Defining well-being in psoriasis: A Delphi consensus among healthcare professionals and patients.

Psoriasis is a chronic skin disease that negatively impacts on patient's life. A holistic approach integrating well-being assessment could improve disease management. Since a consensus definition of well-being in psoriasis is not available, we aim to achieve a multidisciplinary consensus on well-being definition and its components. A literature review and consultation with psoriasis patients facilitated the design of a two-round Delphi questionnaire targeting healthcare professionals and psoriasis patients. A total of 261 panellists (65.1% patients with psoriasis, 34.9% healthcare professionals) agreed on the dimensions and components that should integrate the concept of well-being: emotional dimension (78.9%) [stress (83.9%), mood disturbance (85.1%), body image (83.9%), stigma/shame (75.1%), self-esteem (77.4%) and coping/resilience (81.2%)], physical dimension (82.0%) [sleep quality (81.6%), pain/discomfort (80.8%), itching (83.5%), extracutaneous manifestations (82.8%), lesions in visible areas (84.3%), lesions in functional areas (85.8%), and sex life (78.2%)], social dimension (79.5%) [social relationships (80.8%), leisure/recreational activities (80.3%), support from family/friends (76.6%) and work/academic life (76.5%)], and satisfaction with disease management (78.5%) [treatment (78.2%), information received (75.6%) and medical care provided by the dermatologist (80.1%)]. This well-being definition reflects patients' needs and concerns. Therefore, addressing them in psoriasis will optimise management, contributing to better outcomes and restoring normalcy to the patient's life.

Consensus Statement on the Psychological Needs of Patients With Chronic Inflammatory Skin Diseases. / Documento de consenso sobre las necesidades psicológicas de los pacientes con enfermedades inflamatorias crónicas dermatológicas.

OBJECTIVE: To establish recommendations to determine, identify, and manage the psychological and emotional needs of patients with chronic inflammatory skin diseases in clinical practice. METHODS: A guided discussion was held at meeting of a nominal group of expert dermatologists and psychologists on the psychological and emotional needs of patients with chronic inflammatory skin diseases, how to manage these cases, and which referral criteria to employ. Based on the results of the discussion, and with the aid of a patient focus group and a review of the literature, a master document was drawn up with recommendations for discussion. A Delphi survey was circulated among a larger group of dermatologists and psychologists to assess the level of agreement with the recommendations. RESULTS: Ten recommendations were established and can be summarized as follows: explore the psychological sphere of the patients with open questions at the time of diagnosis and during the course of the disease; provide patients with clear explanations that address their concerns and inform them of the existence of patient associations; investigate symptoms of anxiety and depression and, if confirmed by means of a Hospital Anxiety and Depression score (HADS) of 11 or greater, consider referral to a mental-health specialist; and, during visits, create a climate of trust, empathize with patients, agree goals and treatment options with them, and motivate them to adhere to those treatments. CONCLUSIONS: These recommendations may help health care professionals address psychological and emotional aspects of their patients in daily clinical practice.

Role of the Benzodioxole Group in the Interactions between the Natural Alkaloids Chelerythrine and Coptisine and the Human Telomeric G-Quadruplex DNA. A Multiapproach Investigation.

The binding properties toward the human telomeric G-quadruplex of the two natural alkaloids coptisine and chelerythrine were studied using spectroscopic techniques, molecular modeling, and X-ray diffraction analysis. The results were compared with reported data for the parent compounds berberine and sanguinarine. Spectroscopic studies showed modest, but different rearrangements of the DNA-ligand complexes, which can be explained considering particular stereochemical features for these alkaloids, in spite of the similarity of their skeletons. In fact, the presence of a dioxolo moiety rather than the two methoxy functions improves the efficiency of coptisine and sanguinarine in comparison to berberine and chelerythrine, and the overall stability trend is sanguinarine > chelerythrine ≈ coptisine > berberine. Accordingly, the X-ray diffraction analysis confirmed the involvement of the benzodioxolo groups in the coptisine/DNA binding by means of π···π, O···π, and CH···O interactions. Similar information is provided by modeling studies, which, additionally, evidenced reasons for the quadruplex vs double-helix selectivity shown by these alkaloids. Thus, the analyses shed light on the key role of the benzodioxolo moieties in strengthening the interaction with the G4-folded human telomeric sequence and indicated the superior G4 stabilizing properties of the benzophenanthridine scaffold with respect to the protoberberine one and conversely the better G4 vs dsDNA selectivity profile of coptisine over the other alkaloids.

