Complement component 3c and tumor necrosis factor-α systemic assessment after Candida antigen immunotherapy in cutaneous warts.

BACKGROUND: Cutaneous warts are the commonest benign lesion produced by human papillomavirus. Lesions often regress spontaneously yet have a high rate of recurrence. They impair patients' quality of life and carry the potential risk of cancer. Nowadays, Candida antigen immunotherapy has become an encouraging therapeutic modality for warts. We tried to assess the role of the complement pathway and T helper 1 immune response in clinical response to Candida antigen immunotherapy via complement component 3c (C3c) and tumor necrosis factor (TNF)-α, respectively. METHODS: A total of 44 patients with cutaneous warts were enrolled in the study. Patients were injected with Candida antigen at 2-week interval until complete clearance of the lesion or for a maximum of 5 sessions. Blood samples were collected before initiation and after completion of immunotherapy. C3 and C4 were measured using an automated turbidimetric method. Mannose-binding lectin (MBL), C3c, and TNF-α were measured using enzyme-linked immune sorbent assay. RESULTS: A total of 56.4%, 17.9%, and 25.7% of the patients showed complete, partial, and no response to immunotherapy, respectively. Lesions on the dorsum of the foot and sole showed significant clearance (p value = 0.037). All patients had no deficient C3, C4, and MBL serum levels. C3c and TNF-α serum levels were significantly higher in non-responder group (p value < 0.001 and < 0.001, respectively). C3c and TNF-α serum levels were strongly correlated in all the studied patients (r = 0.8, p value < 0.001). CONCLUSIONS: Candida antigen immunotherapy is an effective therapeutic modality for cutaneous warts. C3c and TNF-α serum levels were higher in patients who failed to respond to immunotherapy. CLINICAL TRIAL REGISTRY NUMBER: NCT04399577 , May 2020 "retrospectively registered".

Intralesional immunotherapy with purified protein derivative (PPD) for cryotherapy-resistant warts.

BACKGROUND: Cryotherapy and immunotherapeutic modalities elicit nonspecific immune response against the human papillomavirus. There is a paucity of literature on the effects of a sequential shift to immunotherapy in cryotherapy-resistant warts. AIM: To study the efficacy of intralesional purified protein derivative (PPD) immunotherapy in cryotherapy-resistant warts. METHODS: Patients with cryotherapy-recalcitrant cutaneous warts were given intralesional injections of PPD into the index warts (oldest or largest) at 2-week intervals until complete clearance or up to a maximum of six injections. The response in the treated index and distant warts was defined as complete, partial, and no response (<25%). Complete responders were followed up for another 3 months to check for recurrence. RESULTS: Twenty-eight patients completed the study protocol. Of the eight patients with single warts, four (50%), one (12.5%), and three (37.5%) patients had complete, partial, and no response, respectively. Of the 20 patients with multiple warts, nine (45%) had complete clearance of all warts, two (10%) each had complete and partial response in the index wart, respectively, with no response of the distant warts, and seven (35%) had no response in all warts. Complete response was seen in an average of 3.1 injections (range 1-5). There was no recurrence at the follow-up visit. CONCLUSION: Immunotherapy with PPD has potential in producing regional and remote wart regression even in cryotherapy-resistant warts. It is a safe and economical modality in children, multiple warts, and difficult-to-treat warts.

Decision tree-based methodology to select a proper approach for wart treatment.

The human papillomaviruses (HPVs) can be responsible for various types of benign tumors called warts. Although warts can grow on all parts of the human body, common warts and plantar warts (as the most prevalent warts) grow principally on the hands and feet soles, respectively. Different treatment approaches such as cryotherapy and immunotherapy can be used to conquer the disease. However, the best healing method should be selected based on the patient circumstances. This study employs the classification and regression tree (CART) algorithm to develop accurate predictive models capable of analyzing the response of patients having common and/or plantar warts to the cryotherapy and/or immunotherapy methods. To develop a CART classifier for the cryotherapy method, independent parameters including the age and gender of patient, number of warts, type of wart, surface area of warts, and the time elapsed before treatment are used. In the case of immunotherapy, in addition to the above-mentioned variables, the induration diameter of the initial test is also considered. The error analysis reveals that the implemented CART models provide the highest achievable accuracy for the application of interest. Moreover, the proposed decision tree-based models are simple to use and more reliable, in contrast to the literature models that are mainly originated from the fuzzy rule-based method. Hence, the models introduced in this study can assist both patients and physicians save cost/time and improve the quality of healing operation.

Plantar Warts: Epidemiology, Pathophysiology, and Clinical Management.

