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Application of protection motivation theory (PMT) on skin cancer preventive behaviors amongst primary school students in rural areas of Fasa city-Iran.
Khani Jeihooni, A, Bashti, S, Erfanian, B, Ostovarfar, J, Afzali Hasirini, P
BMC cancer. 2022;(1):21
Abstract
BACKGROUND Considering that exposure to sunlight in childhood and adolescence has an important role in skin cancer, so it seems that training protective behaviors in this period is more effective. OBJECTIVES To survey the application of protection motivation theory (PMT) on skin cancer preventive behaviors among students in rural areas of Fasa city, Iran. METHODS This study was done in two stages: Phase I of this study, the descriptive-analytic and cross-sectional study was conducted in 2018 to investigate the predictive value of the protection motivation theory on skin cancer preventive behaviors. In the second stage, a quasi-experimental interventional study was conducted on 400 primary school students in 2019. The educational intervention was performed in the experimental group for 8 sessions. Data were collected using a demographic information questionnaire and protection motivation theory before and six months after the intervention. RESULTS The constructs of protection motivation theory predicted 58.6% of skin cancer preventive behaviors. The results indicated that there was no significant difference between the two groups in terms of knowledge, perceived sensitivity, perceived severity, reward, fear, protection motivation, response efficacy, self-efficacy, response costs, and the skin cancer preventive behaviors in before the intervention (p > 0.05). However, six months after the intervention, the experimental group showed a significant increase in each of the mentioned constructs and skin cancer protective behaviors (p < 0.05). CONCLUSION This study showed the effectiveness of the intervention based on the PMT constructs in adoption of skin cancer preventive behaviors in 6 months' post intervention in primary school students.
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Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program.
Simpson, EL, Silverberg, JI, Nosbaum, A, Winthrop, KL, Guttman-Yassky, E, Hoffmeister, KM, Egeberg, A, Valdez, H, Zhang, M, Farooqui, SA, et al
American journal of clinical dermatology. 2021;(5):693-707
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BACKGROUND Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy. OBJECTIVE The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study. METHODS Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported. RESULTS Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19. CONCLUSION Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD. TRIAL REGISTRIES ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.
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Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients.
Davar, D, Dzutsev, AK, McCulloch, JA, Rodrigues, RR, Chauvin, JM, Morrison, RM, Deblasio, RN, Menna, C, Ding, Q, Pagliano, O, et al
Science (New York, N.Y.). 2021;(6529):595-602
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Anti-programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti-PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti-PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-PD-1 in patients with PD-1-refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti-PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8-expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti-PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of PD-1 advanced melanoma.
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E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma: A phase I study.
Ohmachi, K, Ando, K, Ogura, M, Uchida, T, Tobinai, K, Maruyama, D, Namiki, M, Nakanishi, T
Cancer science. 2018;(3):794-802
Abstract
E7777, a recombinant cytotoxic fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2, shares an amino acid sequence with denileukin diftitox but has improved purity and an increased percentage of active protein monomer species. A phase I study was carried out to evaluate the tolerability, safety, pharmacokinetics, and antitumor activity of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma. E7777 (6, 12, and expanded 9 μg/kg/day) was given to 13 patients by i.v. infusion on five consecutive days per 21-day cycle. Dose-limiting toxicities, including increased alanine aminotransferase, hyponatremia (n = 2), hypokalemia, lymphopenia, fatigue, hypoalbuminemia, rash, and increased lipase (n = 1), were observed in all three patients in the 12 μg/kg/day cohort, whereas two of six patients in the 9 μg/kg/day cohort showed decreased appetite or fatigue. The maximum tolerated and recommended dose of E7777 was 9 μg/kg/day for five consecutive days per 21-day cycle. The objective response rate was 38% (5/13) and did not appear to depend on tumor expression of CD25. E7777 was well tolerated, assuming careful management of adverse events during treatment, and preliminary but clinically meaningful antitumor activity was observed. Subsequent studies of E7777 for T-cell lymphomas are warranted. This study was registered with www.ClinicalTrials.gov (NCT1401530).
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Socioeconomic Status and Poor Health Outcome at 10 Years of Follow-Up in the Multi-Ethnic Study of Atherosclerosis.
