Validity of clinical psoriatic arthritis diagnoses made by rheumatologists in the Swedish National Patient Register.

OBJECTIVES: : Knowledge of the correspondence between clinical ICD diagnoses and classification criteria fulfilment is crucial to interpret studies identifying cases via ICD codes. We assessed the degree to which patients registered with ICD-10 diagnoses of psoriatic arthritis (PsA) in the Swedish National Patient Register (NPR) fulfil established PsA classification criteria. METHOD: Four hundred patients with at least one outpatient visit to one of five rheumatology or internal medicine departments (three university/two county departments across Sweden) in 2013-2015, with a main ICD-10 diagnosis of PsA (L40.5, M07.0-M07.3), were randomly selected (80 cases/site). Through a structured medical record review, positive predictive values (PPVs) for fulfilment of the following classification criteria were assessed: CASPAR, Moll and Wright, Vasey and Espinoza, and modified ESSG criteria for PsA. A subset analysis regarding CASPAR fulfilment was also performed among cases with available rheumatoid factor and peripheral X-ray status (central CASPAR items; n = 227). RESULTS: Of the 400 patients with a main ICD-10 diagnosis of PsA, 343 (86%) fulfilled at least one of the four PsA classification criteria. PPVs for the different criteria were: CASPAR 69% (82% in the subset analysis), Moll and Wright 51%, Vasey and Espinoza 76%, and modified ESSG 64%. Overall, only 6.5% of the 400 PsA diagnoses were judged as clearly incorrect by the medical record reviewers. CONCLUSION: The validity of rheumatologist-made, clinical ICD-10 diagnoses for PsA in the Swedish NPR is good, with PPVs of 69-82% for CASPAR fulfilment and 86% for meeting any established PsA classification criteria.

Gout in Dalarna, Sweden - a population-based study of gout occurrence and compliance to treatment guidelines.

OBJECTIVE: This study aimed to describe the incidence and prevalence of gout, describe the use of allopurinol among prevalent gout cases, and determine persistence with allopurinol and degree of compliance with treat-to-target recommendations before and after the publication of Swedish national guidelines in 2016. METHOD: Prospectively registered data on gout diagnoses and allopurinol prescriptions were used to calculate incidence and prevalence, and the proportion of prevalent patients on allopurinol. Gout patients starting allopurinol during 2013-2015 versus 2016-2018 were compared regarding persistence and compliance with treat-to-target principles. RESULTS: The incidence of gout was 221-247 per 100 000 person-years during 2014-2019, prevalence in 2018 was 2.45%. Among prevalent cases, the proportion on allopurinol ranged from 21% to 25%. Allopurinol persistence was better for individuals starting therapy during 2016-2018 compared with 2013-2015 (45% vs 39%, p = 0.031), as were several outcomes related to treat-to-target principles, e.g. measuring baseline serum urate (SU) (84% vs 77%, p < 0.001), follow-up SU (50% vs 36%, p < 0.001), and the proportion of patients reaching an SU level < 360 µmol/L (45% vs 30%, p < 0.001). CONCLUSION: Incidence and prevalence were slightly higher than in previous Swedish reports. Allopurinol use among prevalent gout patients did not increase during 2014-2019. Only a minor improvement in persistence was seen, and a moderate increase in compliance with guidelines, suggesting a need for improved management and extended patient involvement to increase and optimize the use of urate lowering therapy.

Spiritual well-being and quality of life among Icelanders receiving palliative care: data from Icelandic pilot-testing of a provisional measure of spiritual well-being from the European Organisation for Research and Treatment of Cancer.

