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  • 1.
    Andersson, Rolf
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Quirk, Chris
    Royal Perth Hospital, WA Australien.
    Sullivan, John
    Liverpool Hospital, NSW Australien.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Cutaneous manifestations of internal disease2008In: Drug Discovery Today : Disease Mechanisms, ISSN 1740-6765, E-ISSN 1740-6765, Vol. 5, no 1, p. e113-e123Article in journal (Refereed)
    Abstract [en]

    The skin mirrors the individual's well being. Visible for both the patient and the attending physician, it can be a source of information for the diagnosis of multi-system diseases and diseases of internal organs. Therapy is usually directed at the primary disease. Pharmaco-therapeutic options for internal diseases are at present not always optimal and specific management of side effects of drugs with vital indication may be necessary. Better understanding of the mechanisms of the cutaneous manifestations may help develop more efficacious, better tolerated therapy and improve the patient's situation.

  • 2.
    Assarsson, Malin
    et al.
    Div Dermatol and Venereol, Sweden.
    Duvetorp, Albert
    Div Dermatol and Venereol, Sweden.
    Dienus, Olaf
    Div Med Diagnost, Sweden.
    Söderman, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Div Med Diagnost, Sweden.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Div Dermatol and Venereol, Sweden.
    Significant Changes in the Skin Microbiome in Patients with Chronic Plaque Psoriasis after Treatment with Narrowband Ultraviolet B2018In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 98, no 4, p. 428-436Article in journal (Refereed)
    Abstract [en]

    Changes in the skin microbiome have been shown to promote cutaneous inflammation. The skin microbiome of patients with chronic plaque type psoriasis was analysed before and after treatment with narrowband ultraviolet B (UVB). Swab samples of the microbiome were taken from lesional and non-lesional skin of 26 patients. Microbiotas were characterized by sequencing 16S rRNA bacterial genes on the Illumina MiSeq platform. Lesional skin microbiome diversity correlated with psoriasis severity (measured with the Psoriasis Area and Severity Index; PASI). There was a significantly lower abundance of the phylum Firmicutes and the genus Staphylococcus in lesional skin compared with non-lesional skin before UVB treatment. Responders (amp;gt; 75% target Psoriasis Severity Index (PSI) improvement) had significantly lower abundance of the phyla Firmicutes in lesional and non-lesional skin and lower abundance of the genera Staphylococcus, Finegoldia, Anaerococcus, Peptoniphilus, Gardnerella, Prevotella and Clostridium in lesional skin after UVB treatment. Pseudomonas significantly decreased in lesional and non-lesional skin of treatment responders. These results suggest that skin microbiome alterations after UVB treatment could be related to treatment and treatment response.

  • 3.
    Assarsson, Malin
    et al.
    Ryhov Hosp, Sweden.
    Soderman, Jan
    Ryhov Hosp, Sweden.
    Duvetorp, Albert
    Skanes Univ Hosp, Sweden.
    Mrowietz, Ulrich
    Univ Med Ctr Schleswig Holstein, Germany.
    Skarstedt, Marita
    Ryhov Hosp, Sweden.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Narrowband UVB treatment induces expression of WNT7B, WNT10B and TCF7L2 in psoriasis skin2019In: Archives of Dermatological Research, ISSN 0340-3696, E-ISSN 1432-069X, Vol. 311, no 7, p. 535-544Article in journal (Refereed)
    Abstract [en]

    WNT/beta-catenin signaling pathways play a pivotal role in the human immune defense against infections and in chronic inflammatory conditions as psoriasis. Wnt gene alterations are linked to known comorbidities of psoriasis as obesity, diabetes and Crohns disease. The objective of this study was to investigate WNT7B, WNT10B, WNT16 and TCF7L2 gene and protein expression in lesional and non-lesional skin and in the peripheral blood of patients with chronic plaque psoriasis compared with healthy individuals. To investigate the effect of narrowband UVB radiation, expression of these genes were analyzed before and after narrowband UVB treatment. Associations between single nucleotide polymorphisms for WNT7B, WNT10B, WNT16 and TCF7L2 genes and psoriasis were tested. Our results show significantly decreased WNT7B, WNT10B and TCF7L2 gene expression in lesional skin compared with non-lesional skin and healthy controls. Narrowband UVB treatment significantly increased expression of these genes in lesional skin. Immunohistochemistry shows increased WNT16 expression in lesional skin. No significant differences in allele or genotype frequencies for Wnt or TCF7L2 gene polymorphisms were found between patient and control group. This study shows for the first time significant UVB induced upregulation of WNT7B, WNT10B and TCF7L2 in patients with psoriasis and suggests a potential role of these genes in psoriasis pathogenesis.

  • 4.
    Bergfors, Elisabet
    et al.
    Univ Gothenburg, Sweden.
    Inerot, Annica
    Univ Gothenburg, Sweden.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Nyström Kronander, Ulla
    Region Östergötland, Heart and Medicine Center, Allergy Center.
    Trollfors, Birger
    Sahlgrens Univ Hosp, Sweden.
    Patch testing children with aluminium chloride hexahydrate in petrolatum: A review and a recommendation2019In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 81, no 2, p. 81-88Article, review/survey (Refereed)
    Abstract [en]

    Background: According to studies on adults, patch testing with aluminium chloride hexahydrate 2% pet. is insufficient to detect aluminium allergy, and a 10% preparation is recommended. Other studies suggest that a 2% preparation is sufficient for testing children. Objectives: To review three previously published Swedish studies on patch testing children with aluminium chloride hexahydrate 2% pet. Patients/Methods: Altogether, 601 children with persistent itching subcutaneous nodules (granulomas) induced by aluminium-adsorbed vaccines were patch tested with aluminium chloride hexahydrate 2% pet. and metallic aluminium in (a) a pertussis vaccine trial, (b) clinical practice, and (ca) prospective study. Results: Overall, 459 children had positive reactions to the 2% pet. preparation. Another 10 reacted positively only to metallic aluminium. An extreme positive reaction (+++) was seen in 65% of children aged 1 to 2 years as compared with 22% of children aged 7 years. From 8 years onwards, extreme positive reactions were scarce. Conclusions: Aluminium chloride hexahydrate 2% pet. is sufficient to trace aluminium allergy in children. Small children are at risk of extreme reactions. We thus suggest that aluminium chloride hexahydrate 10% pet. should not be used routinely in children before the age of 7 to 8 years.

  • 5.
    Bergfors, Elisabet
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Lundmark, Katarzyna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Nyström Kronander, Ulla
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    A child with a long-standing, intensely itching subcutaneous nodule on a thigh: an uncommon (?) reaction to commonly used vaccines2013In: BMJ Case Reports, ISSN 1757-790XArticle in journal (Refereed)
    Abstract [en]

    A 2-year-old girl presented with an intensely itching subcutaneous nodule on the front of a thigh. The nodule persisted for 10 months until it was excised. Subsequent investigation for malignancy and systemic disease showed no pathological findings. The diagnosis, persistent itching vaccination granuloma, was revealed by hazard almost 2 years after the onset of symptoms. Persistent itching subcutaneous nodules at the injection site for aluminium containing vaccines (mostly diphtheria-tetanus-pertussis combination vaccines for primary immunisation of infants) may appear with a long delay after the vaccination (months), cause prolonged itching (years) and are often associated with contact allergy to aluminium. The condition is poorly recognised in Health Care which may lead to prolonged symptoms and unnecessary investigations.

  • 6.
    Bivik, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Regulation of UV induced apoptosis in human melanocytes2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Malignant melanoma arises from the pigment producing melanocytes in epidermis and is the most aggressive type of skin cancer. The incidence of malignant melanoma is increasing faster than any other type of cancer in white population worldwide, with a doubling rate every 10-20 years. So far, the only identified external risk factor for malignant melanoma is UV exposure. Elimination of photodamaged cells by apoptosis (programmed cell death) is essential to prevent tumor formation. Melanocytes are considered relatively resistant to apoptosis, however, the regulation of apoptosis in melanocytes is still unknown.

    The aim of this thesis was to investigate the apoptotic process following ultraviolet (UV) irradiation in primary cultures of human melanocytes. Focus was on regulation of mitochondrial stability by Bcl-2 family proteins and the possible participation of lysosomal proteases, cathepsins. UV irradiation activated the mitochondrial pathway of apoptosis, leading to cytochrome c release, caspase activation, and nuclear fragmentation. No change in protein expression of Bax and Bcl-2 was observed in response to UV. Instead, translocation of the Bcl-2 family proteins from cytosol to mitochondia was important in the regulation of survival and death of melanocytes. The findings further demonstrated permeabilization of the lysosomal membrane to occur early in the apoptotic process, resulting in cathepsin release into the cytosol. The cathepsins were potent pro-apoptotic mediators and triggered apoptosis upstream of Bax translocation and mitochondrial membrane permeabilization. In response to both heat and UV irradiation, there was a marked increase in expression of stress-induced heat shock protein 70 (Hsp70), which inhibited apoptosis by binding lysosomal and mitochondrial membranes and counteracting the release of cathepsins and cytochrome c. Furthermore, UV irradiation activated c-jun N-terminal kinase (JNK), which triggered apoptosis upstream of cathepsins release from the lysosomes. In addition, JNK mediated apoptosis through phosphorylation of pro-apoptotic Bim, which was released from anti-apoptotic Mcl-1, by UV induced Mcl-1 depletion.

    This thesis illustrates that permeabilization of mitochondria and lysosomes and release of their constituents to the cytosol participates in UV induced apoptosis signaling in human melanocytes in vitro. The process is regulated by a complex network of pro- and anti-apoptotic proteins, exerting their effects through intracellular translocation and alteration of protein expression.

    List of papers
    1. Wavelength specific effects on UVB induced apoptosis in melanocytes. A study of the Bcl-2/Bax expression and keratinocyte rescue effects
    Open this publication in new window or tab >>Wavelength specific effects on UVB induced apoptosis in melanocytes. A study of the Bcl-2/Bax expression and keratinocyte rescue effects
    2005 (English)In: Melanoma Research, ISSN 0960-8931, Vol. 15, no 1, p. 7-13Article in journal (Refereed) Published
    Abstract [en]

    Apoptosis and alterations in Bcl-2 and Bax messenger RNA (mRNA) and protein expression were examined in cultured human epidermal melanocytes following UVB irradiation (50 mJ/cm2). The effects of various spectral ranges within UVB were investigated. A co-culture system was set up to study the interplay between melanocytes and keratinocytes in response to UVB. Melanocytes expressed high basal levels of the anti-apoptotic protein Bcl-2 compared with keratinocytes. Different wavelengths within the UVB spectrum induced diverse response patterns of Bcl-2 and Bax mRNA and had different apoptotic power. Both Bcl-2 and Bax mRNA were upregulated to preserve protein levels and only a slight increase in apoptosis was noted 24 h after UVB ([lambda]>305 nm). Increasing UVB between 280 and 305 nm enhanced apoptosis and upregulated Bcl-2, whilst Bax mRNA was unaltered. However, no change in protein levels was detected. A redistribution of Bax protein from different compartments within the cell may be more important than direct upregulation for the acceleration of apoptosis, but it cannot be excluded that other apoptotic pathways may be induced by shorter UVB wavelengths. The increase in apoptosis was significantly lower in melanocytes co-cultured with irradiated matched keratinocytes than in melanocytes from pure cultures, indicating that melanocytes are protected from UVB-induced apoptosis by the release of substance(s) from keratinocytes. This rescue response concurred with a fast and significant increase in Bcl-2 mRNA level in melanocytes.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14399 (URN)10.1097/00008390-200502000-00003 (DOI)
    Available from: 2008-11-13 Created: 2008-11-13 Last updated: 2009-04-28
    2. UVA/B induced apoptosis in human melanocytes involves translocation of cathepsins and Bcl-2 family members
    Open this publication in new window or tab >>UVA/B induced apoptosis in human melanocytes involves translocation of cathepsins and Bcl-2 family members
    Show others...
    2006 (English)In: Journal of Investigative Dermatology, ISSN 0022-202X, Vol. 126, no 5, p. 1119-1127Article in journal (Refereed) Published
    Abstract [en]

    We demonstrate UVA/B to induce apoptosis in human melanocytes through the mitochondrial pathway, displaying cytochrome c release, caspase-3 activation, and fragmentation of nuclei. The outcome of a death signal depends on the balance between positive and negative apoptotic regulators, such as members of the Bcl-2 protein family. Apoptotic melanocytes, containing fragmented nucleus, show translocation of the proapoptotic proteins Bax and Bid from the cytosol to punctate mitochondrial-like structures. Bcl-2, generally thought to be attached only to membranes, was in melanocytes localized in the cytosol as well. In the fraction of surviving melanocytes, that is, cells with morphologically unchanged nucleus, the antiapoptotic proteins Bcl-2 and Bcl-XL were translocated to mitochondria following UVA/B. The lysosomal proteases, cathepsin B and D, which may act as proapoptotic mediators, were released from lysosomes to the cytosol after UVA/B exposure. Proapoptotic action of the cytosolic cathepsins was confirmed by microinjection of cathepsin B, which induced nuclear fragmentation. Bax translocation and apoptosis were markedly reduced in melanocytes after pretreatment with either cysteine or aspartic cathepsin inhibitors. No initial caspase-8 activity was detected, excluding involvement of the death receptor pathway. Altogether, our results emphasize translocation of Bcl-2 family proteins to have central regulatory functions of UV-induced apoptosis in melanocytes and suggest cathepsins to be proapoptotic mediators operating upstream of Bax.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14400 (URN)10.1038/sj.jid.5700124 (DOI)
    Available from: 2008-11-13 Created: 2008-11-13 Last updated: 2017-08-30
    3. Hsp70 protects against UVB induced apoptosis by preventing release of cathepsins and cytochrome c in human melanocytes
    Open this publication in new window or tab >>Hsp70 protects against UVB induced apoptosis by preventing release of cathepsins and cytochrome c in human melanocytes
    2007 (English)In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 28, no 3, p. 537-544Article in journal (Refereed) Published
    Abstract [en]

    Stress-induced heat shock protein 70 (Hsp70) effectively protects cells against apoptosis, although the anti-apoptotic mechanism is still undefined. Exposure of human melanocytes to heat and subsequent UVB irradiation increased the level of Hsp70 and pre-heating reduced UVB induced apoptosis. Immunofluorescence staining of Hsp70 in combination with staining of lysosomes (Lamp2) or mitochondria (Mitotracker®) in pre-heated UVB exposed cells showed co-localization of Hsp70 with both lysosomes and mitochondria in the surviving cell population. Furthermore, UVB induced apoptosis was accompanied by lysosomal and mitochondrial membrane permeabilization, detected as release of cathepsin D and cytochrome c, respectively, which were prevented by heat pre-treatment. In purified fractions of lysosomes and mitochondria, recombinant Hsp70 attached to both lysosomal and mitochondrial membranes. Moreover, in apoptotic cells Bax was translocated from a diffuse cytosolic location into punctate mitochondrial-like structures, which was inhibited by Hsp70 induction. Such inhibition of Bax translocation was abolished by transfection with Hsp70 siRNA. Furthermore, Hsp70 siRNA eliminated the apoptosis preventive effect observed after pre-heating. These findings show Hsp70 to rescue melanocytes from UVB induced apoptosis by preventing release of cathepsins from lysosomes, Bax translocation and cytochrome c release from mitochondria.