Shea, S, Lima, J, Diez-Roux, A, Jorgensen, NW, McClelland, RL
PloS one. 2016;(11):e0165651
Abstract
BACKGROUND/OBJECTIVES Predictors of healthy aging have not been well-studied using longitudinal data with demographic, clinical, subclinical, and genetic information. The objective was to identify predictors of poor health outcome at 10 years of follow-up in the Multi-Ethnic Study of Atherosclerosis (MESA). DESIGN Prospective cohort study. SETTING Population-based sample from 6 U.S. communities. PARTICIPANTS 4,355 participants In the MESA Study. MEASUREMENTS Poor health outcome at 10 years of follow-up was defined as having died or having clinical cardiovascular disease, depression, cognitive impairment, chronic obstructive pulmonary disease, or cancer other than non-melanoma skin cancer. Absolute risk regression was used to estimate risk differences in the outcome adjusting for demographic variables, clinical and behavioral risk factors, subclinical cardiovascular disease, and ApoE genotype. Models were weighted to account for selective attrition. RESULTS Mean age at 10 years of follow-up was 69.5 years; 1,480 participants had a poor health outcome, 2,157 participants were in good health, and 718 were unknown. Older age, smoking, not taking a statin, hypertension, diabetes, and higher coronary calcium score were associated with higher probability of poor health outcome. After multivariable adjustment, participants in the lowest income and educational categories had 7 to 14% greater absolute risk of poor health outcome at 10 years of follow-up compared to those in the next highest categories of income or education (P = 0.002 for both). Those in the lowest categories of both income and education had 21% greater absolute risk of poor health outcome compared to those in the highest categories of both income and education. CONCLUSIONS Low income and educational level predict poor health outcome at 10 years of follow-up in an aging cohort, independent of clinical and behavioral risk factors and subclinical cardiovascular disease.
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Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials.
Surjana, D, Halliday, GM, Martin, AJ, Moloney, FJ, Damian, DL
The Journal of investigative dermatology. 2012;(5):1497-500
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Topical treatment of actinic keratoses with potassium dobesilate 5% cream. a preliminary open-label study.
Cuevas Sánchez, P, Espinoza, W, Pérez, C, Angulo, J, Giménez-Gallego, G
European journal of medical research. 2011;(2):67-70
Abstract
BACKGROUND Fibroblast growth factor (FGF) is involved in skin tumorigenesis: it promotes cell viability, induces angiogenesis and stimulates invasiveness. Dobesilate is a drug that blocks the activity of FGF. The primary objective was to evaluate the efficacy and tolerability of potassium dobesilate 5% cream in the treatment of actinic keratoses. METHODS Potassium dobesilate 5% cream was applied twice daily for 16 weeks to actinic keratosis lesions in 30 patients. The lesions were evaluated clinically at an initial baseline visit, at intermediate visits, and at 16 weeks of treatment. - RESULTS The use of potassium dobesilate 5% cream for 16 weeks induced complete regression in 70% of evaluated actinic keratoses, corresponding to grade I, II and III clinical variants, and a partial response (at least 75% reduction of lesions) in 20% of the cases. CONCLUSION Our preliminary trial shows that potassium dobesilate exerts anti-tumorigenic effects and may play a useful role in the chemoprevention of skin cancers.
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Dose response of retinol and isotretinoin in the prevention of nonmelanoma skin cancer recurrence.
Clouser, MC, Roe, DJ, Foote, JA, Harris, RB, Alberts, DS
Nutrition and cancer. 2010;(8):1058-66
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Using data from a randomized, double blind, study of the efficacy of retinol or isotretinoin vs. placebo on recurrence of nonmelanoma skin cancer in high-risk subjects, a reanalysis of the original intent to treat analysis was performed in a dose-response format. Cox proportional hazards models describe the relationship between dose quartiles of isotretinoin and retinol use and time to first occurrence of squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) in crude and adjusted models. Neither the isotretinoin nor retinol models showed any significance at any quartile for reduction in first BCC or SCC occurrence. Crude and adjusted retinol models show a statistically significant increase in risk of developing an SCC in the first quartile, whereas only the crude model shows a statistically significant increase in risk in the first quartile of the isotretinoin model. For retinol and SCC, hazard ratios (HRs) for the first quartile were as follows: HR = 2.92, 95% confidence interval (CI) = 1.67-5.10 crude; HR = 1.95, 95% CI = 1.00-3.80 adjusted. For isotretinoin and SCC, HRs for the first quartile were as follows: HR = 2.38, 95% CI = 1.35-4.19 crude; HR = 1.69, 95% CI = 0.87-3.31 adjusted. Test for trend was not significant in any of the models. These analyses confirm the results of the original intent to treat analyses and raise an interesting question related to the potential for increased risk for patients in the first quartile of retinol dose.