6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 is essential for p53-null cancer cells.

The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 (PFKFB4) controls metabolic flux through allosteric regulation of glycolysis. Here we show that p53 regulates the expression of PFKFB4 and that p53-deficient cancer cells are highly dependent on the function of this enzyme. We found that p53 downregulates PFKFB4 expression by binding to its promoter and mediating transcriptional repression via histone deacetylases. Depletion of PFKFB4 from p53-deficient cancer cells increased levels of the allosteric regulator fructose-2,6-bisphosphate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose-phosphate pathway. PFKFB4 was also required to support the synthesis and regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) in p53-deficient cancer cells. Moreover, depletion of PFKFB4-attenuated cellular biosynthetic activity and resulted in the accumulation of reactive oxygen species and cell death in the absence of p53. Finally, silencing of PFKFB4-induced apoptosis in p53-deficient cancer cells in vivo and interfered with tumour growth. These results demonstrate that PFKFB4 is essential to support anabolic metabolism in p53-deficient cancer cells and suggest that inhibition of PFKFB4 could be an effective strategy for cancer treatment.

The Spanish Psoriasis Patients' Association According to Its Members: Cross-Sectional Descriptive Study of Members' Opinions of the Association's Functions. / Función y respaldo a la asociación de pacientes con psoriasis en España según sus miembros: estudio descriptivo transversal.

INTRODUCTION: Patient associations form part of health care systems, but little is known about how their members' view the functionality of these associations and whether they endorse their goals and activities. OBJECTIVE: To study how the members of the leading Spanish association of patients with psoriasis and their relatives view the group's functioning. MATERIAL AND METHODS: Survey study using a self-administered questionnaire answered by members of the association (total membership, 26 349 persons). The credibility of the association and respondents' confidence in and satisfaction with it were studied and compared with their attitudes toward other agents in the health care system. A Rasch model was used to analyze respondents' ranking of functions. Analysis of variance was used to study between-group differences. RESULTS: A total of 746 members participated (response rate 2.83%). The association's credibility was rated in second place, after that of specialists who treat psoriasis. Support for the association functions was good (7.53 on a scale of 0 to 10). The function the members rated highest was the raising of societal awareness of psoriasis and its problems. Rated lowest were functions related to personal services for members. Educational level was the only participant factor associated with significant differences in evaluations (P<.05). CONCLUSIONS: The psoriasis association contributes by disseminating information about the disease and patient care, and it serves to represent patients. Health professionals and institutions should take the association into account in their efforts to deal with the disease and in designing effective policies.

Patient perspectives on triggers, adherence to medical recommendations, and disease control in atopic dermatitis: the DATOP study.

INTRODUCTION AND OBJECTIVES: To analyze the triggers of atopic dermatitis (AD), adherence to medical recommendations, disease control, and health-related quality of life (HRQOL) from the patient's perspective. PATIENTS AND METHODS: This was a multicenter, cross-sectional, epidemiological study with the participation of adults (age >16 years; n=125) and children (age, 2-15 years, n=116). Patients had a history of at least 12 months of moderate to severe AD with a moderate to severe flare (Investigator Global Assessment score>2) at the time of recruitment. The Mann-Whitney U test was used to evaluate relationships between disease severity, determined according to the Scoring in Atopic Dermatitis index, and triggers reported by patients, adherence to recommendations and pharmacological therapy, HRQOL, and patient-perceived control. RESULTS: The most common triggers were cosmetic products, clothing, mites, detergents/soaps, and changes in temperature. In 47.2% of adults and 39.7% of children, pharmacological therapy was not initiated at flare onset. Adherence was highest to pharmacological therapy, skin moisturizing, and medical care recommendations. Disease control was considered insufficient by 41.6% of adults and 27. 6% of pediatric patients and, in adults, this was associated with the severity of AD (P=.014). CONCLUSIONS: The therapeutic control of AD is susceptible to improvement, especially in adults. Although patients state that they follow medical recommendations, a significant percentage of patients do not apply recommended treatments correctly. Better education about the disease and its management would appear to be necessary to improve disease control and HRQOL.

