Alopecia areata and risk of common infections: a population-based cohort study.

BACKGROUND: It is not known whether alopecia areata (AA) is associated with a greater or reduced risk for infection. AIM: We undertook a population-based study exploring associations between AA and common infections. METHODS: We extracted primary care records from the UK Oxford-Royal College of General Practitioners Research and Surveillance Centre database (trial registration: NCT04239521). The incidence of common and viral infection composite outcomes, and individual respiratory, gastrointestinal (GI), skin, urinary tract, genital and herpes infections, were compared in people with AA (AA group, n = 10 391) and a propensity-matched control group (n = 41 564). Adjusted hazard ratios (aHRs), controlling for sociodemographic and clinical covariates, and comorbidities were used to estimate the association between AA and each infection over 5 years. RESULTS: The incidence (per 100 person-years) of common infections was slightly higher in the AA group [14.2, 95% confidence interval (CI) 13.8-14.6] than the control group (11.7, 95% CI 11.5-11.9). In adjusted analysis, positive associations were observed for composite outcomes (common infections aHR 1.13, 95% CI 1.09-1.17; viral infections aHR 1.11, 95% CI 1.07-1.16) and with respiratory tract, GI, skin and herpes simplex infections (aHR range 1.09-1.32). Excluding people in the control group without a recent consultation with their general practitioner showed no association between AA and infection (common infections aHR 1.01, 95% CI 0.98-1.05, viral infections aHR 0.99, 95% CI 0.95-1.03). CONCLUSIONS: The association between AA and common infection may represent a higher propensity of people with AA to engage with healthcare services (and thereby to have infections recorded), rather than a true association between AA and infection. Overall our findings suggest that AA is not associated with a clinically significantly increased or decreased incidence of common infections.

The associated burden of mental health conditions in alopecia areata: a population-based study in UK primary care.

BACKGROUND: Alopecia areata (AA) is a common cause of nonscarring hair loss that can have a profound psychological impact. OBJECTIVES: To assess the co-occurrence of depression and anxiety in adults with AA compared with the general population, and to evaluate the mental health treatment burden and impact on time off work and unemployment. METHODS: In total, 5435 people with newly diagnosed AA in UK primary care were identified from the Oxford Royal College of General Practitioners Research and Surveillance Centre network database, and matched to 21 740 controls. In cases and controls, we compared the prevalence and incidence of depressive episodes, recurrent depressive disorder and anxiety disorder, rates of time off work and unemployment, and, in those with pre-existing mental health conditions, rates of mental health-related prescribing and referral rates. This observational was registered with ClinicalTrials.gov (NCT04239521). RESULTS: Depression and anxiety were more prevalent in people diagnosed with AA than in controls (P < 0·001). People with AA were also more likely to subsequently develop new-onset depression and anxiety: adjusted hazard ratio (aHR) for recurrent depressive disorder 1·38 [95% confidence interval (CI) 1·13-1·69], depressive episodes aHR 1·30 (95% CI 1·04-1·62) and anxiety disorder aHR 1·33 (95% CI 1·09-1·63); to be issued time off work certificates (aHR 1·56, 95% CI 1·43-1·71); and to be recorded as unemployed (aHR 1·82, 95% CI 1·33-2·49). Higher rates of antidepressant prescribing were also seen in people with AA. CONCLUSIONS: People with AA have higher rates of depression and anxiety than those without AA. This impacts deleteriously on mental health treatment burden, time off work and unemployment. Evidence-based mental health treatment programmes are needed for people with AA.

Epidemiology, management and the associated burden of mental health illness, atopic and autoimmune conditions, and common infections in alopecia areata: protocol for an observational study series.

INTRODUCTION: Alopecia areata (AA) is a common cause of immune-mediated non-scarring hair loss. Links between AA and common mental health, autoimmune and atopic conditions, and common infections have previously been described but remain incompletely elucidated and contemporary descriptions of the epidemiology of AA in the UK are lacking. METHODS AND ANALYSIS: Retrospective study series using a large population-based cohort (5.2 million) from the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database, exploring four themes: AA epidemiology, mental health comorbidities, autoimmune/atopic associations and common infections.In the epidemiology theme, we will describe the incidence and point prevalence of AA overall and by age, sex and sociodemographic factors. Healthcare utilisation (primary care visits and secondary care referrals) and treatments for AA will also be assessed. In the mental health theme, we will explore the prevalence and incidence of mental health conditions (anxiety, depressive episodes, recurrent depressive disorder, adjustment disorder, agoraphobia, self-harm and parasuicide) in people with AA compared with matched controls. We will also explore the mental health treatment patterns (medication and psychological interventions), time off work and unemployment rates. Within the autoimmune/atopic associations theme, we will examine the prevalence of atopic (atopic dermatitis, allergic rhinitis, asthma) and autoimmune conditions (Crohn's disease, ulcerative colitis, coeliac disease, type 1 diabetes, Hashimoto's thyroiditis, Graves' disease, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus (SLE), polymyalgia rheumatica, Sjögren's syndrome, psoriasis, vitiligo, multiple sclerosis, pernicious anaemia) in people with AA compared with matched controls. We will also estimate the incidence of new-onset atopic and autoimmune conditions after AA diagnosis. Within the common infections theme, we will examine the incidence of common infections (respiratory tract infection, pneumonia, acute bronchitis, influenza, skin infection, urinary tract infection, genital infections, gastrointestinal infection, herpes simplex, herpes zoster, meningitis, COVID-19) in people with AA compared with matched controls. ETHICS AND DISSEMINATION: The Health Research Authority decision tool classed this a study of usual practice, ethics approval was not required. Study approval was granted by the RCGP RSC Study Approval Committee. Results will be disseminated through peer-reviewed publications. OBSERVATIONAL STUDY REGISTRATION NUMBER: NCT04239521.

