[Effects of a smoke-free policy on healthcare staff attitudes and aggression in psychiatry]. / Effecten van een rookvrijbeleid op attitudes zorgpersoneel en agressie in de psychiatrie.

Background The prevalence of smoking among patients with psychiatric disorders is 3-4 times higher than the general population. However, smoking is still permitted in many psychiatric clinics. The National Prevention Agreement (2018) mandates that all psychiatric wards be smoke-free by 2025. The UMC Utrecht clinics have been smoke-free since November 2020. Aim To examine healthcare workers’ attitudes before and after implementing the smoke-free policy. Method In an observational study with quantitative data analysis, data were collected in one center from healthcare workers in psychiatry departments with surveys. We collected demographic information, smoking status, attitudes towards the smoke-free policy, and its impact on patients and care. Incidents of aggression were prospectively recorded and reported in the MAP (aggression incidents in patient care). Results Out of 172 healthcare workers invited to participate, 30% (n = 52) completed the pre-implementation survey, and 20% (n = 34) completed the post-implementation survey. Prior to implementation, 62% (n = 32/52) of healthcare workers had a positive attitude towards the smoke-free policy, which increased to 77% (n = 26/34) post-implementation. Expectations of increased aggression incidents were reported by 62% (n = 32/52) during the pre-implementation phase. The number of aggression incidents was 46 in the one-year period before implementation (November 2019 – February 2020) and 45 incidents after implementation (November 2020 – February 2021). Conclusion This study supports the implementation of a smoke-free policy in psychiatric clinics due to the lack of a significant increase in aggression incidents. Healthcare workers perceived this outcome and observed quicker granting of ‘green’ freedoms.

[Translated article] Drug Survival in Cyclosporine Treatment for Moderate to Severe Atopic Dermatitis: Analysis of the Spanish Atopic Dermatitis Registry (BIOBADATOP).

BACKGROUND: The past 5 years have seen a proliferation of new treatments for atopic dermatitis (AD). We analyzed recent drug survival data for cyclosporine in this setting. Because the Spanish National Healthcare system requires patients with AD to be treated with cyclosporine before they can be prescribed other systemic treatments, drug survival for cyclosporine may be shorter than in other diseases. MATERIAL AND METHOD: Multicenter, observational, prospective cohort study using data from the Spanish Atopic Dermatitis Registry (BIOBADATOP). Data from the Spanish Registry of Systemic Treatments in Psoriasis (BIOBADADERM) were used to create a comparison cohort. RESULTS: We analyzed data for 130 patients with AD treated with cyclosporine (median drug survival, 1 year). Median cyclosporine survival in the psoriasis comparison group (150 patients) was 0.37 years. Drug survival was significantly longer in AD than in psoriasis (P<.001). CONCLUSION: Drug survival of cyclosporine in the BIOBADATOP registry is similar to that described in other series of patients with AD and longer than that observed in the BIOBADADERM psoriasis registry.

Drug Survival in Cyclosporine Treatment for Moderate to Severe Atopic Dermatitis: Analysis of the Spanish Atopic Dermatitis Registry (BIOBADATOP). / Supervivencia de la ciclosporina en el tratamiento de la dermatitis atópica moderada-grave: Registro Español de Dermatitis Atópica (BIOBADATOP).

BACKGROUND: The past 5 years have seen a proliferation of new treatments for atopic dermatitis (AD). We analyzed recent drug survival data for cyclosporine in this setting. Because the Spanish National Healthcare system requires patients with AD to be treated with cyclosporine before they can be prescribed other systemic treatments, drug survival for cyclosporine may be shorter than in other diseases. MATERIAL AND METHOD: Multicenter, observational, prospective cohort study using data from the Spanish Atopic Dermatitis Registry (BIOBADATOP). Data from the Spanish Registry of Systemic Treatments in Psoriasis (BIOBADADERM) were used to create a comparison cohort. RESULTS: We analyzed data for 130 patients with AD treated with cyclosporine (median drug survival, 1 year). Median cyclosporine survival in the psoriasis comparison group (150 patients) was 0.37 years. Drug survival was significantly longer in AD than in psoriasis (P<.001). CONCLUSION: Drug survival of cyclosporine in the BIOBADATOP registry is similar to that described in other series of patients with AD and longer than that observed in the BIOBADADERM psoriasis registry.

