Therapeutic applications of germline testing for cancer predisposition genes in Asia in the real world.

BACKGROUND: Germline genetic testing is traditionally carried out in patients suspected with hereditary cancer syndrome for enhanced cancer surveillance and/or preventive strategies, but is increasingly carried out for therapeutic indications. MATERIALS AND METHODS: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility. RESULTS: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71). CONCLUSIONS: One-third of cancer patients tested carried a PGV and ∼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics.

Validation of five patient-reported outcomes for atopic dermatitis severity in adults.

BACKGROUND: Structured patient-reported outcomes of atopic dermatitis (AD) severity are not standardized in clinical practice. OBJECTIVES: To determine the construct validity, internal consistency, cross-cultural validity and floor or ceiling effects of multiple AD severity assessments. METHODS: This is a cross-sectional, population-based study of 2893 adults, including 602 adults who met a modified set of U.K. diagnostic criteria for AD. AD severity was assessed using self-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD) and its objective and subjective components, and numerical rating scale (NRS)-itch. Quality of life was assessed using Short-Form (SF)-12 mental and physical health scores, Short-Form Six Dimensions (SF-6D) health utility scores and Dermatology Life Quality Index (DLQI). Mental health was assessed with the Hospital Anxiety and Depression Scale (HADS). RESULTS: PO-SCORAD, PO-SCORAD objective and subjective subscores, NRS-itch and POEM all had moderate-to-strong correlations with each other and DLQI, fair-to-moderate correlations with HADS-anxiety and HADS-depression, and inverse correlations with SF-12 mental component score and SF-6D (Pearson correlations, P < 0·001). All scores showed good criterion validity as judged by anova and receiver operator characteristics. PO-SCORAD, PO-SCORAD objective subscore and POEM had similarly good internal consistency (Cronbach's alpha = 0·84, 0·82 and 0·86); the PO-SCORAD subjective subscore was less internally consistent (alpha = 0·57). All scores showed potentially poor cross-cultural validity as demonstrated by uniform and nonuniform differential item functioning by age, sex and/or race/ethnicity for multiple items. There were floor effects for POEM, but not for the other assessments. CONCLUSIONS: PO-SCORAD, PO-SCORAD objective and subjective subscores, NRS-itch and POEM appear to be valid for assessing AD severity in clinical practice. What's already known about this topic? Few studies have demonstrated the validity of the atopic dermatitis severity assessments Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD), PO-SCORAD subscores, numerical rating scale (NRS)-itch and Patient-Oriented Eczema Measure (POEM). What does this study add? This study demonstrates that PO-SCORAD, PO-SCORAD subscores, NRS-itch and POEM all had good construct validity in the assessment of atopic dermatitis severity in adults. Only POEM demonstrated floor effects. What are the clinical implications of this work? PO-SCORAD, PO-SCORAD subscores, NRS-itch and POEM all appear to have sufficient validity to be used as assessments of atopic dermatitis severity in clinical practice.

Symptoms and diagnosis of anxiety and depression in atopic dermatitis in U.S. adults.