     

    Abbreviations: AIF, apoptosis-inducing factor; Hsp, heat shock protein; NAG, ß-N-acetylglucosaminidase; tBid, truncated Bid; UV, ultraviolet

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14401 (URN)10.1093/carcin/bgl152 (DOI)
    Available from: 2007-05-14 Created: 2007-05-14 Last updated: 2017-12-13
    4. JNK mediates UVB-induced apoptosis upstream lysosomal membrane permeabilization and Bcl-2 family proteins
    Open this publication in new window or tab >>JNK mediates UVB-induced apoptosis upstream lysosomal membrane permeabilization and Bcl-2 family proteins
    2008 (English)In: Apoptosis (London), ISSN 1360-8185, E-ISSN 1573-675X, Vol. 13, no 9, p. 1111-1120Article in journal (Refereed) Published
    Abstract [en]

    UVB irradiation induced phosphorylation of JNK and subsequent apoptosis in human melanocytes. Depletion of both JNK1 and JNK2 expression using siRNA transfection, protected against apoptosis, as detected by decreased nuclear fragmentation and caspase-3 activity, as well as reduced translocation of Bax to mitochondria. Moreover, release of cathepsin B and D from lysosomes to the cytosol was reduced when JNK expression was suppressed by siRNA, demonstrating a JNK dependent regulation of lysosomal membrane permeabilization. In unirradiated control melanocytes, coimmunoprecipitation showed that Bim was sequestered by Mcl-1, which had a pro-survival function. After UVB irradiation, a significant decrease in Mcl-1 protein level was found, which was prevented by addition of a proteasome inhibitor. The interaction between Bim and Mcl-1 was reduced in response to UVB irradiation and Bim was phosphorylated in a JNK dependent manner. In conclusion, these findings Suggest JNK to have an important pro-apoptotic function following UVB irradiation in human melanocytes, by acting upstream of lysosomal membrane permeabilization and Bim phosphorylation.

    Keywords
    UV, Cathepsin, JNK, Mcl-1, Bim
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-16886 (URN)10.1007/s10495-008-0240-7 (DOI)
    Note
    The original publication is available at www.springerlink.com: Cecilia Bivik and Karin Öllinger, JNK mediates UVB-induced apoptosis upstream lysosomal membrane permeabilization and Bcl-2 family proteins, 2008, Apoptosis (London), (13), 9, 1111-1120. http://dx.doi.org/10.1007/s10495-008-0240-7 Copyright: Springer Science Business Media http://www.springerlink.com/ Available from: 2009-04-29 Created: 2009-02-20 Last updated: 2017-12-13Bibliographically approved
  • 7.
    Bivik, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Regulation of UV-induced apoptosis in human melanocytes2009In: Forum for Nordic Dermato-Venerology, ISSN 1402-2915, Vol. 14, no 1, p. 25-26Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 8.
    Bivik Eding, Cecilia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Domer, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wäster, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Jerhammar, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases2015In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, no 7, p. 792-797Article in journal (Refereed)
    Abstract [en]

    Ultraviolet (UV) irradiation is a risk factor for development of malignant melanoma. UVA-induced lysosomal exocytosis and subsequent cell growth enhancement was studied in malignant melanoma cell lines and human skin melanocytes. UVA irradiation caused plasma membrane damage that was rapidly repaired by calcium-dependent lysosomal exocytosis. Lysosomal content was released into the culture medium directly after irradiation and such conditioned media stimulated the growth of non-irradiated cell cultures. By comparing melanocytes and melanoma cells, it was found that only the melanoma cells spontaneously secreted cathepsins into the surrounding medium. Melanoma cells from a primary tumour showed pronounced invasion ability, which was prevented by addition of inhibitors of cathepsins B, D and L. Proliferation was reduced by cathepsin L inhibition in all melanoma cell lines, but did not affect melanocyte growth. In conclusion, UVA-induced release of cathepsins outside cells may be an important factor that promotes melanoma growth and progression.

  • 9.
    Brohede, Sabina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Wyon, Yvonne
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Wingren, Gun
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wijma, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Wijma, Klaas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Body dysmorphic disorder in female Swedish dermatology patients2017In: International Journal of Dermatology, ISSN 0011-9059, E-ISSN 1365-4632, Vol. 56, no 12, p. 1387-1394Article in journal (Refereed)
    Abstract [en]

    BackgroundIndividuals with body dysmorphic disorder (BDD) are highly distressed and impaired owing to perceived defects in their physical appearance that are not noticeable to others. They are frequently concerned about their skin and often present to dermatologists rather than psychiatrists. However, BDD patients attending dermatology clinics may be at risk of not receiving an appropriate assessment and beneficial treatment. The aims of this study were to estimate the BDD prevalence rate among Swedish female dermatology patients and to assess the psychological condition of BDD patients compared to that of other dermatology patients. MethodsThe occurrence of BDD was estimated using the Body Dysmorphic Disorder Questionnaire (BDDQ), a validated self-report measure for BDD. Symptoms of depression and anxiety were measured by the Hospital Anxiety and Depression Scale (HADS), and quality of life was assessed using the Dermatology Life Quality Index (DLQI). ResultsThe prevalence rate of BDD among female Swedish dermatology patients was 4.9% (95% CI 3.2-7.4). Anxiety (HADS A11) was 4-fold more commonly reported by patients with positive BDD screening (48% vs. 11%), and depression (HADS D11) was over 10-fold more common in patients with positive BDD screening (19% vs. 1.8%) (Pamp;lt;0.001). The median DLQI score was 18 in the BDD group, compared to a score of 4 in the non-BDD group (Pamp;lt;0.001). ConclusionsOur results indicate that BDD is fairly common among female Swedish dermatology patients (4.9%) and that BDD patients have high levels of depression and anxiety and severely impaired quality of life.

  • 10.
    Carlsson, Annica
    et al.
    Lund University, Sweden; Ängelholm Hospital, Sweden.
    Svensson, Åke
    Lund University, Sweden.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Baranovskaya, Irina
    Lund University, Sweden.
    Hindsen-Stenstrom, Monica
    Lund University, Sweden.
    Holt, Ingebjorg
    Angelholm Hospital, Sweden.
    Meding, Birgitta
    Karolinska Institute, Sweden.
    Stenberg, Berndt
    Umeå University, Sweden.
    Stenlund, Hans
    Umeå University, Sweden.
    Ganemo, Agneta
    Lund University, Sweden.
    Scoring of Hand Eczema: Good Reliability of the Hand Eczema Extent Score (HEES)2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 2, p. 193-197Article in journal (Refereed)
    Abstract [en]

    There is good agreement between dermatological staff and patients using the Hand Eczema Extent Score (HEES). The aim of this study was to assess inter-and intra-observer reliability of the HEES in dermatologists and intra-observer reliability of the HEES in patients with hand eczema. Six dermatologists assessed 18 patients twice. Only the hands of the patients were visible to the assessors. Patients performed a selfassessment twice. Inter-and intra-observer reliability was tested with intraclass correlation coefficient (ICC). The mean HEES score for all dermatologists assessments was 21.0 (range 3.6-46.3). The corresponding mean scores for all patients own assessments were 24.9 (range 4.0-54.0). Inter-observer reliability in the dermatologists observations ICC classification was very good, median value 0.82 (range 0.56-0.92). The overall intra-observer reliability for the 6 dermatologists ICC classification was very good (range 0.88-0.94). Intra-observer reliability in the patients 2 self-assessments ICC classification was very good (ICC 0.95). In conclusion, HEES is a reliable tool for both dermatologists and patients to grade the extent of hand eczema.

  • 11.
    Clifford, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences.
    Gold allergy: In vitro studies using peripheralblood mononuclear cells2009Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Positive patch test reactions to gold are commonly seen in dermatology clinics, but it is veryunusual for the patients to actually have any clinical symptoms. It is also common with irritantreactions that are not linked to adaptive immunity. Therefore, a deeper understanding of themechanisms underlying allergic contact dermatitis (ACD) reaction, and the search for acomplementing diagnostic tool, is important.

    In paper I we included three subject groups; one with morphologically positive patch testreactions to gold sodium thiosulphate (GSTS, the gold salt used in patch testing), one withnegative patch tests, and one with irritant reactions to gold. Blood samples were collected andexamined regarding the proliferation rate and which cytokines were secreted after culturingwith GSTS. We saw that the cultured lymphocytes from the allergic donors proliferated at asignificantly higher rate than the two other subject groups, and that the cells secreted cytokinesof both Th1 (Interferon (IFN) -g and Interleukin (IL) -2) and Th2 (IL-13 and IL-10) types. Theallergic donors secreted significantly higher levels of IFN-g, IL-2 and IL-13 than the two othersubject groups. Both the negative and irritant subject groups showed suppressed levels of thecytokines as compared with the unstimulated cultures, demonstrating the immunosuppressingeffects of gold.

    We also examined whether any of the analyzed markers, alone or combined, could be usedas an aid for diagnosing ACD to gold. We found that the IFN-g assay yielded the highestsensitivity (81.8 %) and specificity (82.1 %), and also identified 87.5 % of the irritant group asnon-allergic.

    In paper II we decided to investigate what cell types and subsets that reacted to the goldstimulation. We analyzed proliferation rate and expression of CD45RA, CD45R0, cutaneouslymphocyte-associated antigen (CLA) and the chemokine receptors CXCR3, CCR4 andCCR10. Similar to what has previously been published about nickel (Ni) allergy, the cells fromthe gold-allergic subjects that reacted to the GSTS stimulation expressedCD3+CD4+CD45R0+CLA+. However, contrary to findings in studies on Ni-reactive cells, wesaw no differences between allergic and non-allergic subjects regarding any of the chemokine receptors studied.

    In conclusion, we found that analysis of IFN-g might be a useful complement to patchtesting, possibly of interest in avoiding the need for repeated tests to rule out irritant reactions.We also saw that the cells that proliferated in response to gold were memory T-cells expressingCD4 and CLA, the marker for skin-homing. However, these cells did not express elevatedlevels of any of the chemokine receptors analyzed, showing that there are both similarities anddifferences between the mechanisms for Ni allergy and gold allergy.

    List of papers
    1. Interferon-gamma secreted from peripheral blood mononuclear cells as a possible diagnostic marker for allergic contact dermatitis to gold
    Open this publication in new window or tab >>Interferon-gamma secreted from peripheral blood mononuclear cells as a possible diagnostic marker for allergic contact dermatitis to gold
    Show others...
    2006 (English)In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 55, no 2, p. 101-112Article in journal (Refereed) Published
    Abstract [en]

    10% of patch-tested patients have a positive reaction to gold. Most lack clinical symptoms, but allergic contact dermatitis (ACD) to gold is increasing. In this study, 77 dermatological outpatients were divided into 3 groups depending on epicutaneous patch test outcomes: a group positive to gold (EPI+), a group negative to gold (EPI-), and a group with irritant reactions to gold (EPI-IR). Lymphocytes were stimulated in vitro with gold sodium thiosulfate. Proliferation was assessed using the lymphocyte transformation test (LTT), and cytokine secretion was assessed using a multibead array (Luminex; Linco Research Inc., St. Charles, MO, USA), in order to evaluate whether an in vitro method with high diagnostic accuracy could be devised. The EPI+ group showed a significantly increased secretion of interferon (IFN)-gamma, interleukin (IL)-2, and IL-13 and also showed a significantly higher stimulation indexes for LTT, compared to the other 2 subject groups. Sensitivity and specificity were calculated for all methods individually and combined, but IFN-gamma assessment alone was the most accurate method for identifying ACD to gold, with sensitivity and specificity of 81.8% and 82.1%, respectively. This method also identified 87.5% of the EPI-IR subjects as non-allergic. Therefore, assessment of secretion of IFN-gamma should be a valuable complement to patch test for diagnosing gold allergy.

    Keywords
    Allergic contact dermatitis, cytokines, gold, interferon-γ, lymphocyte transformation test, multibead assay
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-20564 (URN)10.1111/j.1600-0536.2006.00908.x (DOI)16930235 (PubMedID)
    Available from: 2009-09-14 Created: 2009-09-14 Last updated: 2017-12-13Bibliographically approved
    2. T-cells expressing CD4, CD45RO and CLA from gold-allergic but not healthy subjects react to gold sodium thiosufate in vitro
    Open this publication in new window or tab >>T-cells expressing CD4, CD45RO and CLA from gold-allergic but not healthy subjects react to gold sodium thiosufate in vitro
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Patch test positivity to gold is common in western societies, but in contrast to nickel (Ni) allergy it is uncommon that the patch test positive patient shows any clinical symptoms. In this study we investigated cytotoxic effects of gold sodium thiosulphate (GSTS) on peripheral blood mononuclear cells (PBMC), including different T-cell subsets. We also separated lymphocytes from allergic and non-allergic subjects into CD45RA and CD45R0 cell fractions. We also expressed CLA. The fraction of analyzed the effects of GSTS using lymphocyte transformation test, propidium iodide staining and flow cytometry to determine lymphocyte memory status, expression of chemokine receptors and cutaneous lymphocyte-associated antigen (CLA), and compared the results to what has previously been reported on Ni allergy. We found that only the cells from the allergic subjects proliferated in the lymphocyte transformation test (LTT), and in the CD45R0 fraction there was a dose-dependent increase in the fraction of CD3/CD4 cells. Similar to Ni-allergy, these CD3/CD4/CD45R0 cells also expressed CLA. The fraction of CD3/CD8 in the CD45R0 enriched fraction decreased with GSTS exposure. In contrast to Ni allergy, however, we found no differences between the allergic and non-allergic subjects regarding the chemokine receptors CCR4, CXCR3 and CCR10.

