Zinc-α2-glycoprotein is associated with non-albuminuric chronic kidney disease progression in type 2 diabetes: a retrospective study with 4-year follow-up.

AIM: To investigate the association between baseline plasma zinc-α2-glycoprotein and non-albuminuric chronic kidney disease progression in type 2 diabetes. METHODS: Adults with normoalbuminuria at entry (n=341; age 57±10 years, 52% men) were analysed. Chronic kidney disease progression was defined as a decrease in chronic kidney disease stage and a decline of ≥25% in estimated GFR from baseline. Baseline plasma zinc-α2-glycoprotein levels were quantified by immunoassay, and analysed either as a continuous variable or by tertiles in Cox proportional hazards models. Model discrimination was assessed using Harrell's C-index. A sensitivity analysis was performed on a subset of individuals who maintained normoalbuminuria during follow-up. RESULTS: Chronic kidney disease progression occurred in 54 participants (16%). Zinc-α2-glycoprotein levels were elevated in chronic kidney disease progressors (P = 0.011), and more progressors were assigned to the higher zinc-α2-glycoprotein tertile than non-progressors. In the unadjusted Cox model, zinc-α2-glycoprotein, both as a continuous variable (hazard ratio 1.72, 95% CI 1.08-2.75) and tertile 3 (vs tertile 1; hazard ratio 2.14, 95% CI 1.10-4.17), predicted chronic kidney disease progression. The association persisted after multivariable adjustment. The C-index of the Cox model increased significantly after incorporation of zinc-α2-glycoprotein into a base model comprising renin-angiotensin system antagonist usage. Sensitivity analysis showed that zinc-α2-glycoprotein independently predicted chronic kidney disease progression among individuals who maintained normoalbuminuria during follow-up. CONCLUSIONS: Plasma zinc-α2-glycoprotein is associated with chronic kidney disease progression, and may serve as a useful early biomarker for predicting non-albuminuric chronic kidney disease progression in type 2 diabetes.

Clinical Signs, Staphylococcus and Atopic Eczema-Related Seromarkers.

Childhood eczema or atopic dermatitis (AD) is a distressing disease associated with pruritus, sleep disturbance, impaired quality of life and Staphylococcus aureus isolation. The pathophysiology of AD is complex and various seromarkers of immunity are involved. We investigated if anti-staphylococcal enterotoxin IgE (anti-SE), selected seromarkers of T regulatory (Treg), T helper (Th) and antigen-presenting cells (APC) are associated with clinical signs of disease severity and quality of life. Disease severity was assessed with the Scoring Atopic Dermatitis (SCORAD) index, and quality of life with the Children's Dermatology Life Quality Index (CDLQI) in AD patients ≤18 years old. Concentrations of anti-staphylococcus enterotoxin A and B immunoglobulin E (anti-SEA and anti-SEB), selected Treg/Th/APC chemokines, skin hydration and transepidermal water loss (TEWL) were measured in these patients. Forty patients with AD [median (interquartile range) age of 13.1 (7.9) years) were recruited. Backward stepwise linear regression (controlling for age, personal allergic rhinitis and asthma, and other blood markers) showed the serum anti-SEB level was positively associated with S. aureus and S. epidermidis isolations, objective SCORAD, clinical signs and CDLQI. TNF-α (a Th1 cytokine) was positively associated with objective SCORAD (B = 4.935, p = 0.010), TGF-ß (a Treg cytokine) negatively with disease extent (B = -0.015, p = 0.001), IL-18 (an APC cytokine) positively with disease extent (B = 0.438, p = 0.001) and with TEWL (B = 0.040, p = 0.010), and IL-23 (an APC cytokine) negatively with disease extent (B = -2.812, p = 0.006) and positively with pruritus (B = 0.387, p = 0.007). CONCLUSIONS: Blood levels of anti-SEB, Th1, Treg and APC cytokines are correlated with various clinical signs of AD. AD is a systemic immunologic disease involving Staphylococcus aureus, cellular, humoral, cytokine and chemokine pathophysiology.

Ethnic disparities in risk of cardiovascular disease, end-stage renal disease and all-cause mortality: a prospective study among Asian people with Type 2 diabetes.

