Associations between metabolic factors and radiographic knee osteoarthritis in early disease - a cross-sectional study of individuals with knee pain.

OBJECTIVE: Metabolic factors have been shown to be associated to severe radiographic knee osteoarthritis (RKOA). However, more knowledge is needed in early clinical knee osteoarthritis (KOA). The aim was to study associations between metabolic factors and radiographic knee osteoarthritis (OA) in individuals with knee pain. A second aim was to study associations between metabolic factors and RKOA in those with normal BMI and in those overweight/obese, respectively. METHOD: This cross-sectional study included 282 individuals with knee pain (without cruciate ligament injury) and aged 30-67 years, and 70% women. Waist circumference, body mass index (BMI), proportion of fat and visceral fat area (VFA) were assessed. RKOA was defined as Ahlbäck grade 1 in at least one knee. Fasting blood samples were taken and triglycerides, cholesterol (total, low density lipoprotein (LDL) and high density lipoprotein (HDL)), C-reactive protein (CRP), glucose, HbA1C were analysed. Metabolic syndrome was defined in accordance with the International Diabetes Federation (IDF). Associations were analysed by logistic regression. RESULTS: Individuals with RKOA were older, had higher BMI, higher VFA, larger waist circumference and had increased total cholesterol, triglycerides and LDL-cholesterol, but not fasting glucose. There was no difference between the group with RKOA vs. non-radiographic group regarding the presence of metabolic syndrome. In a subgroup analysis of individuals with normal BMI (n = 126), those with RKOA had higher VFA, more central obesity, higher levels of CRP and total cholesterol, compared with individuals without RKOA. In individuals with obesity, age was the only outcome associated to RKOA. CONCLUSION: There were clear associations between metabolic factors and RKOA in individuals with knee pain, also in those with normal BMI. In individuals with obesity age was the only variable associated to RKOA. TRIAL REGISTRATION: clinicalTrials.gov Identifier: NCT04928170.

The educational needs of patients with undifferentiated spondyloarthritis: Validation of the ENAT questionnaire and needs assessment.

OBJECTIVES: The aim of the present study was to validate the Swedish version of the educational needs assessment tool (SwENAT) in undifferentiated spondyloarthritis (USpA) and use it to study the educational needs of patients with USpA. METHODS: This was a cross-sectional study, recruiting a random sample of patients with USpA from a hospital register in Sweden. Educational needs data were collected, together with disease activity and function indices (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] and Bath Ankylosing Spondylitis Functional Index [BASFI]). Rasch analysis was utilized to evaluate the construct validity, internal consistency and unidimensionality of the SwENAT before studying differences in educational needs between patient subgroups (gender, age and disease severity). RESULTS: Complete responses were obtained from 77 patients (48 women), with a mean age (standard deviation [SD]) of 50 (12) years, a disease duration of 16 (11) years, a BASDAI score of 4.9 (1.9) and a BASFI score of 3.1 (2.3). The SwENAT satisfied the requirements of the Rasch model (χ2 = 11.488; p = 0.119), including strict unidimensionality. Overall, the mean (SD) SwENAT score was 86 (32). Women reported higher needs than men in the domains of pain (mean [SD] 13.1 [6.8] versus 10.1 [6.0]; p = 0.05); movement (mean [SD] 13.0 [5.5] versus 9.9 [5.7]; p = 0.02) and self-help (mean [SD] 17.0 [5.8] versus 14.1 [5.0]; p = 0.03). Higher disease activity (BASDAI >4) was associated with higher educational needs (mean [SD] 92.6 [31.9] versus 73.7 [29.4]; p = 0.02). CONCLUSIONS: These data suggest that the SwENAT is valid in USpA. Women and patients with higher disease activity are more likely to have high levels of educational needs, so special attention and strategies to target patient education are warranted.

Prognostic factors for change in self-reported anxiety and depression in spondyloarthritis patients: data from the population-based SpAScania cohort from southern Sweden.