    Keywords
    contact dermatitis t-cell CD45RA CD45R0 CLA gold
    National Category
    Dermatology and Venereal Diseases
    Identifiers
    urn:nbn:se:liu:diva-19965 (URN)
    Available from: 2009-09-14 Created: 2009-08-21 Last updated: 2010-01-14Bibliographically approved
  • 12.
    Clifford, Jenny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Dermatology and Venerology UHL.
    Karin, Cederbrant
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences.
    Hultman, Per
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences.
    T-cells expressing CD4, CD45RO and CLA from gold-allergic but not healthy subjects react to gold sodium thiosufate in vitroManuscript (preprint) (Other academic)
    Abstract [en]

    Patch test positivity to gold is common in western societies, but in contrast to nickel (Ni) allergy it is uncommon that the patch test positive patient shows any clinical symptoms. In this study we investigated cytotoxic effects of gold sodium thiosulphate (GSTS) on peripheral blood mononuclear cells (PBMC), including different T-cell subsets. We also separated lymphocytes from allergic and non-allergic subjects into CD45RA and CD45R0 cell fractions. We also expressed CLA. The fraction of analyzed the effects of GSTS using lymphocyte transformation test, propidium iodide staining and flow cytometry to determine lymphocyte memory status, expression of chemokine receptors and cutaneous lymphocyte-associated antigen (CLA), and compared the results to what has previously been reported on Ni allergy. We found that only the cells from the allergic subjects proliferated in the lymphocyte transformation test (LTT), and in the CD45R0 fraction there was a dose-dependent increase in the fraction of CD3/CD4 cells. Similar to Ni-allergy, these CD3/CD4/CD45R0 cells also expressed CLA. The fraction of CD3/CD8 in the CD45R0 enriched fraction decreased with GSTS exposure. In contrast to Ni allergy, however, we found no differences between the allergic and non-allergic subjects regarding the chemokine receptors CCR4, CXCR3 and CCR10.

  • 13.
    Cuijpers, Pim
    et al.
    Linköping University, Faculty of Arts and Sciences. Vrije University of Amsterdam, Netherlands; EMGO Institute Health and Care Research, Netherlands; Karolinska Institute, Sweden.
    De Wit, Leonore
    Vrije University of Amsterdam, Netherlands; EMGO Institute Health and Care Research, Netherlands.
    Weitz, Erica
    Vrije University of Amsterdam, Netherlands; EMGO Institute Health and Care Research, Netherlands.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institute, Sweden.
    Huibers, Marcus J. H.
    Vrije University of Amsterdam, Netherlands; EMGO Institute Health and Care Research, Netherlands.
    THE COMBINATION OF PSYCHOTHERAPY AND PHARMACOTHERAPY IN THE TREATMENT OF ADULT DEPRESSION: A COMPREHENSIVE META-ANALYSIS2015In: JOURNAL OF EVIDENCE-BASED PSYCHOTHERAPIES, ISSN 2360-0853, Vol. 15, no 2, p. 147-168Article in journal (Refereed)
    Abstract [en]

    No meta-analysis in the field of depression has examined the effects of combined treatment compared with pill placebo, nor has any meta-analysis integrated the comparison of combined treatment against pharmacotherapy alone and psychotherapy alone (i.e., mono treatments). In this comprehensive meta-analysis, we found that combined treatment had a moderate effect on depression compared with pill placebo (g=0.46), and small to moderate effects compared against pharmacotherapy (g=0.38) alone, psychotherapy (g=0.34) alone, and psychotherapy plus placebo (g=0.23). There were some indications for publication bias when combined therapy was compared against placebo (adjusted effect size g=0.31). In multivariate metaregression analyses we found no significant differential predictors for the four comparisons. There were some indications that the use of interpersonal psychotherapy in the combined treatment was associated with a smaller effect size, but this has to be considered with caution, because of the correlational nature of this association. Despite limitations (small number of studies; suboptimal quality of studies) this meta-analysis suggests that combined treatment of depression may be the best treatment available for adult depression, and that it is significantly more effective than placebo, pharmacotherapy alone, psychotherapy alone and the combination of psychotherapy and placebo.

  • 14.
    Dahlen Gyllencreutz, J.
    et al.
    Skaraborg Hospital, Sweden.
    Paoli, J.
    University of Gothenburg, Sweden.
    Bjellerup, M.
    Lund University, Sweden.
    Bucharbajeva, Z.
    Umeå University, Sweden.
    Gonzalez, H.
    University of Gothenburg, Sweden.
    Nielsen, K.
    Lund University, Sweden.
    Sandberg, C.
    University of Gothenburg, Sweden.
    Synnerstad, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Linköping University, Faculty of Medicine and Health Sciences.
    Terstappen, K.
    Skaraborg Hospital, Sweden.
    Wennberg Larko, A. -M.
    University of Gothenburg, Sweden.
    Diagnostic agreement and interobserver concordance with teledermoscopy referrals2017In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 31, no 5, p. 898-903Article in journal (Refereed)
    Abstract [en]

    BackgroundMalignant melanoma and non-melanoma skin cancers are among the fastest increasing malignancies in many countries. With the help of new tools, such as teledermoscopy referrals between primary health care and dermatology clinics, the management of these patients could be made more efficient. ObjectiveTo evaluate the diagnostic agreement and interobserver concordance achieved when assessing referrals sent through a mobile teledermoscopic referral system as compared to referrals sent via the current paper-based system without images. MethodsThe referral information from 80 teledermoscopy referrals and 77 paper referrals were evaluated by six Swedish dermatologists. They were asked to answer questions about the probable diagnosis, the priority, and a management decision. ResultsTeledermoscopy generally resulted in higher diagnostic agreement, better triaging and more malignant tumours being booked directly to surgery. The largest difference between the referral methods was seen for invasive melanomas. Referrals for benign lesions were significantly more often correctly resent to primary health care with teledermoscopy. However, referrals for cases of melanoma in situ were also incorrectly resent five times. The interobserver concordance was moderate with both methods. ConclusionBy adding clinical and dermoscopic images to referrals, the triage process for both benign and dangerous skin tumours can be improved. With teledermoscopy, patients with melanoma especially can receive treatment more swiftly.

  • 15.
    Danielsen, Kjersti
    et al.
    UiT, Norway; Univ Hosp North Norway, Norway.
    Duvetorp, Albert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Skanes Univ Sjukhus, Sweden.
    Iversen, Lars
    Aarhus Univ Hosp, Denmark.
    Ostergaard, Mikkel
    Univ Copenhagen, Denmark.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Steinar Tveit, Kare
    Haukeland Hosp, Norway.
    Skov, Lone
    Univ Copenhagen, Denmark.
    Prevalence of Psoriasis and Psoriatic Arthritis and Patient Perceptions of Severity in Sweden, Norway and Denmark: Results from the Nordic Patient Survey of Psoriasis and Psoriatic Arthritis2019In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 99, no 1, p. 18-25Article in journal (Refereed)
    Abstract [en]

    Optimal clinical management of psoriasis and psoriatic arthritis (PsA) requires understanding of the impact on patients. The NORdic PAtient survey of Psoriasis and PsA (NORPAPP) aimed to obtain current data on disease prevalence and patient perceptions in Sweden, Denmark and Norway. Among 22,050 individuals questioned, the reported prevalence of psoriasis and/or PsA was 9.7% (5.7% physician-diagnosed plus 4.0% self-diagnosed only); prevalence was similar in Sweden (9.4%) and Denmark (9.2%) but significantly higher in Norway (11.9%). Of those reporting a physicians diagnosis, 74.6% reported psoriasis alone, 10.3% PsA alone and 15.1% both. Patients with PsA perceived their disease to be more severe than those with psoriasis; patients with PsA and psoriasis reported greater disease severity than those with each condition alone. Patients perceptions of psoriasis severity correlated weakly (Spearmans rho 0.42) with clinical severity; both patient perceptions and clinical measures are important in the assessment and management of psoriasis.

  • 16.
    Duvetorp, Albert
    et al.
    Skane Univ Hosp, Sweden.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Engerstedt Mattsson, Emma
    LEO Pharma AS, Denmark.
    Ryttig, Lasse
    LEO Pharma AS, Denmark.
    A Cost-utility Analysis of Calcipotriol/Betamethasone Dipropionate Aerosol Foam versus Ointment for the Topical Treatment of Psoriasis Vulgaris in Sweden2019In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 99, no 4, p. 393-399Article in journal (Refereed)
    Abstract [en]

    Psoriasis is a chronic inflammatory disorder that imposes a substantial economic burden. We conducted a cost-utility analysis from a Swedish healthcare payers perspective using a decision-tree model with a 12-week time horizon. Patients with psoriasis vulgaris could have two 4-week cycles of topical treatment with calcipotriol 50 mu g/g and betamethasone 0.5 mg/g as dipropionate (Cal/BD) foam or Cal/BD ointment before progressing to phototherapy/methotrexate. In the base-case analysis, Cal/BD foam dominated over Cal/BD ointment. The increased efficacy of Cal/BD foam resulted in fewer consultations and a decreased risk of progressing to phototherapy/methotrexate. Although Cal/BD foam costs more than Cal/BD ointment, this was offset by lower costs for phototherapy/methotrexate or consultation visits. Sensitivity analyses revealed that the base-case net monetary benefit was robust to plausible variations in key parameters. In conclusion, Cal/BD foam was predicted to be more cost-effective than Cal/BD ointment in the treatment of psoriasis vulgaris.

  • 17.
    Duvetorp, Albert
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Skanes Univ Sjukhus, Sweden.
    Ostergaard, M.
    Univ Copenhagen, Denmark.
    Skov, L.
    Univ Copenhagen, Denmark.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Tveit, K. S.
    Haukeland Hosp, Norway.
    Danielsen, K.
    UiT Arctic Univ Norway, Norway; Univ Hosp North Norway, Norway.
    Iversen, Lars
    Aarhus Univ Hosp, Denmark.
    Quality of life and contact with healthcare systems among patients with psoriasis and psoriatic arthritis: results from the NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP)2019In: Archives of Dermatological Research, ISSN 0340-3696, E-ISSN 1432-069X, Vol. 311, no 5, p. 351-360Article in journal (Refereed)
    Abstract [en]

    Psoriasis (skin psoriasis, PsO) is a chronic inflammatory condition. In about one-third of cases, the joints are affected (psoriatic arthritis, PsA). Both conditions, especially PsA, profoundly impact patients health-related quality of life (HRQoL). To describe the impact of psoriasis on HRQoL and patients contact with the healthcare system in Sweden, Denmark, and Norway, the NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP) asked 22,050 adults randomly selected in Sweden, Denmark and Norway if they had psoriasis. 1264 individuals who reported physician-diagnosed PsO/PsA were invited to the full survey; 1221 responded (74.6% diagnosed with PsO alone; 25.4% with PsA +/- PsO). Respondents with PsA most frequently consulted a rheumatologist; however, 14.3% had never seen a rheumatologist. Respondents with PsO alone most frequently consulted a general practitioner and 10.7% had never seen a dermatologist (although those with severe symptoms visited dermatologists more often). Negative impacts on HRQoL were reported by 38.1% of respondents with PsO [mostly limitations on clothing (22.6%), sleep disorders (16%), and depression/anxiety (16%)] and by 73% of respondents with PsA [mostly limitations on clothing (41.8%), sports/leisure (44.0%), or daily routine (45.1%) and sleeping disorders]. Absence from work/education was more common with PsA +/- PsO (51.9%) than PsO alone (15.1%). In this survey in Sweden, Denmark, and Norway, the impact of psoriasis on the respondents HRQoL was profound and was greater for PsA than for PsO, as was sickness absence. Sleeping disorders and depression were common and should not be overlooked.

  • 18.
    Duvetorp, Albert
    et al.
    Regional Jönköping County, Sweden.
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Nyström, Helena
    Regional Jonköping County, Sweden.
    Skarstedt, Marita
    Regional Jonköping County, Sweden.
    Dienus, Olaf
    Regional Jonköping County, Sweden.
    Mrowietz, Ulrich
    University of Medical Centre Schleswig Holstein, Germany.
    Soederman, Jan
    Regional Jonköping County, Sweden.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Expression of low-density lipoprotein-related receptors 5 and 6 (LRP5/6) in psoriasis skin2017In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 26, no 11, p. 1033-1038Article in journal (Refereed)
    Abstract [en]

    Low-density lipoprotein-related receptors 5 and 6 (LRP5/6) are transmembrane receptors with key functions in canonical Wnt signalling. Wnt ligands are thought to play an important role in innate immunity and psoriasis, and recent studies assigned LRP5/6 anti-inflammatory properties. The objective of this study was to investigate the expression of LRP5 and LRP6 in lesional and non-lesional skin in peripheral blood and in mononuclear cells of patients with chronic plaque type psoriasis compared with control individuals. To investigate the effect of UV-B radiation, LRP5/6 skin gene expression was analysed before and after narrowband UV-B treatment. Our results showed significantly decreased gene expression of LRP5 and LRP6 in lesional skin and in peripheral blood from patients with psoriasis compared with non-lesional skin and healthy control skin. Immunohistochemistry did not reveal differences in protein expression of LRP5/6. Narrowband UV-B treatment induced a significant increase in LRP5 and LRP6 gene expression in lesional skin. Decreased gene expression of LRP5/6 in lesional skin and upregulation after nb UV-B treatment suggest a possible role for LRP5/6 in psoriasis.

  • 19.
    Duvetorp, Albert
    et al.
    Regional Jönköping County, Sweden.
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Skarstedt, Marita
    Regional Jonköping County, Sweden.
    Söderman, Jan
    Regional Jonköping County, Sweden.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Psoriasis and Pro-angiogenetic Factor CD93: Gene Expression and Association with Gene Polymorphism Suggests a Role in Disease Pathogenesis2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 8, p. 916-921Article in journal (Refereed)
    Abstract [en]

    CD93 is involved in angiogenesis and inflammation, both of which are key processes in the pathogenesis of psoriasis. CD93 was studied in serum, peripheral blood mononuclear cells and skin of patients with psoriasis and controls. Furthermore, allele frequencies for CD93 single-nucleotide polymorphisms rs2749812 and rs2749817 were assessed in patients with psoriasis compared with controls and the effect of narrow-band ultraviolet B (NB-UVB) treatment on CD93 gene expression was evaluated in the skin of patients with psoriasis. CD93 gene expression was significantly increased in lesional and non-lesional skin from patients with psoriasis compared with controls. Immunohistochemistry revealed CD93 staining in dermal endothelial cells in lesional skin, and psoriasis was significantly associated with rs2749817 CD93 gene polymorphism. NB-UVB treatment of patients with psoriasis did not alter skin CD93 gene expression. Increased protein expression of CD93 psoriatic skin and association with the rs2749817 polymorphism suggests that CD93 plays a role in psoriasis disease pathogenesis.