Verrucae plantaris (plantar warts) are common cutaneous lesions of the plantar aspect of the foot that are caused by the human papillomavirus (HPV). Ubiquitous in our environment, asymptomatic infection with HPV occurs frequently, with most infections controlled or cleared by cellular and humoral immune responses. However, certain populations have been observed to manifest plantar warts at higher rates compared with the general population, placing them at increased risk for wart-induced pain and complications. Plantar warts shed HPV, which can then infect other sites in the plantar region or spread to other people. Although controlling risk factors is useful in preventing infection, the pervasive nature of HPV makes these preventive measures frequently impractical. This literature review outlines the current knowledge regarding the relationship between plantar wart pathophysiology, HPV transmission, and epidemiologic characteristics. Given the high propensity for treatment resistance of plantar warts and no established, practical, and reliable method of prevention, HPV prophylaxis for populations that demonstrate high rates of plantar warts may be of benefit in controlling the spread of lesions.

The EVerT2 (Effective Verruca Treatments 2) trial: a randomized controlled trial of needling vs. nonsurgical debridement for the treatment of plantar verrucae.

BACKGROUND: Verrucae are a common foot skin pathology, which can in some cases persist for many years. Plantar verrucae can be unsightly and painful. There are a range of treatment options including needling. OBJECTIVES: The EVerT2 (Effective Verruca Treatments 2) trial aimed to evaluate the clinical and cost-effectiveness of the needling procedure for the treatment of plantar verrucae, relative to callus debridement. METHODS: This single-centre randomized controlled trial recruited 60 participants (aged ≥ 18 years with a plantar verruca). Participants were randomized 1 : 1 to the intervention group (needling) or the control group (debridement of the overlying callus). The primary outcome was clearance of the index verruca at 12 weeks after randomization. Secondary outcomes included recurrence of the verruca, clearance of all verrucae, number of verrucae, size of the index verruca, pain and participant satisfaction at 12 and 24 weeks. A cost-effectiveness analysis was carried out from the National Health Service perspective over 12 weeks. RESULTS: Sixty eligible patients were randomized (needling group n = 29, 48%; debridement group n = 31, 52%) and 53 were included in the primary analysis (needling n = 28, 97%; debridement n = 25, 81%). Clearance of the index verruca occurred in eight (15%) participants (needling n = 4, 14%; debridement n = 4, 16%; P = 0·86). The needling intervention costs were on average £14·33 (95% confidence interval 5·32-23·35) more per patient than for debridement. CONCLUSIONS: There is no evidence that the needling technique is more clinically or cost-effective than callus debridement. The results show a significant improvement in pain outcomes after needling compared with the debridement treatment alone.

Implementation of blinded outcome assessment in the Effective Verruca Treatments trial (EverT) - lessons learned.

BACKGROUND: Trials using inadequate levels of blinding may report larger effect sizes than blinded studies. It has been suggested that blinded outcome assessment in open trials may in some cases be undertaken by assessments of photographs. The aim of this paper is to explore the effect of using different methods to assess the primary outcome in the EVerT (Effective Verruca Treatments) trial. It also aims to give an overview of the experiences of using digital photographs within the trial. METHODS: We undertook a secondary analysis to explore the effect of using three different methods to assess the primary outcome in the EVerT trial: assessment of digital photographs by blinded healthcare professionals; blinded healthcare professional assessment at the recruiting site and patient self-report. The verruca clearance rates were calculated using the three different methods of assessment. A Cohen's kappa measure of inter-rater agreement was used to assess the agreement between the methods. We also investigated the experiences of healthcare professionals using digital photographs within the trial. RESULTS: Digital photographs for 189 out of 240 (79 %) patients in the trial were received for outcome assessment. Of the 189 photographs, 30 (16 %) were uninterpretable. The overall verruca clearance rates were 21 % (43/202,) using the unblinded patient self-reported outcome, 6 % (9/159,) using blinded assessment of digital photographs and 14 % (30/210,) using blinded outcome assessment at the site. CONCLUSIONS: Despite differences in the clearance rates found using different methods of outcome assessment, this did not change the original conclusion of the trial, that there is no evidence of a difference in effectiveness between cryotherapy and salicylic acid. Future trials using digital photographs should consider individual training needs at sites and have a backup method of assessment agreed a priori. TRIAL REGISTRATION: ISRCTN Registry ISRCTN18994246.

Treatment of warts and molluscum: what does the evidence show?

