The lifetime risk and impact of vitiligo across sociodemographic groups: a UK population-based cohort study.

BACKGROUND: Vitiligo is an autoimmune skin disorder characterised by depigmented patches of skin, which can have significant psychological impacts. OBJECTIVES: To estimate lifetime incidence of vitiligo, overall, by ethnicity, and across other sociodemographic subgroups, and to investigate the impacts of vitiligo on mental health, work, and healthcare utilisation. METHODS: Incident vitiligo cases were identified in the Optimum Patient Care Database of primary care records in the UK between 01/01/2004 and 31/12/2020. Lifetime incidence of vitiligo was estimated at age 80 using modified time-to-event models with age as the timescale, overall and stratified by ethnicity, sex and deprivation. Depression, anxiety, sleep disturbance, healthcare utilisation and work-related outcomes were assessed in the two years after vitiligo diagnosis compared to matched unaffected controls. RESULTS: 9,460 adults and children were newly diagnosed with vitiligo. Overall cumulative lifetime incidence was 0.92% at age 80 years (95% Confidence Interval [CI] 0.90, 0.94). Cumulative incidence was similar in females 0.94% (95%CI 0.92, 0.97) and males 0.89% (95%CI 0.86, 0.92). There were substantial differences in lifetime incidence across ethnic groups; Asian 3.58% (95%CI 3.38, 3.78), black 2.18% (95%CI 1.85, 2.50), mixed 2.03% (95%CI 1.58, 2.47), other 1.05% (95%CI 0.94, 1.17) and white ethnicity 0.73% (95%CI, 0.71, 0.76).People with vitiligo had an increased risk of depression (adjusted Odds Ratio [aOR] 1.08; 95%CI 1.01, 1.15), anxiety (aOR 1.19; 95%CI 1.09, 1.30), depression or anxiety (aOR 1.10; 95%CI 1.03, 1.17) and sleep disturbance (adjusted Hazard Ratio [aHR] 1.15; 95%CI 1.02, 1.31) compared to matched controls. People with vitiligo also had a greater number of primary care encounters (adjusted incidence rate ratio 1.29; 95%CI 1.26, 1.32) and a greater risk of time off work (aHR 1.15; 95%CI 1.06, 1.24). There was little evidence of disparities in vitiligo related impacts across ethnic subgroups. CONCLUSIONS: Clinicians should be aware of the markedly increased incidence of vitiligo in people of non-white ethnicity. The negative impact of vitiligo on mental health, work and healthcare utilisation highlights the importance of monitoring people with vitiligo to identify those who need additional support.The study protocol for this retrospective observational study was registered with ClinicalTrials.gov (Identifier: NCT06097494).

Risk of Melanoma and Nonmelanoma Skin Cancer in People with Vitiligo: United Kingdom Population-Based Cohort Study.

Although genetic studies have found an inverse relationship between vitiligo and skin cancer, epidemiological evidence is conflicting. We investigated the risk of skin cancer in adults with vitiligo using United Kingdom electronic primary care records from the Optimum Patient Care Research Database 2010-2020. Vitiligo cases were age, sex, and general practitioner practice matched to population controls without vitiligo. Incidence of melanoma, nonmelanoma skin cancers (squamous cell carcinoma and basal cell carcinoma), and actinic keratoses was compared between vitiligo cases and controls using Cox regression. A total of 15,156 vitiligo cases were matched to 60,615 controls. Vitiligo was associated with a 38% reduced risk of new-onset skin cancer (adjusted hazard ratio [aHR] = 0.62, 95% confidence interval [CI] = 0.52-0.75, P < 0.001) and skin cancer subtypes; melanoma (aHR = 0.39, 95% CI = 0.23-0.65, P < 0.001), squamous cell carcinoma (aHR = 0.67, 95% CI = 0.49-0.90, P < 0.01), basal cell carcinoma (aHR = 0.65, 95% CI = 0.51-0.83, P < 0.001). There was no significant association for actinic keratosis (aHR = 0.88, 95% CI = 0.77-1.01). People with vitiligo have a markedly reduced incidence of melanoma and nonmelanoma skin cancer. Given concerns that some treatments, such as phototherapy, may increase skin cancer risk, this finding provides reassurance to people with vitiligo and clinicians managing the condition.

Efficacy and safety of abrocitinib monotherapy in adolescents and adults: a post hoc analysis of the phase 3 JAK1 atopic dermatitis efficacy and safety (JADE) REGIMEN clinical trial.