  • 20.
    Duvetorp, Albert
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Skane Univ Hosp, Sweden.
    Söderman, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Assarsson, Malin
    Ryhov Cty Hosp, Sweden.
    Skarstedt, Marita
    Ryhov Cty Hosp, Sweden.
    Svensson, Ake
    Skane Univ Hosp, Sweden.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Observational study on Swedish plaque psoriasis patients receiving narrowband-UVB treatment show decreased S100A8/A9 protein and gene expression levels in lesional psoriasis skin but no effect on S100A8/A9 protein levels in serum2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 3, article id e0213344Article in journal (Refereed)
    Abstract [en]

    S100A8 and S100A9 proteins are highly upregulated in patients with psoriasis and have been proposed as potential biomarkers for psoriasis. The present study was designed to analyze the effect of narrowband ultraviolet B therapy on these proteins. S100A8, S100A9 gene expression and S100A8/A9 heterocomplex protein levels were analyzed in lesional and non-lesional skin before and after narrowband-UVB treatment in patients with chronic plaque type psoriasis. In addition, disease severity was measured by psoriasis area and severity index (PASI) and serum protein levels of S100A8/A9 were repeatedly analyzed. Narrowband-UVB treatment significantly reduced S100A8, S100A9 gene expression and S100A8/A9 protein levels in lesional skin while serum levels showed no significant change. No correlation between PASI and serum S100A8/A9 protein levels was found. These results implicate a role of S100A8/A9 in the anti-inflammatory effect of narrowband-UVB. Serum S100A8/A9 levels do not respond to treatment suggesting that serum S100A8/A9 does not originate from psoriasis skin keratinocytes. Serum S100A8/A9 levels do not correlate with PASI questioning serum S100A8/A9 as a biomarker for psoriasis skin activity.

  • 21.
    Ekman, Anna-Karin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Ingrid Asp Psoriasis Research Center.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Ingrid Asp Psoriasis Research Center.
    Lack of preclinical support for the efficacy of histone deacetylase inhibitors in the treatment of psoriasis.2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 174, no 2, p. 424-426Article in journal (Refereed)
  • 22.
    Ekman, Anna-Karin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Vegfors, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Bivik, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Overexpression of Psoriasin (S100A7) Contributes to Dysregulated Differentiation in Psoriasis.2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 4, p. 441-448Article in journal (Refereed)
    Abstract [en]

    Psoriasin, which is highly expressed in psoriasis, is encoded by a gene located within the epidermal differentiation complex. The aim of this study was to investigate the effect of endogenous psoriasin on disturbed keratinocyte differentiation in psoriasis. Immunohistochemical staining revealed a gradient of psoriasin expression in the psoriatic epidermis with highest expression in the suprabasal, differentiated layers. Induction of keratinocyte differentiation caused concurrent expression of psoriasin and the differentiation marker involucrin. The differentiation-induced psoriasin expression was found to be mediated by the protein kinase C pathway. The downregulation of psoriasin expression by small interfering RNA revealed that psoriasin mediates the expression of involucrin, desmoglein 1, transglutaminase 1 and CD24 in normal differentiation. The lentivirus-mediated overexpression of psoriasin, mimicking the psoriatic milieu, gave rise to an altered regulation of differentiation genes and an expression pattern reminiscent of that in psoriatic epidermis. These findings suggest that psoriasin contributes to the dysregulated differentiation process in the psoriasis epidermis.

  • 23.
    Eldh, Maria
    et al.
    1.Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    Olofsson Bagge, Roger
    1.Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital.
    Lässer, Cecilia
    1.Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    Svanvik, Joar
    Sahlgrenska universitetssjukhuset, Göteborg.
    Sjöstrand, Margareta
    1.Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    Mattsson, Jan
    1.Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital.
    Lindnér, Per
    1.Transplant Institute, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital.
    Choi, Dong-Sic
    1.Division of Molecular and Life Sciences, Department of Life Science, Pohang University of Science and Technology (POSTECH).
    Gho, Yong Song
    1.Division of Molecular and Life Sciences, Department of Life Science, Pohang University of Science and Technology (POSTECH).
    Lötvall, Jan
    1.Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma2014In: BMC Cancer, ISSN 1471-2407, Vol. 14, no 962, p. 1-10Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Uveal melanoma is a tumour arising from melanocytes of the eye, and 30 per cent of these patients develop liver metastases. Exosomes are small RNA containing nano-vesicles released by most cells, including malignant melanoma cells. This clinical translational study included patients undergoing isolated hepatic perfusion (IHP) for metastatic uveal melanoma, from whom exosomes were isolated directly from liver perfusates. The objective was to determine whether exosomes are present in the liver circulation, and to ascertain whether these may originate from melanoma cells.

    METHODS:

    Exosomes were isolated from the liver perfusate of twelve patients with liver metastases from uveal melanoma undergoing IHP. Exosomes were visualised by electron microscopy, and characterised by flow cytometry, Western blot and real-time PCR. Furthermore, the concentration of peripheral blood exosomes were measured and compared to healthy controls.

    RESULTS:

    The liver perfusate contained Melan-A positive and RNA containing exosomes, with similar miRNA profiles among patients, but dissimilar miRNA compared to exosomes isolated from tumor cell cultures. Patients with metastatic uveal melanoma had a higher concentration of exosomes in their peripheral venous blood compared to healthy controls.

    CONCLUSIONS:

    Melanoma exosomes are released into the liver circulation in metastatic uveal melanoma, and is associated with higher concentrations of exosomes in the systemic circulation. The exosomes isolated directly from liver circulation contain miRNA clusters that are different from exosomes from other cellular sources.

  • 24.
    Eriksson, Hanna
    et al.
    Department of Oncology-Pathology, Karolinska Institutet, and Deptartment of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Lyth, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Andersson, Therese M-L
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    The proportion cured of patients diagnosed with Stage III-IV cutaneous malignant melanoma in Sweden 1990-2007: A population-based study.2016In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 138, no 12Article in journal (Refereed)
    Abstract [en]

    The survival in cutaneous malignant melanoma (CMM) is highly dependent on the stage of the disease. Stage III-IV CMM patients are at high risk of relapse with a heterogeneous outcome, but not all experience excess mortality due to their disease. This group is referred to as the cure proportion representing the proportion of patients who experience the same mortality rate as the general population. The aim of this study was to estimate the cure proportion of patients diagnosed with Stage III-IV CMM in Sweden. From the population-based Swedish Melanoma Register, we included 856 patients diagnosed with primary Stage III-IV CMM, 1990-2007, followed-up through 2013. We used flexible parametric cure models to estimate cure proportions and median survival times (MSTs) of uncured by sex, age, tumor site, ulceration status (in Stage III patients) and disease stage. The standardized (over sex, age and site) cure proportion was lower in Stage IV CMMs (0.15, 95% CI 0.09-0.22) than non-ulcerated Stage III CMMs (0.48, 95% CI 0.41-0.55) with a statistically significant difference of 0.33 (95% CI = 0.24-0.41). Ulcerated Stage III CMMs had a cure proportion of 0.27 (95% CI 0.21-0.32) with a statistically significant difference compared to non-ulcerated Stage III CMMs (difference 0.21; 95% CI = 0.13-0.30). The standardized MST of uncured was approximately 9-10 months longer for non-ulcerated versus ulcerated Stage III CMMs. We could demonstrate a significantly better outcome in patients diagnosed with non-ulcerated Stage III CMMs compared to ulcerated Stage III CMMs and Stage IV disease after adjusting for age, sex and tumor site.

  • 25.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Anogenital Chlamydia trachomatis Infection Including Lympho­granuloma Venereum: Clinical Guidelines, Sweden2009In: Forum for Nordic Dermato-Venerology, ISSN 1402-2915, Vol. 14, no 4, p. 101-103Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 26.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Challenges of treatment for urethritis and cervicitis, (SY06:5)2012Conference paper (Other academic)
    Abstract [en]

    Challenges of treatment for urethritis and cervicitis

     

    Urethritis in men caused by gonorrhoea is symptomatic. Non-gonorrhoic-urethritis (NGU) i.e. caused by Chlamydia trachomatis, Mycoplasma genitalium and occasionally other bacteria is in most cases an asymptomatic infection. Swartz’ definition of microscopic urethritis > 4 polymorphonucleated leucocytes (PML) per high power field (HPF) in > 4 HPF is the general accepted, but has limitations and is dependant on the sampling, microscope, the physician and the patient as well. Cervicitis is even more cumbersome since it is even more often asymptomatic. Other factors such as which contraception method is used, concurrent infections (bacterial vaginosis, candidosis), the microscope and the physician, may have a great impact. Brunham proposed as definition observed mucopurulent discharge from the cervix orifice combined with > 10 PML per HPF in stained endocervical smear. Lindner proposed sign of friability of the portio cervicis. Weström found a correlation of more PML than vaginal epithelial cells in wet mount. The variety of definitions causes problem in comparing scientific studies and at the clinic as well. The intention to treat also means testing and treatment of a current sexual partner as well.

     

    The ever emerging decreased susceptibility of various antibiotics especially against Neisseria gonorrhoeae and M. genitalium makes it even more important to choose whether to treat immediately without having positive tests or to miss a treatment of a potential serious infection. N. gonorrhoeae is visible microscopically in urethral stains from men, but can be missed in smears from endocervix and urethra in women. Cefixim 400 mg stat is the recommended first line antibiotic treatment. Ceftriaxone 500 mg is under consideration to become the first treatment of choice due to emerging decreased susceptibility. M.genitalium will be discussed in another speech by Jørgen Skov Jensen. There are some few reports of antibiotic resistance of Chlamydia trachomatis but this infection is generally still eradicated by tetracycline and macrolide treatment. In an NGU and or unspecific cervicitis doxycycline 100 mg bid for one week is the first treatment of choice. Azithromycin 1 g stat should be used with precaution. If there are persisting signs and or symptoms after doxycycline treatment, azithromycin 500 mg day 1 and 250 mg following four days should be prescribed. Bacterial vaginosis may give symptoms and signs of cervicitis and is also a very common concurrent infection in women with C. trachomatis and M.genitalium as well and treatment with metronidazole or clindamycin should be considered. The fast ways of communication via the Internet and the easy accessible and legal way of an individual to buy antibiotics just for safe or to avoid attending a clinic is a big threat now and even more in the future because of the potential rapid increasing antibiotic resistance of many bacterial infections including STIs

  • 27.
    Falk, Lars
    Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Clinical Guidelines in Sweden - Anogenital Chlamydia trachomatis Infection Including Lymphogranuloma Venereum2009In: Forum for Nordic Dermato-Venerology, Vol. 14, no 4, p. 101-103Article in journal (Other academic)
  • 28.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    The overall agreement of proposed definitions of mucopurulent cervicitis in women at high risk of chlamydia infection2010In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, ISSN 0001-5555, Vol. 90, p. 506-511Article in journal (Refereed)
    Abstract [en]

    The overall agreement between different criteria for cervicitis in women infected with Chlamydia trachomatis and/or Mycoplasma genitalium, and in women who tested negative was examined. Women attending a clinic for sexually transmitted diseases were enrolled because of sexual partners’ suspected chlamydia infection. M. genitalium was tested in a sample of first-catch urine and an endocervical specimen, whereas specimens from four different sites were used for detection of C. trachomatis. Signs of friability and purulent endocervical discharge were documented at gynaecological examination. Specimens for microscopy were taken from the endocervix and urethra as well as the vaginal discharge, and bacterial vaginosis was examined for. The criteria being evaluated included cervical friability and/or pus; polymorphonuclear leukocytes (PMNL)/epithelium cell ratio in the vaginal discharge; and more than 30 PMNL per high-power field in the endocervical smear. The overall agreement of the indicators of cervicitis in women infected with C. trachomatis and/or M. genitalium was 40.5% (15/37), and for those women with negative tests 35.3% (12/34). The criteria for cervicitis require further evaluation, including study of a control group of women at low risk of having a sexually transmitted infection.

  • 29.
    Falk, Lars
    et al.
    Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland. Linköping University, Faculty of Health Sciences.
    Coble, Britt-Inger
    Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Mjörnberg, Per-Anders
    Ryhov County Hospital, Jönköping.
    Fredlund, Hans
    Örebro Universitet.
    Sampling for Chlamydia trachomatis infection – a comparison of vaginal, first-catch urine, combined vaginal and first-catch urine and endocervical sampling2010In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, ISSN 0956-4624, Vol. 21, no 4, p. 283-287Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to evaluate the sensitivity of patients' self-sampled vaginal specimens, first-catch urine (FCU), combined vaginal/FCU specimens and endocervical specimens for detecting chlamydial infection in women. Women attending sexually transmitted disease clinics, youth clinics and a women's health clinic were enrolled. They self-collected a vaginal specimen with two swabs, which were placed into a sterile tube and into a tube containing a buffer medium, respectively. An FCU sample was collected and aliquoted into both an empty tube and the tube containing the vaginal swab. A clinician collected an endocervical swab. The samples were sent to laboratories for analysis using polymerase chain reaction testing and strand displacement amplification testing, respectively. The sensitivities calculated in all 171 Chlamydia trachomatis-infected women were equal for endocervical specimens (97.1%), vaginal specimens (96.5%) and combined vaginal/FCU specimens (95.3%), whereas the sensitivity for FCU was significantly lower (87.7%). The sensitivity of vaginal specimens for the detection of C. trachomatis is as high as that of combined vaginal/FCU specimens.

  • 30.
    Falk, Lars
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Linköping University, Faculty of Medicine and Health Sciences.
    Enger, Martin
    Vastervik Hosp, Vastervik, Sweden.
    Jensen, Jorgen Skov
    Statens Serum Institut Köpenhamn.
    Time to eradication of Mycoplasma genitalium after antibiotic treatment in men and women.2015In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 70, no 11, p. 3134-3140Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    The objectives of this study were to evaluate the time to a Mycoplasma genitalium-negative test after start of treatment and to monitor if and when antibiotic resistance developed.