AIM: To study prospectively the ethnic-specific risks of cardiovascular disease, end-stage renal disease and all-cause mortality in patients with Type 2 diabetes mellitus among native Asian subpopulations. METHODS: A total of 2337 subjects with Type 2 diabetes (70% Chinese, 17% Malay and 13% Asian Indian) were followed for a median of 4.0 years. Time-to-event analysis was used to study the association of ethnicity with adverse outcomes. RESULTS: Age- and gender-adjusted hazard ratios for cardiovascular disease in ethnic Malay and Asian Indian subjects were 2.01 (1.40-2.88; P<0.0001) and 1.60 (1.07-2.41; P=0.022) as compared with Chinese subjects. Adjustment for conventional cardiovascular disease risk factors, including HbA1c , blood pressure and lipid profile, slightly attenuated the hazards in Malay (1.82, 1.23-2.71; P=0.003) and Asian Indian subjects (1.47, 0.95-2.30; P=0.086); However, further adjustment for baseline renal function (estimated GFR) and albuminuria weakened the cardiovascular disease risks in Malay (1.48, 0.98-2.26; P=0.065) but strengthened that in Asian Indian subjects (1.81, 1.14-2.87; P=0.012). Competing-risk regression showed that the age- and gender-adjusted sub-distribution hazard ratio for end-stage renal disease was 1.87 (1.27-2.73; P=0.001) in Malay and 0.39 (0.18-0.83; P=0.015) in Asian Indian subjects. Notably, the difference in end-stage renal disease risk among the three ethnic groups was abolished after further adjustment for baseline estimated GFR and albuminuria. There was no significant difference in risk of all-cause mortality among the three ethnic groups. CONCLUSIONS: Risks of cardiovascular and end-stage renal diseases in native Asian subjects with Type 2 diabetes vary substantially among different ethnic groups. Differences in prevalence of diabetic kidney disease may partially explain the ethnic disparities.

A randomized controlled trial of self-regulated modified constraint-induced movement therapy in sub-acute stroke patients.

BACKGROUND AND PURPOSE: Emerging research suggests the use of self-regulation (SR) for improving functional regain in patients post stroke. SR is proposed to produce an added effect to effective modified constraint-induced movement therapy (mCIMT). This study aimed to examine the effect of a self-regulated mCIMT programme (SR-mCIMT) for functional regain in patients with sub-acute stroke. METHODS: Eighty-six patients completed the trial: SR-mCIMT, n = 29; mCIMT, n = 31; or conventional functional rehabilitation, n = 26. All interventions were 2-week therapist-guided training. Outcome measurements, taken by a blinded assessor, examined arm function [Action Research Arm Test (ARAT), Fugl-Meyer Assessment (FMA)], daily task performance [Lawton Instrumental Activities of Daily Living Scale (Lawton IADL)] and self-perceived arm use in functional tasks [Motor Activity Log (MAL)]. RESULTS: Significant differences were found with the SR-mCIMT outperforming the other groups after the intervention (ARAT, P = 0.006; FMA, Lawton IADL and MAL, all Ps < 0.001). In terms of the carry-over effect, the SR-mCIMT group outperformed in the hand and coordination subscales of ARAT and FMA (P = 0.012-0.013) and the self-perceived quality of arm use (P = 0.002). CONCLUSION: A combination of SR and mCIMT could produce an added effect in functional regain in patients post stroke.

High normal albuminuria is independently associated with aortic stiffness in patients with Type 2 diabetes.

BACKGROUND: High normal albuminuria is associated with higher cardiovascular risk in patients with diabetes. Increased aortic stiffness is an established risk factor of vascular events. However, the relationship between albuminuria within the normal range (0-30 mg/g) and aortic stiffness in patients with Type 2 diabetes is unknown. METHODS: A total of 614 normoalbuminuric subjects with Type 2 diabetes with spot urinary albumin:creatinine ratio ≤ 30 mg/g and estimated glomerular filtration rate ≥ 60 ml min⁻¹ 1.73 m⁻² were included in the study. Aortic stiffness was assessed by carotid-femoral pulse wave velocity. RESULTS: Pulse wave velocity increased progressively with the increase of albumin:creatinine ratio within the normoalbuminuric range (0-30 mg/g). Only 2.6% of the subjects with an albumin:creatinine ratio in the lowest quartile (0.7-3.4 mg/g) were classified as having aortic stiffness (pulse wave velocity ≥12 m/s). In contrast, the proportion of subjects with aortic stiffness increased significantly with the increase of albumin:creatinine ratio level (11.0%, 10.4% and 13.6% in albumin:creatinine ratio quartiles 2, 3 and 4, respectively, P = 0.008). A logistic regression model revealed that the odds of having aortic stiffness were increased by 56% with a 1-SD increase of log albumin:creatinine ratio after adjustment for age, gender, duration of diabetes, HbA1c , blood pressure, HDL and LDL cholesterol, estimated glomerular filtration rate, BMI, usage of renin-angiotensin system antagonists, statins and insulin. CONCLUSIONS: High normal albuminuria is associated with aortic stiffness in patients with Type 2 diabetes, which may in part explain their increased cardiovascular risk.