PURPOSE OF REVIEW: Warts and molluscum contagiosum are very common viral skin infections, usually presenting in childhood. Despite the large number of people affected by them, high-quality trials of treatment are few and treatment is often chosen on the basis of cost, convenience and tradition. RECENT FINDINGS: Over recent years, two further trials of the most commonly used treatments for warts, salicylic acid and cryotherapy, have been performed and for molluscum contagiosum, there is growing evidence for the use of irritants. For both infections, there are new evaluations of immunological approaches to therapy. SUMMARY: Strong, high-quality evidence for treatments used very frequently for warts or molluscum is still lacking, but recent publications have helped to strengthen or weaken belief in commonly used therapies and to add weight to the immunological approach to management.

EVerT2-needling versus non-surgical debridement for the treatment of verrucae: study protocol for a single-centre randomised controlled trial.

INTRODUCTION: Verrucae are extremely common, and are experienced by most people at some time during their lives. Although most verrucae will spontaneously disappear without treatment, many patients seek treatment, often because they have persisted for many years, are unsightly or painful or prevent them from doing sports or other activities. There are many different treatments available; including the Falknor's needling procedure. To date, there has only been one small trial evaluating the clinical effectiveness of this treatment and no health economic analysis has been undertaken. The Effective Verruca Treatments (EVerT2) trial aims to evaluate the clinical and cost-effectiveness of the needling procedure for the treatment of verrucae. METHODS AND ANALYSIS: This single-centre randomised controlled trial will recruit 58 participants (aged 18 years and over with a plantar verruca) from Salford Podiatry Clinic patient lists and the surrounding area. If the participant presents with multiple verrucae, an 'index' verruca (largest and thickest lesion) will be identified and patients will be randomised 1:1 to the intervention group to receive the needling treatment or the control group to have the callus overlying the verruca debrided. The primary outcome is complete clearance of the index verruca at 12 weeks after randomisation. Secondary outcomes include clearance and recurrence of the treated verruca, clearance of all verrucae, number of verrucae remaining, change in size of the index verruca, pain, and participant satisfaction. A cost-effectiveness analysis of the needling versus callus debridement will be carried out from the perspective of health services over a time horizon of 12 weeks. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the University of Salford, Department of Health Sciences Ethical Approval Committee (HSCR15/24) and the University of York, Department of Health Sciences Research Governance Committee (HSRGC/2014/98/B). Findings will be disseminated through publication and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN16429440.

A new patent-based approach for technology mapping in the pharmaceutical domain.

The key factor in decision-making is the quality of information collected and processed in the problem analysis. In most cases, patents represent a very important source of information. The main problem is how to extract such information from the huge corpus of documents with a high recall and precision, and in a short time. This article demonstrates a patent search and classification method, called Knowledge Organizing Module, which consists of creating, almost automatically, a pool of patents based on polysemy expansion and homonymy disambiguation. Since the pool is done, an automatic patent technology landscaping is provided for fixing the state of the art of our product, and exploring competing alternative treatments and/or possible technological opportunities. An exemplary case study is provided, it deals with a patent analysis in the field of verruca treatments.

The EVERT (effective verruca treatments) trial protocol: a randomised controlled trial to evaluate cryotherapy versus salicylic acid for the treatment of verrucae.

BACKGROUND: Verrucae are a common, infectious and sometimes painful problem. The optimal treatment for verrucae is unclear due to a lack of high quality randomised controlled trials. The primary objective of this study is to compare the clinical effectiveness of two common treatments for verrucae: cryotherapy using liquid nitrogen versus salicylic acid. Secondary objectives include a comparison of the cost-effectiveness of the treatments, and an investigation of time to clearance of verrucae, recurrence/clearance of verrucae at six months, patient satisfaction with treatment, pain associated with treatment, and use of painkillers for the treatments. METHODS/DESIGN: This is an open, pragmatic, multicentre, randomised controlled trial with two parallel groups: cryotherapy using liquid nitrogen delivered by a healthcare professional for a maximum of 4 treatments (treatments 2-3 weeks apart) or daily self-treatment with 50% salicylic acid for a maximum of 8 weeks. Two hundred and sixty-six patients aged 12 years and over with a verruca are being enrolled into the study. The primary outcome is complete clearance of all verrucae as observed on digital photographs taken at 12 weeks compared with baseline and assessed by an independent healthcare professional. Secondary outcomes include self-reported time to clearance of verrucae, self-reported clearance of verrucae at 6 months, cost-effectiveness of the treatments compared to one another, and patient acceptability of both treatments including possible side effects such as pain. The primary analysis will be intention to treat. It is planned that recruitment will be completed by December 2009 and results will be available by June 2010. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18994246.

To freeze or not to freeze: a cost-effectiveness analysis of wart treatment.

