Low-dose oral isotretinoin in the treatment of recalcitrant facial flat warts: A clinical case and review of literature.

Background and Aims: The treatment of recalcitrant facial flat warts has always been challenging for dermatologists. The pain related to the application of the different treatments, side effects and costs are determining factors in the choice of therapy. To date, it is known that oral isotretinoin administered at a dose of 0.5 mg/kg/day is effective and safe; However, the different adverse effects reported have a dose-dependent behavior and they could limit their use. Our aim is to assess the effect of low-doses of oral isotretinoin to reducing side effects in the complete removal of recalcitrant facial flat warts and the current evidence in this regard. Methods: An extensive literature review was conducted to identify articles relating to low doses of oral isotretinoin for recalcitrant flat warts treatment, regardless of design up to May 2023. Results: The literature search yielded eight articles of 324 reviewed meeting criteria. Isotretinoin was administered in doses of 0.1-0.5 mg/kg/day. Complete elimination of the lesions occurred in 65.13% of the patients and a partial response in 19.26%. Four relapses were documented at the 4-month follow-up. The most frequent adverse effect was cheilitis. Conclusion: We might consider low doses of oral isotretinoin for the treatment of recalcitrant facial flat warts in which side effects need to be reduced. However, current published works have several limitations, including small sample sizes, lack of control group and follow-up periods. Larger, randomized, controlled studies are needed to verify the efficacy and safety of different doses of isotretinoin.

[Atopic dermatitis in adults during the COVID-19 pandemic]. / Dermatitis atópica en adultos durante la pandemia por COVID-19.

OBJECTIVE: To evaluate the clinical course of atopic dermatitis (AD) in adults during the COVID-19 pandemic and to evaluate their comorbidities and cardiovascular risk. METHODS: A cross-sectional study was conducted in adults with AD. Severity and control of AD, quality of life, levels of psychological stress, depression and cardiovascular risk were measured. RESULTS: Forty-two patients were included. A decrease in POEM score (11.83 vs 10.12; p=0.004) and PO-SCORAD (37.77 vs 32.49; p= 0.001) was observed in comparison to the scores at pandemic onset. The quality of life correlated with the severity of AD (p<0.0001) while the levels of stress and depression did not show association. Most patients had a low cardiovascular risk. CONCLUSIONS: The results suggest a decrease in the current severity of AD compared with severity before pandemic. Quality of life is associated with AD severity.

OBJECTIVO: Evaluar el curso clínico de pacientes adultos con dermatitis atópica durante la pandemia por COVID-19, e identificar las comorbilidades y el riesgo cardiovascular. MÉTODOS: Estudio transversal, llevado a cabo en adultos con dermatitis atópica. Se evaluó la gravedad y el control de la dermatitis, la calidad de vida, el grado de estrés psicológico, depresión y riesgo cardiovascular. RESULTADOS: Se seleccionaron 42 pacientes.Se observó una disminución en el puntaje del POEM (11.83 vs 10.12; p=0.004) y del PO-SCORAD (37.77 vs 32.49; p= 0.001) con relación al inicio de la pandemia. La calidad vida se correlacionó con la gravedad de la dermatitis atópica (p<0.0001) a diferencia de los grados de estrés y depresión. La mayoría de los pacientes tuvo riesgo cardiovascular bajo. CONCLUSIONES: Se encontró disminución de la gravedad actual de la dermatitis atópica comparada con la gravedad antes de la pandemia. La calidad de vida se asocia con la gravedad de la dermatitis atópica.

Interventions for preventing keratinocytic cancer in patients with a history of a previous keratinocytic carcinoma: A systematic review.

Keratinocyte cancer (KC) is the most common cancer worldwide. It is important to analyze the actual interventions that are available for the prevention of patients with a previous history of a KC. We aim to review the existent literature to assess the efficacy and safety of interventions to prevent KC in patients with a history of previous KC. We searched clinical trials in which the main outcome was the prevention of KC in patients with a previous history of KC using the strategy published in the International Prospective Register of Systematic Reviews (PROSPERO registry), CRD42016045981. We analyzed 18 clinical trials from which eight reported a benefit with their respective intervention but had methodological flaws and a variable risk of bias. Two clinical trials (regarding celecoxib and oral supplementation with nicotinamide) seemed to have the most beneficial results reducing the incidence of KC in treated groups. However, all of the studies are highly heterogeneous, which does not allow a meta-analysis to be performed. New studies with greater epidemiological value should be conducted.

