OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains.
METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey.
RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments.
CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.
OBJECTIVES: To develop a novel in vitro skin glycation model as a screening tool for topical formulations with antiglycation properties and to further characterize, at the molecular level, the glycation stress-driven skin ageing mechanism.
METHODS: The glycation model was developed using human reconstituted full-thickness skin; the presence of N(ε) -(carboxymethyl) lysine (CML) was used as evidence of the degree of glycation. Topical application of emulsion containing a well-known antiglycation compound (aminoguanidine) was used to verify the sensitivity and robustness of the model. Cytokine immunoassay, quantitative real-time polymerase chain reaction and histological analysis were further implemented to characterize the molecular mechanisms of skin ageing in the skin glycation model.
RESULTS: Transcriptomic and cytokine profiling analyses in the skin glycation model demonstrated multiple biological changes, including extracellular matrix catabolism, skin barrier function impairment, oxidative stress and subsequently the inflammatory response. Darkness and yellowness of skin tone observed in the in vitro skin glycation model correlated well with the degree of glycation stress.
CONCLUSIONS: The newly developed skin glycation model in this study has provided a new technological dimension in screening antiglycation properties of topical pharmaceutical or cosmeceutical formulations. This study concomitantly provides insights into skin ageing mechanisms driven by glycation stress, which could be useful in formulating skin antiageing therapy in future studies.
OBJECTIVES: To generate consensus among dermatologists on the content of an outpatient discharge checklist, to create one and to seek clinicians' opinions on its usefulness.
METHODS: Seventeen consultant dermatologists from five National Health Service trusts completed a 72-item Delphi questionnaire. A five-point Likert scale was used to rate each item for importance in contributing to a high-quality discharge decision. Eighteen clinicians completed a questionnaire evaluating checklist use.
RESULTS: Consensus was determined when ≥ 75% of consultants rated an item 'very important' or 'important'. There was strong inter-rater reliability (intraclass correlation coefficient = 0·958) and fair inter-rater agreement (Fleiss kappa = 0·269). There were 26 consensus-agreed items, condensed to 13 that formed the 'traffic-light' checklist. These are disease-related issues (diagnostic certainty, disease severity, treatment appropriateness, patient manageable in primary care, patient's benefit from follow-up), patient empowerment issues (understanding diagnosis and treatment outcome, having a clear plan, treatment side-effects, ability to self-manage) and addressing concerns (patient concerns, easy reaccess to secondary care, whether patient and clinician are happy with the decision). Twelve clinicians (67%) found the checklist useful, 11 (61%) wanted to use it in future, 10 (56%) thought it was useful for training and three (17%) said it helped their thinking. Clinicians suggested its use for auditing and for training clinicians and administrators.
CONCLUSIONS: Items were identified to create an outpatient discharge information checklist, which demonstrated high acceptability.
OBJECTIVES: To determine the prevalence and descriptive epidemiology of atopic dermatitis among school children in the general community in Singapore.
METHODS: This is a questionnaire study of 12 323 students done over a 1-year period, comprising 7 year olds (4605), 12 year olds (3940) and 16 year olds (3778) from 19 primary and 17 secondary schools randomly selected in Singapore. All children had a complete cutaneous examination. The diagnosis of atopic dermatitis was based on the U.K. Working Party diagnostic criteria. The questionnaire was translated into Chinese and both the English and Chinese versions were issued simultaneously to the students.
RESULTS: The 1-year period prevalence of atopic dermatitis was 20.8%. Atopic dermatitis was present in 22.7% of 7 year olds, 17.9% of 12 year olds and 21.5% of 16 year olds. The overall sex ratio was equal. There were slightly more boys with atopic dermatitis among the younger children (6 and 12 year olds, 1.18 : 1 and 1.19 : 1, respectively) but more girls were affected (1.57 : 1) among the 16 year olds. Atopic dermatitis was more common among the Chinese (21.6%) and Malays (19.8%) compared with the Indians (16%) and other races (14%). The onset of the disease occurred before the age of 10 years in 49.5% of the 16 year olds. "Pure" atopic dermatitis without concomitant respiratory allergies was noted in 788 respondents (30.7%); 1775 (69.3%) suffered from a "mixed" type, with 34.3% having allergic rhinitis, 9.5% having asthma and 25.5% having both asthma and allergic rhinitis. More boys had atopic dermatitis and concomitant respiratory allergies whereas more girls were affected with "pure" atopic dermatitis alone (1.4 : 1). At least one first-degree family member with atopy was noted in 1435 children (56%): atopic dermatitis (70%), asthma (62%) and allergic rhinitis (68%). Among siblings with one parent with atopic dermatitis, 37% had either a father or a mother with atopic dermatitis. Common aggravating factors reported included exercise, heat and sweating, grass intolerance, thick clothing and stress. Pityriasis alba was noted in 25% of the study population, keratosis pilaris in 13% and ichthyosis vulgaris in 8%. Most respondents had mild to moderate atopic dermatitis that could be controlled with a fairly simple regimen of moisturizers, topical steroids, antihistamines and antibiotics.