Cumulative life course impairment: the imprint of psoriasis on the patient's life.

We now realize that moderate to severe psoriasis takes a toll on the patient's overall health beyond the effects on the skin itself, and so we use quality of life (QOL) measures to assess how the individual perceives both the impact of disease and the response to treatment. However, available instruments give us a cross-sectional assessment of QOL at a specific moment, and we lack longitudinal studies of how a disease affects each and every aspect of a patient's life over time-including physical and psychological wellbeing, social and emotional relationships, vocational and employment decisions, and how they change the individual's outlook. A new concept, cumulative life course impairment (CLCI), captures the notion of the ongoing effect of a disease, providing us with a new paradigm for assessing the impact of psoriasis on QOL. Unlike conventional measurement tools and scales, which focus on a specific moment in the patient's life, a CLCI tool investigates the repercussions of disease that accumulate over a lifetime, interfering with the individual's full potential development and altering perspectives that might have been different had psoriasis not been present. The accumulated impact will vary from patient to patient depending on circumstances that interact differently over time as the burden of stigmatization, concomitant physical and psychological conditions associated with psoriasis, coping mechanisms, and external factors come into play and are modulated by the individual's personality.

Health-related quality of life, patient satisfaction, and adherence to treatment in patients with moderate or severe atopic dermatitis on maintenance therapy: the CONDA-SAT study.

OBJECTIVE: To evaluate health-related quality of life (HRQOL), patient satisfaction, and adherence to treatment in patients with moderate or severe atopic dermatitis on maintenance therapy. MATERIAL AND METHODS: We performed a national, multicenter, cross-sectional, epidemiological study in adults and children with moderate or severe atopic dermatitis of at least 16 months' duration who were receiving maintenance therapy. We used the Dermatology Life Quality Index (DLQI), the children's version of this scale (cDLQI), and the Morisky medication adherence scale. Visual analog scales were used to measure treatment satisfaction. We used the Mann-Whitney U test to compare HRQOL between patients with moderate and severe disease and the Wilcoxon test to compare the frequency and duration of flares before and after the start of maintenance therapy. RESULTS: We studied 141 children and 141 adults; the prevalence of moderate AD in these groups was 85.8% and 79.4%, respectively. The impact of AD on HRQOL was mild to moderate. Maintenance therapy led to a significant decrease in the frequency and duration of flares (P < .001). While treatment satisfaction was high in both groups, adherence was poor (18.4%-42.6% in children and 14.9%-27.0% in adults). CONCLUSIONS: Patients with moderate and severe AD receiving maintenance therapy experience a reduction in the number and duration of flares and an improvement in HRQOL. While treatment satisfaction is high, adherence rates could be improved.

Restoration of hepatic glycogen deposition reduces hyperglycaemia, hyperphagia and gluconeogenic enzymes in a streptozotocin-induced model of diabetes in rats.