Palliative care focuses on improving quality of life (QoL). This study examined the feasibility of the Icelandic version of a provisional European Organisation for Research and Treatment of Cancer (EORTC) measure of spiritual well-being (SWB), and explored the relationship between SWB and QoL for palliative care patients in Iceland. Instruments from the EORTC were used: the provisional measure of SWB, which was undergoing pilot-testing in Iceland, and the EORTC QLQ C15-PAL. The correlation between scores was examined and descriptive statistics were used. Structured interviews explored feasibility. Thirty persons participated with average age 72 years. Belief in God or a higher power had the mean 3.33 on a 1-4 scale and the mean for overall SWB was 5.73 on a 1-7 scale. The mean score for global health/QoL was 59.4, physical functioning 48.5 and emotional functioning 78.9 on a 0-100 scale. Overall QoL was positively correlated with SWB showing r(30) = 0.386, P = 0.035. The participants found that answering the provisional EORTC QLQ-SWB prompted an emotional response and took the opportunity to discuss the subject. The provisional SWB measure was found relevant for the Icelandic context, and the study indicates that SWB and QoL are closely connected.

Validity of ankylosing spondylitis and undifferentiated spondyloarthritis diagnoses in the Swedish National Patient Register.

OBJECTIVES: Epidemiological studies of spondyloarthritis (SpA), using ICD codes from the Swedish National Patient Register (NPR), offer unique possibilities but hinge upon an understanding of the validity of the codes. The aim of this study was to validate the ICD codes for ankylosing spondylitis (AS) and undifferentiated SpA (uSpA) in the NPR against the established classification criteria [modified New York (mNY), Assessment of SpondyloArthritis international Society (ASAS), Amor, and European Spondyloarthropathy Study Group (ESSG) criteria]. METHOD: All patients with an ICD-8/9/10 code of AS or uSpA in the NPR 1966-2009 at a visit to a specialist in rheumatology or internal medicine or corresponding hospitalization, alive and living in Sweden 2009, were identified (n=20,089). Following a structured procedure to achieve geographical representativeness, 500 random patients with a diagnosis of AS or uSpA in 2007-2009 were selected. Based on a structured review of clinical records, positive predictive values (PPVs) for fulfilling the criteria sets were calculated. RESULTS: For those having received an ICD code for AS, the PPVs for fulfilling the mNY criteria or any set of SpA criteria were 70% and 89%, respectively. For those with an uSpA diagnosis (and never an AS diagnosis), the corresponding PPVs were 20% and 79%. The subset with both AS and uSpA diagnoses (overlap=12%) were as likely to fulfil the mNY criteria as the group that had been coded as AS only. CONCLUSIONS: The diagnosis codes for AS or uSpA had high PPVs, suggesting that our case identification in the Swedish NPR can be used for nationwide, population-based, epidemiological studies of these diseases.

The Effect of Everolimus Initiation and Calcineurin Inhibitor Elimination on Cardiac Allograft Vasculopathy in De Novo Recipients: One-Year Results of a Scandinavian Randomized Trial.

Early initiation of everolimus with calcineurin inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of calcineurin inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete calcineurin inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (± SD) recipient age was 49.9 ± 13.1 years. The everolimus group (n = 47) demonstrated significantly reduced CAV progression as compared to the calcineurin inhibitor group (n = 48) (ΔMaximal Intimal Thickness 0.03 ± 0.06 and 0.08 ± 0.12 mm, ΔPercent Atheroma Volume 1.3 ± 2.3 and 4.2 ± 5.0%, ΔTotal Atheroma Volume 1.1 ± 19.2 mm(3) and 13.8 ± 28.0 mm(3) [all p-values ≤ 0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the calcineurin inhibitor group (p = 0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients.

Everolimus initiation and early calcineurin inhibitor withdrawal in heart transplant recipients: a randomized trial.