Keratosis Pilaris Treatment: Evidence from Intervention Studies.

Keratosis pilaris is a common dermatosis observed in daily dermatologic practice. The diagnosis is clinical and usually asymptomatic, although sometimes patients may complain of mild pruritus and its cosmetic appearance. Few reports exist about its treatment. There are clinical trials assessing topical treatments and laser surgery, but no systematic reviews on its management were found in literature. An online research was conducted to identify evidence-based recommendations. Lactic acid, salicylic acid, and the 1064-nm Nd:YAG laser seem to be the most effective and safe treatment options for keratosis pilaris among patients aged 12 years and older; however, high-quality randomized controlled trials with long-term outcomes are required. (SKINmed. 2022;20:258-271).

Development and Validation of a New Scoring Tool to Evaluate the Clinical Evolution of Adult Patients with Nonsegmental Vitiligo.

BACKGROUND: Vitiligo has an unpredictable course and a variable response to treatment. Furthermore, the improvement of some vitiligo lesions cannot be considered a guarantee of a similar response to the other lesions. Instruments for patient-reported outcome measures (PROM) can be an alternative to measure complex constructions such as clinical evolution. OBJECTIVE: The aim of this study was to validate a PROM that allows to measure the clinical evolution of patients with nonsegmental vitiligo in a simple but standardized way that serves to gather information for a better understanding of the disease. METHODS: The instrument was created through expert consensus and patient participation. For the validation study, a prospective cohort design was performed. The body surface area affected was measured with the Vitiligo Extension Score (VES), the extension, the stage, and the spread by the evaluation of the Vitiligo European Task Force assessment (VETFa). Reliability was determined with test-retest, construct validity through hypothesis testing, discriminative capacity with extreme groups, and response capacity by comparing initial and final measurements. RESULTS: Eighteen semi-structured interviews and 7 cognitive interviews were conducted, and 4 dermatologists were consulted. The instrument Clinical Evolution-Vitiligo (CV-6) was answered by 119 patients with a minimum of primary schooling. A wide range was observed in the affected body surface; incident and prevalent cases were included. The average time to answer the CV-6 was 3.08 ± 0.58 min. In the test-retest (n = 53), an intraclass correlation coefficient was obtained: 0.896 (95% CI 0.82-0.94; p < 0.001). In extreme groups, the mean score was 2 (2-3) and 5 (4-6); p < 0.001. The initial CV-6 score was different from the final one and the change was verified with VES and VETFa (p < 0.05, n = 92). CONCLUSIONS: The CV-6 instrument allows patient collaboration, it is simple and brief, and it makes it easier for the doctor to focus attention on injuries that present changes at the time of medical consultation.

Diagnostic Accuracy of Dermoscopy of Actinic Keratosis: A Systematic Review.

INTRODUCTION: Dermoscopy is a tool that aids clinicians in the diagnosis of actinic keratosis; however, few diagnostic accuracy studies have determined its sensitivity and specificity for this diagnosis. OBJECTIVE: Determine the diagnostic accuracy of dermoscopy on actinic keratosis. METHODS: A systematic review was conducted on EMBASE, PubMed, Scopus and the Cochrane Central Registry of Controlled Trials from inception to August 2019. RESULTS: We screened 485 titles and abstracts. Two studies comprising 219 actinic keratoses were eligible for qualitative analysis. The number and heterogeneity of included studies limited a quantitative analysis. CONCLUSIONS: Studies that focus specifically on the diagnostic accuracy of dermoscopy for actinic keratosis are lacking.

Prognostic Factors in Mexican Patients with Patchy and Other Types of Alopecia Areata.

INTRODUCTION: Some clinical features have been associated with the progression and remission of alopecia areata (AA). We aim to determine possible prognostic factors in Mexican patients with AA. METHODS: This prospective study of a 1-year follow-up included Mexican patients with a clinical diagnosis of AA. We evaluated disease activity with the SALT score at the first visit and 1-year follow-up; progression, no progression, and remission were defined according to score changes. We used multiple linear regression model to detect factors associated with progression and remission. RESULTS: One hundred and four patients concluded the study. Ninety-seven patients (93.3%) had patchy AA. Fifteen patients showed disease progression and 89 no progression, of which 35 patients had remission. Body hair involvement was related to disease progression and adherence to treatment with disease remission and progression. CONCLUSIONS: Body hair involvement is related to poor prognosis. Adherence to treatment is a modifiable prognostic factor associated with the course of AA in Mexican patients.