BACKGROUND: The relationship between atopic dermatitis (AD), anxiety and depression in the U.S. adult population is not well established. OBJECTIVES: To determine the relationship of AD and its severity with symptoms and diagnosis of anxiety and depression in U.S. adults. METHODS: A cross-sectional, population-based study of 2893 adults was performed. AD was determined using modified U.K. Diagnostic Criteria. RESULTS: Adults with AD vs. those without AD had higher mean Hospital Anxiety and Depression Scale anxiety (HADS-A) (7·7 vs. 5·6) and depression (HADS-D) (6·0 vs. 4·3) scores and higher prevalences of abnormal (≥ 11) HADS-A (28·6% vs. 15·5%) and HADS-D (13·5% vs. 9·0%) scores. In multivariable linear and logistic regression models controlling for sociodemographics, AD was associated with significantly higher mean HADS-A and HADS-D scores (7·7 and 6·0) and higher odds of abnormal HADS-A [odds ratio (OR) 2·19, 95% confidence interval (CI) 1·65-2·91] and HADS-D scores (OR 1·50, 95% CI 1·04-2·17) (P ≤ 0·03 for all). Mean and abnormal HADS-A and HADS-D scores were increased in moderate and severe/very severe self-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Patient-Oriented Scoring AD (PO-SCORAD), PO-SCORAD itch and sleep (P < 0·0001 for all). All respondents with severe PO-SCORAD, POEM and PO-SCORAD itch had borderline or abnormal HADS-A and HADS-D scores. Adults with AD vs. those without AD had higher prevalence of self-reported healthcare-diagnosed anxiety or depression in the past year (40·0% vs. 17·5%). Many adults with AD who had borderline and/or abnormal HADS-A or HADS-D scores reported no diagnosis of anxiety or depression. CONCLUSIONS: AD is associated with significantly increased anxiety and depression, which may go undiagnosed. What's already known about this topic? Previous studies found higher rates of anxiety and depression in clinical cohorts of patients with atopic dermatitis. What does this study add? This study found dramatically higher rates of anxiety and depression among adults with atopic dermatitis in the U.S. population, which was primarily driven by atopic dermatitis severity. Anxiety and depression often go undiagnosed in adults with atopic dermatitis.

Distribution of atopic dermatitis lesions in United States adults.

BACKGROUND: The distribution of atopic dermatitis (AD) lesions and its impact on quality of life (QOL) is not well established in the US adult population. OBJECTIVE: To elucidate the distribution of AD lesions and its impact on QOL in US adults with AD. METHODS: A cross-sectional, population-based study of 602 adults was performed. AD was determined using modified UK Diagnostic Criteria, and its lesional distribution was assessed. QOL was assessed using Dermatology Life Quality Index (DLQI). Latent class analysis (LCA) was used to determine distinct phenotypes of AD lesional distribution. Multivariable logistic regression was used to determine the relationship between DLQI and distinct phenotypes. RESULTS: The most common sites of skin lesions were reported to be the popliteal fossae, lower legs, dorsal feet and antecubital fossae. Most persons reported partial (19.0%) or complete (63.0%) symmetry of lesions on the extremities. Lesions on the trunk were significantly more common in blacks and Hispanics. Age ≥ 60 years was associated with significantly lower proportions of active lesions on the face and scalp, and significantly higher proportion of lesions on the buttocks or genitals. LCA identified 5 classes of lesional distribution: 1. lower probabilities of lesions affecting any sites; 2. Higher probability of lesions involving the anterior and posterior neck and trunk; 3. lesions involving the antecubital fossae and upper extremities; 4. lesions involving the arms, posterior hands, genitals and buttocks, and to a lesser extent face, palms and legs; 5. lesions affecting all sites. Class-2 (multivariable logistic regression; adjusted odds ratio [95% confidence interval]: 7.19 [3.21-16.07], class-3 (7.11 [3.20-15.80]), class-4 (6.90 [3.07-15.50]) and class-5 (7.92 [3.54-17.71]) were all significantly associated with higher DLQI scores compared to class 1. CONCLUSION: AD is associated with heterogeneous distribution of AD lesions, and distinct phenotypes that are associated with QOL impact.

A case of atopic dermatitis and erythema multiforme.

We report a case of a two-year-old boy with atopic dermatitis treated with antibiotics for pharyngitis and acute otitis media and subsequently developed targetoid and ulcerated blister mucocutaneous lesions. Diagnostic workup revealed eczema herpeticum and HSV viremia. To our knowledge, this is the first reported case of a patient with atopic dermatitis presenting with erythema multiforme likely secondary to eczema herpeticum and HSV viremia.

Participation in continuing professional development by dental practitioners in Victoria, Australia in 2007.