Associations between pigment epithelium-derived factor, insulin resistance and high density lipoprotein.

AIMS: To measure serum pigment epithelium-derived factor in control subjects with normal fasting glucose, and in subjects with impaired fasting glucose and those with newly diagnosed Type 2 diabetes, before treatment initiation, and to measure pigment epithelium-derived factor prospectively in patients being treated with HDL-raising therapy, niacin. METHODS: We enrolled 89 individuals attending an institutional health screen. Biochemical indices including lipids, homeostasis model assessment-insulin resistance, high-sensitivity C-reactive protein and pigment epithelium-derived factor were analysed in fasting blood. To validate the association between HDL and pigment epithelium-derived factor, we analysed samples from a separate study cohort with low HDL, followed up for 12-weeks while on niacin treatment. Secreted pigment epithelium-derived factor from 3T3-L1 adipocytes, after HDL treatment (24-h), was measured using Western blot analysis. RESULTS: Mean (± sd) serum pigment epithelium-derived factor was significantly higher in subjects with impaired fasting glucose [13.99 (± 3.06) µg/ml] and Type 2 diabetes [12.94 (± 2.61)] µg/ml, compared with control subjects [11.83 (± 2.85) µg/ml (P = 0.014)]. In multivariate analyses, serum pigment epithelium-derived factor concentration was associated with BMI (ß = 0.32, 0.007), homeostasis model assessment-insulin resistance (ß = 0.33, P = 0.01) and HDL (ß = -0.24, P = 0.05), after adjustment for age, gender and high-sensitivity C-reactive protein. In the niacin study, on-treatment HDL was an independent determinant of pigment epithelium-derived factor (ß = -0.439, P = 0.033), after adjusting for age, homeostasis model assessment-insulin resistance and treatment. Adipocytes treated with HDL were found to have reduced pigment epithelium-derived factor secretion [24.8% (50 µg/ml), 28.4% (100 µg/ml) HDL; P < 0.05)], compared with the control samples. CONCLUSION: Serum pigment epithelium-derived factor is positively associated with homeostasis model assessment-insulin resistance and negatively associated with HDL. Further studies are needed to understand the mechanism of low HDL and raised pigment epithelium-derived factor and to determine if they are causally related to the pathobiology of insulin resistance.

The effect of proanthocyanidins on the bond strength and durability of resin sealer to root dentine.

AIM: To investigate the effect of proanthocyanidins (PAs)-rich grape seed extract on the biodegradation resistance of demineralized root dentine and on the bond strength and durability between resin-based sealer and root dentine. METHODOLOGY: Single-rooted premolars (n = 28) were divided into PAs-treated and nontreated specimens. Root canals were instrumented to apical size 40, filled with RealSeal SE sealer/Core, sectioned into slices of 1 mm thickness from middle and coronal thirds and stored for 1 week or 3 months in distilled water. Specimens were subjected to push-out strength testing with the load applied perpendicularly in an apical to coronal direction using a universal testing machine. Remaining apical thirds were viewed by scanning electron microscopy after 3-months storage. Additional root canals were filled with rhodamine-B-labelled sealer and viewed by confocal laser scanning microscopy. Unfilled roots (n = 6) were sliced, demineralized, PAs-treated or left untreated and exposed to 24 h collagenase to determine hydroxyproline release in the supernatant. Two-way anova was used to test the effect of both dentine treatment with PAs and anatomical locations on bond strength and hydroxyproline release. Tukey-Kramer multiple comparison post hoc test was used to compare between groups. RESULTS: No difference in bond strength was found after 1-week storage between both PAs-treated (crosslinked) and untreated (noncrosslinked) groups in the coronal thirds. However, treatment with PAs revealed higher 1-week bond strength values (P ≤ 0.05) in the middle thirds. Generally, 3-month storage decreased the bond strength compared to 1-week within each of the crosslinked and noncrosslinked groups. However, the decrease in the bond strength after 3 months was less for the crosslinked specimens compared to the noncrosslinked specimens. Confocal images revealed a relatively uniform fluorescent interfacial layer and tubular penetration after 1 week in both groups. SEM images revealed more intact resin sealer/dentine interfaces with PAs crosslinking after 3 months. In addition, hydroxyproline release was significantly less (P ≤ 0.05) with crosslinked specimens. CONCLUSION: Treating root dentine with PAs-rich grape seed extracts improved the biodegradation resistance of demineralized root dentine and enhanced the bond strength and durability between resin-based sealer and root dentine after short-term water storage.