[Translated article] Acne Fulminans: A Narrative Review.

Acne fulminans is a severe and rare form of inflammatory acne. Lesion severity and subsequent scarring has a negative impact on the patient's quality of life. We conducted a narrative review of the literature on acne fulminans based on a search for relevant English- and Spanish-language articles published in Medline. We included case reports and case series. The main aim was to describe the clinical and demographic characteristics of patients with acne fulminans. A secondary aim was to determine whether quality of life was affected by the site or extent of lesions. We reviewed 91 articles describing 212 cases of acne fulminans. The mean age of the patients (91.94% male) was 16.6 years. A personal and family history of acne vulgaris was reported for 97.63% and 54.90% of patients, respectively. A trigger was identified in 44.79% of cases. The main cause was pharmacologic (96.63%) and the main drug isotretinoin (65.28%). The sites most often affected were the face (89.31%), the posterior trunk (77.86%), and the anterior trunk (74.81%). The predominant disease subtype was acne fulminans with systemic symptoms (59.12%), which were mostly general (97.06%). Systemic corticosteroids were the most widely used treatment (81.03%). The impact of the disease on quality of life was reported for two patients. In conclusion, acne fulminans mainly affects the face and trunk of male adolescents with a history of acne vulgaris. The main subtype was acne fulminans with systemic symptoms, and most patients were treated with systemic corticosteroids. The effect of acne fulminans on quality of life is under-reported.

Acne Fulminans: A Narrative Review. / Acné fulminans: revisión narrativa de la literatura.

Acne fulminans is a severe and rare form of inflammatory acne. Lesion severity and subsequent scarring has a negative impact on the patient's quality of life. We conducted a narrative review of the literature on acne fulminans based on a search for relevant English- and Spanish-language articles published in Medline. We included case reports and case series. The main aim was to describe the clinical and demographic characteristics of patients with acne fulminans. A secondary aim was to determine whether quality of life was affected by the site or extent of lesions. We reviewed 91 articles describing 212 cases of acne fulminans. The mean age of the patients (91.94% male) was 16.6 years. A personal and family history of acne vulgaris was reported for 97.63% and 54.90% of patients, respectively. A trigger was identified in 44.79% of cases. The main cause was pharmacologic (96.63%) and the main drug isotretinoin (65.28%). The sites most often affected were the face (89.31%), the posterior trunk (77.86%), and the anterior trunk (74.81%). The predominant disease subtype was acne fulminans with systemic symptoms (59.12%), which were mostly general (97.06%). Systemic corticosteroids were the most widely used treatment (81.03%). The impact of the disease on quality of life was reported for 2 patients. In conclusion, acne fulminans mainly affects the face and trunk of male adolescents with a history of acne vulgaris. The main subtype was acne fulminans with systemic symptoms, and most patients were treated with systemic corticosteroids. The effect of acne fulminans on quality of life is underreported.

BIOBADATOP Spanish Atopic Dermatitis Registry: Description and Early Findings. / BIOBADATOP: Registro Español de Dermatitis Atópica. Descripción y primeros resultados.

BACKGROUND: In recent years, remarkable improvements in our understanding of atopic dermatitis (AD) have revolutionized treatment perspectives, but access to reliable data from clinical practice is essential. MATERIALS AND METHOD: The Spanish Atopic Dermatitis Registry, BIOBADATOP, is a prospective, multicenter database that collects information on patients of all ages with AD requiring systemic therapy with conventional or novel drugs. We analyzed the registry to describe patient characteristics, diagnoses, treatments, and adverse events (AEs). RESULTS: We studied data entries for 258 patients who had received 347 systemic treatments for AD. Treatment was discontinued in 29.4% of cases, mostly due to a lack of effectiveness (in 10.7% of cases). A total of 132 AEs were described during follow-up. Eighty-six AEs (65%) were linked to a systemic treatment, most commonly dupilumab (39AEs) and cyclosporine (38AEs). The most common AEs were conjunctivitis (11patients), headache (6), hypertrichosis (5), and nausea (4). There was 1severe AE (acute mastoiditis) associated with cyclosporine. CONCLUSIONS: Initial findings on AEs from the Spanish BIOBADATOP registry are limited by short follow-up times precluding comparisons or calculation of crude and adjusted incidence rates. At the time of our analysis, no severe AEs had been reported for novel systemic therapies. BIOBADATOP will help answer questions on the effectiveness and safety of conventional and novel systemic therapies in AD.

