Association between exposure to ambient air pollution, meteorological factors and atopic dermatitis consultations in Singapore-a stratified nationwide time-series analysis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting approximately 20% of children globally. While studies have been conducted elsewhere, air pollution and weather variability is not well studied in the tropics. This time-series study examines the association between air pollution and meteorological factors with the incidence of outpatient visits for AD obtained from the National Skin Centre (NSC) in Singapore. The total number of 1,440,844 consultation visits from the NSC from 2009 to 2019 was analysed. Using the distributed lag non-linear model and assuming a negative binomial distribution, the short-term temporal association between outpatient visits for AD and air quality and meteorological variability on a weekly time-scale were examined, while adjusting for long-term trends, seasonality and autocorrelation. The analysis was also stratified by gender and age to assess potential effect modification. The risk of AD consultation visits was 14% lower (RR10th percentile: 0.86, 95% CI 0.78-0.96) at the 10th percentile (11.9 µg/m3) of PM2.5 and 10% higher (RR90th percentile: 1.10, 95% CI 1.01-1.19) at the 90th percentile (24.4 µg/m3) compared to the median value (16.1 µg/m3). Similar results were observed for PM10 with lower risk at the 10th percentile and higher risk at the 90th percentile (RR10th percentile: 0.86, 95% CI 0.78-0.95, RR90th percentile: 1.10, 95% CI 1.01-1.19). For rainfall for values above the median, the risk of consultation visits was higher up to 7.4 mm in the PM2.5 model (RR74th percentile: 1.07, 95% CI 1.00-1.14) and up to 9 mm in the PM10 model (RR80th percentile: 1.12, 95% CI 1.00-1.25). This study found a close association between outpatient visits for AD with ambient particulate matter concentrations and rainfall. Seasonal variations in particulate matter and rainfall may be used to alert healthcare providers on the anticipated rise in AD cases and to time preventive measures to reduce the associated health burden.

Validation of the Recap of Atopic Eczema (RECAP) Measurement Instrument for Eczema Control in Adult Patients in an Asian Clinical Setting.

Recap of atopic eczema (RECAP) is a self-reported 7-item questionnaire recommended by the Harmonising Outcome Measures in Eczema initiative to measure eczema control. As RECAP has not been validated in a real-world clinical population in Asia, RECAP was investigated as a measure of eczema control in Singapore. Patients with atopic eczema at the National Skin Centre from July 2019 to January 2020 were included for analysis. Both patient- and physician-reported outcome measures were available for correlation analyses. Correlation analysis was also performed to investigate construct validity, and floor or ceiling effects of RECAP. A total of 260 atopic eczema patients aged between 15 and 87 years were recruited. There were minimal floor and ceiling effects for RECAP scores. There were strong, significant correlations of RECAP with POEM (r = 0.84, p < 0.001) and DLQI (r = 0.81, p < 0.001). Correlation with SCORAD was moderate (r = 0.60, p < 0.001). Correlations remained similar after age, gender, and ethnicity adjustments. Discriminative validity was demonstrated by a significant linear trend of increasing RECAP scores with increasing eczema severity. RECAP demonstrates good discriminative and construct validity evidenced by strong correlations with symptoms and quality of life and moderate correlations with eczema signs. RECAP is useful to measure eczema control in Singapore.

Epidemiology and Outcomes of Non-Small Cell Lung Cancer in South Korea.

