An intersectional analysis of sociodemographic disparities in Covid-19 vaccination: A nationwide register-based study in Sweden.

BACKGROUND: Studies on sociodemographic disparities in Covid-19 vaccination uptake in the general population are still limited and mostly focused on older adults. This study examined sociodemographic differences in Covid-19 vaccination uptake in the total Swedish population aged 18-64 years. METHODS: National Swedish register data within the SCIFI-PEARL project were used to cross-sectionally investigate sociodemographic differences in Covid-19 vaccination among Swedish adults aged 18-64 years (n = 5,987,189) by 12 October 2021. Using logistic regression models, analyses were adjusted for sociodemographic factors, region of residence, history of Covid-19, and comorbidities. An intersectional analysis approach including several cross-classified subgroups was used to further address the complexity of sociodemographic disparities in vaccination uptake. FINDINGS: By 12 October 2021, 76·0% of the Swedish population 18-64 years old had received at least two doses of Covid-19 vaccine, an additional 5·5% had received only one dose, and 18·5% were non-vaccinated. Non-vaccinated individuals were, compared to vaccinated, more often younger, male, had a lower income, were not gainfully employed, and/or were born outside Sweden. The social patterning for vaccine dose two was similar, but weaker, than for dose one. After multivariable adjustments, findings remained but were attenuated indicating the need to consider different sociodemographic factors simultaneously. The intersectional analysis showed a large variation in vaccine uptake ranging from 32% to 96% in cross-classified subgroups, reflecting considerable sociodemographic heterogeneity in vaccination coverage. INTERPRETATION: Our study, addressing the entire Swedish population aged 18-64 years, showed broad sociodemographic disparities in Covid-19 vaccine uptake but also wide heterogeneities in coverage. The intersectional analysis approach indicates that focusing on specific sociodemographic factors in isolation and group average risks without considering the heterogeneity within such groups will risk missing the full variability of vaccine coverage. FUNDING: SciLifeLab / Knut & Alice Wallenberg Foundation, Swedish Research Council, Swedish government ALF agreement, FORMAS.

The Swedish National Airway Register (SNAR): development, design and utility to date.

BACKGROUND: The Swedish National Airway Register (SNAR) was initiated in 2013 to ensure and improve the quality of care for patients with asthma and COPD. AIM: To describe the development and design of SNAR, and to study the 2019 data to evaluate its potential utility related to improvement of quality of care. METHODS: SNAR includes data from patients with asthma (both children and adults) and COPD from primary, secondary and tertiary care, and also, for COPD inpatient care. Data on diagnostic investigations (e.g. spirometry, blood sample, skin prick test), symptom-scores, comorbidities and prescribed treatments are registered. The registrations are entered manually by healthcare professionals, or directly transferred from electronic medical records to a web-based platform. RESULTS: In 2019, 1000 clinics participated and data were directly transferred by about 88% of them. The register included data on 205,833 patients with asthma and 80,372 with COPD (of these, 5% had both diagnoses). Registrations of new patients and follow-up visits from primary and secondary/tertiary care in 2019 were completed for 75,707 patients with asthma (11,818 children <12 yr, 6545 adolescents 12-17 yr, and 57,344 adults >17 yr) and 38,117 with COPD. Depending on age and disease group, 43-77% had performed spirometry, 36-65% Asthma Control Test, and 60% COPD Assessment Test. The prevalence of current smoking was about 2% in adolescents, 10% in adults with asthma, and 34% in COPD. For these, smoking cessation support was offered to 27%, 38% and 51%, respectively. Overall, limited data were available on investigation of allergy, 6-min walk test, patient education and written treatment plans. Regarding asthma, sex-differences in disease management were evident. CONCLUSION: SNAR has cumulatively registered data from over 270,000 individuals, and the register is important for patients, caregivers, authorities, politicians and researchers to evaluate the effect of treatment and to ensure high and equal quality of care nationwide.

Higher self-reported severity of atopic dermatitis in adults is associated with poorer self-reported health-related quality of life in France, Germany, the U.K. and the U.S.A.