OBJECTIVES: Anxiety and depression symptoms are more common in patients with spondyloarthritis (SpA) than in the general population. This study describes prognostic factors for change in self-reported anxiety and depression over 2 years in a well-defined SpA cohort. METHOD: In 2009, 3716 adult patients from the SpAScania cohort received a postal questionnaire to assess quality of life (QoL) and physical and mental functioning. A follow-up survey was performed in 2011. The Hospital Anxiety and Depression Scale indicated 'no', 'possible', and 'probable' cases of anxiety and depression. Transitions between the three different categories were analysed and logistic regression analysis determined prognostic factors (patient-reported outcomes and characteristics) for improvement or deterioration. RESULTS: In total, 1629 SpA patients responded to both surveys (44%) (mean ± SD age 55.8 ± 13.1 years, disease duration 14.6 ± 11.7 years); 27% had ankylosing spondylitis, 55% psoriatic arthritis, and 18% undifferentiated SpA. The proportion of patients reporting possible/probable anxiety decreased from 31% to 25% over 2 years, while no changes in depression were seen. Factors associated with deterioration or improvement were largely the same for anxiety as for depression: fatigue, general health, QoL, level of functioning, disease activity, and self-efficacy. However, reporting chronic widespread pain (CWP) at baseline increased the risk of becoming depressed and decreased the probability of recovering from anxiety. CONCLUSION: Self-reported anxiety and depression is common and fairly stable over time in SpA patients. The association between mental health and CWP indicates that both comorbidities need to be acknowledged and treated in the clinic.

Demonstration of post-growth wavelength setting of VCSELs using high-contrast gratings.

We demonstrate, for the first time, post-growth wavelength setting of electrically-injected vertical-cavity surface-emitting lasers (VCSELs) by using high-contrast gratings (HCGs) with different grating parameters. By fabricating HCGs with different duty cycle and period, the HCG reflection phase can be varied, in effect giving different optical cavity lengths for HCG-VCSELs with different grating parameters. This enables fabrication of monolithic multi-wavelength HCG-VCSEL arrays for wavelength-division multiplexing (WDM). The GaAs HCG is suspended in air by removing a sacrificial layer of InGaP. Electrically-injected 980-nm HCG-VCSELs with sub-mA threshold currents indicate high reflectivity from the GaAs HCGs. Lasing over a wavelength span of 15 nm was achieved, enabling a 4-channel WDM array with 5 nm channel spacing. A large wavelength setting span was enabled by an air-coupled cavity design and the use of only the HCG as top mirror.

European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.

BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

Antibody targeting of anaplastic lymphoma kinase induces cytotoxicity of human neuroblastoma.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in neuroblastoma, a devastating pediatric cancer of the sympathetic nervous system. Germline and somatically acquired ALK aberrations induce increased autophosphorylation, constitutive ALK activation and increased downstream signaling. Thus, ALK is a tractable therapeutic target in neuroblastoma, likely to be susceptible to both small-molecule tyrosine kinase inhibitors and therapeutic antibodies-as has been shown for other receptor tyrosine kinases in malignancies such as breast and lung cancer. Small-molecule inhibitors of ALK are currently being studied in the clinic, but common ALK mutations in neuroblastoma appear to show de novo insensitivity, arguing that complementary therapeutic approaches must be developed. We therefore hypothesized that antibody targeting of ALK may be a relevant strategy for the majority of neuroblastoma patients likely to have ALK-positive tumors. We show here that an antagonistic ALK antibody inhibits cell growth and induces in vitro antibody-dependent cellular cytotoxicity of human neuroblastoma-derived cell lines. Cytotoxicity was induced in cell lines harboring either wild type or mutated forms of ALK. Treatment of neuroblastoma cells with the dual Met/ALK inhibitor crizotinib sensitized cells to antibody-induced growth inhibition by promoting cell surface accumulation of ALK and thus increasing the accessibility of antigen for antibody binding. These data support the concept of ALK-targeted immunotherapy as a highly promising therapeutic strategy for neuroblastomas with mutated or wild-type ALK.

Prevalence of spondyloarthritis and its subtypes in southern Sweden.

OBJECTIVE: To estimate the prevalence of spondyloarthritis and its subtypes. METHODS: The Swedish healthcare organisation comprises a system where all inpatient and outpatient care is registered by a personal identifier. For the calendar years 2003-7, all residents aged ≥ 15 years in the southernmost county of Sweden (1.2 million inhabitants) diagnosed by a physician with spondyloarthritis (ankylosing spondylitis (AS), psoriatic arthritis (PsA), inflammatory arthritis associated with inflammatory bowel disease (Aa-IBD) or undifferentiated spondylarthritis (USpA)) were identified. To obtain valid point estimates of prevalence by the end of 2007, identification numbers were cross-referenced with the population register to exclude patients who had died or relocated. RESULTS: The authors estimated the prevalence of spondyloarthritis (not including chronic reactive arthritis) as 0.45% (95% CI 0.44% to 0.47%). The mean (SD) age of patients with prevalent spondyloarthritis by the end of 2007 was 53 (15) years. Among the component subtypes, PsA accounted for 54% of cases, AS 21.4%, USpA 17.8% and Aa-IBD 2.3% with a prevalence of 0.25%, 0.12%, 0.10% and 0.015%, respectively. The remaining 6.4% had some form of combination of spondyloarthritis diagnoses. The prevalence of spondyloarthritis at large was about the same in men and women. However, the subtype PsA was more prevalent in women and AS was more prevalent in men. CONCLUSION: In Sweden the prevalence of spondyloarthritis leading to a doctor consultation is not much lower than rheumatoid arthritis. PsA was the most frequent subtype followed by AS and USpA, and the two most frequent subtypes PsA and AS also display some distinct sex patterns.