Importance: Valuable evidence regarding clinical characteristics, treatments, and outcomes for non-small cell lung cancer (NSCLC) is limited to individual hospital databases or national-level registries. The common data and federated analysis framework developed through the Extensible Platform for Observational Research in Lung Cancer (EXPLORE-LC) initiative allows for research across multiple high-quality data sources, which may provide a deeper understanding of the NSCLC landscape and identification of unmet needs of subpopulations. Objective: To describe clinical characteristics, initial treatment patterns, subsequent treatment, and overall survival (OS) of patients with NSCLC in South Korea. Design, Setting, and Participants: This multicenter cohort study included patients aged 18 years and older who were diagnosed with NSCLC between 2014 and 2019 and followed up until March 2020 at 3 tertiary hospitals in South Korea. Clinical data were collected using a common data model and clinical data warehouse. Patients who had an initial diagnosis of nonsquamous (NSQ) or squamous (SQ) NSCLC and who had received at least 1 treatment for NSCLC were included in the study. Data were analyzed from June through November 2022. Main Outcomes and Measures: The primary outcome was clinical OS for patients with NSCLC. Secondary outcomes were clinical characteristics and treatment patterns subsequent to the diagnosis of NSCLC. Results: Among 22 101 patients with NSCLC who received anticancer treatment analyzed in this study, 17 350 patients (78.5%) had NSQ and 4751 patients (21.5%) had SQ NSCLC. Clinical characteristics and outcomes and treatment patterns were assessed for 13 084 patients with NSQ cancer who had known EGFR and ALK status (75.4%; mean [SD] 62.2 [10.5] years; 6552 males [50.1%]) and all 4751 patients with SQ cancer (mean [SD] age, 67.1 [8.6] years; 4427 males [93.2%]). More than half of patients with NSQ cancer were never smokers (7399 patients [56.6%]). Patients with SQ cancer were mostly males and former or current smokers (4235 patients [89.1%]) and were diagnosed at a later clinical stage than patients with NSQ cancer (eg, stage I: 1165 patients [24.5%] vs 5388 patients [41.2%]). Patients with EGFR-positive and ALK-positive NSQ cancer diagnosed between 2017 and 2019 had better median OS than similar patients diagnosed between 2014 and 2016 (EGFR-positive: not reached [95% CI, 35.9 months to not reached] vs 28.4 months [95% CI, 25.8 to 30.0 months]; P < .001; ALK-positive: not reached [95% CI, not reached] vs 49.5 months [95% CI, 35.1 months to not reached]; P < .001). No significant difference was observed in OS from first-line treatment for patients with SQ cancer. Conclusions and Relevance: This study, which pooled medical data from multiple clinical data warehouses to produce a large study cohort, may provide meaningful insights into the clinical practice of NSCLC and underscores the value of a common data model approach. The analyzable dataset may hold great promise for future comprehensive identification of subpopulations and unmet needs.

Safety and efficacy of dupilumab in adult atopic dermatitis in Singapore.

INTRODUCTION: Dupilumab, a biologic approved for treatment of moderate-to-severe atopic dermatitis (AD), has been reported to be largely effective with minimal adverse effects. However, being a targeted therapy, its effectiveness and side effects are expected to be varied in a heterogeneous ethnic population. Currently, the majority of studies on dupilumab are based on Western populations. METHODS: A retrospective cohort of 51 patients with moderate-to-severe AD treated with dupilumab at a tertiary skin institute from January 2018 to February 2020 was included. Outcome measures such as Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI) and Dermatology Quality of Life Index (DLQI) were analysed at baseline and after 16 weeks of treatment. Laboratory tests at the respective time points were also measured. RESULTS: Patients treated with dupilumab showed consistent reduction in body surface area (BSA) involved, SCORAD, EASI and DLQI scores. Concurrently, serum immunoglobulin E (IgE) and absolute eosinophil count showed a downward trend at 4 months of treatment. There was a transient increase in mean serum IgE at 1 month of dupilumab treatment. Also, 42.0% and 35.3% of patients developed eye symptoms, and head and neck dermatitis, respectively, but there were no major adverse events reported. Childhood-onset AD was more likely to have improved BSA scores compared to adult-onset AD. CONCLUSIONS: Our study confirms the efficacy of dupilumab with real-world data in an adult Asian population. Higher proportions of eye symptoms, and head and neck dermatitis were observed in our cohort compared to other Asian clinical cohort studies. Further studies are needed to evaluate these differences.

In vivo imaging of patients with chronic pruritus of unknown origin reveals partial sweat duct obstruction with partial itch resolution upon retinoid treatment.