Longitudinal associations between alcohol use, smoking, genetic risk scoring and symptoms of depression in the general population: a prospective 6-year cohort study.

BACKGROUND: Alcohol consumption, smoking and mood disorders are leading contributors to the global burden of disease and are highly comorbid. Yet, their interrelationships have remained elusive. The aim of this study was to examine the multi-cross-sectional and longitudinal associations between (change in) smoking and alcohol use and (change in) number of depressive symptoms. METHODS: In this prospective, longitudinal study, 6646 adults from the general population were included with follow-up measurements after 3 and 6 years. Linear mixed-effects models were used to test multi-cross-sectional and longitudinal associations, with smoking behaviour, alcohol use and genetic risk scores for smoking and alcohol use as independent variables and depressive symptoms as dependent variables. RESULTS: In the multi-cross-sectional analysis, smoking status and number of cigarettes per day were positively associated with depressive symptoms (p < 0.001). Moderate drinking was associated with less symptoms of depression compared to non-use (p = 0.011). Longitudinally, decreases in the numbers of cigarettes per day and alcoholic drinks per week as well as alcohol cessation were associated with a reduction of depressive symptoms (p = 0.001-0.028). Results of genetic risk score analyses aligned with these findings. CONCLUSIONS: While cross-sectionally smoking and moderate alcohol use show opposing associations with depressive symptoms, decreases in smoking behaviour as well as alcohol consumption are associated with improvements in depressive symptoms over time. Although we cannot infer causality, these results open avenues to further investigate interventions targeting smoking and alcohol behaviours in people suffering from depressive symptoms.

Effect of Drug Compounding on Quality of Life in Patients With Genodermatoses: A Cross-Sectional Study. / Formulación magistral en pacientes con genodermatosis. Impacto en la calidad de vida: un estudio transversal.

BACKGROUND: Cutaneous manifestations are complicated to treat in rare diseases. The main aim of this study was to analyze the impact of compounded drugs prepared by hospital pharmacists on the quality of life of patients with genodermatoses. MATERIAL AND METHODS: We undertook a cross-sectional study of patients with genodermatoses treated with topical medications compounded and dispensed by the pharmacy at Complejo Hospitalario Universitario in Pontevedra, Spain. We collected demographic data and answers to questionnaires examining generic and disease-specific quality of life, treatment satisfaction, and treatment adherence. RESULTS: Nine patients were included. We observed a significant improvement in health-related quality of life following treatment with compounded drugs. Satisfaction with the topical medications was 2.8 on a scale of 0 (greatest satisfaction) to 25. Treatment adherence was 59%. CONCLUSIONS: Drug compounding facilitates access to orphan drugs that are not available for many rare diseases. Few studies, however, have analyzed impact on quality of life in this setting. In this series of patients with genodermatoses, topical medications compounded and dispensed by a hospital pharmacy improved health-related quality of life. This preliminary study has given rise to a multicenter study of compounding for ichthyosis. We expect that analysis of a larger sample will confirm our findings.

Intraoperative crystalloid utilization variability and association with postoperative outcomes: A post hoc analysis of two multicenter prospective cohort studies.