Quality of clinical trials for the prevention of keratinocyte cancer.

Keratinocyte cancer (KC) is the most common form of cancer in humans. To our knowledge, no previous publications assessing the methodological quality of clinical trials for the prevention of KC have been recently published. We aim to assess the methodological quality of clinical trials focused on the prevention of KC in high-risk groups not receiving immunosuppressive therapy (NRIT) and propose solutions to improve the design of future trials. We searched clinical trials in which the main outcome was the prevention of KC in high-risk NRIT groups using the strategy published in the International Prospective Register of Systematic Reviews (PROSPERO registry), CRD42016045981. Consolidated Standards of Reporting Trials (CONSORT) criteria and the Cochrane Collaboration risk of bias tool were used to assess methodological quality. We analyzed 23 clinical trials. We found a high risk of attrition and reporting bias in 86.9% and 60.9% of the trials, respectively. Regarding the CONSORT criteria, in at least 40% of the trials, the authors omitted the following information: a description of the trial design, the number of losses and exclusions after randomization, the results of subgroup and adjusted analysis, the estimated effect size and the precision of primary and secondary outcomes. Methodological quality was improved in the recently published clinical trials compared to those published before the CONSORT criteria development. All clinical trials should report in detail the information used to assess potential risks of bias.

Content validity of psoriatic arthritis screening questionnaires: systematic review.

BACKGROUND: Psoriatic arthritis (PsA) is the main entity associated with psoriasis (PsO). Consequently, several PsA screening instruments have been developed, most of them are self-administered questionnaires, known as patient-reported outcome measures (PROMs). OBJECTIVE: To identify, summarize, and systematically evaluate the evidence of the content validity of PsA screening PROMs, in patients with PsO, by the dermatologist, based on COSMIN methodology. METHODS: A structured literature search was performed, until June 2019, that included development and/or validation studies of a questionnaire for the screening of PsA in patients with PsO. The evaluation was based on the PROMs' development, relevance, comprehensiveness, and comprehensibility. RESULTS: Eleven PROMs were included in the systematic review with four additional validation studies of the included instruments. Only ToPAS2 (Toronto Psoriatic Arthritis Screen) questionnaire had an adequate content validity. CONTEST (Comparison of three screening tools to detect psoriatic arthritis in patients with psoriasis), CEPPA (Center of Excellence for Psoriasis sand Psoriatic Arthritis), and SiPAS (Simple Psoriatic Arthritis Screening questionnaire) qualified as inadequate. CONCLUSIONS: Despite the existence of eleven validated PsA screening PROMs, none were supported by very high-quality evidence of their content validity, which brings the opportunity for the creation of a new proposal PROM for the screening of PsA.

Psychological Profile and Quality of Life of Patients with Alopecia Areata.

Alopecia areata (AA) is a nonscarring alopecia with an autoimmune etiology, unpredictable course, multiple presentations, and variable psychological distress. We conducted a cross-sectional study which included 126 patients with AA. A complete medical history was documented using the Severity Alopecia Tool (SALT) to assess the severity of the disease, and the following questionnaires were applied to the participants: the Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), Plutchik Suicide Risk Scale, and the Perceived Stress Scale (PSS-14) for adults. The Child Dermatology Life Quality Index (cDLQI) and the Birleson Depression Self-Rating Scale questionnaires were applied for children. Quality of life (QoL) disturbance was detected in 77.6% of adult participants, 65.9% of them had signs of depression or anxiety, and 12.8% were at risk of committing suicide. The PSS-14 average score for adults was 24.5. QoL disturbance was detected in 76.7% of children participants, and 6.3% of them showed signs of depression with the Birleson Depression Self-Rating Scale. We conclude that patients with AA could experience changes in their QoL and signs of depression, anxiety, and suicide risk, mainly in the adult population, during the course of the disease.

Systematic Review of Clinimetric Instruments to determine the severity of Non-segmental Vitiligo.