Background: Chronic pruritus of unknown origin (CPUO) is poorly understood and lacks effective treatment options. Objectives: We aimed to elucidate abnormalities in the sweat apparatus of patients with CPUO, and to assess efficacy and safety of treatment with systemic retinoids. Methods: An initial case-control study included 20 affected patients and five healthy controls, for whom heat and sweating were induced, either through a standardized exercise protocol or ingestion of hot water. In vivo high-definition optical coherence tomography, whole-body starch-iodine testing, and skin biopsy for immunofluorescence staining were done to evaluate for sweat duct obstruction. A subsequent retrospective cohort analysis included 56 patients with CPUO, seen at an Itch subspecialty clinic of a single tertiary referral centre, who failed conventional treatments and were treated with isotretinoin and/or acitretin from May 2014 to November 2020. Treatment response to retinoids was defined as a sustained reduction in itch score of ≥2/10. Safety was assessed by proportion stopping treatment due to side effects. Results: In vivo imaging in 19 (95%) patients revealed features of partial keratinaceous sweat duct obstruction with statistically significant luminal dilatation compared to controls. Immunofluorescence studies of three patients' paired lesional/non-lesional biopsies revealed dermcidin accumulation within sweat glands coupled with dermcidin leakage in itchy skin. Fifty-six patients (mean [SD] age 55.2 [17.5] years, 69.6% male) were treated with systemic retinoids. Mean (SD) duration of itch was 116.3 (140.4) months and mean (SD) itch score was 8.2 (1.8). Forty-one (73.2%) initially received isotretinoin, and 15 (26.8%) acitretin. At three months, mean itch score reduced by 2.38 (95% CI -3.2 to -1.6, p < 0.0001). Thirty-eight (67.9%) had a sustained response. Eight (14.81%) achieved an itch score of 0 or 1, with four stopping treatment for a mean (SD) of 318.5 (291.2) days without relapse. Eight (14.3%) stopped or switched retinoid due to adverse effects, with similar incidences between both retinoids, the commonest being dryness. Conclusion: Based on novel findings from physiological imaging studies identifying partial keratinaceous sweat duct obstruction in CPUO, we instituted systemic retinoid treatment to address the underlying pathology. In patients who failed conventional therapies, the treatment appears effective and safe.

Clinical and patient-reported outcomes from the first 4 years of a Psoriasis Biologics Registry in Singapore.

Interim analysis of the National Skin Centre Singapore Psoriasis Biologics Registry (SINGPSOR) from August 2017 to May 2021, in which 58 patients were analysed, showing that those receiving biologic treatment had significantly more severe psoriasis based on PASI (Psoriasis Area and Severity Index), BSA (body surface area) and PGA (Physician Global Assessment) measures at baseline, demonstrated a statistically non-significant trend towards greater improvement with treatment, and had a lower percentage of adverse events compared to those receiving conventional systemic therapy. Future analyses of SINGPSOR, with larger sample size and longer follow-up, will be invaluable to further characterize these patients and their treatment outcomes.

Evaluating and comparing the clinical characteristics between adult-onset and childhood-onset atopic dermatitis in an Asian clinical cohort.

BACKGROUND: Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin conditions. We aimed to describe the clinical features of adult-onset and childhood-onset AD in a multi-ethnic Asian population. METHODS: A retrospective study was performed of 188 patients with AD managed at a tertiary skin institution in Singapore. Patient demographics, clinical features and disease scores were analysed. RESULTS: Clinical features related to pigmentary changes, such as orbital darkening and Dennie-Morgan folds were more prevalent among childhood-onset AD patients than in adult-onset AD patients. Similarly, features related to prolonged scratching or friction, such as anterior neck folds, perifollicular accentuation and infra-auricular/infranasal fissuring were also more prevalent in childhood-onset AD patients. Disease scores such as SCORAD and EASI were not different between patients with childhood versus adult-onset disease. CONCLUSION: There were significant differences in clinical features between childhood-onset and adult-onset AD. Certain features are related to pigmentary changes and might be more accentuated in patients with skin of colour. Further studies are needed to understand how the different features might be clinically significant and related to the various AD endotypes and disease trajectories.

Incidence of skin malignancies in patients with vitiligo or psoriasis who received narrowband ultraviolet B phototherapy (308 nm/311 nm): A retrospective review of 3730 patients.