BACKGROUND: Better understanding of the relationship between atopic dermatitis (AD) severity and health-related quality of life (HRQoL) could help improve knowledge of a more effective treatment for people with AD. OBJECTIVES: To assess the relationship between AD severity and HRQoL and perception of AD symptoms in adults with moderate-to-severe AD in Europe and the U.S.A. METHODS: Participants for this cross-sectional, internet-based survey were recruited from the larger population-based National Health and Wellness Survey. AD severity was measured by Patient-Oriented SCORing of AD. HRQoL was measured by the five-level EuroQol-5D, Dermatology Life Quality Index (DLQI) and Patient-Oriented Eczema Measure (POEM). RESULTS: Altogether, 1232 respondents were included: 1098 (89·1%) with moderate-to-severe AD [221 (20·1%) from France, 209 (19·0%) from Germany, 118 (10·7%) from the U.K. and 550 (50·1%) from the U.S.A.]. An additional 134 (10·9%) respondents with mild AD were included. Sociodemographic and clinical AD characteristics were similar between countries. In adults with moderate-to-severe AD, higher AD severity correlated with poorer HRQoL (Spearman's r = -0·38 and 0·61 for EQ-5D and DLQI, respectively; both P < 0·001). AD severity was positively correlated with POEM (Spearman's r = 0·51; P < 0·001). People with moderate-to-severe vs. those with mild AD had poorer health outcomes (EQ-5D, DLQI and POEM, P < 0·001 for all). These results were similar and consistent for the European and the U.S. populations separately. CONCLUSIONS: Higher AD severity is associated with poorer HRQoL across Europe and the U.S.A. This is a burden for patients and may provide encouragement for more effective management of AD. What's already known about this topic? Atopic dermatitis (AD) is associated with a detrimental effect on health-related quality of life (HRQoL), including sleep disturbance, anxiety and depression. Limited data describing the relationship between different levels of AD severity and self-reported HRQoL have been published. What does this study add? There is a positive association between increasing AD severity (Patient-Oriented SCORing of AD) and decreasing HRQoL (EQ-5D and Dermatology Life Quality Index) and the perception of AD symptoms (Patient-Oriented Eczema Measure) from the patient's perspective. AD severity according to geographic locations was explored (France, Germany, the U.K., and the U.S.A.), showing that the decreasing HRQoL associated with increasing AD severity was quite consistent between the geographic locations. What are the clinical implications of this work? The results of this study showed that higher AD severity is associated with poorer HRQoL from the subject's perspective in both Europe and the US. This fact confirms that there is a burden for these patients and may provide encouragement for a more effective management of AD, especially among those with greater AD severity.

Developing classification criteria for skin-predominant dermatomyositis: the Delphi process.

BACKGROUND: The European League Against Rheumatism/American College of Rheumatology classification criteria for inflammatory myopathies are able to classify patients with skin-predominant dermatomyositis (DM). However, approximately 25% of patients with skin-predominant DM do not meet two of the three hallmark skin signs and fail to meet the criteria. OBJECTIVES: To develop a set of skin-focused classification criteria that will distinguish cutaneous DM from mimickers and allow a more inclusive definition of skin-predominant disease. METHODS: An extensive literature review was done to generate items for the Delphi process. Items were grouped into categories of distribution, morphology, symptoms, antibodies, histology and contextual factors. Using REDCap™, participants rated these items in terms of appropriateness and distinguishing ability from mimickers. The relevance score ranged from 1 to 100, and the median score determined a rank-ordered list. A prespecified median score cut-off was decided by the steering committee and the participants. There was a pre-Delphi and two rounds of actual Delphi. RESULTS: There were 50 participating dermatologists and rheumatologists from North America, South America, Europe and Asia. After a cut-off score of 70 during the first round, 37 of the initial 54 items were retained and carried over to the next round. The cut-off was raised to 80 during round two and a list of 25 items was generated. CONCLUSIONS: This project is a key step in the development of prospectively validated classification criteria that will create a more inclusive population of patients with DM for clinical research. What's already known about this topic? Proper classification of patients with skin-predominant dermatomyositis (DM) is indispensable in the appropriate conduct of clinical/translational research in the field. The only validated European League Against Rheumatism/American College of Rheumatology criteria for idiopathic inflammatory myopathies are able to classify skin-predominant DM. However, a quarter of amyopathic patients still fail the criteria and does not meet the disease classification. What does this study add? A list of 25 potential criteria divided into categories of distribution, morphology, symptomatology, pathology and contextual factors has been generated after several rounds of consensus exercise among experts in the field of DM. This Delphi project is a prerequisite to the development of a validated classification criteria set for skin-predominant DM.

