Assessment of stigma related to visible skin diseases: a systematic review and evaluation of patient-reported outcome measures.

Misconceptions about visible skin diseases are widespread, and patients often face discrimination and stigmatization due to their condition. The associated negative health and psychosocial consequences of stigmatization in skin diseases have prompted an increase in research activity in recent times, resulting in a wide variety of assessment measures. This study aimed at aggregating and evaluating evidence of psychometric properties and methodological quality of published measures to assess stigma in visible skin diseases. Studies assessing stigmatization in visible skin diseases were searched in four databases (Medline, PsycINFO, Web of Science and Embase) until February 2021. The review followed PRISMA guidelines. Papers regarding development and/or validation of measures were identified by two independent researchers. Inclusion criteria were defined as follows: (i) quantitative studies in (ii) populations with skin diseases using (iii) questionnaires explicitly assessing (iv) perceived or public stigmatization or discrimination available in (iv) English or German language. The COnsensus-based Standards of health Measurement INstruments (COSMIN) checklist was used to evaluate their psychometric properties and risk of bias. 35 studies using 21 instruments were identified. Twenty instruments focused on assessing the perceived reality of those affected by visible skin diseases, while public stigma was only assessed by two instruments. Twelve scales could be recommended for use, while nine instruments had the potential to be recommended after further studies have assessed their quality. Some limitations are to be noted. Only studies in English and German were included. Research on self-constructed instruments can lead to new validated instruments, but they were not included in the review at this point. Several validated instruments could be recommended for use. Future research is needed regarding the assessment of stigma across different visible skin diseases, in children and adolescents, and in the general public.

Perception and determinants of stigmatization of people with psoriasis in the German population.

BACKGROUND: Perception of psoriasis in the general population is characterized by knowledge deficits and prejudice against those affected. The extent and possible predictors of stigmatizing attitudes remain unclear. OBJECTIVES: The aim was to assess prejudices and stigmatization of people with psoriasis and to identify sociodemographic and attitude-related variables accounting for stigmatization. METHODS: Representative telephone surveys of 2004 (in 2017) and 2001 (in 2018) adults using a standardized questionnaire. Descriptive analyses were applied to living area, age, gender, educational status, general knowledge and attitudes about psoriasis. Logistic regression analyses were carried out to determine which variables are associated with the assessment of prejudices of 'others' against people with psoriasis. Those prejudices were specified by the following statements: 'they should take better care of themselves', 'don't want to touch people with psoriasis' and 'disgusted by psoriasis'. RESULTS: The majority of those surveyed (74%) believe that people with psoriasis are disadvantaged. Similarly, a majority (69%) said that most people find psoriasis disgusting, do not want to touch people with psoriasis (59%) and think that people with psoriasis need to take better care of themselves (45%). 'Willing to enter a relationship with an affected person' (OR = 0.330, P = 0.029), higher age (OR = 1.027, P <0.001) and male gender (OR = 1.263, P = 0.034) proved to be significantly associated with 'psoriasis is disgusting'. Education (OR = 1.648, P = 0.016) and lower age (OR = 0.847, P  <0.001) are significantly associated with 'they need to take better care of themselves'. CONCLUSIONS: Data suggest that stigmatization of skin diseases is still entrenched. This overview shows the need for interventions against stigmatization of those affected. Results imply that gender, age and education level and related health literacy of the target groups of respective interventions should be taken into account.

Strategies to reduce stigma related to visible chronic skin diseases: a systematic review.

Many patients with a visible chronic skin disease experience discrimination and stigmatization. This results in psychosocial impairments in addition to the burden of disease and emphasizes the urgency to implement effective stigma-reduction strategies. To synthesize what is known globally about effective interventions to reduce stigma associated with visible chronic skin diseases, a systematic review was conducted. Four electronic databases were searched until May 2018. Studies evaluating interventions to reduce stigmatization in patients with visible chronic skin diseases and applying at least one stigma-related outcome measure were included. Data were extracted on study design, country, study population, outcome measures and main findings. Results were subsequently synthesized in a narrative review. Critical Appraisal Skills Programme tools were used to assess study quality. Nineteen studies were included in the review. Study design was very heterogeneous and study quality rather poor. Thirteen studies addresses patients with leprosy in low- and middle-income countries, and one study each targeted patients with onychomycosis, leg ulcer, facial disfigurement, atopic dermatitis, vitiligo and alopecia. Evaluated interventions were mainly multi-faceted incorporating more than one type of intervention. While 10 studies focused on the reduction in self-stigma and 4 on the reduction in public stigma, another 5 studies aimed at reducing both. The present review revealed a lack of high-quality studies on effective approaches to reduce stigmatization of patients with visible chronic skin diseases. Development and evaluation of intervention formats to adequately address stigma is essential to promote patients' health and well-being.