BACKGROUND: Previous studies regarding the risk of skin malignancy with NBUVB have been performed in Caucasian patients, but few studies have been conducted in Asians. AIM: The aim of the study was to determine the risk of skin cancer in Asian patients with psoriasis and vitiligo receiving NBUVB phototherapy. METHODS: We performed a 9-year retrospective study including all patients with psoriasis and vitiligo receiving NBUVB (either 311 nm wavelength through cabin phototherapy or 308 nm through excimer lamp phototherapy) at the National Skin Centre. We matched the identification numbers of patients to the National Registry of Diseases Office database and collected data on all skin cancers diagnosed. RESULTS: A total of 3730 patients were included. During the course of the study, 12 cases of skin cancer were diagnosed, of which 10 were basal cell carcinomas, and 2 were squamous cell carcinomas. No cases of melanoma were detected in the study. The age-standardized incidence of skin cancer in psoriasis and vitiligo patients who received phototherapy was 47.5 and 26.5, respectively, which is higher than the incidence of skin cancers in the general population. Risk of skin malignancy was positively correlated with the cumulative (p = .008) and maximum dose of phototherapy (p = .011) as well as previous systemic treatments (p = .006). LIMITATIONS: Limitations include a relatively short follow-up period as well as the lack of quantification of solar exposure. CONCLUSIONS: NBUVB phototherapy in Asian skin increases the risk of skin malignancy. The risk of skin malignancy is higher with psoriasis patients, greater cumulative and maximal dose of phototherapy as well as the use of systemic therapy. Despite the increased risk, the absolute number of skin malignancies remains low, especially for vitiligo patients, with no cases of melanoma diagnosed-a reassuring finding that phototherapy remains a safe alternative in the treatment of psoriasis and vitiligo.

Epidemiology of occupational dermatoses associated with personal protective equipment use in the COVID-19 pandemic: Risk factors and mitigation strategies for frontline health care workers.

Background: Personal protective equipment (PPE)-related occupational dermatosis (PROD) represents a significant occupational burden to health care workers (HCWs), and understanding its epidemiology is imperative in formulating mitigation strategies. Objectives: To determine the prevalence of PROD in HCWs, characterize its manifestations, identify its risk factors, and evaluate behavioral modifications of HCW. Methods: A cross-sectional study using an online questionnaire was conducted from July to September 2020. HCWs who had direct contact with COVID-19 patients for a minimum of 2 weeks cumulatively were invited to participate. Results: The prevalence of PROD among 416 valid respondents was 73.8% (307/416), with face masks being the most common cause (93.8% [n = 288]). The most common PROD associated with face masks, protective eyewear, hairnets, gowns, and gloves were acne (71.5% [206/288]), pressure-related injuries (70.7% [99/140]), scalp itch (53.3% [16/30]), itch/rash (78.8% [26/33]), and xerosis (75.0% [27/36]), respectively. Exposure to PPE beyond an hour increased the odds of PROD by 4.8-fold. The majority of HCWs made behavioral modifications to mitigate PROD. Conclusions: We underscore evidence-based recommendations for HCWs to be (1) scheduled hourly breaks from PPE wear, (2) fitted to various PPE models, (3) screened for preexisting dermatoses before deployment, and (4) educated on mitigation strategies and avenues for help should they encounter PROD.

Pattern of contact sensitization in patients with and without atopic dermatitis in an Asian dermatology center.

BACKGROUND: Although the traditional understanding is that contact sensitization is less frequent in patients with atopic dermatitis (AD), recent studies have shown similar or higher rates of positive patch-test results in AD patients. OBJECTIVES: We sought to characterise the pattern of contact sensitization in patients with and without AD and evaluate the association between AD and contact sensitization. METHOD: This was a single-center, 10-year retrospective review of patients who underwent patch testing between 2007 and 2017. RESULTS: There were 4903 patients (male-to-female ratio = 1:1.4; mean age 40.1 years) included. About half (2499, 51.0%) of all patients developed at least one positive reaction. The top five frequent reactions were to nickel sulfate (45.4%), potassium dichromate (16.0%), p-phenylenediamine (13.4%), Myroxylon pereirae (11.8%), and fragrance mix I (11.2%). The overall prevalence of contact sensitization was not significantly different between patients with or without AD. Patients with AD were less likely to develop contact allergies to budesonide and thiuram mix, and more likely to develop contact allergies to potassium dichromate. CONCLUSIONS: Contact sensitization was detected in 50% of patients who were patch tested. Nickel sulfate was the most frequently sensitizing allergen. The prevalence of contact allergies in atopic patients is comparable to that in non-atopic patients.