Increasing severity of atopic dermatitis is associated with a negative impact on work productivity among adults with atopic dermatitis in France, Germany, the U.K. and the U.S.A.

BACKGROUND: Atopic dermatitis (AD) is associated with high disease burden, with a significant physical and social impact. However, the association between disease severity and burden of disease, with work productivity and daily activities being one aspect, has not been well characterized. OBJECTIVES: To investigate the impact of disease severity on work productivity and daily activities among adults with AD in Europe (France, Germany and the U.K.) and the U.S.A. METHODS: The survey panel participants for this cross-sectional internet-based survey on AD were sourced from the population-based National Health and Wellness Survey (Europe 2016, U.S.A. 2015 and 2016). AD severity was determined by Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD). Work productivity and work activity impairment were assessed using the Work Productivity and Activity Impairment (WPAI) - Specific Health Problem questionnaire for AD. RESULTS: The study survey was completed by 1098 respondents with moderate-to-severe AD and 134 with mild AD. Overall, the negative impact on work productivity (all WPAI items) was suggested to increase with increasing AD severity (PO-SCORAD) at the regional level (Europe and U.S.A.) and in the total sample. For overall work impairment due to AD, respondents with mild AD reported a mean of 2·4 h per week of potential work productivity lost, respondents with moderate AD 9·6 h and respondents with severe AD 19·0 h. CONCLUSIONS: Higher AD severity was associated with a greater negative impact on work productivity in adults. This impact is a burden not only for the patient but also for society and may provide incentives for treatment optimization and more effective management of AD. What's already known about this topic? Atopic dermatitis (AD) is associated with a high disease burden. AD has a negative impact on several aspects of health-related quality of life, one of which is work productivity. What does this study add? By using a population of participants with AD recruited from the National Health and Wellness Survey, which collects broad and representative data from the general population, survey data could be obtained from U.S. and European populations of patients with AD. The present study suggests an increasingly negative impact on work productivity with increasing severity of AD. The data indicate no regional differences in the impact of AD severity on work productivity.

S2k guideline for treatment of cutaneous lupus erythematosus - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV).

Cutaneous lupus erythematosus (CLE) is a rare inflammatory autoimmune disease with heterogeneous clinical manifestations. To date, no therapeutic agents have been licensed specifically for patients with this disease entity, and topical and systemic drugs are mostly used 'off-label'. The aim of the present guideline was to achieve a broad consensus on treatment strategies for patients with CLE by a European subcommittee, guided by the European Dermatology Forum (EDF) and supported by the European Academy of Dermatology and Venereology (EADV). In total, 16 European participants were included in this project and agreed on all recommendations. Topical corticosteroids remain the mainstay of treatment for localized CLE, and further topical agents, such as calcineurin inhibitors, are listed as alternative first-line or second-line topical therapeutic option. Antimalarials are recommended as first-line and long-term systemic treatment in all CLE patients with severe and/or widespread skin lesions, particularly in patients with a high risk of scarring and/or the development of systemic disease. In addition to antimalarials, systemic corticosteroids are recommended as first-line treatment in highly active and/or severe CLE. Second- and third-line systemic treatments include methotrexate, retinoids, dapsone and mycophenolate mofetil or mycophenolate acid, respectively. Thalidomide should only be used in selected therapy-refractory CLE patients, preferably in addition to antimalarials. Several new therapeutic options, such as B-cell- or interferon α-targeted agents, need to be further evaluated in clinical trials to assess their efficacy and safety in the treatment of patients with CLE.