    METHODS:

    Sexually transmitted disease (STD) clinic attendees with suspected or verified M. genitalium infection were treated with azithromycin (5 days, 1.5 g; n = 85) or moxifloxacin (n = 5). Subjects with symptomatic urethritis or cervicitis of unknown aetiology were randomized to either doxycycline (n = 49) or 1 g of azithromycin as a single dose (n = 51). Women collected vaginal specimens and men collected first-catch urine 12 times during 4 weeks. Specimens were tested for M. genitalium with a quantitative MgPa PCR and for macrolide resistance-mediating mutations with a PCR targeting 23S rRNA.

    CLINICAL TRIALS REGISTRATION:

    NCT01661985.

    RESULTS:

    Ninety M. genitalium cases were enrolled. Of 56 patients with macrolide-susceptible strains before treatment with azithromycin (1.5 g, n = 46; 1 g single oral dose, n = 10), 54 (96%) had a negative PCR test within 8 days. In four patients, M. genitalium converted from macrolide susceptible to resistant after a 10 day lag time with negative tests (azithromycin 1.5 g, n = 3; 1 g single oral dose, n = 1). Moxifloxacin-treated subjects (n = 4) were PCR negative within 1 week. Six of eight (75%) remained positive despite doxycycline treatment.

    CONCLUSIONS:

    PCR for M. genitalium rapidly became negative after azithromycin treatment. Macrolide-resistant strains were detected after initially negative tests. Test of cure should be recommended no earlier than 3-4 weeks.

  • 31.
    Falk, Lars
    et al.
    Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Fredlund, Hans
    Örebro University Hospital.
    Letter: Re: Sampling for Chlamydia trachomatis infection2010In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 21, no 12, p. 847-847Article in journal (Other academic)
  • 32.
    Falk, Lars
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Dermatology and Venerology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Hegic, Sabina
    Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Wilson, Daniel
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care in Central County.
    Wiréhn, Ann-Britt
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Home-sampling as a Tool in the Context of Chlamydia trachomatis Partner Notification: A Randomized Controlled Trial2014In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 94, no 1, p. 72-74Article in journal (Other academic)
  • 33.
    Falk, Lars
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Skov Jensen, Jorgen
    Microbiology and Infection Control, Sexually Transmitted Infections, Research and Development, Statens Serum Institut, Copenhagen, Denmark.
    Successful outcome of macrolide-resistant Mycoplasma genitalium urethritis after spectinomycin treatment: a case report2017In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 72, no 2, p. 624-625Article in journal (Refereed)
  • 34.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care in Central County. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Self-estimation or Phototest Measurement of Skin UV Sensitivity and its Association with Peoples Attitudes Towards Sun Exposure2014In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 2, p. 797-803Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Fitzpatrick's classification is the most common way of assessing skin UV sensitivity. The study aim was to investigate how self-estimated and actual UV sensitivity, as measured by phototest, are associated with attitudes towards sunbathing and the propensity to increase sun protection, as well as the correlation between self-estimated and actual UV sensitivity.

    PATIENTS AND METHODS:

    A total of 166 primary healthcare patients filled-out a questionnaire investigating attitudes towards sunbathing and the propensity to increase sun protection. They reported their skin type according to Fitzpatrick, and a UV sensitivity phototest was performed.

    RESULTS:

    Self-rated low UV sensitivity (skin type III-VI) was associated with a more positive attitude towards sunbathing and a lower propensity to increase sun protection, compared to high UV sensitivity. The correlation between the two methods was weak.

    CONCLUSION:

    The findings might indicate that individuals with a perceived low but in reality high UV sensitivity do not seek adequate sun protection with regard to skin cancer risk. Furthermore, the poor correlation between self-reported and actual UV sensitivity, measured by phototest, makes the clinical use of Fitzpatrick's classification questionable.

  • 35.
    Falk, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Towards a broader use of phototesting: in research, clinical practice and skin cancer prevention2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In western societies, skin cancer incidence has increased dramatically over recent decades, due predominantly to increased sun exposure habits. Ultraviolet (UV) light exposure and individual light sensitivity of the skin constitute two important factors affecting the risk for skin cancer development. Individuals with a heightened propensity to get sunburnt have a higher risk for skin malignancies, and need to protect themselves more systematically from the sun. Individual UVlight sensitivity can be determined either by self-estimation of tendency to burn and tan, as in the Fitzpatrick’s classification, or by use of a phototest. Although phototesting constitutes a considerably more objective method, it is only sparsely used, chiefly due to financial and resource related factors, and is mainly limited to investigation of photodermatoses or dose-management in photo therapy.

    The general aim of this thesis was to develop and improve aspects of the phototest procedure in rder to broaden the utilisation of phototesting within the fields of research, clinical practice and skin cancer prevention. As a first step, a new phototesting technique, using a divergent UVB beam was evaluated. The principle of the method is to provoke a circular UVB-erythema in the skin, the diameter of which is related to the administered dose and thus the Minimal Erythema Dose (MED). In a test group of healthy subjects, naked eye reading by a trained observer resulted in a more exact, estimation of UVB-sensitivity, compared to traditional phototesting. Since the diffuse border of the provoked erythema was challenging for the untrained observer to read, the need for an objective, bio-engineering technique for test reading was clear. In this thesis, Laser Doppler perfusion imaging (LDPI) has been used. This data also enabled an objective description of doseresponse for the reaction, an outcome not possible in traditional testing. The divergent beam method was also shown to be useful as a model for evaluation of the effect of topically applied substances.

    In order to broaden the utilisation of phototests in general, a test procedure built on patient performed self-reading of skin tests (a traditional phototest and an irritant patch test) was evaluated. The reliability of these self-readings was shown to be substantial when compared to the control readings of a trained observer.

    Using the self-reporting procedure, phototesting was evaluated as a tool in primary prevention of skin cancer. The study focussed on sun habits and sun protection behaviour, and also on investigating the impact of different forms of presentation of the preventive information. Results showed significantly higher impact for a personally mediated preventive message than by letterform. For individuals with heightened UV-sensitivity the performance of a phototest led to a greater tendency to adopt sun protection behaviour than for subjects with a lower UV-sensitivity, suggesting that phototesting is a useful way to improve the outcome in terms of preventive behaviours for this group of susceptible, at-risk individuals.

    Divergent beam phototesting, patient-performed self-reading, and the application of phototesting in skin cancer prevention emerge as three novel, previously little investigated, aspects of phototesting, for which promising results could be demonstrated.

    List of papers
    1. Phototesting based on a divergent beam: a study on normal subjects
    Open this publication in new window or tab >>Phototesting based on a divergent beam: a study on normal subjects
    2001 (English)In: Photodermatology, Photoimmunology & Photomedicine, ISSN 0905-4383, E-ISSN 1600-0781, Vol. 17, no 4, p. 189-196Article in journal (Refereed) Published
    Abstract [en]

    In a previous publication from our group, phototesting based on a single exposure to a divergent UVB beam with radially decreasing irradiance values was suggested. The aim of the present study was to evaluate technical, practical and biological aspects of the suggested method in normal subjects. Twenty healthy volunteers were provoked on the back with both a collimated beam (four fixed doses, in circular areas with a diameter of 1.5 cm) and the divergent beam (a continuous, radially attenuating dose spectrum covering an area with a diameter of 4.5 cm). Eleven of the subjects were subjected to double provocation with the divergent beam. Assessment was carried out at 6 and 24 h after exposure by measuring the diameter of the reactions both visually and by mapping the skin blood flow change with laser Doppler perfusion imaging (LDPI). Minimal erythemal dose (MED) was determined for both the collimated and the divergent provocation. The reaction diameters were used to decide MED by combination to a mm for mm mapped dose spectrum of the divergent beam profile. Dose-response curves were plotted using the quantitative response data of the LDPI-images against the corresponding dosimetry data. No systematic difference could be proven between LDPI and visual diameters and a 95% confidence interval for the mean difference was calculated to (-0.8, 2.0). Slightly greater diameters were found at the visual assessment performed at 6 h compared to 24 h (95% confidence interval (-0.1, 2.8)). Double provocation showed a good reproducibility both for the visual and the LDPI assessment (P<0.05). The divergent beam provocation allowed a more detailed discrimination of MED compared to the collimated beam provocation. The MED values determined with the divergent beam were, however, generally higher, especially in the lower range of MED values. Technical factors related to the beam divergence and the correct measurement of erythemal effective irradiance are believed to be the explanation for this phenomenon, which is thus correctable. In conclusion, the results from this study support our belief that the phototesting protocol based on a divergent beam constitutes a good opportunity for improved phototesting, since MED and dose-response characteristics may be extracted in more detail from a single UV exposure.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12817 (URN)10.1034/j.1600-0781.2001.170409.x (DOI)
    Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2017-12-14
    2. Inter-observer variability in reading of phototest reactions with sharply or diffusely delineated borders
    Open this publication in new window or tab >>Inter-observer variability in reading of phototest reactions with sharply or diffusely delineated borders
    2008 (English)In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 14, no 4, p. 397-402Article in journal (Refereed) Published
    Abstract [en]

    Background: In both clinical and experimental phototesting, naked eye assessment of erythema has been the main assessment parameter. As with all subjective assessment, variability in recorded results due to variable circumstances around the performance and reading of tests influences reliability and utility of data whether they be interpreted for an individual patient or for a group of research subjects.

    Methods: In the present study, variability in the reporting of diameter of ultraviolet B (UVB) erythema has been studied. The erythematous reactions were assessed by the naked eye and with the help of a millimetre-graded ruler by a group of dermatologists and dermatological trainees. Reaction size, objectively quantified by means of laser Doppler perfusion imaging (LDPI) using thresholding of the reaction perfusion, and known size of UVB provocation were used as yardsticks in order to quantify this variability.

    Results: Agreement between observers, against known size, was excellent for reactions with a sharp border, but for reactions with a diffuse or indistinct border there was a substantial inter-observer variability. This was also true for the comparison between naked-eye reading and LDPI assessment of the reaction size.

    Conclusion: It is concluded that if naked-eye readings are to be the outcome measurement, then provocations/protocols producing distinct borders are an advantage. If borders between provoked and unprovoked skin can be expected to be diffuse, i.e. part of a continuum of response, the use of objective, bioengineering techniques such as LDPI is required. Quantitative methods are also the basis for more detailed presentation and interpretation of test results including information on dose response above the minimal erythema dose.

    Keywords
    erythema, phototesting, UVB, LDPI, observer variability
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12818 (URN)10.1111/j.1600-0846.2008.00305.x (DOI)
    Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2017-12-14
    3. Phototesting with a divergent UVB beam in the investigation of anti-inflammatory effects of topically applied substances
    Open this publication in new window or tab >>Phototesting with a divergent UVB beam in the investigation of anti-inflammatory effects of topically applied substances
    2003 (English)In: Photodermatology, Photoimmunology & Photomedicine, ISSN 0905-4383, E-ISSN 1600-0781, Vol. 19, no 4, p. 195-202Article in journal (Refereed) Published
    Abstract [en]

    Background: Phototesting based on a single exposure to a divergent ultraviolet B (UVB) beam with radially decreasing UVB doses can be used to determine an individual's minimal erythema dose (MED). Laser Doppler perfusion imaging (LDPI) data can be combined with dosimetry data to produce objective dose–response plots in addition to the MED. The aim of this study was to investigate whether the divergent beam protocol could be used to demonstrate and quantify the anti-inflammatory effects of clobetasol diproprionate (Dermovate®), pharmaceutical-grade acetone and a gel vehicle, applied after skin provocation by UVB.

    Method: Sixteen Caucasian subjects were illuminated with the divergent beam on three areas close together on the left side of their upper backs. Two of the provoked areas on each subject were treated with acetone, gel vehicle or Dermovate®, and one area was left untreated as a control. Skin blood perfusion was assessed 6 and 24 h after UVB illumination using LDPI. The reaction diameter, the mean perfusion, and the average dose–response plots for each group and treatment were extracted from the LDPI data.

    Results: Application of the topical steroid clobetasol diproprionate after UVB provocation markedly decreased the inflammatory response. Acetone and the gel vehicle also showed mild anti-inflammmatory effects in two of the parameters but not for the mean perfusion response. The mean diameter differences between controls and treated reactions had predominantly positive 99% confidence intervals. Analysis of the dose–response data at doses higher than the MED showed a linear relationship (0.89≤R2≤0.98) for all reactions but with lower gradients in treated reactions, mostly marked for clobetasol diproprionate.

    Conclusions:  The divergent beam protocol can be used to demonstrate and quantify the effects of topical agents on the UVB reaction, in terms of reaction diameter, mean perfusion and changes in dose–response characteristics. The dose–response approach seems to be applicable even in diagnostic testing of an individual patient's response to UVB.

    Place, publisher, year, edition, pages
    Wiley-Blackwell Publishing Inc., 2003
    Keywords
    acetone, anti-inflammatory effects, clobetasol diproprionate, erythema, gel vehicle, laser Doppler perfusion imaging, phototesting.
    National Category
    Microbiology in the medical area
    Identifiers
    urn:nbn:se:liu:diva-12819 (URN)10.1034/j.1600-0781.2003.00037.x (DOI)000184575000006 ()2-s2.0-0042925506 (Scopus ID)
    Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2018-01-13Bibliographically approved
    4. Can patients read their own UVB minimal erythema dose and irritant skin tests
    Open this publication in new window or tab >>Can patients read their own UVB minimal erythema dose and irritant skin tests
    2010 (English)Article in journal (Refereed) Submitted
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12820 (URN)
    Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2012-03-27
    5. Prevention of skin cancer in primary health care: an evaluation of three different prevention effort levels and the applicability of a phototest
    Open this publication in new window or tab >>Prevention of skin cancer in primary health care: an evaluation of three different prevention effort levels and the applicability of a phototest
    2008 (English)In: European Journal of General Practice, ISSN 1381-4788, E-ISSN 1751-1402, Vol. 14, no 2, p. 68-75Article in journal (Refereed) Published
    Abstract [en]

    Background/objective: The high skin cancer incidence in western society, and its known association with sun exposure habits, makes the area an important target for prevention. We investigated, in a primary healthcare setting, differentiated levels of prevention efforts directed at the propensity of the patient to change his/her sun habits, sun protection behaviour, and attitudes, after information intervention. Additionally, the impact of the performance of a phototest to determine individual sun sensitivity was evaluated. Methods: 308 patients visiting a primary healthcare centre in southern Sweden completed a questionnaire concerning sun habits, sun protection behaviour, and attitudes, and were randomized into one of three groups, representing increasing levels of prevention effort in terms of resources. Feedback on their questionnaire and general preventive sun protection advice was given, in the first group by means of a letter, and in the second and third groups by a doctor's consultation. Group 3 also underwent a phototest, with a self-reading assessment and a written follow-up of the phototest result. Change of sun habits, behaviour, and attitudes, based on the Transtheoretical Model of Behaviour Change and on Likert scale scorings, was evaluated after 6 months, by a repeated questionnaire. Results: Prevention mediated by a doctor's consultation had a clearly better impact on the subjects. The addition of a phototest did not further reinforce this effect in the group as a whole, but it did for a subgroup of individuals with high ultraviolet (UV) sensitivity, as determined by the phototest itself, suggesting that this might actually be a tool to improve outcome in this high-risk group. Conclusion: A personal doctor's consultation is a valuable tool in the effective delivery of preventive information in the general practice setting. In individuals with high UV-sensitivity and thus high risk for skin cancer the performance of a photo-test reinforces a positive outcome in habits, behaviour and attitudes.