This systematic review of measurement instruments for vitiligo outcomes included validation articles published from 2011 to May 2018. According to the PRISMA statement, the search was carried out in EMBASE (via OvidSP); MEDLINE (via OvidSP and PubMed). The COSMIN taxonomy will be used to define the measurement properties. Inclusion criteria were original studies reporting measuring properties. Exclusion criteria were clinical trials using scales whose measurement properties were not assessed, studies of cross-cultural adaptation, scales focused on other aspects of the disease such as quality of life, satisfaction, disease's burden. Fourteen studies were identified, which described 15 instruments to measure vitiligo outcomes. Nine of them, measured properties related to the severity of the disease: Vitiligo extent score (VES), Self-Assessment Vitiligo Extent Score (SA-VES), Self-Assessed Vitiligo Area Scoring Index (SAVASI), Vitiligo Area Scoring Index (VASI), Vitiligo European Task Force assessment (VETFa), Vitíligo Noticeability Scale (VNS), Koebner's phenomenon in vitiligo score (K-VSCOR), Vitiligo Extent Tensity Index (VETI), Potential Repigmentation Index (PRI). The most effective tool to asses affected Body Surface Area (BSA) is VES. The VASI is useful to stratify by severity. There is not enough evidence to recommend the use of SAVASI. The VETFa does not offer any difference to calculate the affected BSA compared with the rule of 9's. The VNS and K-VSCOR lack of reliability evidence.

[Diagnóstico tardío de psoriasis: motivos y consecuencias]. / Late diagnosis of psoriasis: Reasons and consequences.

BACKGROUND: Psoriasis is an autoimmune skin disease that may be associated with articular manifestations, and the most common clinical presentation is the variety "in plaques". In Mexico, in the Centro Dermatológico Pascua, it is the eighth leading cause of consultation. The aim of this study was to determine the diagnostic process of patients in a reference center for diseases of the skin. METHODS: Performing an analytical cross-sectional study that included 100 patients where the diagnostic process was questioned, clinimetric scales were applied and evaluated anthropometric. RESULTS: It was found that 70% of patients had taken over a month to get medical care (median: 3 months; IQR: 11 months), having consulted in 61% to a general physician as a doctor of first contact and 89% being diagnosed by a dermatologist. Eighty-eight percent of the patients were overweight or obese. We found as a factor of delay, a partnership with the variable of having an Institutional Medical Service (p = 0.019; U = 695.5). CONCLUSION: it is necessary to design a system to shorten the diagnostic process, not only in psoriasis, in addition to emphasizing dermatological education.

[Transcultural translation-adaptation to Spanish of the Infants' Dermatitis Quality of Life questionnaire for children under four years with atopic dermatitis]. / Traducción-adaptación transcultural al español del cuestionario Infants Dermatology Quality of Life para niños menores de cuatro años con dermatitis atópica.

BACKGROUND: Atopic dermatitis is observed in up to 20% of children, hence the importance of tools to support its evaluation. OBJECTIVE: To determine the validity and reliability of the Spanish adaptation of the IDQOL questionnaire in patients <4 years of age with atopic dermatitis (AD). METHODS: Translation and back-translation of the questionnaire; a pilot test was done in 30 children with AD to arrive at a final version. Internal reliability (Cronbach's alpha) and correlation of IDQOL and SCORAD scores (Pearson correlation coefficient) were measured. RESULTS: 102 children aged between two and 48 months were included. The Pearson correlation coefficient (r) of IDQOL and SCORAD scores was 0.697 (p = 0.0001), indicating a high positive correlation. The correlation between the severity measured by the caregiver and the SCORAD score (r = 0.565, p = 0.0001) proved to be low positive. The internal consistency of IDQOL using Cronbach's alpha was 0.84, indicating good consistency of the instrument for assessing quality of life. CONCLUSION: The IDQOL questionnaire in Spanish is a valid measure of quality of life in patients < 4 years with AD and is useful in monitoring and in clinical trials.