CONCLUSIONS: The high prevalence of atopic dermatitis in Singapore is similar to that observed in developed countries, suggesting that environmental factors may be important in determining the expression of the disease.
OBJECTIVE: To identify CPGs on AD worldwide and assess with validated instruments if those CPGs are clear, unbiased, trustworthy and evidence based (CUTE).
METHODS: We searched MEDLINE, Embase, PubMed, Web of Science, Cochrane Library, Emcare, Epistemonikos, PsycINFO and Academic Search Premier for CPGs on AD published between 1 April 2016 and 1 April 2021. Additionally we hand searched prespecified guideline resources. Screening, data extraction and quality assessment of eligible guidelines were independently carried out by two authors. Instruments used for quality assessment were the Appraisal of Guidelines for Research and Evaluation (AGREE) II Reporting Checklist, the U.S. Institute of Medicine's (IOM) criteria of trustworthiness and Lenzer's Red Flags.
RESULTS: Forty CPGs were included, mostly from countries with a high socio-demographic index. The reported quality varied enormously. Three CPGs scored 'Excellent' on all AGREEII-domains: Columbia, the Netherlands and United Kingdom (UK; antimicrobials). Three CPGs scored 'Poor' on all domains: Poland (phototherapy), Romania and Serbia. We found no association between AGREEII-scores and a country's gross domestic product. One CPG fully met all nine IOM criteria (Malaysia) and two fully met eight (European dupilumab and UK antimicrobials). Three CPGs had no red flags: Malaysia, South Korea and UK antimicrobials. 'Applicability' and 'Rigour of development' were the lowest scoring AGREEII domains; 'Lack of external review', 'Updating procedures' and 'Rating strength of recommendations' met the least IOM criteria; and most red flags were for 'Limited or no involvement of methodological expertise' and 'No external review'. Management of conflict of interests (COI) appeared challenging. When constructs of the instruments overlapped, they showed high concordance, strengthening our conclusions.
CONCLUSIONS: Overall, many CPGs are not clear, unbiased, trustworthy or evidence based (CUTE) enough and lack applicability. Therefore improvement is warranted, for which using the AGREEII instrument is recommended. Some improvements can be easily accomplished through robust reporting. Others, such as transparency, applicability, evidence foundation and managing COI, might require more effort.
OBJECTIVES: To determine the incidence and prevalence of psoriasis over 11 years in multiethnic Johor Bahru, Malaysia.
METHODS: A population-based cohort study was made using the Teleprimary Care database between January 2010 and December 2020. Cases of psoriasis, identified by ICD-10 diagnostic codes, were validated by dermatologists. Annual prevalence and incidence were estimated and stratified by age, sex and ethnicity.
RESULTS: We identified 3932 people with dermatologist-confirmed psoriasis, including 1830 incident cases, among 1 164 724 Malaysians, yielding an 11-year prevalence of 0·34% [95% confidence interval (CI) 0·33-0·35] and incidence of 34·2 per 100 000 person-years (95% CI 32·6-35·8). Rates were higher in Indian patients; the prevalences were 0·54% (0·50-0·58) in Indian, 0·38% (0·36-0·40) in Chinese and 0·29% (0·28-0·30) in Malay patients, and the respective incidences per 100 000 person-years were 52·5 (47·3-57·7), 38·0 (34·1-41·8) and 30·0 (28·2-31·8). Rates were higher in males; the prevalence was 0·39% (0·37-0·41) in males and 0·29% (0·27-0·30) in females, and the respective incidences per 100 000 person-years were 40·7 (38·2-43·2) and 28·3 (26·4-30·3). Between 2010 and 2020, annual psoriasis prevalence and incidence increased steadily from 0·27% to 0·51% and from 27·8 to 60·9 per 100 000 person-years, respectively. Annual rates were consistently higher in male and Indian patients. Overall, psoriasis was significantly more common in males than females [odds ratio (OR) 1·37, 95% CI 1·29-1·46] and in Indian and Chinese patients vs. Malay (OR 1·85, 1·71-2·01 and OR 1·30, 1·20-1·41, respectively). Prevalence increased with age, with the highest rates in the groups aged 50-59 and 60-69 years at 0·67% and 0·66%, respectively. A modest bimodal trend in age of psoriasis onset was observed, with first and second peaks at 20-29 and 50-59 years. Disease onset was significantly earlier in females than males [mean (SD) 36·8 (17·3) vs. 42·0 (17·2) years, P
OBJECTIVES: To determine the incidence and prevalence of GPP in the Malaysian population and characterize its flares and trigger factors.
