial of conservative treatment. MAIN OUTCOME MEASURES: Need of operative treatment. Incidence of bowel strangulation, complications and death. RESULTS: There were 166 cases of SBO. Twenty patients were operated on early among whom bowel was strangulated in 9. Among the 146 patients initially treated conservatively 93 (64%) settled without operation, 9 (6%) had strangulated bowel and 3 (2%) died. Of the 91 patients with partial obstruction but no sign of strangulation, 72 (79%) resolved on conservative treatment. CONCLUSIONS: Patients with partial obstruction with no sign of strangulation should initially be treated conservatively. When complete obstruction is present, it may settle on conservative management, but the use of supplementary diagnostic tools might be desirable to find the patients who will need early operative treatment.

Complications and death after surgical treatment of small bowel obstruction: A 35-year institutional experience.

OBJECTIVE: To study factors influencing complications and death after operations for small bowel obstruction (SBO) using multifactorial statistical methods. SUMMARY BACKGROUND DATA: Death after surgery for SBO is believed to be influenced by factors such as old age, comorbidities, bowel gangrene, and delay in treatment. No studies have been reported in which adverse factors related to death and complications have been systematically investigated with modern statistical methods. METHODS: The authors studied retrospectively 877 patients who underwent 1,007 operations for SBO from 1961 to 1995. Patients with paralytic ileus, intussusception, and abdominal cancer were excluded. Odds ratios for death, complications, postoperative hospital stay, and strangulation were calculated by means of logistic regression analyses. RESULTS: Death and complication rates decreased during the study period. Old age, comorbidity, nonviable strangulation, and a treatment delay of more than 24 hours were significantly associated with an increased death rate. The rate of nonviable strangulation increased markedly with patient age. Major factors increasing the complication rate were old age, comorbidity, a treatment delay of more than 24 hours, and the need for repeat surgery. CONCLUSION: Death and complication rates after SBO decreased from 1961 to 1995. Major factors influencing the rates were age, comorbidity, nonviable strangulation, and treatment delay. Nonviable strangulation was more common in old patients.

Upper gastrointestinal contrast study in the management of small bowel obstruction--a prospective randomised study.

OBJECTIVE: To find out whether contrast radiography helps to resolve small bowel obstruction. DESIGN: Prospective randomised trial. SETTING: University hospital, Norway. SUBJECTS: 98 consecutive patients with symptoms of small bowel obstruction and a plain abdominal radiograph that confirmed the diagnosis. INTERVENTIONS: The patients were randomly allocated to receive a mixture of barium and sodium diatrizoate (Gastrografin) (n = 48) or not (n = 50). Both groups were followed up clinically and by repeated abdominal films. MAIN OUTCOME MEASURES: Non-operative resolution of small bowel obstruction; number of patients with strangulated bowel; bowel resections; mortality; complications; hospital stay; and time from admission to operation. RESULTS: No significant differences were observed between the groups in the incidence of non-operative resolution (31/48 in contrast group, 35/50 in control group, OR: 0.89), strangulation obstruction (1/48 in contrast group, 4/50 in control group, OR: 0.24), bowel resection (3/48 in contrast group, 4/50 in control group, OR: 0.76), complications (8/48 in contrast group, 5/50 in control group, OR: 1.80), mortality (3/48 in contrast group, 1/50 in control group, OR: 3.26), and hospital stay (0-7 days: 34/48 in contrast group, 38/50 in control group, p = 0.95). The contrast group had a shorter interval between admission and operation than the control group (0-24 hours: 12/48 in contrast group, 3/50 in control group, p = 0.005). CONCLUSION: The contrast examination did not contribute to the resolution of small bowel obstruction.

Smoking and ulcer perforation.

BACKGROUND: The use of ulcerogenic drugs is the only well documented risk factor for peptic ulcer perforation, but accounts for only a quarter of the events. Smoking is a well known risk factor for uncomplicated ulcer disease, and patients with ulcer bleeding have increased death rates from smoking related disorders. AIM: To assess the role of smoking in ulcer perforation. SUBJECTS: A total of 168 consecutive patients with gastroduodenal ulcer perforation and 4469 control subjects from a population based health survey. METHODS: The association between ulcer perforation and smoking habits was analysed by logistic regression while adjusting for age and sex. RESULTS: Current smoking increased the risk for ulcer perforation 10-fold in the age group 15-74 years (OR 9.7, 95% CI 5.9 to 15.8) and there was a highly significant dose-response relationship (p < 0.001). The results were similar in men (OR 9.3, 95% CI 4.9 to 17) and women (OR 11.6, 95% CI 5.3 to 25), and for gastric (OR 10.5, 95% CI 4.5 to 25) and duodenal (OR 8.6, 95% CI 4.9 to 15.4) ulcer perforation. No increase in risk was found in previous smokers (OR 0.8, 95% CI 0.2 to 2.2). CONCLUSION: Our findings suggest that smoking is a causal factor for ulcer perforation and accounts for a major part of ulcer perforations in the population aged less than 75 years.