BACKGROUND: The optimal regimen for intravenous administration of intraoperative fluids remains unclear. Our goal was to analyze intraoperative crystalloid volume administration practices and their association with postoperative outcomes. METHODS: We extracted clinical data from two multicenter observational studies including adult patients undergoing colorectal surgery and total hip (THA) and knee arthroplasty (TKA). We analyzed the distribution of intraoperative fluid administration. Regression was performed using a general linear model to determine factors predictive of fluid administration. Patient outcomes and intraoperative crystalloid utilization were summarized for each surgical cohort. Regression models were developed to evaluate associations of high or low intraoperative crystalloid with the likelihood of increased postoperative complications, mainly acute kidney injury (AKI) and hospital length of stay (LOS). RESULTS: 7580 patients were included. The average adjusted intraoperative crystalloid infusion rate across all surgeries was to 7.9 (SD 4) mL/kg/h. The regression model strongly favored the type of surgery over other patient predictors. We found that high fluid volume was associated with 40% greater odds ratio (OR 1.40; 95% confidence interval 1.01-1.95, p = 0.044) of postoperative complications in patients undergoing THA, while we found no associations for the other types of surgeries, AKI and LOS CONCLUSIONS: A wide variability was observed in intraoperative crystalloid volume administration; however, this did not affect postoperative outcomes.

Postoperative radiotherapy after flap reconstructive surgery in patients with head and neck cancer: A retrospective monocentric study with flap delineation to assess toxicity and relapse.

PURPOSE: Flaps are increasingly used during reconstructive surgery of head and neck cancers to improve functional outcomes. There are no guidelines as to whether the whole flap or its anastomotic border should be included in the primary tumour target volume of postoperative radiotherapy to prevent local relapses. Relapse and toxicity rates can increase substantially if the whole flap received full dose. Our aim was to determine whether flaps were included in the primary tumour target volume and to report the patterns of relapse and toxicity. MATERIALS AND METHODS: Consecutive patients in 2014 through 2016, with or without a flap, receiving postoperative radiotherapy were selected in a retrospective monocentric control study. Flaps were homogenously delineated blind to treating radiation oncologists using a flap-specific atlas. Tumour recurrence, acute and late toxicity were evaluated using univariate and propensity score analyses. RESULTS: A hundred patients were included; 54 with a flap. Median flap volume included in the tumour volume was 80.9%. Twelve patients experienced local recurrences: six with a flap, among whom two within their flap (3.7%). Patients with flaps had larger median tumour volumes to be irradiated (25cm3 versus 58cm3, p<0.001) and higher acute/late toxicity rates (p<0.001) even after adjustment on biases (more advanced T stage, oral cavity, active smoking in patients with flaps). Locoregional recurrence and survival rates were similar between patients with/without a flap. CONCLUSION: Recurrences within a flap were rare in this series when including the whole flap body in the 60Gy-clinical target volume but inclusion of the flap in the primary tumour target volume increased toxicity. Multicentric studies are warranted.

Last-Minute Recovery of a Psychiatric Patient Requesting Physician-Assisted Death.

Physician-assisted death is becoming legal in an increasing number of jurisdictions, but psychiatric patients are often explicitly excluded. However, in some countries, including the Netherlands, physician-assisted death of psychiatric patients is allowed. This Open Forum describes a patient with schizophrenia and symptoms diagnosed as refractory musical hallucinations. The patient requested assistance in dying only to recover after a mandatory second opinion, where his complaints were recognized as intrusive thoughts and treated accordingly. This case is used to reflect on how to deal with uncertainty about physician-assisted death of psychiatric patients and to argue for implementation of a due-diligence procedure, such as the one proposed in the Dutch Psychiatric Association's recent guideline concerning this issue.

A new Monte Carlo model of a Cyberknife® system for the precise determination of out-of-field doses.