A multicenter photoprovocation study to identify potential biomarkers by global peptide profiling in cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE) is an inflammatory autoimmune skin disease in which abnormal photosensitivity is an important pathogenetic factor but is difficult to predict, creating a challenge in determining treatment efficacy. Although photosensitivity in CLE patients may change over time, photoprovocation testing with ultraviolet (UV) A and UVB irradiation can be a helpful tool to explore differences between responders and nonresponders during photoprovocation. To identify biomarkers that could substitute for the clinical endpoint lesion development, we performed a global peptidomics profiling analysis of CLE subjects in a controlled photoprovocation study. Plasma and skin biopsy samples were collected before and after UV-irradiation from 13 healthy volunteers and 47 CLE subjects. Twenty-two of the 47 CLE subjects developed skin lesions. The samples were analyzed using a label-free quantitative peptidomics workflow combined with univariate and multivariate statistical analyses. The primary finding was identification of a specific plasma peptide signature separating responders versus nonresponders at baseline. The peptide signature consisted of beta 2-microglobulin (B2MG), human beta-defensin-1, and peptides derived from CD99, polymeric immunoglobulin receptor, and immunoglobulin kappa light chains. In skin, elevated B2MG levels correlated with lesion formation. Our results show that the peptidome is a rich source of potential biomarkers for predicting photosensitivity in CLE.

Redefining cutaneous lupus erythematosus: a proposed international consensus approach and results of a preliminary questionnaire.

There is currently no uniform definition of cutaneous lupus erythematosus (CLE) upon which to base a study population for observational and interventional trials. A preliminary questionnaire was derived from and sent to a panel of CLE experts which demonstrated consensus agreement that (1) there is a need for new definitions for CLE (2) CLE is distinct from systemic lupus erythematosus and that a CLE grouping scheme should remain apart from current systemic lupus erythematosus schema (3) current CLE grouping schemes are inadequate around communication, prognostic information and to meet the needs of researchers, clinicians, patients and payers.

Small constrained SP1-7 analogs bind to a unique site and promote anti-allodynic effects following systemic injection in mice.

Previous results have shown that the substance P (SP) N-terminal fragment SP1-7 may attenuate hyperalgesia and produce anti-allodynia in animals using various experimental models for neuropathic pain. The heptapeptide was found to induce its effects through binding to and activating specific sites apart from any known neurokinin or opioid receptor. Furthermore, we have applied a medicinal chemistry program to develop lead compounds mimicking the effect of SP1-7. The present study was designed to evaluate the pharmacological effect of these compounds using the mouse spared nerve injury (SNI) model of chronic neuropathic pain. Also, as no comprehensive screen with the aim to identify the SP1-7 target has yet been performed we screened our lead compound H-Phe-Phe-NH2 toward a panel of drug targets. The extensive target screen, including 111 targets, did not reveal any hit for the binding site among a number of known receptors or enzymes involved in pain modulation. Our animal studies confirmed that SP1-7, but also synthetic analogs thereof, possesses anti-allodynic effects in the mouse SNI model of neuropathic pain. One of the lead compounds, a constrained H-Phe-Phe-NH2 analog, was shown to exhibit a significant anti-allodynic effect.

Recombinant human growth hormone improves cognitive capacity in a pain patient exposed to chronic opioids.