In a randomized, open-label trial, everolimus was compared to cyclosporine in 115 de novo heart transplant recipients. Patients were assigned within 5 days posttransplant to low-exposure everolimus (3­6 ng/mL) with reduced-exposure cyclosporine (n = 56), or standard-exposure cyclosporine (n = 59), with both mycophenolate mofetil and corticosteroids. In the everolimus group, cyclosporine was withdrawn after 7­11 weeks and everolimus exposure increased (6­10 ng/mL). The primary efficacy end point, measured GFR at 12 months posttransplant, was significantly higher with everolimus versus cyclosporine (mean ± SD: 79.8 ± 17.7 mL/min/1.73 m2 vs. 61.5 ± 19.6 mL/min/1.73 m2; p < 0.001). Coronary intravascular ultrasound showed that the mean increase in maximal intimal thickness was smaller (0.03 mm [95% CI 0.01, 0.05 mm] vs. 0.08 mm [95% CI 0.05, 0.12 mm], p = 0.03), and the incidence of cardiac allograft vasculopathy (CAV) was lower (50.0% vs. 64.6%, p = 0.003), with everolimus versus cyclosporine at month 12. Biopsy-proven acute rejection after weeks 7­11 was more frequent with everolimus (p = 0.03). Left ventricular function was not inferior with everolimus versus cyclosporine. Cytomegalovirus infection was less common with everolimus (5.4% vs. 30.5%, p < 0.001); the incidence of bacterial infection was similar. In conclusion, everolimus-based immunosuppression with early elimination of cyclosporine markedly improved renal function after heart transplantation. Since postoperative safety was not jeopardized and development of CAV was attenuated, this strategy may benefit long-term outcome.

Virtual histology assessment of cardiac allograft vasculopathy following introduction of everolimus--results of a multicenter trial.

In this 12-month multicenter Scandinavian study, 78 maintenance heart transplant (HTx) recipients randomized to everolimus with reduced calcineurin inhibitor (CNI) exposure or continued standard CNI-therapy underwent matched virtual histology (VH) examination to evaluate morphological progression of cardiac allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.9 ± 3.8% and 1.6 ± 3.9%, respectively; p = 0.65). However, VH analysis revealed a significant increase in calcified (2.4 ± 4.0 vs. 0.3 ± 3.1%; p = 0.02) and necrotic component (6.5 ± 8.5 vs. 1.1 ± 8.6%; p = 0.01) among everolimus patients compared to controls. The increase in necrotic and calcified components was most prominent in everolimus patients with time since HTx >5.1 years and was accompanied by a significant increase in levels of von Willebrand (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03). Conversion to everolimus and reduced CNI is associated with a significant increase in calcified and necrotic intimal components and is more prominent in patients with a longer time since HTx. A significant increase in vWF and VCAM accompanied these qualitative changes and the prognostic implication of these findings requires further investigation.

Influence from genetic variability on opioid use for cancer pain: a European genetic association study of 2294 cancer pain patients.

Cancer pain patients need variable opioid doses. Preclinical and clinical studies suggest that opioid efficacy is related to genetic variability. However, the studies have small samples, findings are not replicated, and several candidate genes have not been studied. Therefore, a study of genetic variability with opioid doses in a large population using a confirmatory validation population was warranted. We recruited 2294 adult European patients using a World Health Organization (WHO) step III opioid and analyzed single nucleotide polymorphisms (SNPs) in genes with a putative influence on opioid mechanisms. The patients' mean age was 62.5 years, and the average pain intensity was 3.5. The patients' primary opioids were morphine (n=830), oxycodone (n=446), fentanyl (n=699), or other opioids (n=234). Pain intensity, time on opioids, age, gender, performance status, and bone or CNS metastases predicted opioid dose and were included as covariates. The patients were randomly divided into 1 development sample and 1 validation sample. None of 112 SNPs in the 25 candidate genes OPRM1, OPRD1, OPRK1, ARRB2, GNAZ, HINT1, Stat6, ABCB1, COMT, HRH1, ADRA2A, MC1R, TACR1, GCH1, DRD2, DRD3, HTR3A, HTR3B, HTR2A, HTR3C, HTR3D, HTR3E, HTR1, or CNR1 showed significant associations with opioid dose in both the development and the validation analyzes. These findings do not support the use of pharmacogenetic analyses for the assessed SNPs to guide opioid treatment. The study also demonstrates the importance of validating findings obtained in genetic association studies to avoid reporting spurious associations as valid findings. To elicit knowledge about new genes that influence pain and the need for opioids, strategies other than the candidate gene approach is needed.

Circulating oxidized LDL is associated with the occurrence of echolucent plaques in the carotid artery in 61-year-old men.