[Perception of stigmatization in people with psoriasis-qualitative analysis from the perspective of patients, relatives and healthcare professionals]. / Stigmatisierungserleben bei Psoriasis ­ qualitative Analyse aus Sicht von Betroffenen, Angehörigen und Versorgern.

BACKGROUND: Numerous studies have shown that psoriasis is associated with severe losses in almost all dimensions of health-related quality of life. An important aspect is the stigmatization experience of those affected. OBJECTIVE: The aim of this study was to examine the perception of stigmatization from the perspective of patients, relatives and healthcare professionals using a qualitative approach. MATERIAL AND METHODS: Qualitative surveys in the form or focus groups and interviews with patients, relatives and healthcare providers were conducted. The data were analyzed by qualitative content analysis. RESULTS: The results show that stigmatization is perceived by all groups surveyed. It also became clear that self-stigmatization plays a special role. Affected persons, relatives and medical care providers described self-stigmatization as the greatest burden or restriction of affected persons in various areas of life, such as work, leisure and partnership. There were no crucial differences between sex or age groups. CONCLUSION: Possible knowledge deficits of non-affected persons and wrong assumptions of the affected persons about the attitudes of non-affected persons can be reduced, for example, in the context of encounters between affected persons and non-affected persons as well as between affected persons and medical care providers and thus reduce the public as well as the self-stigma.

Enhanced transmission through squeezed modes in a self-cladding magnonic waveguide.

We study spin-wave propagation in 360-nm wide Ni(80)Fe(20) nanowires using all-electrical spin-wave spectroscopy. Creating a zigzag-like magnetization state, we find enhanced spin-wave transmission compared to the states of more homogeneous magnetization. Micromagnetic simulations show that the spin waves propagate in narrow channels, which in particular, are remotely positioned from the edges. The internal channels reflect field-controlled self-cladding. Interestingly, rotation of the magnetic field at a specific value is found to vary the propagation velocity without changing the eigenfrequency. This opens the perspective of the velocity modulation transistor following a concept known from semiconductor electronics.

Spin wave diffraction and perfect imaging of a grating.

We study the diffraction of Damon-Eshbach-type spin waves incident on a one-dimensional grating realized by microslits in a thin Permalloy film. By means of time-resolved scanning Kerr microscopy, we observe unique diffraction patterns behind the grating which exhibit replications of the spin wave field at the slits. We show that these spin wave images, with details finer than the wavelength of the incident Damon-Eshbach spin wavelength, arise from the strongly anisotropic spin wave dispersion.

Evidence of a negative feedback system regulating the total beta-cell volume in nondiabetic rats that received pancreas transplants.

BACKGROUND: The aim of the present study was to investigate the long-term regulation of pancreatic beta-cell volume after pancreas transplantation into adult rats. METHODS: A syngeneic pancreaticoduodenal transplantation was made in normoglycemic Wistar-Furth rats. By this means, the recipients doubled their pancreatic islet volume. Nine months after transplantation, the total beta-cell volume was measured in serial pancreatic sections immunostained for insulin from both the native and transplanted pancreata, and in the native pancreas of age-matched Wistar-Furth rats that did not receive transplants. RESULTS: No changes in the volume of individual beta-cells were seen. A 50% decrease in total beta-cell volume was observed in both the native and transplanted pancreas when compared with that of age-matched controls. However, the combined beta-cell volumes of the native and transplanted pancreas in the rats that received transplants were similar to those of the native pancreas in control animals. No signs of increased apoptosis in any of the glands could be seen during the first postoperative week or after 9 months. CONCLUSIONS: These findings provide evidence of a negative feedback system, which regulates the total beta-cell volume to the levels seen in age-matched rats that did not receive transplants. The underlying mechanisms for the decreased beta-cell volume are unknown, but may involve a diminished replicatory rate of the beta-cells.