During recent decades, the increasing use of opioids for chronic non-cancer pain has raised concerns regarding tolerance, addiction, and importantly cognitive dysfunction. Current research suggests that the somatotrophic axis could play an important role in cognitive function. Administration of growth hormone (GH) to GH-deficient humans and experimental animals has been shown to result in significant improvements in cognitive capacity. In this report, a patient with cognitive disabilities resulting from chronic treatment with opioids for neuropathic pain received recombinant human growth hormone (rhGH) replacement therapy. A 61-year-old man presented with severe cognitive dysfunction after long-term methadone treatment for intercostal neuralgia and was diagnosed with GH insufficiency by GH releasing hormone-arginine testing. The effect of rhGH replacement therapy on his cognitive capacity and quality of life was investigated. The hippocampal volume was measured using magnetic resonance imaging, and the ratios of the major metabolites were calculated using proton magnetic resonance spectroscopy. Cognitive testing revealed significant improvements in visuospatial cognitive function after rhGH. The hippocampal volume remained unchanged. In the right hippocampus, the N-acetylaspartate/creatine ratio (reflecting nerve cell function) was initially low but increased significantly during rhGH treatment, as did subjective cognitive, physical and emotional functioning. This case report indicates that rhGH replacement therapy could improve cognitive behaviour and well-being, as well as hippocampal metabolism and functioning in opioid-treated patients with chronic pain. The idea that GH could affect brain function and repair disabilities induced by long-term exposure to opioid analgesia is supported.

Frondoside A enhances the antiproliferative effects of gemcitabine in pancreatic cancer.

Pancreatic cancer has a very poor prognosis. While gemcitabine is the mainstay of therapy and improves quality of life, it has little impact on survival. More effective treatments are desperately needed for this disease. Frondoside A is a triterpenoid glycoside isolated from the Atlantic sea cucumber, Cucumaria frondosa. Frondoside A potently inhibits pancreatic cancer cell growth and induces apoptosis in vitro and in vivo. The aim of the present study was to investigate whether frondoside A could enhance the anti-cancer effects of gemcitabine. Effects of frondoside A and gemcitabine alone and in combination on proliferation were investigated in two human pancreatic cancer cell lines, AsPC-1 and S2013. To investigate possible synergistic effects, combinations of low concentrations of the two drugs were used for a 72 h treatment period in vitro. Growth inhibition was significantly greater with the drug combinations than their additive effects. Combinations of frondoside A and gemcitabine were tested in vivo using the athymic mouse model. Xenografts of AsPC-1 and S2013 cells were allowed to form tumours prior to treatment with the drugs alone or in combination for 30 days. Tumours grew rapidly in placebo-treated animals. Tumour growth was significantly reduced in all treatment groups. At the lowest dose tested, gemcitabine (4 mg/kg/dose), combined with frondoside A (100 µg/kg/day) was significantly more effective than with either drug alone. To conclude: The present data suggest that combinations of frondoside A and gemcitabine may provide clinical benefit for patients with pancreatic cancer.

Cholesteryl ester transfer protein polymorphisms, statin use, and their impact on cholesterol levels and cardiovascular events.

The association of nonfunctional variants of the cholesteryl ester transfer protein (CETP) with efficacy of statins has been a subject of debate. We evaluated whether three functional CETP variants influence statin efficacy. The effect of CETP genotype on achieved levels of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), and total cholesterol during statin treatment was estimated by meta-analysis of the linear regression outcomes of three studies (11,021 individuals). The effect of these single-nucleotide polymorphisms (SNPs) on statin response in protecting against myocardial infarction (MI) was estimated by meta-analysis of statin × SNP interaction terms from logistic regression in five studies (16,570 individuals). The enhancer SNP rs3764261 significantly increased HDLc by 0.02 mmol/l per T allele (P = 6 × 10(-5)) and reduced protection against MI by statins (interaction odds ratio (OR) = 1.19 per T allele; P = 0.04). Focusing on functional CETP variants, we showed that in carriers of the rs3764261 T variant, HDLc increased more during statin treatment, and protection against MI by statins appeared to be reduced as compared with those in noncarriers.

The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism.