OBJECTIVE: The aim of this study was to elucidate the relationship between the echogenicity of carotid artery plaques and the following risk factors: circulating oxLDL, hsCRP, the metabolic syndrome (MetS), and several of the traditional cardiovascular (CV) risk factors. MATERIAL AND METHODS: A cross-sectional population-based study of 513 sixty-one-year-old men. The levels of circulating oxLDL were determined in plasma samples by sandwich ELISA utilizing a specific murine monoclonal antibody (mAb-4E6). High-sensitivity CRP was measured in plasma by ELISA. Plaque occurrence, size and echogenicity were evaluated from B-mode ultrasound registrations in the carotid arteries. Plaque echogenicity was assessed based on a four-graded classification scale. RESULTS: A higher frequency of echolucent carotid plaques was observed with increasing levels of oxLDL and systolic blood pressure (p = 0.008 and p = 0.041, respectively). Subjects with the MetS had a significantly higher frequency of echogenic plaques than subjects without the MetS (p = 0.009). In a multiple logistic regression analysis, oxLDL turned out to be independently associated with echolucent carotid plaques. CONCLUSIONS: The occurrence of echolucent carotid plaques was associated with oxLDL and systolic blood pressure, and oxLDL was associated with echolucent carotid plaques independently of systolic blood pressure.

Circulating matrix metalloproteinase 9 levels in relation to sampling methods, femoral and carotid atherosclerosis.

OBJECTIVES: To examine whether circulating levels of matrix metalloproteinase 9 (MMP-9) were associated with ultrasound-assessed intima-media thickness (IMT) and echolucent plaques in the carotid and femoral arteries. To examine preanalytical sources of variability in MMP-9 concentrations related to sampling procedures. SUBJECTS AND DESIGN: Plasma and serum MMP-9 levels were compared with ultrasound assessed measures of femoral and carotid atherosclerosis, in a cross-sectional study of 61-year-old men (n = 473). Preanalytical sources of variability in MMP-9 levels were examined in 10 healthy subjects. Main outcome measures were circulating levels of MMP-9 in serum and plasma, IMT of the carotid and femoral arteries, and plaque status based on size and echolucency. SETTING: Research unit at university hospital. RESULTS: Plasma concentrations of total and active MMP-9 were associated with femoral artery IMT independently of traditional cardiovascular risk factors, and were higher in subjects with moderate to large femoral plaques. Plasma MMP-9 concentration was higher in men with echolucent femoral plaques (P = 0.006) compared with subjects without femoral plaques. No similar associations were found for carotid plaques. MMP-9 concentrations were higher in serum than in plasma, and higher when sampling was performed with Vacutainer than with syringe. MMP-9 levels in serum were more strongly associated with peripheral neutrophil count compared with MMP-9 levels in plasma. CONCLUSIONS: Plasma MMP-9 levels were associated with atherosclerosis in the femoral artery, and total MMP-9 concentration was higher in men with echolucent femoral plaques. The choice of sample material and sampling method affect the measurements of circulating MMP-9 levels.

Important needs of families in acute and palliative care settings assessed with the family inventory of needs.

Family support has been recognized in the development of palliative care in Iceland, yet studies focusing on family needs are lacking. The aims of this study were to evaluate the perceived care needs of family members of patients receiving palliative care, to what extent these needs were met, and whether needs differed based on background characteristics and site of care. Family members of 111 patients from acute and palliative care settings agreed to participate, and 67 (60%) completed the study. The Family Inventory of Needs was used to quantify family needs and to what extent they were met. All 20 needs measured were considered important. The number of needs did not differ by site of palliative care. Overall, health care professionals met 67% of needs. Needs were more likely to be met in specialized palliative care settings than on acute units and the needs of spouses were more likely to be met than others.

Circulating oxidized low-density lipoprotein (LDL) is associated with risk factors of the metabolic syndrome and LDL size in clinically healthy 58-year-old men (AIR study).