Hemophilus aphrophilus endocarditis with a probable primary dental focus of infection.

A case of Hemophilus aphrophilus endocarditis in association with a prosthetic valve is reported in which the organism was isolated from dental plaque as well as blood. We emphasize the need for treating the primary source of the infection; in this case, periodontal disease. To the best of our knowledge, this is the first reported case of H aphrophilus endocarditis in which an oral primary focus has been demonstrated.

The treatment of persistent knee effusions with intra-articular radioactive gold: preliminary report.

Eighteen chronic knee effusions unresponsive to the usual methods of therapy were treated by intra-articular injections of radioactive gold ((198)Au) and followed up for one year. Ten patients had classical rheumatoid arthritis; three intermittent hydrarthrosis (both knees were treated in one patient); two ankylosing spondylitis, and one synovitis of undetermined cause. In 12 knees the effusion completely disappeared, usually within three months. Temporary increased pain and swelling occurred during the first week in five cases. Radiation dosimetry is discussed in detail.

Treatment of persistent knee effusions with intra-articular radioactive gold.

Patients with a total of 112 chronic knee effusions unresponsive to the usual conservative methods of therapy were treated with intra-articular injections of radioactive gold and followed from 6 months to 5 years. Most patients in the study had rheumatoid arthritis but others had ankylosing spondylitis, psoriatic arthritis, intermittent hydrathrosis and undiagnosed synovitis. After 6 months 81% showed improvement. This figure diminished to approximately 70% at 1 and 2 years, 60% at 3 and 4 years and 50% at 5 years. The mose beneficial results were seen in patients with intermittent hydrarthrosis. Twelve patients with a synovial cyst and/or rupture improved. Patients with thin synovia and anatomic stage I or II disease did best, but those with stage III disease also did well. After the injection 33% of the patients had a reactive synovitis. A variable amount of radioactive material escaped from the knee to the regional lymph nodes and general circulation.

Clinical and roentgenographic aspects of pseudogout: a study of 50 cases and a review.

Pseudogout, defined as recurrent acute arthritis due to intrasynovial deposition of calcium pyrophosphate dihydrate crystals, is a relatively common arthritic disorder of the elderly. The clinical and roentgenographic aspects of 50 cases of pseudogout in hospitalized patients are reviewed in this paper. Oligoarticular and polyarticular episodes were observed in half of these patients. Antecedent problems included infection, trauma, surgery and vascular events. Consistent with previous reports, most patients had roentgenographic evidence of chondrocalcinosis. A third had asymptomatic capsular or periarticular calcific deposits or both, and a third had pyrophosphate arthropathy, a progressive, destructive, accelerated form of osteoarthritis. An attack of pseudogout may offer a clue to the presence of an unsuspected metabolic disease, such as primary hyperparathyroidism or idiopathic hemochromatosis.

Intubation via the LMA using a Cook retrograde intubation kit.

PURPOSE: We report two cases of difficult intubation where a laryngeal mask airway (LMA) was used and changed to a conventional endotracheal tube using a retrograde intubation set. CLINICAL FINDINGS: In two patients, following induction of anaesthesia, the trachea could not be intubated in the conventional fashion with a blade. In both patients an LMA was inserted to achieve an airway. In both patients intubation with a conventional endotracheal tube was required. A Cook Retrograde Intubation Kit and fibreoptic bronchoscope were used to change the LMA to conventional endotracheal tube without problems. CONCLUSION: The Cook retrograde intubation allows an LMA to be replaced with an endotracheal tube with an ID greater than 6 mm with a #3 or 7 mm with a #5 LMA. This technique places an exchange stylet into the airway which is superior to a conventional guidewire. This method allows the airway to be maintained until the LMA is exchanged with an endotracheal tube. Anaesthesia may be maintained and the airway instrumented without difficulty using this technique.

A role for calcium in stabilizing transport vesicle coats.