Enhancement of tioconazole ungual delivery: Combining nanocapsule formulation and nail poration approaches.

This work investigated the impact of formulation including in vitro release profile, repeated dosing, and nail poration on the ex vivo nail delivery performance of antifungal formulations. Chitosan coated and uncoated tioconazole-loaded nanocapsules and a nano-based film-forming vehicle were assessed via in vitro release and in vitro permeation tests using an artificial membrane and human nail clippings, respectively. The later involved single and daily dosing experiments with intact and porated nails. Additional experiments with Nile Red-loaded formulations evaluated the depth of penetration of the fluorescent marker into the nail by laser scanning confocal microscopy. The nanocapsule formulations prolonged release of tioconazole for longer than the control solutions and this ability was related to an enhanced nail penetration of the drug. Further, the new film-forming formulation delivered its drug payload more efficiently than a marketed product. Daily dosing of the formulations doubled the amount of drug recovered from the nails. Porating the nails enhanced tioconazole delivery in single dose experiments only. The depth of penetration of Nile Red into the nails clippings ranged between 90-160 µm. This research suggests that ensuring prolonged release of a drug is fundamental to develop efficacious topical nail formulations.

Drug delivery into microneedle-porated nails from nanoparticle reservoirs.

This study demonstrates the potential of polymeric nanoparticles as drug reservoirs for sustained topical drug delivery into microneedle-treated human nail. Laser scanning confocal microscopy was used to image the delivery of a fluorescent model compound from nanoparticles into the nail. A label-free imaging technique, stimulated Raman scattering microscopy, was applied, in conjunction with two-photon fluorescence imaging, to probe the disposition of nanoparticles and an associated lipophilic 'active' in a microneedle-porated nail. The results provide clear evidence that the nanoparticles function as immobile reservoirs, sequestered on the nail surface and in the microneedle-generated pores, from which the active payload can be released and diffuse laterally into the nail over an extended period of time.

Molecular diffusion in the human nail measured by stimulated Raman scattering microscopy.

The effective treatment of diseases of the nail remains an important unmet medical need, primarily because of poor drug delivery. To address this challenge, the diffusion, in real time, of topically applied chemicals into the human nail has been visualized and characterized using stimulated Raman scattering (SRS) microscopy. Deuterated water (D2O), propylene glycol (PG-d8), and dimethyl sulphoxide (DMSO-d6) were separately applied to the dorsal surface of human nail samples. SRS microscopy was used to image D2O, PG-d8/DMSO-d6, and the nail through the O-D, -CD2, and -CH2 bond stretching Raman signals, respectively. Signal intensities obtained were measured as functions of time and of depth into the nail. It was observed that the diffusion of D2O was more than an order of magnitude faster than that of PG-d8 and DMSO-d6. Normalization of the Raman signals, to correct in part for scattering and absorption, permitted semiquantitative analysis of the permeation profiles and strongly suggested that solvent diffusion diverged from classical behavior and that derived diffusivities may be concentration dependent. It appeared that the uptake of solvent progressively undermined the integrity of the nail. This previously unreported application of SRS has permitted, therefore, direct visualization and semiquantitation of solvent penetration into the human nail. The kinetics of uptake of the three chemicals studied demonstrated that each altered its own diffusion in the nail in an apparently concentration-dependent fashion. The scale of the unexpected behavior observed may prove beneficial in the design and optimization of drug formulations to treat recalcitrant nail disease.

Investigation into the impact of sub-populations of agglomerates on the particle size distribution and flow properties of conventional microcrystalline cellulose grades.

Microcrystalline cellulose (MCC) is regarded as one of the most versatile tablet filler binders, finding a wide use in both granulation and direct compression operations. It has been shown that MCC particle populations consist of a mixture of 'rod like' primary particles, and agglomerates, and that the proportion of these primary particles and agglomerates differs within the different grades of materials, contributing to the different bulk properties of these materials. However, the proportion of primary particles and agglomerates has not previously been fully elucidated, and their contribution to the performance factors such as flow explained. In this paper we use a novel microscopy-based characterization technique to demonstrate that the proportion of 'agglomerates' in the series of MCC grades between PH101 and PH200 is, by number, very low, but sufficient to perturb a volume-based particle size method by significant amounts.

Investigation into the degree of variability in the solid-state properties of common pharmaceutical excipients-anhydrous lactose.

This paper reports the batch-to-batch and vendor-to-vendor variations in the solid-state characteristics of multiple batches of lactose anhydrous from each of three vendors and the subsequent impact of these differences on processability and/or functionality.