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Intervention studies require all participants to originate from the same population, with random allocation to intervention groups to ensure comparability. Randomization is crucial for minimizing confounding factors, allowing differences in outcomes to be attributed to the intervention. Simple randomization performs well for large samples (>100 per group), but smaller samples may require block or stratified randomization to balance group sizes and covariates. When randomization isn't feasible, quasi-randomized methods (e.g., based on dates or enrollment order) can help but must compensate with multivariate adjustments. Moreover, blinding and allocation concealment enhance internal validity and reproducibility. Allocation concealment (e.g., sealed envelopes) prevents bias during participant assignment while blinding mitigates detection and performance biases. Precise methodological descriptions in clinical trial registrations and publications enhance study reliability and reproducibility, highlighting the importance of rigorous planning and transparent reporting in intervention research. This article reviews the key concepts of randomization, blinding, and allocation concealment in interventional studies., Competing Interests: Conflicts of interest: No conflicts of interest declared concerning the publication of this article., (Copyright© 2024 The authors.)

Background: Trials evaluating the effectiveness of topical treatments for actinic cheilitis (AC) are scarce. Despite no comparative data, phenol-croton peeling has been reported as effective in treating this condition., Methods: An open, randomized trial was conducted to compare the effectiveness and tolerability of 1.6% phenol-croton peeling versus topical 5% imiquimod for the treatment of AC. Thirty-six patients with biopsy-proven AC were allocated into two groups (1:1): the 5%-IMI group received 5% topical imiquimod three times a week for 30 days, and the 1.6%-CROTON group underwent one session of 1.6% phenol-croton peeling. The primary outcome was the clearance of AC after 56 days. Secondary outcomes included clinical and histological parameters, adverse effects, and clinical results after 180 days., Results: Complete clinical clearance of AC at D56 and D180 occurred in 17 (94%) participants from the 1.6%-CROTON group but in none from the 5%-IMI group (p<0.01). Improvement in all clinical parameters was more prominent in the 1.6%-CROTON group (p≤0.01). Complete histologic normalization at D56 occurred in 72% of the 1.6%-CROTON group and only 17% in the 5%-IMI group (p<0.01). Histological parameters such as atypia, solar elastosis, and hyperkeratosis reduced in intensity only in the 1.6%-CROTON group (p<0.05). Adverse effects were most intense on D7 in the 1.6%-CROTON group and persisted until D21 in the 5%-IMI group. The study was prematurely terminated at the interim analysis., Conclusions: A single session of 1.6% phenol-croton peeling produced clinically and histologically superior results with less downtime compared to imiquimod for treating AC., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: 5-Fluorouracil (5-FU) is a first-line drug to treat cutaneous field cancerization (CFC). There are few clinical trials with topical colchicine (COL)., Objective: To evaluate the effectiveness of 0.5% COL cream versus 5% 5-FU cream in the treatment of CFC., Method: This was a randomized, open, self-controlled clinical trial. Forty-five patients (90 forearms), with three to ten actinic keratoses (AK) on each forearm, used 0.5% COL cream 2×/day for seven days on one forearm, and 5% 5-FU cream 2× /day, for 21 days, on the other forearm. The dosages were defined based on previous clinical trials for each drug. Adverse effects were evaluated after 14 days and outcomes after 90 days of inclusion. The primary outcome was complete AK clearance and the secondary outcomes were: partial clearance (≥50%), reduction in AK count, assessment of the Forearm Photoaging Scale (FPS), AK Severity Score (AKSS), and adverse effects., Results: After 90 days, there was complete clearance of AK in 37% (95% CI 24%-49%) and partial clearance in 85% (95% CI 76%-93%) of the forearms treated with 5-FU,versus 17% (95% CI 7%-27%) and 78% (95% CI 66%-88%) for COL (p > 0.07). There was a percentage reduction of 75% in the AK count of the forearms treated with 5-FU (95% CI 66%-83%) and 64% in those treated with COL (95% CI 55%-72%). Regarding FPS and AKSS, there was improvement in both groups, with no difference regarding FPS (p = 0.654), and 5-FU superiority for AKSS (p = 0.012)., Study Limitations: Single-center study., Conclusions: 5-FU and COL are effective for treating CFC, with neither showing superiority regarding the reduction in AK counts., (Copyright © 2024 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Thalidomide is the drug of choice for the treatment of type 2 leprosy reactions and is often associated with corticosteroids. The use of these drugs in multiple myeloma is associated with the risk of cardiovascular events, but there have been few studies assessing this risk in leprosy patients., Objective: To evaluate the occurrence of cardiovascular events in patients with multibacillary leprosy and their correlation with the use of thalidomide and prednisone., Methods: Analytical cross-sectional study of all patients diagnosed with multibacillary leprosy treated at the Dermatology Service between 2012 and 2022, using electronic medical records. Thromboembolic vascular events, both arterial and venous, including acute myocardial infarction, were considered. The main independent variable was the concomitant use of thalidomide and prednisone during