Calcium has been implicated in regulating vesicle fusion reactions, but its potential role in regulating other aspects of protein transport, such as vesicle assembly, is largely unexplored. We find that treating cells with the membrane-permeable calcium chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM), leads to a dramatic redistribution of the vesicle coat protein, coatomer, in the cell. We have used the cell-free reconstitution of coat-protomer I (COPI) vesicle assembly to characterize the mechanisms of this redistribution. We find that the recovery of COPI-coated Golgi vesicles is inhibited by the addition of BAPTA to the cell-free vesicle budding assay. When coatomer-coated membranes are incubated in the presence of calcium chelators, the membranes "uncoat," indicating that calcium is necessary for maintaining the integrity of the coat. This uncoating is reversed by the addition of calcium. Interestingly, BAPTA, a calcium chelator with fast binding kinetics, is more potent at uncoating the coatomer-coated membrane than EGTA, suggesting that a calcium transient or a calcium gradient is important for stabilizing COPI vesicle coat. The primary target for the effects of calcium on coatomer recruitment is a step that occurs after ADP-ribosylation factor binding to the membrane. We suggest that a calcium gradient may serve to regulate the timing of vesicle uncoating.

Multicenter dose-finding trial for thrombolysis with urokinase preactivated pro-urokinase (TCL 598) in acute myocardial infarction. German Preactivated Pro-Urokinase Study Group.

In a multicenter dose-finding study, the thrombolytic potency of urokinase preactivated pro-urokinase was evaluated. Sixty-two patients were randomly assigned to receive 250,000 U of urokinase plus either 4.5 mega U (group I: n = 33) or 6.5 mega U (group II: n = 29) of pro-urokinase. Patency rates were 36.4% (20.4-54.9%) vs. 54.5% (36.3-71.9%) (n = 27) at 60 minutes and 55.6% (32.5-70.6%) vs. 62.1% (42.3-79.3%) at 90 min into thrombolysis (n.s.). In a third group of 12 patients treated with 500,000 U of urokinase plus 6.5 mega U of pro-urokinase patency was achieved in 33.3% (9.9-65.1%) and 41.7% (15.2-72.3%) at 60 and 90 min, respectively. Patency rates at 24 hr follow-up angiography (n = 35) were 78.6% (49.2-95.3%), 85.7% (57.2-98.2%), and 85.7% (42.1-99.6%). Coagulation analysis in 37 patients revealed similar alterations in the three treatment groups with minor decreases in fibrinogen levels, moderate drops in plasminogen and alpha-2-antiplasmin levels, and moderate increases in the concentrations of the total fibrinogen/fibrin degradation products, the differences between the groups not being significant. Bleeding complications were observed in 12.9%, 13.8%, and 25% of patients in groups I, II, and III, respectively, mainly related to catheter sites. Hence, the safety profile of urokinase preactivated pro-urokinase seems comparable to other thrombolytic regimens. Reopening of occluded coronary arteries, however, is achieved relatively slowly. Thus, in its use for thrombolysis in myocardial infarction, urokinase preactivated pro-urokinase does not seem to offer superior advantages.

Polymorphic gene regulation and interindividual variation of UDP-glucuronosyltransferase activity in human small intestine.

UDP-glucuronosyltransferases (UGTs) convert dietary constituents, drugs, and environmental mutagens to inactive hydrophilic glucuronides. Recent studies have shown that the expression of the UGT1 and UGT2 gene families is regulated in a tissue-specific fashion. Human small intestine represents a major site of resorption of dietary constituents and orally administered drugs and plays an important role in extrahepatic UGT directed metabolism. Expression of 13 UGT1A and UGT2B genes coupled with functional and catalytic analyses were studied using 18 small intestinal and 16 hepatic human tissue samples. Hepatic expression of UGT gene transcripts was without interindividual variation. In contrast, a polymorphic expression pattern of all the UGT genes was demonstrated in duodenal, jejunal, and ileal mucosa, with the exception of UGT1A10. To complement these studies, interindividual expression of UGT proteins and catalytic activities were also demonstrated. Hyodeoxycholic acid glucuronidation, catalyzed primarily by UGT2B4 and UGT2B7, showed a 7-fold interindividual variation in small intestinal duodenal samples, in contrast to limited variation in the presence of 4-methylumbelliferone, a substrate glucuronidated by most UGT1A and UGT2B gene products. Linkage of RNA expression patterns to protein abundance were also made with several mono-specific antibodies to the UGTs. These results are in contrast to a total absence of polymorphic variation in gene expression, protein abundance, and catalytic activity in liver. In addition, the small intestine exhibits considerable catalytic activity toward most of the different classes of substrates accepted for glucuronidation by the UGTs, which is supported by immunofluorescence analysis of UGT1A protein in the mucosal cell layer of the small intestine. Thus, tissue-specific and interindividual polymorphic regulation of UGT1A and UGT2B genes in small intestine is identified and implicated as molecular biological determinant contributing to interindividual prehepatic drug and xenobiotic metabolism in humans.