OBJECTIVE: An elevated level of total plasma homocysteine (tHcy) has been associated with risk of coronary heart disease (CHD). The level of tHcy is affected by lifestyle, in addition to genetic predisposition. The methylene tetrahydrofolate reductase (MTHFR) 677C>T polymorphism (rs1801133) is among the strongest genetic predictors of tHcy. We examined whether the association between tHcy and CHD is modified by the MTHFR 677C>T polymorphism. DESIGN AND SETTING: Data from two case-control studies of first-time myocardial infarction (MI), Stockholm Heart Epidemiology Programme (SHEEP), and for MI and unstable angina, INTERGENE, were analysed in parallel. PATIENTS: THcy was determined in a total of 1150 cases and 1753 controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The outcome comprised first-time MI and unstable angina, subsumed as CHD. Logistic regression was used to investigate the association between tHcy and CHD, and its modification by genotype. RESULTS: High tHcy was confirmed to be a risk factor for CHD in both studies. In SHEEP, the association between tHcy and MI was observed in MTHFR 677 C-homozygotes (OR=1.4, 95% CI 1.2 to 1.6, for a difference by 1 SD of log tHcy) and in heterozygotes (OR=1.3, 95% CI 1.1 to 1.6) but not in T-homozygotes, independent of smoking, physical activity and obesity. An effect modification of similar magnitude was observed but not statistically significant in the smaller INTERGENE study, and confirmed in a meta-analysis of both studies. CONCLUSIONS: Two Swedish case-control studies showed that the association between elevated tHcy and CHD was confined to carriers of the MTHFR 677 C-allele, which could have implications for the efficiency of tHcy-lowering treatment.

Subacute cutaneous lupus erythematosus and its association with drugs: a population-based matched case-control study of 234 patients in Sweden.

BACKGROUND: Numerous case reports about drug-induced (DI) subacute cutaneous lupus erythematosus (SCLE) have been published. Various drug types with different latencies has been proposed as triggers for this autoimmune skin disease. OBJECTIVES: To evaluate the association between exposure to certain suspected drugs (previously implicated to induce SCLE) and a subsequent diagnosis of SCLE. METHODS: We performed a population-based matched case-control study in which all incident cases of SCLE (n=34) from 2006 to 2009 were derived from the National Patient Register. The control group was selected from the general population, matched (1:10) for gender, age and county of residence. The data were linked to the Prescribed Drug Register. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the association between exposures to certain suspected drugs and the development of SCLE. RESULTS: During the 6 months preceding SCLE diagnosis, 166 (71%) of the patients with SCLE had at least one filled prescription of the suspected drugs. The most increased ORs were found for terbinafine (OR 52.9, 95% CI 6.6-∞), tumour necrosis factor-α inhibitors (OR 8.0, 95% CI 1.6-37.2), antiepileptics (OR 3.4, 95% CI 1.9-5.8) and proton pump inhibitors (OR 2.9, 95% CI 2.0-4.0). CONCLUSIONS: We found an association between drug exposure and SCLE. More than one third of the SCLE cases could be attributed to drug exposure. No significant OR was found for thiazides, which might be due to longer latency and therefore missed with this study design. DI-SCLE is reversible once the drug is discontinued, indicating the importance of screening patients with SCLE for potentially triggering drugs. A causal relationship cannot be established from this study and the underlying pathogenesis remains unclear.

Increased risk of cancer among 3663 patients with cutaneous lupus erythematosus: a Swedish nationwide cohort study.

BACKGROUND: Other autoimmune diseases have been associated with higher risks for cancer, and numerous case reports of cutaneous lupus erythematosus (CLE) and different cancer types are available. OBJECTIVES: To estimate the overall and specific cancer risks in a nationwide cohort study of patients diagnosed with CLE in Sweden and compare that risk with that in a control cohort without CLE. METHODS: A cohort of 3663 individuals with CLE and a matched control cohort from the general population (three controls to each CLE case) without a diagnosis of CLE were derived from the Swedish National Patient Register, 1997-2007, and were electronically linked to the Swedish Cancer Register and the Swedish Cause of Death Register. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to compare the observed vs. the expected numbers of cancers. RESULTS: A total of 183 incident cancers occurred within the observation interval, yielding a HR of 1·8 (95% CI 1·5-2·2) for cancer overall. Median follow-up was 4·1 years. About a fourfold risk increase was seen for buccal cancer, lymphomas, respiratory cancer and nonmelanoma skin cancer. CONCLUSIONS: Patients with CLE appear to have an elevated risk for certain cancer types, an increase that remains when excluding patients also diagnosed with systemic lupus erythematosus. Our findings point to the importance of counselling about not smoking and sun avoidance, and underscore the need for specialized monitoring of this patient group along with bench-to-bedside research efforts to clarify pathogenesis.

Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats.

BACKGROUND AND PURPOSE: The designer drug 1-(4-methylphenyl)-2-methylaminopropan-1-one (4-methylmethcathinone, mephedrone) is reported to possess psychostimulant, entactogenic and hallucinogenic effects. The purpose of this study was to examine the effects of acute administration of mephedrone on extracellular levels of dopamine (DA) and 5-HT in the nucleus accumbens of awake rats and compare these effects with those induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and amphetamine. EXPERIMENTAL APPROACH: Microdialysis sampling was performed while simultaneously recording locomotor activity in rats and the monoamines were determined by HPLC with electrochemical detection. KEY RESULTS: Mephedrone (3 mg·kg(-1) s.c.) and (+)-amphetamine (1 mg·kg(-1) s.c.) caused rapid increases in extracellular DA levels of 496% and 412%, respectively, whereas MDMA (3 mg·kg(-1) s.c.) showed only a moderate effect (235%). The corresponding 5-HT levels increased to 941% (mephedrone) and 911% (MDMA), but only to 165% following amphetamine. The calculated t(1/2) values for elimination rate of mephedrone, MDMA and amphetamine-induced increases in extracellular DA levels were 25, 303 and 51 min, the corresponding t(1/2) values for 5-HT were 26, 48 and 84 min, respectively. Locomotor activity was increased most by amphetamine, whereas both mephedrone and MDMA showed about three times lower and shorter-lasting effects. CONCLUSIONS AND IMPLICATIONS: The neurochemical and functional properties of mephedrone resemble those of MDMA, but it also shows an amphetamine-like effect in that it evokes a rapid release and elimination of DA in the brain reward system, a feature that may contribute to its potent reinforcing properties.

Cutaneous lupus erythematosus and the association with systemic lupus erythematosus: a population-based cohort of 1088 patients in Sweden.

BACKGROUND: Studies reporting the incidence of isolated cutaneous lupus erythematosus (CLE) are rare. OBJECTIVES: To examine in a population-based cohort study the incidence of CLE and its subsets in Sweden. The short-term probability of receiving an additional diagnosis of systemic lupus erythematosus (SLE) is also assessed. METHODS: A population-based open cohort study including all patients with CLE [International Classification of Diseases (ICD) code, ICD-10: L93] in Sweden, 2005-2007. Patients (n=1088) were identified in the Swedish National Patient Register. RESULTS: The incidence of CLE was 4·0/100,000; the female/male ratio was 3:1. Mean age at disease onset was 54 years. The most common subset was discoid lupus erythematosus (DLE) (80%, n = 868). A quarter of the patients (24%, n=260) were already diagnosed with SLE at the time they were diagnosed with CLE. During the whole observation period (2005-2007), an additional 18% (n = 107) were diagnosed with SLE, the probability of receiving an additional SLE diagnosis being highest for the subacute CLE (SCLE) subset. CONCLUSIONS: This is the first nationwide epidemiological study on CLE. We found the incidence of CLE to be about equal to that of SLE, and found a higher short-term probability for receiving an additional diagnosis with SLE than previously described for CLE. Subsets other than DLE and SCLE were rarely reported in our system; an update of the ICD codes for this diagnostic group could increase reporting of these more unusual cases. Our study clarifies that monitoring and follow-up are called for in this patient group due to the risk for SLE, and underscores the need for clear criteria for risk assessment in the large group of patients with CLE who also fulfil criteria for SLE.

Evaluation of disease activity and damage in different subtypes of cutaneous lupus erythematosus using the CLASI.