AIMS/HYPOTHESIS: Glycogen deposition is impaired in diabetes, thus contributing to the development of hyperglycaemia. Several glucose-lowering strategies have attempted to increase liver glycogen deposition by modulating targets, which eventually trigger the activation of liver glycogen synthase (LGS). However, these targets also alter several other biological processes, and therefore their therapeutic use may be limited. Here we tested the approach of directly activating LGS and evaluated the potential of this strategy as a possible treatment for diabetes. METHODS: In this study, we examined the efficacy of directly overproducing a constitutively active form of LGS in the liver to ameliorate streptozotocin-induced diabetes in rats. RESULTS: Activated mutant LGS overproduction in the liver of streptozotocin-induced diabetic rats normalised liver glycogen content, despite low levels of glucokinase and circulating insulin. Moreover, this overproduction led to a decrease in food intake and in the production of the main gluconeogenic enzymes, glucose-6-phosphatase, fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase. The resulting combined effect was a reduction in hyperglycaemia. CONCLUSIONS/INTERPRETATION: The restoration of liver glycogen ameliorated diabetes and therefore is considered a potential strategy for the treatment of this disease.

The role of transmembrane protein 27 (TMEM27) in islet physiology and its potential use as a beta cell mass biomarker.

AIMS/HYPOTHESIS: Transmembrane protein 27 (TMEM27) is a membrane protein cleaved and shed by pancreatic beta cells that has been proposed as a beta cell mass biomarker. Despite reports of its possible role in insulin exocytosis and cell proliferation, its function in beta cells remains controversial. We aimed to characterise the function of TMEM27 in islets and its potential use as a beta cell mass biomarker. METHODS: To determine TMEM27 function, we studied TMEM27 gene expression and localisation in human healthy and diabetic islets, the correlation of its expression with cell cycle and insulin secretion genes in human islets, its expression in tungstate-treated rats, and the effects of its overproduction on insulin secretion and proliferation in a beta cell line and islets. To elucidate its utility as a beta cell mass biomarker, we studied TMEM27 cleavage in a beta cell line, islets and primary proximal tubular cells. RESULTS: TMEM27 mRNA levels in islets are lower in diabetic donors than in controls. Its gene expression correlates with that of insulin and SNAPIN in human islets. TMEM27 expression is downregulated in islets of tungstate-treated rats, which exhibit decreased insulin secretion and increased proliferation. TMEM27 overproduction in a beta cell line and islets significantly enhanced glucose-induced insulin secretion, with modest or no effects on proliferation. Finally, TMEM27 is cleaved and shed by renal proximal tubular cells and pancreatic islets. CONCLUSIONS/INTERPRETATION: Our data support a role for TMEM27 in glucose-induced insulin secretion but not in cell proliferation. The finding that its cleavage is not specific to beta cells challenges the current support for its use as a potential beta cell mass biomarker.

A survey of Cambodian health-care providers' HIV knowledge, attitudes and intentions to take a sexual history.

Cambodia has one of the highest prevalence rates of HIV in Asia and is scaling up HIV testing. We conducted a cross-sectional survey with 358 health care providers in Phnom Penh, Cambodia to assess readiness for voluntary testing and counselling for HIV. We measured HIV knowledge and attitudes, and predictors of intentions to take a sexual history using the Theory of Planned Behaviour. Over 90% of health care providers correctly answered knowledge questions about HIV transmission, but their attitudes were often not positive towards people living with HIV. The Theory of Planned Behaviour constructs explained 56% of the variance in intention to take a sexual history: the control providers perceive they have over taking a sexual history was the strongest contributor (51%), while social pressure explained a further 3%. Attitudes about taking a sexual history did not contribute to intention. Interventions with Cambodian health care providers should focus on improving skills in sexual history-taking.

Severe Vaso-Occlusive Episodes Associated with Use of Systemic Corticosteroids in Patients with Sickle Cell Disease.

Patients with sickle cell disease (SCD) are occasionally prescribed systemic corticosteroids to treat steroid-responsive conditions. Additionally, use of systemic corticosteroids for sickle cell pain episodes and acute chest syndrome is under investigation. We report 4 patients with SCD who developed severe vaso-occlusive events following the administration of systemic steroids. We also review similar cases from the literature and suggest measures for reducing the potential risk associated with use of systemic corticosteroids in this group of patients. We conclude that corticosteroids should be used with caution in patients with SCD.

Clinical characteristics and psychopathological profile of patients with vulvodynia: an observational and descriptive study.