METHODS: We conducted a population-based cohort study using the Teleprimary Care database between January 2010 and December 2020. We identified 230 dermatologist-confirmed GPP cases using International Classification of Diseases, 10th revision, diagnostic codes. Annual prevalence and incidence rates were stratified by age, sex and ethnicity. We compared data regarding flares and trigger factors for patients with GPP who had associated psoriasis vulgaris (PV) with those who did not have associated PV.
RESULTS: The prevalence of GPP was 198 per million (267 women, 127 men) and incidence was 27.2 per million person-years [95% confidence interval (CI) 22.8-31.6]; 35.3 (28.4-42.2) per million person-years for women and 18.3 (13.1-23.5) per million person-years for men. Rates were higher in Chinese individuals [prevalence 271 per million; incidence 41.6 per million person-years (28.9-54.3)] than in the Malay population [prevalence 186; incidence 24.6 (19.4-29.7)] or the Indian ethnic group [prevalence 179; incidence 25.0 (13.8-36.3)]. Annual prevalence was consistently higher in women than in men and highest among the Chinese population, followed by the Indian and Malay populations. Overall, 67% of patients with GPP had associated PV. The prevalence and incidence of GPP without PV were lower than GPP with PV at 66 vs. 132 per million and 19.3 (95% CI 15.6-23.0) vs. 8.0 (95% CI 5.6-10.3) per million person-years, respectively. The mean age at GPP onset was 42.7 years (SD 18.4). A bimodal trend in the age of GPP onset was observed, with first and second peaks at age 20-29 years and age 50-59 years, respectively. Disease onset was significantly earlier in patients with GPP without PV than in those with PV [mean age 37.5 years (SD 20.7) vs. 44.9 years (SD 17.0), P = 0.026]. Flares occurred more frequently in patients without PV than in those with PV [mean number of flares per patient per year was 1.35 (SD 0.77) vs. 1.25 (SD 0.58), P = 0.039]. Common triggers of flares in patients with GPP who did not have PV were infections, pregnancy, menstruation and stress, whereas withdrawal of therapy, particularly systemic corticosteroids, was a more frequent trigger in patients with GPP who also had PV.
CONCLUSIONS: Our findings contribute to the global mapping of GPP, which will help inform the management of this rare condition.
OBJECTIVES: To determine the cost-effectiveness of universal HLA-B*15:02 screening in preventing carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in an ethnically diverse Malaysian population.
METHODS: A hybrid model of a decision tree and Markov model was developed to evaluate three strategies for treating newly diagnosed epilepsy among adults: (i) carbamazepine initiation without HLA-B*15:02 screening (current practice); (ii) universal HLA-B*15:02 screening prior to carbamazepine initiation; and (iii) alternative treatment [sodium valproate (VPA)] prescribing without HLA-B*15:02 screening. Base-case analysis and sensitivity analyses were performed over a lifetime time horizon. Incremental cost-effectiveness ratios were calculated.
RESULTS: Both universal HLA-B*15:02 screening and VPA prescribing were dominated by current practice. Compared with current practice, universal HLA-B*15:02 screening resulted in a loss of 0·0255 quality-adjusted life years (QALYs) at an additional cost of 707 U.S. dollars (USD); VPA prescribing resulted in a loss of 0·2622 QALYs at an additional cost of USD 4127, owing to estimated differences in antiepileptic treatment efficacy.
CONCLUSIONS: Universal HLA-B*15:02 screening is unlikely to be a cost-effective intervention in Malaysia. However, with the emergence of an ethnically diverse population in many other countries, this may render HLA-B*15:02 screening a viable intervention when an increasing proportion of the population is at risk and an equally effective yet safer antiepileptic drug is available.