Aerobic capacity in patients with rheumatoid arthritis: a comparison of two submaximal test methods.

BACKGROUND: In a clinical setting it is important to evaluate aerobic capacity in individuals with rheumatoid arthritis (RA) and to have a choice between tests, owing to disability of varying severity. Two submaximal tests, a bicycle ergometer test and a treadmill walking test, are commonly used. Despite expected differences in the results, these tests have been used interchangeably. The aim of the current study was to compare the results of the two tests, the size of the difference and factors expected to influence the results. METHODS: Fifty-two outpatients with RA performed the two tests. Agreement and correlations between the results of the tests were calculated. Multivariate analysis was used to study the relationships between gender, weight, health assessment questionnaire, global health assessment and the difference between the tests. RESULTS: Sixty per cent of the subjects exhibited a higher estimated value of maximum oxygen uptake (VO(2max)) in the treadmill test. The limits of agreement for the estimated VO(2max) values between the two methods ranged from -13.4 to +18.4 ml x min(-1) x kg(-1), and the intraclass correlation coefficient (ICC(Two-way mixed)) was 0.34 (95% confidence interval [CI] 0.07, 0.56). Body weight was independently associated with the difference between the two tests (regression coefficient 0.3; 95% CI 0.14, 0.42). A higher body weight had a greater impact on the results of the bicycle test (R(2) = 0.28; regression coefficient -0.3; 95% CI -0.47, -0.17) than on the treadmill walking test (R(2) = 0.02; regression coefficient -0.06; 95% CI -0.14, 0.03). CONCLUSIONS: It is not advisable to use the two submaximal methods interchangeably. Weight influenced the difference between the two tests, and to a higher degree in the bicycle test than the treadmill walking test.

Design of multifunctional nanomedical systems.

Multifunctional nanoparticles hold great promise for drug/gene delivery and simultaneous diagnostics and therapeutics ("theragnostics") including use of core materials that provide in vivo imaging and opportunities for externally modulated therapeutic interventions. Multilayered nanoparticles can act as nanomedical systems with on-board molecular programming done through the chemistry of highly specialized layers to accomplish complex and potentially decision-making tasks. The targeting process itself is a multi-step process consisting of initial cell recognition through cell surface receptors, cell entry through the membrane in a manner to prevent undesired alterations of the nanomedical system, re-targeting to the appropriate sub-region of the cell where the therapeutic package can be localized, and potentially control of that therapeutic process through feedback systems using molecular biosensors. This paper describes a bionanoengineering design process in which sophisticated nanomedical platform systems can be designed for diagnosis and treatment of disease. The feasibility of most of these subsystems has been demonstrated, but the full integration of these interacting sub-components remains a challenge for the field. Specific examples of sub-components developed for specific applications are described.

Influence of metoprolol CR/ZOK on plasminogen activator inhibitor (PAI-1) in man: a pilot study.

Recent primary and secondary preventive trials have shown that long-term metoprolol therapy reduces the risk of acute cardiovascular complications. To test whether part of this beneficial long-term effect may be due to effects on the fibrinolytic system, three pilot studies were performed; two in healthy individuals, and one in patients with mild hypertension or uncomplicated atrial fibrillation. The effect of metoprolol CR/ZOK (controlled release) 100-200 mg daily, on plasminogen activator inhibitor activity (PAI-1) in plasma was measured. In addition serum triglycerides and orosomucoid were analyzed. All the individuals were included in double-blind placebo controlled cross-over trials with treatment periods ranging from 4 days to 3 weeks. During metoprolol therapy PAI-1 values were reduced, while orosomucoid and triglyceride levels were unchanged. A linear inverse correlation was found between fibrinolysis and PAI-1 activity in plasma, indicating that PAI-1 activity serves as an indicator of fibrinolysis. PAI-1 activity and triglycerides were significantly correlated during placebo and metoprolol therapy. In conclusion, our results in these pilot studies suggest that metoprolol enhances fibrinolytic activity as seen by reduced PAI-1 activity. These results should be further confirmed and put into relation of clinical effects of the therapy.