In a previous work, a PENELOPE Monte Carlo model of a Cyberknife system equipped with fixed collimator was developed and validated for in-field dose evaluation. The aim of this work is to extend it to evaluate peripheral doses and to determine the precision of the treatment planning system (TPS) Multiplan in evaluating the off-axis doses. The Cyberknife® head model was completed with surrounding components based on manufacturer drawings. The contribution of the different head parts on the out-of-field dose was studied. To model the attenuation and the modification of particle energy caused by components not modelled, the photon transport was modified in one of the added components. The model was iteratively adjusted to fit dose profiles measured with EBT3 films and an ionization chamber for several collimator sizes. Finally, dose profiles were calculated using the two Multiplan TPS algorithms and were compared to our simulations. The contributions to out-of-field dose were identified as scattered radiation from the phantom and head leakage and scatter originating at the secondary collimator level. Particle transport in the additional pieces was modified to model this radiation. The maximum differences between simulated and measured doses are of 20.4%. Regarding the detector responses away from axis, EBT3 films and the Farmer chamber give similar response (less than 20% difference). The TPS Monte Carlo algorithm underestimates the doses away from axis more importantly for the smaller field sizes (up to 98%). Besides, RayTracing simplifies peripheral dose to a constant value with no inclusion of particle transport. A Monte Carlo model of a Cyberknife system for the determination of out-of-field doses up to 14 cm off-axis was successfully developed and validated for different depths and field sizes in comparison with measurements. This study also confirms that TPS algorithms do not model peripheral dose properly.

0.5% 5-Fluorouracil/10% Salicylic Acid for the Treatment of Distal Actinic Keratoses Under Daily Practice Conditions

Background: Actinic keratosis (AKs) are sun-induced skin lesions that are at risk to progress to invasive squamous cell carcinoma (SCC). Treatments have shown to be effective on face or balding scalp area but limited data support their efficacy on distal extremities. Objective: To describe the efficacy of 0.5% 5-fluorouracil/10% salicylic acid (5FU/AS) in the treatment of distally-located AKs in daily clinical practice. Additional objectives were to review tolerance and adherence to this treatment. Methods: Retrospective review of 23 patients with distal grade II to III AKs who were treated with 5FU/AS under daily practice conditions. Primary endpoint included local skin response according to percentage on AKs reduction at week 20 (8 weeks after ending the treatment). Results: 75% (30/40) treatment areas showed a percentage reduction in AKs from to 75% to 100% at week 20. Complete response (100% clearance) was recorded in more than half of the cases (53%, 21/40). Good, partial, and low responses were respectively observed in 22% (9/40), 20% (8/40), and 5% (2/40) of patients. Most adverse events were graded as low, and adherence to treatment was considered correct in 25 patients (63%). In addition, a correct adherence to treatment was significantly related to a better response (P=0.001). Conclusion: Findings indicate that topical 5FU/AS is an effective treatment for multiple distal AKs, with a proper safety profile. J Drugs Dermatol. 2019;18(3):285-288.

Systemic Treatment of Moderate to Severe Psoriasis in Pediatric Patients in Galicia, Spain: A Descriptive Study. / Tratamiento sistémico de la psoriasis moderada-grave en edad pediátrica en Galicia: estudio descriptivo.

BACKGROUND AND OBJECTIVE: Studies on the use of systemic therapy for psoriasis in pediatric patients are scarce. The main aim of this study was to describe the systemic treatments used for moderate to severe psoriasis in pediatric clinical settings. The second aim was to describe the effectiveness and safety of these treatments. MATERIAL AND METHODS: Descriptive, cross-sectional, multicenter study of patients under 18 years of age with moderate to severe psoriasis who were being treated or had been treated with a systemic drug (conventional or biologic) or phototherapy. We recorded demographic and clinical information, treatments received, tolerance, adverse effects, and response to treatment. RESULTS: Data were collected for 40 patients (60% female; mean age, 13 years) who had received 63 treatments in total. The most common first treatment (n=40) was phototherapy (administered to 68% of patients), followed by acitretin (15%). The most common treatments overall (n=63) were phototherapy (57%) and methotrexate (16%). At week 12 (evaluation of systemic treatment and phototherapy), 66% of the patients were classified as good responders and 22% as partial responders. The respective rates for week 24 (evaluation of systemic treatment only) were 36% and 32%. The treatments were well tolerated (97%) and adverse effects were reported in just 11% of cases. There were no treatment discontinuations because of adverse effects. CONCLUSIONS: Phototherapy, followed by methotrexate, was the most common treatment for moderate to severe psoriasis in this series of patients under 18 years. The treatments showed a favorable safety profile and were associated with a good response rate of 66% at week 12 (systemic treatment and phototherapy) and 36% at week 24 (systemic treatment only).