follow-up., Results: A total of 89 patients were included, of which 19 used thalidomide and prednisone concomitantly. There were five cardiovascular events (26.3%), three of which of deep venous thrombosis. The combined use of medications was associated with the events (PR=6.46 [3.92 to 10.65]; p<0.01)., Study Limitations: Small number of events, single-center retrospective study., Conclusion: The hypothesis of an association between cardiovascular events and the concomitant use of thalidomide and prednisone is supported, but more robust prospective studies are required for a better assessment., (Copyright © 2023 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Actinic keratosis (AK) is a skin condition associated with age, sun exposure, and immunosuppression. Certain drugs, such as photosensitizing medications and calcium channel blockers (CCBs), have been linked to AK. This study explores the impact of individual, behavioral, and exposure factors on the severity of AKs on the face and scalp., Methods: A multicenter cross-sectional study was conducted on immunocompetent individuals with at least one AK on their face or scalp and assessed demographic factors, sun exposure and protection, history of skin cancer, and medication use within the last 6 months. The primary outcome was the Actinic Keratosis Area and Severity Index (AKASI) score, and a hierarchical generalized linear model was used to evaluate the variation in AKASI scores, adjusting for gender, age, and skin phototype., Results: Two hundred seventy subjects between 39 and 92 years were evaluated. The majority had phototype I or II (77%), male gender (51%), personal history of skin cancer (55%), and low adherence to sunscreen use (29%). The use of photosensitizing medications was reported by 61%. Through multivariate analysis, older age (β SE  = 0.14; P < 0.01), lighter skin phototype (β SE  = 0.15; P = 0.01), history of skin cancer (β SE  = 0.12; P < 0.01), sunburning (β SE  = 0.12; P < 0.01), and use of CCBs (β SE  = 0.11; P = 0.02) were identified as independent risk factors for AK severity. Photosensitizing drugs were not identified as risk factors., Conclusion: Older age, lower skin phototype classifications, and a personal history of skin cancer were confirmed as severity risk factors for AK, while the use of CCBs was associated with more severe AK., (© 2023 the International Society of Dermatology.)

Background: Several treatments are available for skin with advanced photodamage, which is characterized by the presence of actinic keratoses (AK)., Objectives: Evaluate the efficacy of using sunscreen with photolyase compared to regular sunscreen, as well as to compare the combination of a topical formulation of antioxidants versus placebo in the treatment of advanced photodamage., Methods: This was a randomized, double-blind, factorial clinical trial. Participants with AKs on their forearms were randomized to apply regular sunscreen (SC) or sunscreen with photolyase (SC+P) on both forearms during the day. One of the forearms in each group was randomized again to receive topical antioxidants (AOx), and the other forearm received a placebo cream (both for night application). The four groups were SC/AOx, SC/placebo, SC+P/AOx, and SC+P/placebo. The duration of treatment was 8 weeks. Primary outcomes were total AK clearance, decrease in Forearm Photoaging Scale (FPS), and AK severity scores. Secondary outcomes were reduction in AK count, partial clearance rate, and safety., Results: Forty participants (80 forearms) were included. All groups showed significant improvement in outcomes at week eight. There were no significant differences between SC and SC+P for either outcome. AOx led to a significant reduction in AK count (22%; p < 0.05). Partial clearance was obtained in 18 (47.4%) forearms treated with AOx and in 9 (23.7%) treated with placebo (p < 0.05). All groups reduced the FPS score, without significant differences among them., Conclusions: There is no difference in the treatment of advanced photodamage skin when comparing the use of sunscreen with photolyase and regular sunscreen, and topical antioxidants were more efficient in reducing AK count than placebo., Study Limitations: Short interval of follow-up and absence of re-evaluation in the absence of treatment were limitations of the present study., (Copyright © 2021 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Cutaneous tuberculosis is a rare extrapulmonary manifestation of tuberculosis which, like disseminated tuberculosis, commonly occurs in immunocompromised patients. Poncet reactive arthritis is a seronegative arthritis affecting patients with extrapulmonary tuberculosis, which is uncommon even in endemic countries. We report a previously healthy 23-year-old male patient with watery diarrhea associated with erythematous ulcers on the lower limbs and oligoarthritis of the hands. Histopathological examination of the skin showed epithelioid granulomatous process with palisade granulomas and central caseous necrosis. AFB screening by Ziehl-Neelsen staining showed intact bacilli, the culture was positive for Mycobacterium tuberculosis, and colonoscopy revealed multiple shallow ulcers. Disseminated tuberculosis associated with reactive Poncet arthritis was diagnosed, with an improvement of the clinical and skin condition after appropriate treatment., (Copyright © 2020 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: A skin field cancerization is a cutaneous area with subclinical changes resultant from chronic sun exposure, with a higher predisposition to development of pre-neoplastic and neoplastic lesions. So far, there are no well-defined objective parameters that can indicate their degree of