Novel transdermal device for delivery of triamcinolone for nail psoriasis treatment.

INTRODUCTION: Nail psoriasis treatment is challenging due to difficult drug delivery and systemic therapy toxicities. Self-dissolvable microneedle patches embedded with corticosteroids offers a potentially rapid, minimally invasive drug delivery platform with good efficacy and minimal adverse side effects. METHODS: We conducted a 4-month prospective randomised controlled trial. Subjects with psoriatic nails were randomised to receive microneedle device delivered topical steroids on one hand and control treatment (topical Daivobet gel) on the other. Two independent dermatologists blinded to the treatment assignment scored their Nail Psoriasis Severity Index (NAPSI) during visits at baseline, 2 and 4 months. All treatment was discontinued after 2 months. Average NAPSI score on each hand was analysed. RESULTS: A total of 25 participants were recruited, aged 22 to 73 years. Majority were Chinese (72%), followed by Indian and Malay. There was equal randomisation of treatment to the left and right nail. While there was a rapid significant improvement in average NAPSI score for the control arm at 2 months, the treatment arm had a greater, more sustained improvement of the NAPSI score at 4 months. The average NAPSI score improved for both treatment and control group at 4 months compared to baseline. However, only the NAPSI value improvement in the controls at 2 months compared to baseline was statistically significant (P=0.0039). No severe adverse effects were reported. CONCLUSION: To the best of our knowledge, this is the first prospective randomised control trial comparing microneedle technology against conventional topical steroids in nail psoriasis treatment. Our findings demonstrate microneedle technology is as efficacious as topical therapy.

Pediatric patch testing in a multi-ethnic Asian population: A retrospective review.

BACKGROUND: Pediatric allergic contact dermatitis (ACD) is increasingly prevalent. Patch testing is the gold-standard diagnostic investigation. The aims of our study were to describe the clinical profile of pediatric patients with ACD in a multi-ethnic Asian population and identify the common contact allergens. METHODS: This was a retrospective study involving children and adolescents aged 16 years or younger with clinically suspected ACD who underwent patch testing between January 2007 and March 2020 at two institutions in Singapore. Information pertaining to their demographics, atopy history, clinical presentation, and patch test results was analyzed. RESULTS: A total of 252 patients were included. The mean age was 10.9 years (1.0-16.7 years). The majority were Chinese (79.8%) and girls (57.5%). Many (66.3%) had atopic dermatitis (AD), which was mild. The most common presentation was an acral eczematous rash. The sensitization rate was 50.0%. The most frequent reactions were to nickel sulfate (49.2%) and fragrance mix (19.1%). The overall rate of relevant positive patch tests was 72.5%. Patients with AD were less likely to have a reaction to fragrance mix (p = .019) and more likely to have a reaction to disperse blue (p = .041). Compared to younger children, adolescents were less likely to have a positive patch test (p = .008). Indians were also less likely to have a positive reaction (p = .004). CONCLUSION: Metals and fragrances were the most common allergens causing childhood ACD in Singapore. Patients with AD were less likely to be sensitized to fragrances and more likely to be sensitized to disperse blue dye.

Factors affecting duration of SARS-Cov-2 viral shedding in mildly symptomatic patients isolated in a community facility.