BACKGROUND: Several general practitioner (GP)-prescribed and over-the-counter therapies for warts and verrucae are available. However, the cost-effectiveness of these treatments is unknown. OBJECTIVES: To compare the cost-effectiveness of different treatments for cutaneous warts. METHODS: We designed a decision-analytic Markov simulation model based on systematic review evidence to estimate the cost-effectiveness of various treatments. The outcome measures studied are percentage of patients cured, cost of treatment and incremental cost-effectiveness ratio for each treatment, compared with no treatment, after 18 weeks. RESULTS: Duct tape was most cost-effective but published evidence of its effectiveness is sparse. Salicylic acid was the most cost-effective over-the-counter treatment commonly used. Cryotherapy administered by a GP was less cost-effective than GP-prescribed salicylic acid and less cost-effective than cryotherapy administered by a nurse. CONCLUSIONS: Duct tape could be adopted as the primary treatment for cutaneous warts if its effectiveness is verified by further rigorous trials. Nurse-administered cryotherapy is likely to be more cost-effective than GP-administered cryotherapy.

Human papillomavirus: burden of illness and treatment cost considerations.

The monetary and personal costs to society of human papillomavirus (HPV) infection are enormous. In order to make a comparison of different treatment methods we reviewed the entire literature on HPV treatment from January 1966 to December 2003 using MEDLINE, with particular reference to published meta-analyses, randomized controlled and comparative studies. Patient-applied therapies offer patients the possibility of convenient and, on the whole, pain-free treatment. Podofilox (podophyllotoxin) and salicylic acid for genital and extragenital warts, respectively, have the additional advantage of being the most cost-effective treatments and, on this basis, they are to be commended as appropriate first-line agents. The second-line treatment of choice for common warts is cryotherapy. For recalcitrant common warts possible options include inosine pranobex with cryotherapy or electrosurgery, imiquimod with paring and occlusion, intralesional bleomycin, or diphencyprone. Alternative first-line and second-line treatments for genital warts would be either some form of surgical removal or imiquimod. The first option may be the cheapest but this has to be balanced against a degree of post-operative morbidity. Limited data from comparative studies do not show any clear difference in efficacy between cryotherapy, trichloroacetic acid, scissor excision, electrosurgery, and laser surgery in the treatment of genital warts, and the cost effectiveness of these therapies is probably similar to that of imiquimod. Cryotherapy and trichloroacetic acid are relatively expensive and inconvenient for patients and should be reserved as third-line treatments with certain exceptions, such as cryotherapy for meatal warts. The duration of treatment is significantly related to the number of warts present, the area covered by the warts, and the length of time the warts have been present. For recalcitrant anogenital warts third-line treatment options that show promise include surgery in combination with imiquimod or cidofovir cream. For squamous intraepithelial lesions that cannot easily be excised or physically ablated current treatment options include imiquimod and fluorouracil cream. The latter is an inexpensive option but causes the greatest morbidity. It is hoped that cidofovir may be added to this list if it becomes commercially available, and that protective and therapeutic HPV vaccines will transform the management of HPV in the future.

Comparing therapy costs for physician treatment of warts.

To compare the cost of several common modalities used to treat non-genital warts in immunocompetent patients, we identified studies published in English using standard search strategies and evaluated the literature for the following common non-genital wart therapies: cryotherapy with liquid nitrogen, carbon dioxide and pulsed-dye laser therapy, topical squaric acid, intralesional bleomycin, intralesional interferon alpha injections, and intralesional immunotherapy with Candida antigens. Standard treatment algorithms, compiled by dermatologists experienced in the treatment of patients with moderate wart burdens, were utilized for cost-comparison analyses. Based on the cost analysis model, the least expensive treatment option for non-genital warts were carbon dioxide laser therapy (157 dollars) and Candida antigen injections (190 dollars). The other treatment modalities examined ranged from 495 dollars (bleomycin) to 1227 dollars (interferon alpha). Although treatment with the carbon dioxide laser therapy is the least expensive, pain and post-procedure complications limit the use of this modality.

[Cryotherapy: how to use it and cost analysis]. / Crioterapia. Utilización y análisis de costes.

The authors analyze the results obtained by the use of cryotherapy at the Rochapea Health Clinic from October 1995 until the 30th of June 1997. The authors make known the fundamentals and techniques of cryotherapy to other professionals who are not familiar with it and encourage them to put it into practice. They analyze the treatment given in 203 cases of common warts and plantar papillomas and specifically to the use of cryotherapy in 128 lesions at the Rochapea Health Clinic. The procedure is simple, effective, efficient and easy to learn. It happens to be quicker than conventional surgery and presents very few complications.