BACKGROUND: Differences in atopic dermatitis (AD) disease course and manifestation with age may extend to treatment response. OBJECTIVE: To evaluate response maintenance with continuous-/reduced-dose abrocitinib or withdrawal and response to treatment reintroduction after flare in adolescent and adult participants in JADE REGIMEN (NCT03627767). METHODS: Adolescents (12-17 years) and adults with moderate-to-severe AD responding to abrocitinib 200-mg induction were randomly assigned to 40-week maintenance with abrocitinib (200 mg/100 mg) or placebo. Patients who experienced flare during maintenance received rescue treatment. RESULTS: Of 246 adolescents and 981 adults, 145/246 (58.9%) and 655/981 (66.8%), respectively, responded to induction. Similar proportions of adolescents and adults experienced flare during maintenance with abrocitinib 200 mg (14.9%/16.9%), 100 mg (42.9%/38.9%), and placebo (75.5%/78.0%). From the abrocitinib 200-mg, 100-mg, and placebo arms, respectively, Eczema Area and Severity Index response was recaptured by 28.6%, 25.0%, and 52.9% of adolescents and 34.3%, 33.7%, and 58.0% of adults; Investigator's Global Assessment response, by 42.9%, 50.0%, and 73.5% of adolescents and 34.3%, 50.6%, and 74.1% of adults. Abrocitinib had a similar safety profile regardless of age; nausea incidence was higher in adolescents. LIMITATIONS: Adolescents represented 20% of the trial population. CONCLUSION: Abrocitinib was effective in preventing flare in adolescents and adults.Clinicaltrials.gov listing: NCT03627767.

Real-World Budget Impact of Fidaxomicin versus Vancomycin or Metronidazole for In-Hospital Treatment of Clostridioides difficile Infection

Fidaxomicin, a macrocyclic antibiotic, selectively kills Clostridioides difficile and reduces C. difficile infection (CDI) recurrence compared with vancomycin, but some studies and guidelines report fidaxomicin as being less cost-effective. The aim of this study was to compare the cost-effectiveness and budget impact of fidaxomicin versus vancomycin or metronidazole for treating CDI in a real-world UK setting. Data were retrospectively collected from medical records of 86 patients with CDI treated with vancomycin or metronidazole at a single UK hospital between April 2011 and March 2012, and prospectively from 62 patients with CDI treated with fidaxomicin between August 2012 and July 2013. CDI cases were matched by age, financial year, and healthcare resource use to control cases. CDI recurrence rates were lower with fidaxomicin (6.5%) than vancomycin/metronidazole (19.8%). An estimated 12 additional recurrent CDIs were prevented with fidaxomicin treatment. Patients with CDI had significantly higher healthcare costs than those without CDI, with a mean excess spend of GBP 10,748 and GBP 17,451 per patient in the fidaxomicin (p = 0.015) and vancomycin/metronidazole cohorts (p < 0.001), respectively. A second CDI was associated with mean excess costs of GBP 8373 and GBP 20,249 per patient in the fidaxomicin and vancomycin/metronidazole cohorts, respectively. Despite higher fidaxomicin drug costs, overall cost savings were estimated at GBP 140,292 (GBP 2125 per CDI). In this real-world study, first-line CDI treatment with fidaxomicin reduced healthcare costs versus vancomycin/metronidazole, consistent with previous studies.

The mental health associations of vitiligo: UK population-based cohort study.

BACKGROUND: Vitiligo is an acquired, autoimmune depigmenting skin disorder that may affect psychological well-being. AIMS: To determine the risk and impact of psychological comorbidity in people with new-onset vitiligo. METHOD: We conducted a retrospective observational study, using UK general practice data (2004-2020). Adults diagnosed with vitiligo (n = 7224) were matched 1:4 with controls (n = 28 880). Associations within 2 years of diagnosis were assessed for psychological conditions: recurrent depressive disorder (RDD), depressive episodes, non-phobia-related anxiety disorder, social phobia, adjustment disorder, substance misuse, self-harm and suicide attempts. Healthcare utilisation, time off work and unemployment within 1 year were compared in those with and without a mental health condition at vitiligo diagnosis. RESULTS: At diagnosis, people with vitiligo had a similar prevalence of mental health conditions as controls, except for anxiety disorder (cases 7.9%, controls 7.0%; P = 0.014). Incident RDD and anxiety disorder were more common in people with vitiligo (RDD: adjusted hazard ratio (aHR) 1.25, 95% CI 1.01-1.55; anxiety disorder: aHR 1.23, 95% CI 1.00-1.51). Risk was highest in Black and minority ethnic individuals (RDD: aHR 1.72, 95% CI 1.06-2.79; depressive episodes: aHR 1.56, 95% CI 1.03-2.37). No association was found with other mental health conditions. People with vitiligo and psychological comorbidity had more primary care encounters, more time off workand higher unemployment. CONCLUSIONS: People with vitiligo have a higher incidence of RDD and anxiety disorder than controls, and this risk increase may be greatest in Black and minority ethnic populations.

The formulation of polyhedral boranes for the boron neutron capture therapy of cancer.

The early promise of boron neutron capture therapy as a method for the treatment of cancer has been inhibited by the inherent toxicity associated with therapeutically useful doses of ¹°B-containing pharmacophores, the need for target-tissue specificity and the challenges imposed by biological barriers. Although developments in the synthetic chemistry of polyhedral boranes have addressed issues of toxicity to a considerable extent, the optimisation of the transport and the delivery of boronated agents to the site of action--the subject of this review--is a challenge that is addressed by the development of innovative formulation strategies.