INTRODUCTION: Mildly symptomatic cases of Covid-19 in previously-well individuals form the majority of infections and also serve as potent vectors of transmission. The factors affecting the duration of SARS-CoV-2 RNA viral shedding (DVS) in these patients remain largely unknown. OBJECTIVES: To perform a systematic analysis of the clinical, radiologic, laboratory investigations in patients with few comorbidities infected with mild Covid-19 to identify factors associated with the DVS. METHODS: In this retrospective cohort study, patients with mild or asymptomatic Covid-19 were included. Baseline characteristics including age, nationality, comorbidities, concomitant medications, and type of isolation arrangement in the facility (single or in pairs) were collected. Clinical features and radiologic/haematologic findings were also collected. Taking day 28 as the cut-off, 187 patients who had a negative swab result up to day 28 (no prolonged DVS) were compared to 126 patients with a persistently positive result on or after day 28 (prolonged DVS). RESULTS: Of 964 consecutive patients included, 851 (88.3%) patients were symptomatic. 266 patients had a documented negative RT-PCR assay with a median DVS of 25 days (range: 13 to 96 days; interquartile range (IQR): 22 to 33 days). Patients isolated in pairs were associated with prolonged DVS (OR: 2.7; 95% CI: 1.7 to 4.5; p<0.0001) compared to those isolated individually. Among vital signs, only tachycardia was associated with prolonged DVS (OR: 2.6; 95% CI: 1.0 to 7.1; p = 0.03). Amongst investigations, only a raised CRP was associated with prolonged DVS (OR: 2.7; 95% CI: 1.1 to 6.8; p = 0.02). CONCLUSIONS: In young, mildly symptomatic Covid-19 patients, prolonged DVS was associated with being isolated in pairs compared to individually. In situations where a negative RT-PCR test result is required, retesting in patients who were not isolated individually, or who had baseline tachycardia or a raised CRP, may be delayed to increase the yield of a negative result.

Melanoma in Singapore: A 20-year review of disease and treatment outcomes.

INTRODUCTION: Melanomas in Asians have different clinicopathological characteristics and prognosis from melanomas in Caucasians. This study reviewed the epidemiology and treatment outcomes of cutaneous melanoma diagnosed at a tertiary referral dermatology centre in Singapore, which has a multiracial population. The study also determined whether Asians had comparable relapse-free and overall survival periods to Caucasians in Singapore. METHOD: This is a retrospective review of cutaneous melanoma cases in our centre between 1996 and 2015. RESULTS: Sixty-two cases of melanoma were diagnosed in 61 patients: 72.6% occurred in Chinese, 19.4% in Caucasians and 3.2% in Indians, with an over-representation of Caucasians. Superficial spreading melanoma, acral lentiginous melanoma and nodular melanoma comprised 37.1%, 35.5% and 22.6% of the cases, respectively. The median time interval to diagnosis was longer in Asians than Caucasians; median Breslow's thickness in Asians were significantly thicker than in Caucasians (2.6mm versus 0.9mm, P=0.018) and Asians tend to present at a later stage. The mortality rates for Asians and Caucasians were 52% and 0%, respectively. CONCLUSION: More physician and patient education on skin cancer awareness is needed in our Asian-predominant population for better outcomes.

miR-671-5p Attenuates Neuroinflammation via Suppressing NF-κB Expression in an Acute Ischemic Stroke Model.

This study was designed to investigate the role of miR-671-5p in in vitro and in vivo models of ischemic stroke (IS). Middle cerebral artery occlusion and reperfusion (MCAO/R) in C57BL/6 mice as well as oxygen-glucose deprivation and reoxygenation (OGD/R) in a mouse hippocampal HT22 neuron line were used as in vivo and in vitro models of IS injury, respectively. miR-671-5p agomir, miR-671-5p antagomir, pcDNA3.1-NF-κB, and negative controls were transfected into cells using riboFECT CP reagent. miR-671-5p agomir, pcDNA3.1-NF-κB, and negative vectors were administered into MCAO/R mice via intracerebroventricular injection. The results showed that miR-671-5p was significantly downregulated and that miR-671-5p agomir alleviated injury and neuroinflammation induced by ischemic reperfusion. A dual-luciferase reporter assay confirmed that NF-κB is a direct target of miR-671-5p. Reverse experiments showed that miR-671-5p agomir reduced neuroinflammation via suppression of NF-κB expression in both in vitro and in vivo models of IS. Our data suggest that miR-671-5p may be a viable therapeutic target for diminishing neuroinflammation in patients with IS.