Harm reduction: concepts and practice. A policy discussion paper.

This paper provides an overview of the context, definition, and key features of the harm reduction approach, and provides several examples of current programs in various countries. Both licit and illicit drugs are included in these illustrations. Some of the critical issues, and the strategies needed to advance harm reduction, are discussed. [Translations are provided in the International Abstracts Section of this issue.]

[Incidence of residual thrombi following successful thrombolytic therapy in acute myocardial infarct and their significance for the rate of early re-occlusion. A report of a multicenter dose-finding study for thrombolytic therapy with urokinase preactivated natural prourokinase (TCL 598)]. / Die Häufigkeit von Residualthromben nach erfolgreicher Thrombolysetherapie bei akutem Herzinfarkt und ihre Bedeutung für die Rate früher Reokklusionen. Ein Bericht von der multizentrischen Dosisfindungsstudie zur Thrombolysetherapie mit Urokinase-präaktivierter natürlicher Prourokinase (TCL 598).

Thrombolysis with urokinase preactivated prourokinase was performed in 74 patients. At control angiography, 90 min into thrombolysis, in 39 (52.7%) patients the infarct-related coronary artery was found patent. However, 26 out of the 39 patients (66.7%) with a patent infarct artery demonstrated angiographic signs of residual coronary thrombi. With an estimated average of 75 +/- 25% in both, patients with and without residual thrombus, the severity of the residual stenosis after thrombolysis was found to be independent from the presence of angiographic signs of residual coronary artery thrombosis. In patients with residual coronary thrombi, however, a trend towards poorer coronary perfusion was observed (50% vs 77% of the patients with prompt antegrade [TIMI grade III] perfusion [p less than 0.2]. Control angiography performed 24 to 36h after thrombolysis revealed reocclusion of the infarct artery in 26.3% of the patients with residual coronary thrombi, while none of the infarct vessels without angiographic signs of residual thrombosis had reoccluded (p less than 0.05). At follow-up angiography 17 to 23 days after thrombolysis this difference in the incidence of reocclusions had further increased to 43.8% of patients with vs 12.5% of patients without residual coronary thrombus (p less than 0.01). Thus, after thrombolysis, residual thrombotic material remaining in the infarct related vessel seems to be a major risk factor, indicating early reocclusion of the infarct artery.

Point mutations throughout the GLI3 gene cause Greig cephalopolysyndactyly syndrome.

Greig cephalopolysyndactyly syndrome, characterized by craniofacial and limb anomalies (GCPS; MIM 175700), previously has been demonstrated to be associated with translocations as well as point mutations affecting one allele of the zinc finger gene GLI3. In addition to GCPS, Pallister-Hall syndrome (PHS; MIM 146510) and post-axial polydactyly type A (PAP-A; MIM 174200), two other disorders of human development, are caused by GLI3 mutations. In order to gain more insight into the mutational spectrum associated with a single phenotype, we report here the extension of the GLI3 mutation analysis to 24 new GCPS cases. We report the identification of 15 novel mutations present in one of the patient's GLI3 alleles. The mutations map throughout the coding gene regions. The majority are truncating mutations (nine of 15) that engender prematurely terminated protein products mostly but not exclusively N-terminally to or within the central region encoding the DNA-binding domain. Two missense and two splicing mutations mapping within the zinc finger motifs presumably also interfere with DNA binding. The five mutations identified within the protein regions C-terminal to the zinc fingers putatively affect additional functional properties of GLI3. In cell transfection experiments using fusions of the DNA-binding domain of yeast GAL4 to different segments of GLI3, transactivating capacity was assigned to two adjacent independent domains (TA(1)and TA(2)) in the C-terminal third of GLI3. Since these are the only functional domains affected by three C-terminally truncating mutations, we postulate that GCPS may be due either to haploinsufficiency resulting from the complete loss of one gene copy or to functional haploinsufficiency related to compromised properties of this transcription factor such as DNA binding and transactivation.