BACKGROUND: Vulvodynia is a fairly common dermatological symptom that often interferes with the personal, social and working activities of affected women and results in a significant loss of their quality of life. It is a persistent and tedious clinical disorder which is often resistant to conventional treatments. OBJECTIVES: The aim of this study is to evaluate the main clinical signs, associated psychopathological disorders and outcome after antidepressant treatment of patients with vulvodynia. METHODS: Eighty patients were included. Clinical characteristics and psychopathological profiles were determined by appropriate instruments. The improvement of clinical symptoms after combined antidepressant drug therapy was also evaluated. RESULTS: Pain (70%), burning (63.7%), dyspareunia (57.5%) and stinging (56.2%) were the most commonly reported symptoms. Most patients (56.5%) showed anxiety, and 52.2% of them were reported as having a depression disorder. When evaluated by psychometric tools, 81.4% of patients scored >150 on the Life Event Scale, which means a risk >50% of suffering an illness in the near future, and patients' scores in the Dermatology Life Quality Index showed higher values than the mean of the Spanish validation group. After 6 months of combined treatment with escitalopram (10-20 mg/day), perfenazine (2-4 mg/day) and amytriptiline (10 mg/day), a complete remission of the clinical symptoms was achieved in 41% of patients. In contrast, only 12% of patients who did not follow drug treatment reported a complete resolution of the clinical symptoms. CONCLUSIONS: Our results seem to confirm that vulvodynia is associated with psychiatric co-morbidity such as stress and depression. The study highlights that the psychiatric treatment may be a useful option to improve clinical symptoms. Whether these patients should be evaluated for depression or be referred to a psychiatrist, remains to be investigated.

[The management of stroke in Phnom Penh, Cambodia]. / Prise en charge des accidents vasculaires cérébraux à Phnom Penh, Cambodge.

Stroke ranks first among nervous pathologies in Kampuchea. It's a main cause of disability and mortality in our country. We conducted a prospective study including 100 patients hospitalized in the service of general medicine at the Calmette hospital in Phnom Penh. We analyzed the principal risk factors, clinical signs, nature of stroke, complications and markers of the vital and functional prognosis. This work shows the difficulties encountered in the initial care of stroke: delay or absence of hospitalization, cost of complementary examinations to be carried out to determine the nature and the aetiology of stroke and very low level of follow-up to ensure secondary prevention and functional rehabilitation. It can be explained in part by the socioeconomic and cultural level. Research like this one which assesses local needs for stroke prevention, treatment and rehabilitation should be conducted in developing countries to inform the planning and allocation of health care resources in order to reduce the burden of illness associated with stroke. The progressive improvement of the medical structures, and of the socioeconomic and cultural level will facilitate stroke care management.

[Therapy of dyslipidemia in post-infarction: state of the art]. / Terapia delle dislipidemie nel post-infarto: stato dell'arte.

Between the risks factors involved in the atherogenesis LDL-cholesterol is determinant because highly associated to cardiovascular events. The primary target for the prevention of coronary diseases is a reduction of LDL-cholesterol because that reduces the cardiovascular mortality and the total mortality. The NCEP ATP III 2004 guide-lines propose as therapeutic target for the high-risk patients the reduction of plasma levels of LDL-cholesterol under 100 mg/dl and according to new trials under 70 mg/dl. The dyslipidaemia treatments are based on two approaches, i.e., the therapeutic lifestyle change and the pharmacological therapy. The available drugs are statins, fibrates, anion exchange resins, nicotinic acid. In the acute coronary syndrome patients is desirable to start immediately a therapy with statins since the hospital phase and direct the treatment to aggressive therapy. Unfortunately, the statin doses used in the most secondary prevention trials allow to get LDL-cholesterol under 100 mg/dl in the only half high-risk patients. The innovative therapeutic approach to hypercholesterolemia today is based on a double inhibition of cholesterol synthesis and absorption combining a statin with ezetimibe.