Antecedentes: La dermatitis atópica se observa hasta en 20% de los niños, de ahí la importancia de instrumentos para apoyo de su evaluación. Objetivo: Determinar la validez y confiabilidad de la adaptación al español del cuestionario IDQOL en pacientes <4 años de edad con dermatitis atópica (DA). Métodos: Traducción y retrotraducción del cuestionario; se hizo una prueba piloto en 30 niños con DA para obtener una versión definitiva. Se midió la confiabilidad interna (alfa de Cronbach) y correlación de puntajes del IDQOL y SCORAD (coeficiente de correlación de Pearson). Resultados: Se incluyeron 102 niños con edad entre dos y 48 meses. El coeficiente de correlación de Pearson (r) de los puntajes del IDQOL y SCORAD fue de 0.697 (p=0.0001), indicativo de una correlación positiva alta. La correlación entre la gravedad medida por el cuidador y el puntaje del SCORAD (r=0.565, p=0.0001) resultó ser positiva baja. La consistencia interna del IDQOL mediante alfa de Cronbach fue de 0.84, indicativa de buena consistencia del instrumento para evaluar calidad de vida. Conclusión: El cuestionario IDQOL en español es un válido para medir la calidad de vida en pacientes <4 años con DA y útil en el seguimiento y en los ensayos clínicos.

[Insulin levels in teenagers with comedonal acne]. / Niveles de insulina en adolescentes con acné comedónico.

INTRODUCTION: Acne is considered a multifactorial skin disease secondary to an obstructive process of pilosebaceous units. Some studies suggest a relationship between insulin levels and the presence of acne, but this has not yet been demonstrated. OBJECTIVE: To compare the levels of insulin in patients with and without comedonal acne. MATERIAL AND METHODS: From January to July 2012, we conducted a cross-sectional study in the Dr. Ladislao de la Pascua Dermatologic Center in Mexico city. We recruited men and women from 14 to 25 years old with and without comedonal acne. We measured the insulin levels in all patients with DXI 800 Beckman Coulter equipment in a blood sample. RESULTS: Twenty patients with acne and 20 patients without acne were studied, with an average age of 17 (±3) and 19 (±4) years, respectively. Both groups were different in terms of gender. Body mass index was similar in both groups. We did not find a difference in insulin levels between groups (p=0.818). The average level of insulin was 7.15±4.7 uU/ml for the acne group and 7.85±3.3 uU/mL for the control group. CONCLUSION: Insulin levels are similar in patients with and without comedonal acne. There is no direct relationship between hyperinsulinemia and acne.

A double-blind, randomized, placebo-controlled trial of oral isotretinoin in the treatment of recalcitrant facial flat warts.

UNLABELLED: Abstract Background: Recalcitrant facial flat warts are caused by human papillomavirus and may persist for years despite treatment. Isotretinoin has demonstrated benefits in the treatment of recalcitrant, genital and common warts, but placebo-controlled trials have not been performed. OBJECTIVE: To determine whether isotretinoin is safe and effective for recalcitrant facial flat warts. METHODS: Isotretinoin 30 mg/day or placebo was administered to 16 and 15 patients, respectively, in double-blind, randomized fashion for 12 weeks. Cutaneous lesions were assessed and adverse events including serologic and ophthalmologic changes were recorded. It is considered that warts were recalcitrant if the patient was treated for at least 3 years with at least three of the following options: retinoids, 5-fluorouracil, imiquimod and cryotherapy using liquid nitrogen. RESULTS: Each patient in the istotretinoin group showed complete clearance of all flat warts, while none of the patients in the placebo group showed any improvement (p=0.0001). The most frequent adverse event was cheilitis. There were no statistically significant changes in the laboratory findings. LIMITATIONS: The study design does not permit complete blinding of the dermatologist who can easily recognize the adverse effects of isotretinoin. The clinical findings, however, were so dramatic that this would not have impacted the findings. Another limitation of the study is a lack of follow-up to assess for recurrence after the drug was discontinued. CONCLUSIONS: Isotretinoin is an effective treatment for recalcitrant flat facial warts with a well-known, manageable safety profile.

[Validation of a questionnaire to quantify the risk for skin cancer]. / Validación de un cuestionario para cuantificar el riesgo de cáncer de piel.