OBJECTIVES: Hypothetically the atherogenic effect of the metabolic syndrome may be mediated through the increased occurrence of small LDL-particles which are easily modified to atherogenic oxidized LDL (ox-LDL). The aim of this study was to test this concept by examining the association between circulating ox-LDL, LDL-particle size, and the metabolic syndrome. DESIGN AND RESULTS: A population-based sample of clinically healthy 58-year-old men (n = 391) was recruited. Ox-LDL was measured by ELISA (specific monoclonal antibody, mAb-4E6) and LDL-particle size by gradient gel electrophoresis. The results showed that ox-LDL significantly correlated to factors constituting the metabolic syndrome; triglycerides (r = 0.43), plasma insulin (r = 0.20), body mass index (r = 0.20), waist-to-hip ratio (r = 0.21) and HDL (r = -0.24); (P < 0.001). Ox-LDL correlated also to LDL-particle size (r = -0.42), Apo-B (r = 0.70), LDL (r = 0.65); (P < 0.001) and, furthermore, with Apo A-1 (r = -0.13) and heart rate (r = 0.13); (P < 0.01). CONCLUSION: The metabolic syndrome was accompanied by high plasma ox-LDL concentrations compared with those without the syndrome. Ox-LDL levels were associated with most of the risk factors constituting the metabolic syndrome and was, in addition related to small LDL-particle size. To our knowledge the present study is the first one to demonstrate that circulating ox-LDL levels are associated with small LDL-particle size in a population representative sample of clinically healthy middle-aged men. The high degree of intercorrelation amongst several factors makes it difficult to clarify the independent role of any specific factor.

P53 mutations analysis in benign and malignant breast lesions: using needle rinses from fine-needle aspirations.

The fine-needle aspiration (FNA) technique is a widely used method for diagnostic assessment of breast diseases. In the current study we investigated the feasibility of sampling material for genetic studies from the same FNA samples as would be used for breast cytology. After making smears for cytological examination, the needle was rinsed into phosphate-buffered saline (PBS) solution. The material gained was sufficient for a polymerase chain reaction (PCR)-based study. As the FNA samples reflect a broad range of breast diseases, it is possible to study genetic changes at various stages of the neoplastic process. We looked for mutations in the p53 tumor suppressor gene in 198 FNA needle rinses, 42 from carcinomas and 156 from cytologically benign lesions. In the malignant samples, 22% carried mutations in the p53 gene. We also looked for p53 mutations in matching tissue sections from tumors and found the FNA needle rinses to represent the tumor well. In addition, three mutations in cytologically benign lesions were found, but none of these 3 patients were diagnosed with malignant tumors in the time frame of the study. The clinical significance of p53 mutations in benign breast tissue remains to be determined.

[Predictors of mammography adherence among Icelandic women.].

OBJECTIVE: In Iceland, breast cancer is a second only to lung cancer as a cause of women s cancer related deaths. Despite the widely-recognized utility of mammography for detecting breast cancer at early stages when it is most curable, many Icelandic women do not adhere to mammography screening recommendations. The aim of the present population-based study was to identify factors that facilitate and hinder women s adherence to mammography screening in Iceland. MATERIAL AND METHODS: A randomly selected sample of Icelandic women between the ages of 40-69 years, not previously diagnosed with breast cancer (n=1000), were recruited to the study by mail. Participants (n=619) completed questionnaires assessing: demopgraphic variables, knowledge of screening guidelines, possible facilitators (e.g., physician recommendation) and barriers (e.g. concern about radiation) to adherence, as well as stages of mammography screening adoption (precontemplation, contemplation, action and maintenance). RESULTS: Women in the precontemplation stage were more afraid of radiation than women on other stages. They as well as women on contemplation stage were more afraid that mammography would be painful, and less satisfied with previous service at the mammography screening center. Doctors recommendations, as well as women s knowledge about mammography screening guidelines, were positively related to mammography adherence. CONCLUSIONS: These findings suggest that physicians may have an important role in motivating women to follow mammography screening recommendations. Educating women about mammography screening guidelines and addressing their concern about radiation and pain may increase mammography adherence further. Service at the mammography screening center may also improve adherence.

[Interest in breast cancer genetic testing among Icelandic women.].

