Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients.

BACKGROUND: Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B3) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life. RESULTS: A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups. CONCLUSIONS: In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.).

Beyond skin deep: addressing comorbidities in psoriasis.

Psoriasis is a chronic inflammatory disease that is commonly encountered in primary care and is associated with significant morbidity that extends beyond the skin manifestations. Psoriasis is associated with an elevated risk of psoriatic arthritis, cardiovascular disease, obesity, insulin resistance, mental health disorders, certain types of malignancy, inflammatory bowel disease and other immune-related disorders, and hepatic and renal disease. Enhanced recognition of these comorbidities may lead to earlier diagnosis and potentially better overall health outcomes. Psoriatic nail involvement, severe skin disease and obesity are associated with a greater risk of psoriatic arthritis. Individuals with psoriasis should be routinely screened for psoriatic arthritis to allow for early intervention to improve long term prognosis. Life expectancy is reduced in people with psoriasis due to a variety of causes, with cardiovascular disease and malignancy being the most common aetiologies. Psoriasis affects several factors that contribute to worsened quality of life and increased risk of depression and anxiety. Effective therapies are now available that have been shown to concurrently improve skin disease, quality of life and psychiatric symptoms. As the concordance between psychosocial impact and objective disease severity does not always correlate, it is essential to tailor management strategies specifically to the needs of each individual. Cigarette smoking and excess alcohol consumption are among the most important modifiable risk factors that increase the likelihood of psoriasis development and severity of skin disease. This provides a compelling rationale for smoking cessation and limiting alcohol intake in people with psoriasis beyond their traditional harmful health consequences.

Who is afraid of biosimilars? Openness to biosimilars in an Australian cohort of patients with rheumatoid arthritis.

Biosimilars are increasingly adopted to improve affordability of biologics. An effective introduction of biosimilars requires an understanding of patient acceptance of these agents. We performed a cross-sectional study of 132 patients with rheumatoid arthritis prior to the introduction of biosimilar switching or prescribing in this cohort. Despite being unfamiliar with biosimilars, most patients are willing to accept biosimilar medicines if recommended by their rheumatologist. Patient concerns about biosimilar uptake mainly focus on concerns about its efficacy. There is a significant correlation between patient attitudes towards biosimilar and generic medicines.

Superficial fungal infections.

BACKGROUND: Tinea is a common fungal infection that can affect the skin, nails and hair. Tinea infection has a variety of clinical manifestations and affects all age groups, ranging from tinea pedis in adults to tinea capitis in pre-pubertal children. OBJECTIVE: This article provides an updated overview of the common clinical manifestations and practical approaches to the diagnosis and management of tinea infections. DISCUSSION: While tinea may be suspected on the basis of clinical grounds, it is important to be aware of the various conditions considered in the differential diagnosis that may mimic tinea infections. Topical and systemic antifungal modalities are available and are selected on the basis of the subtypes and severity of tinea infection. Untreated, tinea can cause significant morbidity and predispose to complications, including cellulitis and ulcers on the feet and alopecia on the scalp.

A comparative review of the isotretinoin pregnancy risk management programs across four continents.

Isotretinoin has revolutionized the treatment of severe acne vulgaris, a condition which if left untreated may result in significant socio-psychological implications for those affected. Timely access to isotretinoin therapy is important to avoid the risks of potential physical and emotional scarring. However, due to its high risks of teratogenicity, isotretinoin must be used with care in females of childbearing potential. Since isotretinoin's introduction, numerous risk management programs have been implemented across the world in an attempt to prevent isotretinoin use in pregnancy. This paper aims to provide an evidence-based review of the risk management programs for isotretinoin in Australia, Europe, Singapore, New Zealand, and the United States of America. The effectiveness of these programs and the factors leading to isotretinoin exposure in pregnancy are critically analyzed in an effort to inform the future direction with respect to designing the ideal regulatory program. Stringent risk management programs, such as the iPLEDGE in the US and Pregnancy Prevention Program (PPP) in Europe, may not be effective in reducing the risks of fetal exposure to isotretinoin when used alone. There is evidence that such strenuous regulation results in increased fear of teratogenic risks but does not translate into a reduced rate of pregnancies exposed to isotretinoin. A successful program must prioritize education about effective contraception, while minimizing any extraneous requirements, to ensure that women are not inadvertently undertreated for acne.

Hibernoma: a rare benign soft tissue tumour resembling liposarcoma.

Hibernoma is a rare benign soft tissue tumour that can mimic a liposarcoma on radiographic imaging. Our case series review illustrates the clinical presentation and radiographic appearances of four patients with histologically confirmed hibernoma. Hibernoma is usually hypointense relative to subcutaneous fat on T 1 weighted MRI and demonstrates partial fat suppression on fat-saturated sequences. Large intratumoral vessels likely support the diagnosis of hibernoma but are not invariably present. Fludeoxyglucose avidity on PET scan is not beneficial in distinguishing hibernoma from soft tissue malignancy because of its inherent, metabolically active property. Owing to the radiographic heterogeneity of hibernoma, it is currently not possible to diagnose hibernoma based on imaging characteristics alone. Given the excellent prognosis of hibernoma with marginal excision alone, an appreciation of the radiographic features is helpful in the appropriate pre-operative workup of soft tissue tumours.

Prescription Opioid Misuse and Public Health Approach in Australia.

The number of opioid prescriptions has increased significantly over the last few years due to multiple factors, such as physicians' heightened attention to pain management, greater prevalence of chronic pain due to the aging population, and the availability of sustained-release opioid preparations. Correspondingly, this has been associated with a rise in considerable harm due to opioid misuse, which is recognized as a national health priority in Australia. This article outlines the major public health approaches that have been introduced in Australia to address this issue. Opioid misuse can be addressed through establishing a real-time prescription drug monitoring program, ensuring adequate access to affordable and high quality medication-assisted treatment, and promoting physicians' use of the evidence-based guideline on appropriate opioid prescribing.