INTRODUCTION: Currently, strategies are needed to identify the population at risk for skin cancer in order to implement prevention and for early diagnosis. There are no validated Spanish language instruments to measure skin cancer risk. OBJECTIVES: To design and validate a self-applied questionnaire to quantify the risk of melanoma and non-melanoma skin cancer in a Mexican population. METHODS: A self-applied questionnaire was designed to measure risk factors for skin cancer. Face and content validity was assessed by five experts in skin cancer. The value of each item was weighted according to the relative risk of the risk factors. The questionnaire was applied to extreme groups in order to measure the construct validity. Reliability was evaluated using test-retest method two weeks after the first application. RESULTS: The questionnaire was applied to patients with (n = 147) and without (n = 249) skin cancer from the Dermatologic Center "Dr. Ladislao de la Pascua". The total score of the questionnaire was different in both groups (U = 2,104.5, p = 0.0001) and ROC curve determined that five points or more equals high risk for skin cancer (area 0.964; 95% CI: 0.946-0.981; p = 0.0001). The reliability of the instrument was 0.971 (95% CI: 0.943-0.986; p = 0.0001). CONCLUSION: This is the first Spanish language questionnaire valid to measure risk of skin cancer, whose application at the population level would be useful to identify high-risk individuals who need preventative interventions.

[Mexican guidelines on the diagnosis and treatment of urticaria]. / Guía Mexicana para el Diagnóstico y el Tratamiento de la Urticaria.

BACKGROUND: Urticaria is a disease that a fifth of the population shallsuffer once in a lifetime. Recent clinical guidelines have proposed some fundamental changes in the diagnosis and treatment of urticaria, making the development of a national, multidisciplinary guideline, with wide acceptability among different professional groups -both specialists and primary health care workers-, necessary in Mexico. MATERIAL AND METHOD: Internationally recognized tools for guidelinedevelopment were used. An interdisciplinary group of clinical experts (some of them knowledgeable in methodology of guideline development) determined the objectives and scope of the Evidence Based Clinical Practice Guideline with SCOPE. It was decided to adapt and transculturize international guidelines on the diagnosis and treatment of urticaria. With AGREE-II three high-quality guidelines (Zuberbier 2014, Sánchez-Borges 2012, Powell 2007) were selected to function as basic guidelines (BG). A set of Clinical Questions was formulated that lead to recommendations/suggestions, based on these BG, taking into account the cultural and economic background of Mexico, according to GRADE recommendation development. RESULTS: By a formal process of discussion and voting during several working-sessions, experts and first level healthcare physicians determined the wording of the final guideline, taking particularly care of developing a document, adjusted to the reality, values and preferences of the Mexican patients. The use of oral second generation, non-sedating antihistamines as first line treatment is emphasized. CONCLUSION: This document is an Evidence Based Clinical Practice Guideline for the diagnosis and treatment of acute and chronic urticaria, based on three, high quality, international guidelines. It was developed by a multidisciplinary group. Tables and algorithms make the guideline user-friendly for both, first line health care physicians and specialists.

Antecedentes: la urticaria es una enfermedad que padece una quinta parte de la población en algún momento de su vida. Las guías internacionales recientes han propuesto unos cambios de fondo en su diagnóstico y tratamiento, por lo que había la necesidad de crear una guía nacional y multidisciplinaria, con base amplia en los gremios de especialistas y médicos de primer contacto en México. Material y método: un grupo interdisciplinario de expertos clínicos y algunos expertos en metodología determinó los objetivos y alcances de la Guía de Práctica Clínica Basada en Evidencia con el instrumento SCOPE. Se decidió llevar a cabo la adaptación y transculturización de guías internacionales para el diagnóstico y tratamiento de urticaria. Con el instrumento AGREE-II se seleccionaron las tres guías de alta calidad, como guías base (Zuberbier 2014, Sánchez-Borges 2012, Powell 2007) para formular y contestar la preguntas clínicas clave, en el contexto cultural y económico mexicano, según el método de desarrollo de recomendaciones GRADE. Resultados: mediante un proceso formal de discusión y votación durante varias juntas de expertos, se terminó la redacción de la forma final de la guía, con especial cuidado de lograr un ajuste a las realidades, valores y preferencias de los pacientes de México. Se hace hincapié en la administración de antihistamínicos vía oral de segunda generación, como tratamiento de primera elección. Conclusión: este documento es una Guía de Práctica Clínica Basada en Evidencia para el diagnóstico y tratamiento de urticaria aguda y crónica, basada en tres guías internacionales de alta calidad. Se desarrolló por un grupo multidisciplinario. Los cuadros y algoritmos hacen a la guía amigable para su uso por médicos de primer contacto y por especialistas.