    Place, publisher, year, edition, pages
    London, UK: Informa Healthcare, 2008
    Keywords
    Skin cancer prevention; phototesting; behavioural change; self-assessment; questionnaire
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12821 (URN)10.1080/13814780802423430 (DOI)
    Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2017-12-14Bibliographically approved
  • 36.
    Falk, Magnus
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Primary Health Care Centres.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Measuring sun exposure habits and sun protection behaviour using a comprehensive scoring instrument: An illustration of a possible model based on Likert scale scorings and on estimation of readiness to increase sun protection2012In: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 36, no 4, p. 265-269Article in journal (Refereed)
    Abstract [en]

    Background: Few attempts to present a comprehensive scoring instrument for sun exposure and protection have been made. The present paper aims to describe a possible set of questions suitable for such an instrument, comprising the most important aspects of sun exposure and protection. Methods: The material from a previously performed intervention study, using a questionnaire based on Likert scales and on the Transtheoretical Model of Behaviour Change (TTM), was utilised. 213 primary healthcare patients filled in the questionnaire and were randomised into two groups receiving sun protection advice, in Group 1 in letter-form, and in Group 2 orally during a doctor's consultation. In the original study, increased sun protection/readiness to increase sun protection was demonstrated for several items in Group 2, at six months. To compose a comprehensive scoring instrument, five questions concerning sun exposure/protection (intentional tanning, sunscreen use, choice of SPF, number of occasions with sunburn, and time spent in the sun at midday), were selected to give a 20 point behavioural score. Similarly, four TTM-based questions (giving up sunbathing, using clothes for sun protection, using sunscreens, and staying in the shade) gave a 16 point "propensity-to-change"-score. Results: At follow-up, increased sun protection reflected in the behavioural score occurred only in Group 2 (p<0.001). For the propensity-to-change-score, increased readiness to increase sun protection occurred in both groups, but the change was significantly higher in Group 2 (p<0.05). Categorisation of the 20 point behavioural score, into three risk levels, revealed a significantly higher shift of subjects moving to a lower risk level in Group 2 compared to Group 1 (p<0.05). Conclusions: In conclusion, twinning of a summarised Likert scale behavioural score with a TTM-based propensity-to-change-score seems promising for the creation of a questionnaire-based, comprehensive scoring instrument for sun exposure and protection.

  • 37.
    Fredriksson, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
    Ilias, Michail
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    New mechanical device for effective removal of skin tags in routine health care2009In: Dermatologi Online, ISSN 1087-2108, E-ISSN 1087-2108, Vol. 15, no 2, article id 9Article in journal (Refereed)
    Abstract [en]

    Skin tags (acrochordons) are exceedingly common benign skin lesions. A novel medical device in the form of a flat adhesive patch applies pressure to the base of a skin tag, leading to its removal within 3-6 days. The device was used in a clinical trial to treat and remove skin tags of the neck, upper torso, and axillae in volunteers. In this study, a total of 177 skin tags were treated in 32 individuals. One hundred seventy-two lesions fulfilled intention to treat (ITT) criteria. A majority of ITT lesions (90%) reached final assessment. Successful outcome was highest (90%) for lesions up to 1 mm in base. For lesions up to 2 mm, the rate of successful outcome was 76 percent. The desired outcome was seen in 65 percent of all ITT lesions. The cosmetic outcome after removal was excellent. Discomfort was assessed as minimal during all stages of the procedure. Analysis of data on blood flow in the skin tags during the treatment showed that the outcome was influenced by whether a decrease in blood flow was achieved immediately after application and at 2-3 days, but that the degree of occlusion was not critical. The results of this study illustrate that the device presents a new option for the management of unmet needs in the treatment of skin tags.

  • 38.
    Frölund, Maria
    et al.
    Research Unit for Reproductive Microbiology, Statens Serum Institut, Copenhagen S, Denmark.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Ahrens, Peter
    Research Unit for Reproductive Microbiology, Statens Serum Institut, Copenhagen S, Denmark.
    Jensen, Jorgen Skov
    Research Unit for Reproductive Microbiology, Statens Serum Institut, Copenhagen S, Denmark.
    Detection of ureaplasmas and bacterial vaginosis associated bacteria and their association with non-gonococcal urethritis in men2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203Article in journal (Refereed)
    Abstract [en]

    No aetiology is found in up to 40% of men with symptomatic urethritis. Male partners of women with bacterial vaginosis (BV) may be at higher risk of non-gonococcal urethritis (NGU). The aim of this study was to examine the role of BV associated bacteria in first-void urine (FVU) in 97 asymptomatic men without urethritis (controls) and 44 men (cases) with NGU including 20 men with idiopathic urethritis (IU) attending a Swedish STD-clinic between January and October 2010. BV-associated bacteria and ureaplasmas were detected by quantitative PCR assays. All BV associated bacteria, except Megasphaera-like type 1, were strongly positively correlated with Uurealyticum p<0.005 and even stronger with the combined Uurealyticum and Uparvum load (p<0.0005) suggesting that ureaplasma induced elevated pH may stimulate the growth of BV associated bacteria. No statistically significant differences were found between IU cases and controls in the prevalence or load of BV associated bacteria or ureaplasmas. In multiple logistic regression, Megasphaera-like type 1 was associated with IU (p = 0.03), but most positive FVU samples contained very few bacteria and the finding may not be clinically relevant.

  • 39.
    Hallberg, S.
    et al.
    Quantify Research, Sweden.
    Gandra, S. R.
    Amgen Inc, CA 91320 USA.
    Fox, K. M.
    Strateg Healthcare Solut LLC, MD USA.
    Mesterton, J.
    Quantify Research, Sweden; Karolinska Institute, Sweden.
    Banefelt, J.
    Quantify Research, Sweden.
    Johansson, G.
    Uppsala University, Sweden.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Sobocki, P.
    Karolinska Institute, Sweden; IMS Heatlh, Sweden.
    Healthcare costs associated with cardiovascular events in patients with hyperlipidemia or prior cardiovascular events: estimates from Swedish population-based register data2016In: European Journal of Health Economics, ISSN 1618-7598, E-ISSN 1618-7601, Vol. 17, no 5, p. 591-601Article in journal (Refereed)
    Abstract [en]

    To estimate healthcare costs of new cardiovascular (CV) events (myocardial infarction, unstable angina, revascularization, ischemic stroke, transient ischemic attack, heart failure) in patients with hyperlipidemia or prior CV events. A retrospective population-based cohort study was conducted using Swedish national registers and electronic medical records. Patients with hyperlipidemia or prior CV events were stratified into three cohorts based on CV risk level: history of major cardiovascular disease (CVD), coronary heart disease (CHD) risk-equivalent, and low/unknown risk. Propensity score matching was applied to compare patients with new events to patients without new events for estimation of incremental costs of any event and by event type. A CV event resulted in increased costs over 3 years of follow-up, with the majority of costs occurring in the 1st year following the event. The mean incremental cost of patients with a history of major CVD (n = 6881) was a,not sign8588 during the 1st year following the event. This was similar to that of CHD risk-equivalent patients (n = 3226; a,not sign6663) and patients at low/unknown risk (n = 2497; a,not sign8346). Ischemic stroke resulted in the highest 1st-year cost for patients with a history of major CVD and CHD risk-equivalent patients (a,not sign10,194 and a,not sign9823, respectively); transient ischemic attack in the lowest (a,not sign3917 and a,not sign4140). Incremental costs remained elevated in all cohorts during all three follow-up years, with costs being highest in the major CVD history cohort. Healthcare costs of CV events are substantial and vary considerably by event type. Incremental costs remain elevated for several years after an event.

  • 40.
    Hallert, Eva
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Husberg, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Kalkan, Almina
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Bernfort, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Rheumatoid arthritis is still expensive in the new decade: a comparison between two early RA cohorts, diagnosed 1996-98 and 2006-092016In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 45, no 5, p. 371-378Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    To calculate total costs during the first year after diagnosis in 463 patients with early rheumatoid arthritis (RA) included during 2006-09 (T2) and compare the results with a similar cohort included in 1996-98 (T1).

    METHOD:

    Clinical and laboratory data were collected regularly in both cohorts, and patients completed biannual questionnaires reporting health care utilization and number of days lost from work.

    RESULTS:

    Disease activity was similar in both cohorts T1 and T2 at inclusion. Significant improvements were seen during the first year in both cohorts but were more pronounced in T2. Outpatient care increased and hospitalization decreased in T2 compared with T1. Almost 3% of patients had surgery in both cohorts, but in T2, only women had surgery. Drug costs were higher in T2 than in T1 (EUR 689 vs. EUR 435). In T2, 12% of drug costs were direct costs and 4% were total costs. The corresponding values for T1 were 9% and 3%. In T1, 50% were prescribed disease-modifying anti-rheumatic drugs (DMARDs) at inclusion, compared to T2, where prescription was > 90%. Direct costs were EUR 5716 in T2 and EUR 4674 in T1. Costs for sick leave were lower in T2 than in T1 (EUR 5490 vs. EUR 9055) but disability pensions were higher (EUR 4152 vs. EUR 2139), resulting in unchanged total costs. In T1, direct costs comprised 29% and indirect costs 71% of the total costs. The corresponding values for T2 were 37% and 63%.

    CONCLUSIONS:

    The earlier and more aggressive treatment of RA with traditional DMARDs in T2 resulted in better outcomes compared to T1. Direct costs were higher in T2, partly offset by decreased sick leave, but total costs remained unchanged.

  • 41.
    Heed, Gunilla
    et al.
    Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Det oväntade besöket-syfilisepidemi bland unga män och kvinnor2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, ISSN 0023-7205, Vol. 107, no 19, p. 1314-1316Article in journal (Refereed)
    Abstract [en]

    Early sexually transmissible syphilis is still an infection of major importance worldwide despite the fact that it is nowadays curable, with penicillin treatment. Syphilis has during the last decades been considered in many Western countries to appear mainly among men who have sex with men (MSM). In Sweden only 106 cases were reported (76 MSM) in 2008.In the present paper an epidemic of early syphilis among young heterosexual men and women aged 18 to 23 years is described. The suspected primary index case was a 20 year old woman who had been living for some months in a Mediterranean city. During a period of one year 10 persons living in Norrköping, a town of 128 000 inhabitants, had a confirmed infection. In all, almost 55 men and women were notified and examined. This epidemic shows the dynamic of transmission, the unawareness of care givers and common people as well, but also how efficient contact tracing can be.

  • 42.
    Horner, Patrick J
    et al.
    School of Social and Community Medicine, University of Bristol, UK.
    Karla, Blee
    Bristol Sexual Health Centre, University Hospitals Bristol NHS Foundation Trust, UK.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    van der Meijden, W
    Department of Dermatology, New Cross Hospital, UK..
    Moi, H.
    Olafia Clinic, Oslo University Hospital, Institute of Medicine, University of Oslo, Norway.
    2016 European Guideline on the management of non-gonococcal urethritis2016In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 27, no 11, p. 928-937Article in journal (Refereed)
    Abstract [en]

    We present the updated International Union against Sexually Transmitted Infections guideline for the management of non-gonococcal urethritis in men. This guideline recommends confirmation of urethritis in symptomatic men before starting treatment. It does not recommend testing asymptomatic men for the presence of urethritis. All men with urethritis should be tested for Chlamydia trachomatis and Neisseria gonorrhoeae and ideally M. genitalium using a NAAT as this is highly likely to improve clinical outcomes. If a NAAT is positive for gonorrhoea, a culture should be performed before treatment. In view of the increasing evidence that azithromycin 1 g may result in the development of antimicrobial resistance in Mycoplasma genitalium azithromycin 1 g is no longer recommended as first line therapy, which should be doxycycline 100 mg bd for 7 days. If azithromycin is to be prescribed an extended of 500 mg, then 250 mg daily for 4 days is to be preferred over 1 g stat. In men with persistent NGU, M. genitalium NAAT testing is recommended if not previously undertaken, as is Trichomonas vaginalis NAAT testing in populations where T. vaginalis is detectable in >2% of symptomatic women.

  • 43.
    Hägerlind, Elisabeth
    et al.
    Region Östergötland, Local Health Care Services in Central Östergötland, Primary Health Care in Central County. Linköping University, Faculty of Medicine and Health Sciences.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Primary Health Care in Central County. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Löfstedt, Tommy
    Computational Solutions, Umeå, Sweden.
    Lindholm-Sethson, Britta
    Umeå Univ, Dept Chem, Umeå, Sweden.
    Bodén, Ida
    Ivida AB, Umeå.
    Near infrared and skin impedance spectroscopy - a possible support in the diagnostic process of skin tumours in primary health care.2015In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 21, no 4, p. 493-499Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/PURPOSE: The global incidence of skin cancer has increased drastically in recent decades, especially in Australia and Northern Europe. Early detection is crucial for good prognosis and high survival rates. In general, primary care physicians have considerably lower sensitivity and specificity rates for detection of skin cancer, compared to dermatologists. A probable main reason for this is that current diagnostic tools are subjective in nature, and therefore diagnostic skills highly depend on experience. Illustratively, in Sweden, approximately 155 500 benign skin lesions are excised unnecessarily every year. An objective instrument, added to the clinical examination, might improve the diagnostic accuracy, and thus promote earlier detection of malignant skin tumours, as well as reduce medical costs associated with unnecessary biopsies and excisions. The general aim of this study was to investigate the usefulness of the combination of near infrared (NIR) and skin impedance spectroscopy as a supportive tool in the diagnosis and evaluation of skin tumours in primary health care.

    METHODS: Near infrared and skin impedance data were collected by performing measurements on suspect malignant, premalignant and benign tumours in the skin of patients seeking primary health care for skin tumour evaluation. The obtained data were analysed using multivariate analysis and compared with the diagnosis received by the conventional diagnostic process.