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Safety and efficacy of arsenic trioxide for patients with advanced metastatic melanoma.
Tarhini, AA, Kirkwood, JM, Tawbi, H, Gooding, WE, Islam, MF, Agarwala, SS
Cancer. 2008;(5):1131-8
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BACKGROUND Arsenic trioxide (ATO) cytotoxicity and apoptosis induction has been demonstrated with numerous cancer cell lines, including human melanoma. METHODS A second-line, phase 2, single-arm study of ATO was conducted in patients with inoperable American Joint Committee on Cancer (AJCC) stage IV melanoma. One cycle consisted of a loading dose of 0.32 mg/kg/day for 4 days in Week 1, followed by 0.25 mg/kg/day twice per week for 6 weeks, followed by 1 week of rest, at which time response assessment was performed. RESULTS Twenty-one patients (median age, 63.8 years) were accrued. All had stage IV melanoma including M1a (2 patients), M1b (6 patients), and M1c (13 patients) disease. One patient had metastatic choroidal melanoma and 20 patients had cutaneous melanoma. Twenty patients had received prior therapy. Possible treatment-related grade 3 of 4 toxicities (using the National Cancer Institute Common Toxicity Criteria) included 1 case of idiopathic thrombocytopenic purpura and 1 case of elevated lactate dehydrogenase. Four patients did not complete the first cycle of therapy and were not evaluable for response. Among 17 evaluable patients, 1 patient (6%; 95% confidence interval [95% CI], 0-29%) achieved a partial response lasting 7 months, and 10 patients (59%) had disease stabilization after at least 1 cycle, but all eventually developed disease progression. The median time to disease progression was 17 weeks (95% CI, 11-38 weeks) and the median survival was 13 months (95% CI, 12-26 months). CONCLUSIONS ATO as tested in the current trial was found to be well tolerated and had limited activity in patients with metastatic melanoma. The application of this agent in combination with either chemotherapy or agents that target recognized critical signaling and antiapoptotic pathways of melanoma has not yet been performed.
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Results of a phase II trial of oral bexarotene (Targretin) combined with interferon alfa-2b (Intron-A) for patients with cutaneous T-cell lymphoma.
Straus, DJ, Duvic, M, Kuzel, T, Horwitz, S, Demierre, MF, Myskowski, P, Steckel, S
Cancer. 2007;(9):1799-803
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BACKGROUND Bexarotene is one of the most active single agents for the treatment of recurring or refractory cutaneous T-cell lymphoma (CTCL). Interferon alfa has also been used for many years as an effective treatment for this disease. The results in recent case reports of the combination of bexarotene and interferon alfa have been promising. Based on more extensive results reported with the combination of other retinoids with interferon alfa, the present study attempted to determine the response rate, response duration, and safety of bexarotene (Targretin capsules, Ligand Pharmaceuticals, San Diego, Calif) alone and then with the addition of interferon alfa-2b (Intron-A, Schering-Plough, Kenilworth, NJ). METHODS Patients with biopsy-proven CTCL, TNM stages IB, IIA, IIB-IV, were treated with oral bexarotene 300 mg/m2/day for at least 8 weeks. If a complete response was not seen after 8 weeks, interferon alfa-2b 3 million units (MU) subcutaneously was added, and increased to 5 MU if tolerated, 3 times a week. RESULTS A total of 22 patients were enrolled at 5 sites, and 18 patients were assessable for response. Overall response rate for combined bexarotene and interferon alfa was 39% (95% confidence interval [CI]: 17%-64%), including 1 patient with a clinical complete response, 6 patients with partial response, 3 patients with stable disease, and 8 patients with progressive disease. Three partial responses were first noted during the bexarotene-alone phase. Adverse events were generally manageable, and only 1 patient was withdrawn from study for hypertriglyceridemia. CONCLUSIONS The addition of interferon alfa-2b did not increase the response rate that would have been expected with bexarotene alone.