BACKGROUND: The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a scoring system for patients with cutaneous lupus erythematosus (CLE) to assess disease activity and damage. Objective The aim of this study was to evaluate whether the CLASI is a useful instrument which reflects the different subtypes of CLE comparably well in each parameter. METHODS: A total of 50 patients (42 female, 8 male) with different subtypes of CLE, including acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE) and LE tumidus (LET), from the Departments of Dermatology, University of Düsseldorf, Germany, and Danderyd Hospital, Stockholm, Sweden, were evaluated using the CLASI at one time point. RESULTS: The total CLASI activity score was significantly lower in patients with LET compared with ACLE (P<0.05) and CCLE (P<0.001), and the total CLASI damage score was significantly lower in patients with LET than with ACLE (P<0.05), SCLE (P<0.001) and CCLE (P<0.001). The erythema score and the scale/hypertrophy score were significantly lower in LET than in ACLE (P<0.05, both) and CCLE (P<0.05 and P < 0.001, respectively). The dyspigmentation score was lowest in patients with LET, differing significantly from ACLE (P<0.05), SCLE (P<0.05) and CCLE (P<0.001). The scarring/atrophy/panniculitis score was significantly higher in patients with CCLE in contrast to SCLE and LET (P<0.05 and P<0.001, respectively). CONCLUSION: These data characterize the CLASI as an overall useful instrument to analyse disease activity and damage in CLE. However, the CLASI does not give an accurate assessment of all disease subtypes; therefore, a revision of the CLASI with critical analysis of all parameters is recommended.

Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 2006.

UNLABELLED: The risk of ischaemic heart disease (IHD), and in particular myocardial infarction (MI), is increased amongst patients with established rheumatoid arthritis (RA). Few studies have included contemporary patients with RA. We recently reported that the risk of IHD is not elevated before the onset of RA symptoms. However, when, in relation to RA diagnosis, the risk is increased is unknown. OBJECTIVE: To assess the risk of MI and other IHD events amongst patients diagnosed with RA during the last decade and within 18 months following RA symptom onset, compared to the general population, by time since RA diagnosis, year of RA diagnosis and by rheumatoid factor (RF) status. METHODS AND PATIENTS: A Swedish inception cohort of RA (n = 7469) diagnosed between 1995 and 2006 and a matched general population comparator cohort (n = 37,024), was identified and linked to national registers of morbidity and mortality from IHD. Relative risks (RRs) of MI and other IHD events were estimated using Cox regression. RESULTS: During follow-up, 233 patients with RA and 701 controls developed a first MI, corresponding to an overall RR of MI of 1.6 (95% confidence interval 1.4, 1.9). Increased risks of MI were already detected within 1-4 years following RA diagnosis, as well as in patients diagnosed with RA during the last 5 years, in RF-negative patients and for transmural as well as nontransmural MIs. CONCLUSIONS: MI risk increases rapidly following RA diagnosis, suggesting the importance of additional mechanisms other than atherosclerosis. The elevated short-term risk is present amongst patients diagnosed in recent years, underscoring the importance of MI prevention from the time of RA diagnosis.

Cutaneous manifestations and serological findings in 260 patients with systemic lupus erythematosus.

The prevalence and prognostic value of cutaneous manifestations in patients with systemic lupus erythematosus (SLE) is not clear due to a lack of distinct criteria. Our aim was to investigate the prevalence of cutaneous manifestations in SLE patients according to strict dermatological classification, compare the results with other studies and to assess differences in serological markers between patients with and without cutaneous lupus erythematosus (CLE). Secondary aims were to investigate the validity of the criteria 'malar rash' and 'photosensitivity' for SLE diagnosis. We included 260 consecutive SLE patients, and 164 with skin complaints were examined by a dermatologist. CLE was found in 23% of the 260 SLE patients. There was agreement on the presence of malar rash in only 60% of patients seen by both rheumatologists and dermatologists. A history of polymorphous light eruption (PLE) was found in 42% of patients. Raynaud's phenomenon was significantly more common in patients with CLE. In addition, four malignant melanomas were found. Based on our findings, we suggest that the American College of Rheumatology (ACR) criteria for SLE diagnosis include histopathologically confirmed CLE as one criterion, and that the criteria photosensitivity and malar rash should be re-defined. Regular examination by a dermatologist is called for in SLE patients.