    RESULTS: The observed sensitivity and specificity rates were both 100%, when discriminating malignant and premalignant skin tumours from benign skin tumours, and the observed sensitivity and specificity for separating malignant skin tumours from premalignant and benign skin tumours were also 100%, respectively.

    CONCLUSION: The results of this study indicate that the NIR and skin impedance spectroscopy may be a useful supportive tool for the general practitioner in the diagnosis and evaluation of skin tumours in primary health care, as a complement to the visual assessment.

  • 44.
    Högberg, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Sokolski, Jan
    Department of Dermatology, Norrköping Hospital, Norrköping, Sweden.
    Stenhammar, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Chronic Bullous Dermatosis of Childhood Associated with Coeliac Disease in a 6-year-old Boy2004In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 84, no 2, p. 158-159p. 158-159Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 45.
    Jacobs, Maartje S.
    et al.
    Univ Groningen, Netherlands; Martini Hosp, Netherlands.
    Schouten, Jeroen F.
    Univ Groningen, Netherlands.
    de Boer, Pieter T.
    Univ Groningen, Netherlands.
    Hoffmann, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Postma, Maarten J.
    Univ Groningen, Netherlands; Univ Med Ctr Groningen, Netherlands; Univ Med Ctr Groningen, Netherlands.
    Secondary adherence to non-vitamin-K antagonist oral anticoagulants in patients with atrial fibrillation in Sweden and the Netherlands2018In: Current Medical Research and Opinion, ISSN 0300-7995, E-ISSN 1473-4877, Vol. 34, no 10, p. 1839-1847Article in journal (Refereed)
    Abstract [en]

    Objective: There is limited evidence on patients adherence and the impact of the prescribed dosing regimen in non-vitamin-K oral anticoagulants (NOACs). We aimed to assess secondary adherence to NOACs and to determine the impact of the dosing regimen in patients with atrial fibrillation. Methods: Patients using a NOAC between 2009 and 2013 were identified from the nation-wide Swedish Prescribed Drug Register and the Dutch regional IADB.nl database. Patients using a consistent dosage for at least 180 consecutive days were included. Adherence was calculated using the medication possession ratio (MPR) and adjusted for overlapping dates. Adherence was defined as a MPR amp;gt;= 0.8. Sensitivity analyses were performed using a MPR amp;gt;= 0.9. Logistic regression was performed to compare secondary adherence and to explore the influence of the dosing regimen. Results: A total of 5254 Swedish and 430 Dutch NOAC users were included. The mean MPR was 96.0% (SD 7.8%) in Sweden and 95.1% (SD 10.1%) in the Netherlands. Multivariable logistic regression analysis showed that a twice daily regimen had a lower likelihood of being secondary adherent compared to a once daily regimen in Sweden (odds ratio [OR] 0.21 [95% CI 0.12-0.35]). Limitations: The influence of selection bias introduced by the inclusion criterion of amp;gt;= 2 dispensations covering at least 180 days could not be excluded. Conclusions: This study demonstrated that secondary adherence was high in this specific setting among patients with at least two initial dispensations of a NOAC covering a minimum of 180 days. The use of NOACs in a once daily regimen showed higher adherence compared to a twice daily regimen.

  • 46.
    Karlsson, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Cutaneous melanoma in children and adolescents and aspects of naevus phenotype in melanoma risk assessment2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cutaneous malignant melanoma (CMM) is one of the most rapidly increasing cancers in the Swedish population. The aetiology of melanoma is a complex interplay between genetics, host characteristics and environmental factors. The host characteristic with the strongest association with CMM is a phenotype with high numbers of common naevi and with dysplastic naevi. The principal environmental factor is sun exposure.

    Melanoma risk assessment (paper I)

    In a multi-national study including 986 subjects from Sweden, Denmark, the UK, Germany and the Netherlands, the ability of primary care physicians and nurses to identify individuals at increased melanoma risk was assessed. The atypical mole syndrome (AMS) scoring system for melanoma risk was used. The AMS scoring system consists of a five point check list incorporating total body naevus counts, clinically dysplastic naevi and body distribution of naevi. After brief training, the overall agreement in diagnosis between the trained personnel and experienced dermatologists was 94.5% (kappa value 0.70, p<0.05). The study showed that the scoring system successfully can be taught to personnel in primary care.

    The naevus phenotype in a population in northern Sweden (paper II)

    The naevus phenotype was investigated in a population living in the inland of northern Sweden with a low melanoma incidence. Two hundred and one participants from the community of Storuman were included. The median naevus count was15 common naevi/individual, and the prevalence of dysplastic naevi was 11%. The median naevus count and prevalence of dysplastic naevi were significantly lower than previously described in populations with higher melanoma incidence and higher ambient ultraviolet exposure in southern Sweden. This geographical variation in naevus phenotype might be explained by differences in levels of sun exposure and in genotype.

    Cutaneous malignant melanoma in children and adolescents (papers III–V)

    During the years 1973 to 2002, 250 cases of primary CMM in individuals aged 0-19 years were reported to the Swedish Cancer Registry. Histological material was available for review in 87% of the cases registered during the two first decades (1973–1992). The diagnostic accuracy in the reviewed material was 88%.

    The melanoma incidence doubled in teenagers between the first decade (1973–1982) and the second (1983–1992). During the third decade (1993–2002) the increasing trend was broken. A decrease in incidence was noted in boys during 1993–1997, and in girls during 1998–2002. In younger children the incidence remained extremely low, only 4 cases in children aged 0–9 years were reported during the studied 30-year period. The trunk was the most common melanoma site in boys, and legs and trunk were the most common sites in girls. Superficial spreading melanoma was the most frequent subtype, followed by nodular melanoma. During the two first decades (1973–1992), the median melanoma thickness decreased from 1.5 to 0.9 mm. The melanoma-specific 5-year survival rate was 93%. The most important prognostic factor was melanoma thickness. The prognosis for thin lesions was excellent, during a median follow up time of 12 years, no tumour less than 0.8 mm was lethal according to the Registry.

    The results indicate that CMM in teenagers has many features in common with adult onset melanoma. The tudy also underlines the importance of not neglecting lesions suspected for malignant change in children and adolescents, as early detection and removal is crucial for the prognosis also in this young age group.

    List of papers
    1. Teaching non-specialist health care professionals how to identify the atypical mole syndrome phenotype: a multinational study
    Open this publication in new window or tab >>Teaching non-specialist health care professionals how to identify the atypical mole syndrome phenotype: a multinational study
    Show others...
    2000 (English)In: British Journal of Dermatology, ISSN 0007-0963, Vol. 142, no 2, p. 331-337Article in journal (Refereed) Published
    Abstract [en]

    The atypical mole syndrome (AMS) phenotype is the strongest known risk factor for cutaneous melanoma but recognition of the phenotype has been claimed to be problematic and to require specialist assessment. This study determined the ability of previously unskilled doctors and nurses in five countries to recognize the phenotype after brief training. The system used was the AMS scoring system. This incorporates melanocytic naevus counts, clinical atypia of naevi and distribution of naevi. The agreement in scoring between the dermatologist and trained personnel was determined in 986 patients; overall agreement in diagnosis was 94·5% (kappa 0·70, P < 0·0001). The kappa scores in different countries ranged from 0·65 to 0·77 for individual naevus characteristics, indicative of good agreement. Accurate diagnosis of the atypical mole syndrome phenotype is possible by non-specialists. This has implications for collaborative studies of naevi, for screening and for both primary and secondary prevention of melanoma.

    Keywords
    AMS scoring system, atypical mole syndrome, melanoma, risk factor, teaching
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14135 (URN)10.1046/j.1365-2133.2000.03405.x (DOI)
    Available from: 2008-11-14 Created: 2008-11-14 Last updated: 2009-08-19
    2. Prevalence of pigmented naevi in a Swedish population living close to the Arctic Circle
    Open this publication in new window or tab >>Prevalence of pigmented naevi in a Swedish population living close to the Arctic Circle
    2000 (English)In: Acta Dermato-Venereologica, ISSN 0001-5555, Vol. 80, no 5, p. 335-339Article in journal (Refereed) Published
    Abstract [en]

    The prevalence of common naevi and dysplastic naevi was investigated in a Swedish population with a low incidence of melanoma. A total of 201 subjects aged 30-50 years living in northern Sweden participated. The median number of common naevi per individual was 15, and 11% had dysplastic naevi. Higher numbers of common naevi were found in individuals with dysplastic naevi (median 68) and in those who had spent their childhood in southern Sweden (median 44). The prevalence of common naevi and dysplastic naevi was significantly lower than reported from a previously studied population in southern Sweden, with a melanoma incidence 4 times higher than in the north. The strong variability in naevus phenotype, and in melanoma incidence, between different regions of Sweden seems to be due to different levels of sun exposure rather than to differences in constitutional factors.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14136 (URN)10.1080/000155500459259 (DOI)
    Available from: 2008-11-14 Created: 2008-11-14 Last updated: 2009-08-19
    3. Increasing incidence of cutaneous malignant melanoma in children and adolescents 12–19 years of age in Sweden 1973–92
    Open this publication in new window or tab >>Increasing incidence of cutaneous malignant melanoma in children and adolescents 12–19 years of age in Sweden 1973–92
    Show others...
    1998 (English)In: Acta Dermato-Venereologica, ISSN 0001-5555, Vol. 78, no 4, p. 289-292Article in journal (Refereed) Published
    Abstract [en]

    One-hundred-and-seventy-seven cases of cutaneous malignant melanoma were reported to the Swedish National Cancer Registry in subjects below the age of 20 during the period 1973-92. One-hundred-and-fifty-four (87%) were re-examined histologically, and the original diagnosis of primary cutaneous malignant melanoma was verified in 88%. The age-specific mean annual incidence rate increased to 0.5/100,000 in 1983-92 from 0.2/100,000 in 1973-82. Cutaneous malignant melanoma remained extremely rare in children below the age of 12, where only two cases were found. In subjects aged 12-19, the incidence doubled to 93 cases in the second 10-year period compared to 41 in the first. In boys, most of the melanomas occurred on the trunk, and, in girls, on the legs. Sixty-three percent of the melanomas were of the superficial spreading type, which also was the most rapidly increasing type of melanoma. These results emphasize the importance of surveillance and intensified preventive measures in protecting children and adolescents from the harmful effects of excessive exposure to the sun

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14137 (URN)10.1080/000155598441882 (DOI)
    Available from: 2008-11-13 Created: 2008-11-13 Last updated: 2009-08-19
    4. Cutaneous malignant melanoma in Swedish children and teenagers 1973–1992 clinicopathological: study of 130 cases
    Open this publication in new window or tab >>Cutaneous malignant melanoma in Swedish children and teenagers 1973–1992 clinicopathological: study of 130 cases
    Show others...
    1999 (English)In: International Journal of Cancer, ISSN 0020-7136, Vol. 80, no 5, p. 646-651Article in journal (Refereed) Published
    Abstract [en]

    To assess whether there has been a change in histological features and prognostic factors of primary cutaneous malignant melanoma (CMM) in young individuals in Sweden, an unselected, population-based study was undertaken; 177 cases of primary CMM in persons below 20 years of age were reported to the Swedish National Cancer Registry between 1973 and 1992. In 87% of the cases, original tumor tissue was available for histo-pathological review. The original diagnosis was verified in 88% (n = 126) of these cases. All tumors had histological features similar to adult CMM; 17% had an associated precursor lesion. Superficial spreading melanoma (SSM) was the most common sub-type, constituting 20/36 cases in the first decade and 59/90 in the second. Corresponding figures for nodular melanoma (NM) were 11/36 and 23/90. Only 5 melanomas in situ were diagnosed. In girls, the mean thickness of SSM decreased from 1.5 to 0.6 mm (p < 0.001). Overall mortality was 10%, 22% in the group with CMM diagnosed 0-15 years of age and 8% in individuals 15-19 years. Fatal CMM cases diagnosed below 15 years of age (n = 4) were NM >1.6 mm thick and in subjects 15-19 years (n = 9) 44% of fatal tumors were NM with a mean thickness of 2.2 mm. Breslow index was the single most important prognostic factor. However, when known prognostic factors were adjusted for in a Cox regression analysis, young age remained an independent risk factor, with a relative death rate of 0.21 for individuals aged 15-19 compared with children <15 years of age.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14138 (URN)10.1002/(SICI)1097-0215(19990301)80:5<646::AID-IJC2>3.0.CO;2-H (DOI)
    Available from: 2008-11-14 Created: 2008-11-14 Last updated: 2009-08-20
    5. Cutaneous malignant melanoma in children and adolescents in Sweden, 1993–2002: the increasing trend is broken
    Open this publication in new window or tab >>Cutaneous malignant melanoma in children and adolescents in Sweden, 1993–2002: the increasing trend is broken
    2007 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 121, no 2, p. 323-328Article in journal (Refereed) Published
    Abstract [en]

    The incidence of cutaneous malignant melanoma rose rapidly in teenagers in Sweden during 1973-1992, while it remained low in younger children. To study the further trends and characteristics of melanoma in this young population, data on all cases in individuals under 20 years of age reported to the Swedish Cancer Registry during 1993-2002, and the corresponding pathology reports were examined. Seventy-nine cases were reported to the Registry. There were 24 males and 55 females. Most melanomas occurred on the trunk followed by the legs in both genders. The median tumor thickness was 0.8 mm. Children under age 15 had thicker melanomas than individuals aged 15-19. Superficial spreading melanoma was the most common histological subtype (43/78, 55%). The melanoma-specific 5-year survival rate was 90%. During 1993-2002, the age-standardized incidence fell to 3.6/million from 5.0/million in 1983-1992 (RR 0.74, 95% CI 0.58-0.92). The most pronounced decrease was for melanomas on the trunk in boys and on the legs in girls. The incidence for 15-19-year-old boys peaked for the cohort born between 1968 and 1972 and for girls between 1973 and 1977. The decrease in incidence may be a result of public health campaigns aiming at reducing sun exposure in childhood. A contributing effect from an increased immigration of individuals with darker complexions and at a lower melanoma risk is probable.