activity., Objectives: To describe and compare morphometric aspects and expression of factors related to apoptosis and cell proliferation in actinic keratosis (AK), in both photoexposed and photoprotected epidermis., Methods: A cross-sectional study of patients with actinic keratosis in the forearms, biopsied at two points: the actinic keratosis and the axillary region. The biopsies of the actinic keratosis, perilesional area, and axilla were evaluated through keratinocyte intraepithelial neoplasia (KIN), and immunohistochemistry of p53, survivin, and Ki67. Nuclear morphometry of basal layer cells was performed through digital image analysis: entropy, area, perimeter, Ra, fractal dimension, circularity, color intensity, and largest diameter., Results: There were 13 patients included and 38 actinic keratosis biopsied. In morphometry, 1039 nuclei were analyzed, of which 228 represented axillary skin, 396 demonstrated actinic keratosis, and 415 represented the perilesional area to the actinic keratosis. There was a significant difference (p<0.05) in all variables tested for the topographies evaluated. A significant correlation was identified between nucellar morphometric elements, KIN, proliferation markers, and apoptosis. Joint patterns of p53, Ki67, and KIN discriminated the topographies sampled., Study Limitations: This was a cross-sectional study with a small number of patients., Conclusions: There are patterns of proliferation, resistance to apoptosis, and different cellular morphometrics between photoprotected skin and photoexposed skin. The joint expression of p53, Ki67, and KIN can characterize skin field cancerization activity., (Copyright © 2019 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Skin field cancerization (SFC) is a process that occurs in areas of the skin that have undergone genomic alterations induced by ultraviolet radiation. Actinic keratosis (AK) is a sign of its activity., Objectives: To evaluate the effectiveness and safety of 0·5% colchicine (COL) cream vs. methyl aminolaevulinate photodynamic therapy (MAL-PDT) in the treatment of AK and SFC., Methods: We conducted a randomized, open, intrasubject controlled trial. A total of 36 participants with 3-10 AKs on each forearm were treated with either COL cream (twice daily for 10 days) or a single session of MAL-PDT and were reassessed after 60 days. The clinical evaluation was performed using AK count, forearm photoageing scale (PAS) and AK degree (AKD). Patients underwent central forearm biopsies and histopathological evaluation by keratinocyte intraepithelial neoplasia (KIN) assessment, epithelial atrophy and immunohistochemistry (p53/Ki67)., Results: Overall, 50% of patients were male. The mean age was 70·9 years (SD 8·6) and phototypes I and II were predominant (89%). Total clearance was observed in six (17%) forearms treated with COL and seven (19%) forearms treated with MAL-PDT (P = 0·76); partial clearance was observed in 44% of forearms in the COL group and 67% of forearms in the MAL-PDT group (P = 0·07). In both COL and MAL-PDT groups, reductions in PAS (-6% vs. -6%) and AKD (-45% vs. -40%) were observed. KIN normalized in 28% of patients treated with MAL-PDT and 20% of those treated with COL. Epithelial atrophy reduced after treatment (P < 0·01). Expression levels of Ki67 and p53 were also assessed. Mild or moderate adverse effects were similar for both groups., Conclusions: COL 0·5% cream and MAL-PDT are safe and effective for treating SFC., (© 2018 British Association of Dermatologists.)

Background: The primary clinical manifestation of skin field cancerization is the presence of actinic keratoses (AKs). Current treatments for AKs related to skin field cancerization include photodynamic therapy (PDT) and colchicine. The objective of this study is to evaluate the efficacy and safety of 0.5% colchicine cream versus PDT with methyl aminolevulinate (MAL-PDT) in the treatment of skin field cancerization., Methods: In a randomized controlled and open clinical trial with a blind histopathological and immunohistochemical analysis, 36 patients with up to 10 AKs on their forearms will be included from the outpatient clinic. The forearms will be randomized into two groups, clinically evaluated and biopsied for histopathology and immunohistochemistry (p53 and Ki67). One forearm will be treated with 0.5% colchicine cream for 10 days, and the other forearm will receive one session of MAL-PDT; the forearms will subsequently be reassessed clinically and histologically after 60 days (T60) of treatment. The primary endpoint will be the point of complete clearance of AKs in T60. The sample size will enable a detection in the reduction of over 10% in AK counts between the groups with power of 0.9 and an alpha of 0.05, accounting for an estimated dropout rate of 10%, resulting in 36 patients (72 forearms). All participants included in the randomized study will be part of the analysis, and the final outcomes of any dropouts will be the value of their last visit (LOCF). The statistical analysis will be performed using SPSS 22.0, and a p value < 5% will be considered to be significant., Discussion: It is expected that colchicine will be superior to MAL-PDT in reducing AKs and in the skin field cancerization, and there will be good tolerability in both groups. Colchicine intervention is novel in that it provides a new alternative to MAL-PDT. Moreover, this drug is inexpensive that may be a potential treatment of skin field cancerization that can be prescribed in public health systems with good results., Trial Registration: The trial is registered in Brazilian Registry for Clinical Trials (Registration number: RBR-8y3sj9 , date assigned May 4, 2016, retrospectively registered).