BACKGROUND: Mandatory continuing professional development (CPD) was introduced in 2005 in Victoria, Australia to ensure that dental practitioners maintained their skills, knowledge and kept up-to-date with current topics in dentistry. The aim of this study was to investigate the participation, impact on practice and attitudes of Victorian dentists and dental specialists to CPD activities since the commencement of mandatory CPD. METHODS: A cross-sectional survey of a random sample of registered dentists and dental specialists (n = 895) was conducted from May to August 2008 using an anonymous, postal, self-administered questionnaire. RESULTS: The response rate was 66%. More than three quarters of practitioners believed mandatory CPD is a reasonable requirement for continued registration. Dentists reported attending an average of 30.9 h of certifiable clinical CPD whilst specialists attended an average of 33.2 h of certifiable clinical CPD over a 12-month period. Nearly three quarters of respondents reported changing their practice as a result of CPD activities, whilst one quarter attended CPD mainly to meet the mandatory requirements. CONCLUSIONS: Overall there was a positive attitude towards mandatory CPD and a high level of participation in CPD activities by Victorian dentists and specialists in 2007, although nearly half of the respondents attended <20 h of certified clinical CPD during 2007. A number of barriers exist, particularly for rural and female practitioners in accessing CPD, and further research is required to examine the benefits derived from mandatory CPD.

Late-onset of IgE sensitization to microbial allergens in young children with atopic dermatitis.

Background A significant proportion of young children with atopic dermatitis (AD) is sensitized to microbial allergens, which play a potential role in the pathogenesis of AD inflammation. Objective To study the timing of IgE sensitization to microbial allergens including staphylococcal superantigens, Malassezia species and Candida albicans in young children with AD. Method Specific IgE antibodies to staphylococcal superantigens, Malassezia species, C. albicans and control inhalant/food allergens were measured in 53 young children with mild to moderate AD. The presence of IgE sensitization relative to age (> or = 3 years vs. < 3 years) was analysed by logistic regressions. Results IgE sensitization to the staphylococcal superantigen group, Malassezia species and C. albicans was significantly associated with older age in children with AD [P = 0.02, odds ratio (OR) 4.9; P = 0.02, OR 4.7; and P = 0.05, OR 4.0, respectively]. Conclusion IgE sensitization to microbial allergens is associated with an older age group in young children with mild to moderate AD.

Cross-sectional study of near-work and myopia in kindergarten children in Singapore.

INTRODUCTION: In view of the high and increasing myopia rates amongst young Singaporean children, we aimed to assess the relationship between near-work and myopia in 414 pre-school children aged 4 to 6 years. MATERIALS AND METHODS: We measured near-work indices such as tuition classes outside school and other possible risk factors via a questionnaire. We then measured myopia with a hand-held autorefractor. RESULTS: Children who had 3 or more hours per week of near-work classes outside school had a higher rate [odds ratio 1.39 (95% confidence interval 1.02, 2.53)] of myopia. CONCLUSIONS: This suggests that there may be an association between near-work and myopia, even at such a young age. Given the increasing emphasis on near-work in Singapore, it may be important to call for increased visual health awareness, although further studies will be needed to establish if near-work causes myopia.

Are atopic individuals genetically predisposed to produce a specific protease profile in antigen processing?

Genetic factors play a major role in the development of allergic diseases such as asthma and atopic dermatitis. Since allergic response involves immune processes such as antigen-processing and -presentation, it is conceivable that the genes involved in the regulation of these processes may be crucial in determining an individual's susceptibility to allergic diseases. In this paper, it is proposed that proteases, used in antigen-processing, are involved in the genetic predisposition to allergic diseases.

The mechanisms for the effects of dietary lipid modification on autoimmune diseases: the role of membrane lipid composition in antigen presenting cells.

Several mechanisms have been proposed to explain the effects of dietary lipid modification on autoimmune diseases. One of these being the modification of cell membranes which affects immune functions. In order to further define this mechanism, the author proposes that dietary lipid modification could affect antigen presentation, an immune function responsible for initiating cell-mediated immune responses in body defense or autoimmune diseases, through membrane lipid composition modification.