OBJECTIVE: It is estimated that 6-10% of all breast cancers in Iceland can be attributed to inherited mutations in newly identified breast cancer susceptibility genes (BRCA1 and BRCA2). Before genetic testing becomes widely available in Iceland it is important to understand what motivates women s interest in undergoing testing as that will provide the data necessary for designing effective counseling interventions. Therefore, the aim of this population-based study was to examine interest in and predictors of interest in genetic testing among Icelandic women. MATERIAL AND METHODS: A randomly selected sample of 534 Icelandic women, who had not been previously diagnosed with breast cancer, completed questionnaires assessing, demographic/medical variables, interest in genetic testing, perceived risk of carrying mutations in BRCA1/2 genes, cancer-specific distress and perceived benefits and barriers of genetic testing. The mean age was 53.8 years and 197 of the women had at least one first degree-relative that had been diagnosed with breast cancer. RESULTS: Interest in testing was high with 74% of the women indicating that they were interested in testing. Family history of breast cancer was unrelated to interest in testing whereas perceived risk of being a mutation carrier was significantly and positively related to interest in testing. Interest in testing was also significantly higher among younger women and among women with higher levels of cancer-specific distress. The most commonly cited reasons for wanting to be tested were to increase use of mammography screening and to learn if one s children were at risk for developing cancer. The most commonly citied reasons against being tested were fear of being mutation carrier and worry that test results would not stay confidential. CONCLUSIONS: These results suggest that demand for genetic testing, once it becomes commercially available, among Icelandic women may be high even among women without family history of breast cancer. The results also suggest that genetic counseling needs to address women s breast cancer worries as that may increase the probability that the decision to undergo testing is based on knowledge rather than driven by breast cancer fear and distress.

Seroepidemiology of Mycoplasma pneumoniae infections in Iceland 1987-96.

Mycoplasma pneumoniae is a common cause of respiratory tract infections in humans. The aim of the present study was to analyse the seroepidemiology of M. pneumoniae infections in Iceland during a 10-y period. A retrospective analysis of all serological diagnosis of M. pneumoniae infections at the Department of Medical Virology, National University Hospital in Reykjavík was performed. A total of 13,201 test results from 1987 to 1996 were reviewed and altogether 762 patients were found to have raised M. pneumoniae antibody titres, using a conventional complement fixation assay. Infections were most common amongst young people (< or=16 y) but a second peak in incidence was observed around the age of 35 y. Significant annual (p < 0.0001) and seasonal variations (p=0.0003) were observed; M. pneumoniae infections were most common during the winter period. Three major outbreaks with intervals of three to five years were observed during the observation period. Patients diagnosed during these outbreaks had higher M. pneumoniae titres than those found when infections were less frequent (p=0.0017). Furthermore, the middle aged and elderly patients (> 50 y) had significantly lower M. pneumoniae titres than younger patients (p=0.0014). The findings of this study show that M. pneumoniae infections have definite annual and seasonal variations and also confirm previous studies showing community outbreaks of M. pneumoniae infections every 3-5 y.

Criterion-based validation of the EORTC QLQ-C36 in advanced melanoma: the CIPS questionnaire and proxy raters.

An extensive quality of life (QOL) investigation of the effects of chemotherapy in patients with generalized malignant melanoma included a validation study of involved questionnaires. The QOL domains of the three basic quality of life questionnaires, the EORTC QLQ-C36 (European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire), a study-specific malignant melanoma (MM) module and the Hospital Anxiety and Depression (HAD) scale vs. the Cancer Inventory of Problem Situations (CIPS) were validated by correlation analyses. The value of using attending nurses and/or next of kin to assess the patients situation was also examined. Functional and symptom scales of the C36 and the subscales of the HAD showed appropriate convergent and discriminant validity when compared with the CIPS. The subscales of the MM module had less clear relationships, probably due to lack of accordance in the CIPS. Assessments of attending nurses revealed very low correlations with the patients' measures. They underestimated significantly series of specific symptoms and overestimated nausea and the overall quality of life of the patients. However, assessments of close relatives, mostly spouses, showed moderate to high correlations and no significant difference. These results further strengthen the overall validity of the modular approach of the EORTC QLQ technique. In this context of active chemotherapy in patients with advanced cancer disease, relatives seem to be better surrogates than the attending nurses in assessing the patients' quality of life.