Clinical research at territorial section meetings of the Spanish Academy of Dermatology and Venereology (AEDV). / La investigación clínica en las secciones territoriales de la Academia Española de Dermatología y Venereología (AEDV).

INTRODUCTION: Clinical research is the study of patients with the aim of improving care. Our objectives were to calculate the percentage of presentations at territorial section meetings of the Spanish Academy of Dermatology and Venereology (AEDV) that described clinical research, to assess the level of evidence the research provided, and to analyze change in clinical research volume over time. MATERIAL AND METHODS: We reviewed supplements of the journal Actas Dermo-Sifiliográficas for 2000 through 2015 that contained abstracts of presentations given at the AEDV section meetings in Galicia; the area comprising Asturias, Cantabria, and Castile-Leon (ACCL); and Andalusia. We selected abstracts that met a previously validated definition of clinical research and categorized each according to level of evidence. We also analyzed how the weight of clinical research presentations changed over time. RESULTS: Of the total of 1,188 presentations, 29.6% met the criteria that defined clinical research. Most provided level-4 evidence (95.2%); 44.2% of those presentations reported cross-sectional studies and 55.8% analyzed case series. Clinical research accounted for 26.6% of the presentations in Galicia (94.7% of them, level 4), 22.7% of those at the ACCL meeting (97.6%, level 4), and 37.2% of those in Andalusia (94.3%, level 4). The proportion of clinical research increased significantly over the years studied. CONCLUSIONS: Clinical research accounted for 29.6% of the communications presented at the meetings we reviewed. Most of these presentations concerned case series or cross-sectional studies. The prevalence of clinical research presentations differed between the 3 territories studied, but the levels of evidence were similar. The proportion of clinical research in the programs of these meetings has increased over time.

IL17RA gene variants and anti-TNF response among psoriasis patients.

Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months. All of the patients were Caucasian, older than 18 years old, with chronic plaque Psor, and had completed at least 24 weeks of anti-TNF therapy (adalimumab, etanercept or infliximab). The treatment response to anti-TNF agents was evaluated according to the achievement of PASI50 and PASI75 at weeks 12 and 24. Those who achieved PASI75 at week 24 were considered good responders. All patients were genotyped for the selected single-nucleotide polymorphisms (SNPs) at IL17RA gene. A total of 238 patients were included (57% male, mean age 46 years). One hundred and five patients received adalimumab, 91 patients etanercept and 42 infliximab. The rs4819554 promoter SNP allele A was significantly more common among responders at weeks 12 (P=0.01) and 24 (P=0.04). We found a higher frequency of AA versus AG+GG among responders, but the difference was only significant at week 12 (P=0.03, odd ratio=1.86, 95% confidence of interval=1.05-3.27). Thus, in the study population, the SNP rs4819554 in the promoter region of IL17RA significantly influences the response to anti-TNF drugs at week 12.

Cardiomyopathy in Patients With Hereditary Bullous Epidermolysis. / Miocardiopatía en pacientes con epidermólisis ampollosa hereditaria.

INTRODUCTION AND OBJECTIVE: In recent decades, an association has been reported between epidermolysis bullosa (EB) and dilated cardiomyopathy (DC). DC is typically in an advanced phase when detected, leading to a poorer prognosis. Our objective was to determine the prevalence of DC in patients with EB seen in Hospital San Joan de Déu in Barcelona, Spain, between May 1986 and April 2015. METHODS: This was a descriptive, cross-sectional chart-review study in which we recorded the type and main subtypes of EB and the presence or absence of DC. RESULTS: Fifty-seven patients with EB were found, 19 with EB simplex, 10 with junctional EB, 27 with dystrophic EB (14 dominant dystrophic and 13 recessive dystrophic), and just 1 with Kindler syndrome. DC was detected in only 2 patients with recessive dystrophic EB. Twenty-three patients had presented factors that could have had a causal relationship with the potential onset of DC. CONCLUSION: DC is a possible complication of EB, particularly in recessive dystrophic EB. Periodic follow-up should be performed to make an early diagnosis and start treatment.