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.).

Burden of infective endocarditis in an Australian cohort of people who inject drugs.

BACKGROUND: Infective endocarditis (IE) results in substantial morbidity and mortality in people who inject drugs (PWID). AIMS: To describe the burden of IE and its outcomes in PWID. METHODS: Retrospective cohort study of adults admitted to a tertiary referral centre in Melbourne, Australia, with IE due to injection drug use from 1997 to 2015. RESULTS: Ninety-seven PWID with 127 episodes of IE were identified with a median acute inpatient stay of 37 days (1-84). Admission to an intensive care unit was required in 67/127 (53%) episodes. Twenty-seven percent (34/127) of episodes occurred in patients with a previous episode of endocarditis. One third (43/127, 34%) of episodes involved left-sided cardiac valves. Antimicrobial treatment was completed in 88 (70%) episodes. Valve surgery was performed in 25/127 (20%) episodes. Predictors of surgery in univariable analysis were left-sided cardiac involvement (risk ratio (RR) 6.0), severe valvular regurgitation (RR 2.6) and cardiac failure (RR 2.2) (all P < 0.005). Twenty (16%) episodes resulted in death. Predictors of mortality on univariable analysis were left-sided cardiac involvement (RR 6.4), and not completing treatment (RR 0.12; both P < 0.001). The average estimated cost per episode was AU$74 168. CONCLUSIONS: IE causes a considerable burden of disease in PWID, with significant healthcare utilisation and cost. Surgery and death are not infrequent complications. In addition to ensuring completion of antimicrobial therapy, strategies such as opioid maintenance programmes may be useful in improving health outcomes for PWID.