    Keywords
    childhood, adolescence, melanoma, population-based, epidemiology
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14139 (URN)10.1002/ijc.22692 (DOI)
    Available from: 2006-11-09 Created: 2006-11-09 Last updated: 2017-12-13
  • 47.
    Kirchheiner Rasmussen, Mads
    et al.
    Aarhus Univ Hosp, Denmark.
    Enger, Martin
    Oslo Hudlegesenter, Norway.
    Dahlborn, Anna-Karin
    Novartis Healthcare AB, Sweden.
    Juvik, Sin
    Novartis Norge AS, Norway.
    Fagerhed, Laura
    Novartis Finland Oy, Finland.
    Dodge, Rikke
    Novartis Healthcare, Denmark.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    The Importance of Achieving Clear or Almost Clear Skin for Patients: Results from the Nordic Countries of the Global "Clear about Psoriasis" Patient Survey2019In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 99, no 2, p. 158-163Article in journal (Refereed)
    Abstract [en]

    Psoriasis is a stigmatizing chronic skin condition in which impairment of quality of life is associated with visibility of skin lesions, disease activity and severity. The ultimate goal of treatment is complete clearance of skin symptoms. The worldwide "Clear About Psoriasis" survey explored patients perspectives on clear/almost clear skin and the impact of psoriasis on daily life. We report here results from the Nordic countries (n = 609). Of respondents, 44% achieved clear/almost clear skin with their current treatment, of which 71% were comfortable discussing this expectation with their physician, compared with only 46% of patients who had not achieved clear/almost clear skin. Of patients who achieved clear/almost clear skin, 85% reported treatment satisfaction vs. 39% who had not. Psoriasis profoundly affected daily life, with 88% of respondents reporting discrimination/humiliation and 61% reporting an impact on their professional life. This report highlights stigmatization among Nordic patients with psoriasis and the potential to improve physician-patient communication.

  • 48.
    Lidholm, Anette Gente
    et al.
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Bergfors, Elisabet
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Inerot, Annica
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Blomgren, Ulla
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Gillestedt, Martin
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Trollfors, Birger
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Unexpected loss of contact allergy to aluminium induced by vaccine2013In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 68, no 5, p. 286-292Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    In studies in Gothenburg, Sweden, in the 1990s of an aluminium hydroxide-adsorbed pertussis toxoid vaccine, 745 of ~76 000 vaccinated children developed long-lasting itchy subcutaneous nodules at the vaccination site. Of 495 children with itchy nodules patch tested for aluminium allergy, 376 (76%) were positive.

    OBJECTIVES:

    To study the prognosis of the vaccine-induced aluminium allergy.

    PATIENTS AND METHODS:

    Two hundred and forty-one children with demonstrated aluminium allergy in the previous study were patch tested again 5-9 years after the initial test, with the same procedure as used previously.

    RESULTS:

    Contact allergy to aluminium was no longer demonstrable in 186 of the retested 241 children (77%). A negative test result was more common in children who no longer had itching at the vaccination site; it was also related to the age of the child, the time after the first aluminium-adsorbed vaccine dose, and the strength of the reaction in the first test.

    CONCLUSIONS:

    Patch test reactivity to aluminium seems to disappear or weaken with time.

  • 49.
    Loden, Marie
    et al.
    Research and Development, ACO HUD Nordic AB, Upplands Väsby, Sweden, ACO Hud Nordic AB, Box 622, SE-194 26 Upplands Väsby, Sweden.
    Ungerth, Louise
    Stockholm Consumer Cooperative Society, Stockholm, Sweden.
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Changes in European legislation make it timely to introduce a transparent market surveillance system for cosmetics2007In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 87, no 6, p. 485-492Article in journal (Other (popular science, discussion, etc.))
    Abstract [en]

    Marketing of cosmetics often makes strong claims linked to active ingredients. This is especially so for anti-ageing products, where the presentation and content of "active" ingredients may create new difficulties in their classification as cosmetics or medicinal products. A recent change in European legislation classifies a product as medicinal by virtue of its "function", in addition to the previous definition of "presentation" (i.e. marketing linked to diseases). Thus, formulations that also restore, correct or modify physiological functions by exerting a pharmacological, immunological or metabolic action should henceforth be covered by the Medicinal Products Directive. A cosmetic product must be suitable for its purpose and should not lead to adverse reactions that are disproportional in relation to its intended effect. However, the forthcoming ban on animal testing of cosmetic ingredients and the new European regulation, REACH (Registration, Evaluation and Authorisation of Chemicals), which aims to ensure a high level of chemical safety to protect human health and the environment, will probably have limited impact on the safety assessment of cosmetics. In order to enable consumers to make informed purchasing decisions, greater transparency in the process of assessing the performance of cosmetics is needed. Introduction of a more transparent system, enabling consumers and professionals to examine the scientific evidence for the claimed effect and the safety assessment of cosmetics, is therefore timely. Lack of transparency increases the risk of consumers wasting money on cosmetics that do not deliver the desired effects. This may jeopardize public trust in the cosmetic industry.

  • 50.
    Lyth, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Clinical-epidemiological studies on cutaneous malignant melanoma: A register approach2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The incidence of cutaneous malignant melanoma (CMM) is steadily increasing. Most of the patients have thin CMM with a good prognosis and a 5-year survival of about 90%. The prognosis is highly related to tumour thickness and clinical stage at diagnosis. Effective systemic treatment for patients with metastatic disease has only recently been available. This thesis aims to increase knowledge of trends in tumour thickness, prognostic factors, socioeconomic differences and medical costs in patients with CMM.

    The population-based Swedish melanoma register is the main source of data in all papers in the thesis. Papers I-III include patients from all of Sweden while paper IV is delimited to the County of Östergötland. Cox regression and logistic regression are the main multivariable methods used. Paper IV is focused on stage-specific costs of CMM by comparing direct healthcare costs to a general population.

    For men, there has been a shift over time towards thinner tumours at diagnosis accompanied by an improved survival. Women are still diagnosed with considerably thinner tumours and they experience a better survival than men. Tumour ulceration, tumour thickness and Clark’s level of invasion all showed significant independent long-term prognostic information in T1 CMMs. By combining these factors, three distinct prognostic subgroups were identified. Lower level of education was associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. The direct healthcare costs for CMM patients were significantly higher than for the general population, independent of clinical stage. CMM patients diagnosed in clinical stage III-IV were associated with particularly high costs.

    Even though the survival among Swedish patients with CMM is among the highest in the world and still seems to improve, the results of this thesis emphasise the need of improved early detection strategies. This may be of particular concern in men, older women, and groups with a low level of education. The results also imply that the costs for the management of CMM patients may be reduced if early detection efforts are successful and lead to a more favourable stage distribution. The finding of a better risk stratification of thin CMMs may help to improve the management of this large patient group.

    List of papers
    1. Trends in cutaneous malignant melanoma in Sweden 1997-2011: Thinner tumours and improved survival among men
    Open this publication in new window or tab >>Trends in cutaneous malignant melanoma in Sweden 1997-2011: Thinner tumours and improved survival among men
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    2015 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 172, no 3, p. 700-706Article in journal (Refereed) Published
    Abstract [en]

    Background: Both patient survival and the proportion of patients diagnosed with thin cutaneous malignant melanoma (CMM) have been steadily rising in Sweden as in most western countries, though the rate of improvement in survival appears to have declined in Sweden at the end of last millennium.

    Objectives: To analyse the most recent trends in the distribution of tumour thickness (T-category) as well as CMM-specific survival in Swedish patients diagnosed 1997-2011.

    Methods: This nationwide population-based study included 30 590 patients registered in the Swedish Melanoma Register (SMR) and diagnosed with a first primary invasive CMM 1997-2011. The patients were followed through 2012 in the national Cause-of-Death Register.

    Results: Logistic and Cox regression analyses adjusting for age at diagnosis, tumour site, and health care region were carried out. The odds ratio for being diagnosed with thicker tumours was significantly reduced (P = 0·0008) and the CMM-specific survival significantly improved in men diagnosed 2007-2011 compared to men diagnosed 1997-2001 (hazard ratio=0·81; 95% CI 0·72-0·91, P = 0·0009) while the corresponding differences for women were not significant. Women were diagnosed with significantly thicker tumours during 2002-2006 and a tendency towards decreased survival was observed compared to those diagnosed earlier 1997-2001 and later 2007-2011.

    Conclusion: In Sweden, the CMMs of men are detected earlier over time and this seems to be followed by an improved CMM-specific survival for men. Women are still diagnosed with considerably thinner tumours and they experience a better survival than men.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2015
    Keywords
    malignant melanoma, time trend, survival, tumour thickness, population based
    National Category
    Dermatology and Venereal Diseases
    Identifiers
    urn:nbn:se:liu:diva-113143 (URN)10.1111/bjd.13483 (DOI)000351400500029 ()25323770 (PubMedID)
    Available from: 2015-01-12 Created: 2015-01-12 Last updated: 2017-12-05Bibliographically approved
    2. Prognostic subclassifications of T1 cutaneous melanomas based on ulceration, tumour thickness and Clark’s level of invasion: results of a population-based study from the Swedish Melanoma Register
    Open this publication in new window or tab >>Prognostic subclassifications of T1 cutaneous melanomas based on ulceration, tumour thickness and Clark’s level of invasion: results of a population-based study from the Swedish Melanoma Register
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    2013 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 168, no 4, p. 779-786Article in journal (Refereed) Published
    Abstract [en]

    Background  Survival and prognostic factors for thin melanomas have been studied relatively little in population-based settings. This patient group accounts for the majority of melanomas diagnosed in western countries today, and better prognostic information is needed.

    Objectives  The aim of this study was to use established prognostic factors such as ulceration, tumour thickness and Clark’s level of invasion for risk stratification of T1 cutaneous melanoma.

    Methods  From 1990 to 2008, the Swedish Melanoma Register included 97% of all melanomas diagnosed in Sweden. Altogether, 13 026 patients with T1 melanomas in clinical stage I were used for estimating melanoma-specific 10- and 15-year mortality rates. The Cox regression model was used for further survival analysis on 11 165 patients with complete data.

    Results  Ulceration, tumour thickness and Clark’s level of invasion all showed significant, independent, long-term prognostic information. By combining these factors the patients could be subdivided into three risk groups: a low-risk group (67·9% of T1 cases) with a 10-year melanoma-specific mortality rate of 1·5% (1·2–1·9%); an intermediate-risk group (28·6% of T1 cases) with a 10-year mortality rate of 6·1% (5·0–7·3%); and a high-risk group (3·5% of T1 cases) with a 10-year mortality rate of 15·6% (11·2–21·4%). The high- and intermediate-risk groups accounted for 66% of melanoma deaths within T1.

    Conclusions  Using a population-based melanoma register, and combining ulceration, tumour thickness and Clark’s level of invasion, three distinct prognostic subgroups were identified.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2013
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-92611 (URN)10.1111/bjd.12095 (DOI)000317016100030 ()23066913 (PubMedID)
    Note

    Funding Agencies|regional cancer centre Southeast in Linkoping||

    Available from: 2013-05-16 Created: 2013-05-14 Last updated: 2017-12-06
    3. Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: A nationwide population-based study in Sweden
    Open this publication in new window or tab >>Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: A nationwide population-based study in Sweden
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    2013 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, no 12, p. 2705-2716Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    A worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden.

    METHODS:

    We identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010.

    RESULTS:

    The odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I=1.6; 95% confidence interval (CI)=1.5-1.7. OR stage III-IV versus I=2.3; 95% CI=1.8-2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high=2.02; 95% CI=1.80-2.26; p<0.0001) and intermediate (HR intermediate versus high=1.35; 95% CI=1.20-1.51; p<0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR=1.13; 95% CI=1.01-1.27; p=0.04) but not for intermediate versus high (HR=1.11; 95% CI=0.99-1.24; p=0.08) education. The HR associated with low level of education was significantly higher among female patients, patients <55years, patients with truncal tumours and during the first 5years after diagnosis.

    CONCLUSION:

    Lower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies.

    Place, publisher, year, edition, pages
    Elsevier, 2013
    Keywords
    Melanoma, Survival, Socioeconomic status, Level of education, Stage at diagnosis, Population-based
    National Category
    Medical and Health Sciences Social Sciences
    Identifiers
    urn:nbn:se:liu:diva-95938 (URN)10.1016/j.ejca.2013.03.013 (DOI)000321336800010 ()23583439 (PubMedID)
    Note

    Funding Agencies|Swedish Cancer Society||Radiumhemmet Research Funds||Sigurd and Elsa Goljes Memorial Foundation||Stockholm County Council||

    Available from: 2013-08-19 Created: 2013-08-12 Last updated: 2017-12-06Bibliographically approved
    4. Stage-specific direct healthcare costs in patients with cutaneous malignant melanoma
    Open this publication in new window or tab >>Stage-specific direct healthcare costs in patients with cutaneous malignant melanoma
    2016 (English)In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 30, no 5, p. 789-793Article in journal (Refereed) Published
    Abstract [en]

    Background Clinical stage at diagnosis is a strong prognostic factor for death in cutaneous malignant melanoma (CMM), with worse prognosis at higher stages. However, few studies have investigated how direct healthcare cost per patient varies with clinical stage.

    Objective The aim of this study was to determine the stage-specific direct healthcare costs for CMM patients compared to the healthcare costs in the general population in the County of Östergötland, Sweden.

    Methods CMM patients in the County of Östergötland diagnosed 2005-2012 were identified from the Swedish cancer registry. Information on clinical stage was collected from the Swedish Melanoma Register (SMR) and cost data from the Cost per Patient database (CPP) for 1 075 CMM patients in Östergötland. CPP contains costs associated with all healthcare contacts per patient including inpatient, outpatient, and primary care. The CMM-related costs were defined as the difference in mean healthcare costs between CMM patients and general population.

    Results The first year after CMM diagnosis, the average healthcare costs for CMM patients was 2.8 times higher than in the general population. The healthcare cost ratio varied from 2.0 (stage I) to 10.1 (stage IV) and the CMM-related costs per patient-year varied from €2 670 (stage I) to €29 291 (stage IV). The mean healthcare costs decreased over time but remained significantly higher than in the general population for all clinical stages. During the first year after diagnosis, patients in clinical stage III-IV (7% of CMM patients) accounted for 27% of the total CMM-related healthcare costs.

    Conclusions The direct healthcare costs for CMM patients were significantly higher than in the general population independent of clinical stage. CMM patients diagnosed in clinical stage III-IV were associated with particularly high costs and the healthcare system may save resources by finding CMM patients in earlier stages.

    National Category
    Dermatology and Venereal Diseases
    Identifiers
    urn:nbn:se:liu:diva-113144 (URN)10.1111/jdv.13110 (DOI)000374554200007 ()
    Note

    Funding agencies:Regional cancer center South East in Linkoping

    Vid tiden för disputation förelåg publikationen som manuskript

    Available from: 2015-01-12 Created: 2015-01-12 Last updated: 2017-05-03
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