[Analysis of prescription patterns of antipsychotic agents in psychiatry]. / Análisis de los patrones de prescripción de antipsicóticos en psiquiatría.

INTRODUCTION: We describe the different diseases in which conventional and second generation antipsychotic (APS) prescriptions are made. METHOD: Observational, retrospective, multicenter study based on the review of 300 clinical records of public and private sites, hospital and out-patient clinics, located in Salamanca, Vigo, Bilbao, Barcelona, Valencia, Oviedo and Malaga. RESULTS: The mean age of the population studied was 42 +/- 17 years; 56.6 % were men. Atypical drugs (67 %) were used basically versus classical ones (33 %). Classical APS are basically prescribed in bipolar disorder with/without psychotic symptoms (20.6 %), schizophrenia (18.3%) and delusional disorder (11.5 %). Atypical APS are fundamentally prescribed in schizophrenia (31.5 %), bipolar disorders with/without psychotic symptoms (12.5 %) and other psychotic disorders (8.9 %). When the psychotic disorders are considered by groups (schizophrenia, bipolar disorder with psychotic symptoms, delusional disorder and other psychotic disorders), classical APS are used in 47.4 % and atypical APS in 62.5%. APS were used ((outside the indication)) (off-label) in 32.8%, including resistant depressions, serious obsessive-compulsive disorder and borderline personality disorder, with similar percentages for both conventional and atypical ones. In dementia, atypical APS were used in 5.1 % versus 1.5 % of the conventional ones. The most frequent reasons for prescription of classical APS were control of psychotic symptoms (33.6 %), aggressiveness-agitation (31.3 %), severe insomnia (16 %), impulsivity (6.9 %) and severe anxiety (6.1 %). Atypical APS were preferably used in the control of psychotic symptoms (58.8%) and aggressiveness-agitation (25.5%). CONCLUSIONS: The use of APS basically occurs within their authorized indications (67.2 %). The off-label use (32.8 %) occurs both for the classical as well as atypical APS and occurs in serious diseases in which there are no alternative treatments.

[Quality of life and social functioning in schizophrenic patients treated with olanzapine: 1 year follow-up naturalistic study]. / Calidad de vida y funcionamiento social en pacientes con esquizofrenia en monoterapia con olanzapina: estudio naturalístico de 1 año de seguimiento.

OBJECTIVE: To measure health related quality of life (HRQL) and social functioning in schizophrenic patients treated with olanzapine under regular clinical practice conditions. METHODS: Out-patients diagnosed of schizophrenia and beginning treatment with olanzapine, quetiapine, risperidone or typical oral antipsychotics were included. Information on socio-demographic characteristics was obtained and in each visit (baseline, 3, 6 and 12 months) they were administered the generic HRQL questionnaire Euro-QoL-5D (EQ-5D) and the Social Functioning Scale (SFS). RESULTS: A total of 1,198 patients were followed-up for 12 months. Mean age (SD) was 38.6 (13.3) years and 62.9 % of them were men. In basal conditions the most affected dimensions of EQ-5D were anxiety/depression (76 %), and daily activities (73.6 %). After 12 months treatment the cohort of patients treated with olanzapine showed a better HRQL in the self-care dimension compared to all other treatments (p < 0.05), and in the dimensions of pain/discomfort, anxiety/depression and usual activities compared to the group treated with quetiapine and risperidone (p < 0.05). The Visual Analogue Scale (VAS) of the EQ-5D questionnaire showed a better health state after 12 months in the group treated with olanzapine compared to the groups of quetiapine or risperidone (p < 0.05). The SFS showed a better improvement in the cohort of olanzapine in the three studied dimensions after 12 months: isolation and social relationships in comparison to the risperidone group (p < 0.05), interpersonal communication in comparison to the risperidone and quetiapine group (p < 0.05) and independence performance in comparison to all the other treatments (p < 0,05). CONCLUSION: Schizophrenic patients treated with olanzapine for one year show a better improvement in HRQL and social functioning than those treated with other antipsychotics.