Predictors of decrease in ankle-brachial index among patients with diabetes mellitus.

AIM: Screening for peripheral arterial disease, a complication among patients with diabetes, is performed by periodic assessment of ankle-brachial index. We aimed to study the degree of ankle-brachial index change over time and factors associated with significant change. METHOD: We assessed difference between two ankle-brachial index measurements over time in a consecutive series of 82 patients with Type 2 diabetes. All patients had ankle-brachial index > 0.9 but ≤ 1.3 for the first measurement, and significant ankle-brachial index decrease was defined as a decrease of > 0.1 in the follow-up measurement compared with the baseline. RESULTS: The mean follow-up duration was 27.6 (median 30.0) months. Significant ankle-brachial index decrease was seen in 20.7% of patients, including 5% with follow-up ankle-brachial index of ≤ 0.9, consistent with the diagnosis of peripheral arterial disease. After adjusting for age and gender, higher baseline HbA(1c) and serum creatinine levels, increase in follow-up serum LDL cholesterol levels compared with baseline and history of retinopathy were predictors of significant ankle-brachial index decrease. CONCLUSIONS: Our study suggests that, within two years, one in five patients with diabetes and a normal ankle-brachial index may have significant progression of peripheral arterial disease. Annual ankle-brachial index assessment and better control of hyperlipidaemia may thus be required for at-risk patients with poor glycaemic control, renal impairment and retinopathy.

Adipocytokine zinc α2 glycoprotein (ZAG) as a novel urinary biomarker for normo-albuminuric diabetic nephropathy.

OBJECTIVE: A substantial proportion of diabetic nephropathy individuals are non-albuminuric. Using a proteomic approach, we searched for novel urinary biomarkers. METHODS: We studied three groups (n = 6 per group) of males with Type 2 diabetes: (1) normal renal function; (2) classical diabetic nephropathy (urinary albumin-creatinine ratio > 1000 mg/g and glomerular filtration rate < 60 ml/min.1.73 m(2) ) and (3) non-albuminuric diabetic nephropathy (glomerular filtration rate < 60 ml/min.1.73 m(2) and urinary albumin-creatinine ratio < 30 mg/g). We used two-dimensional fluorescence differential gel electrophoresis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry peptide identification and western blot validation in the study. RESULTS: Sixty protein spots were differentially abundant between the non-albuminuric and macro-albuminuric subjects (> 2.5-fold, P < 0.05). In the non-albuminuric subjects, in addition to previously reported α(1) -microglobulin, the next most interesting spot (upregulated 3.44-fold, P = 0.0026) was human zinc-α(2) -glycoprotein, a novel adipose-cytokine associated with glomerular injury. This was confirmed by western blot and replicated in female diabetic nephropathy subjects. CONCLUSIONS: From our preliminary results, human zinc-α(2) -glycoprotein may be a novel urinary biomarker for non-albuminuric diabetic nephropathy.

Future long-term trials of postmenopausal hormone replacement therapy - what is possible and what is the optimal protocol and regimen?

The ideal long-term, randomized, placebo-controlled trial of hormone replacement therapy (HRT) from near menopause for up to 30 years to assess major morbidity and mortality is impractical because of high cost, participant retention, therapy compliance, and continuity of research staff and funding. Also the trial regimen may become outdated. It is nihilistic to demand such a long-term trial before endorsing HRT. However, medium-term trials using surrogate measures for long-term morbidity and mortality are possible and two are near completion. If these studies have been able to maintain reasonable participant retention, therapy compliance and minimal breach of protocol, they will set standards for trials of new HRT regimens. This paper discusses lessons learnt from past attempts at long-term trials and suggests the currently optimal protocol and cost of assessing new HRT regimens to optimize potential benefits and minimize adverse effects. A 5-7-year randomized, placebo-controlled trial of a flexible transdermal estrogen regimen ± either a selective estrogen receptor modulator, e.g. bazedoxifene, or micronized progesterone is discussed. Mild to moderately symptomatic women, 1-4 years post menopause, can be recruited via general practice and group meetings. Future trials should be funded by independent agencies and are high priority in women's health.

Associations of young onset age and genetic risk of beta cell dysfunction with glycaemic progression in individuals with type 2 diabetes.

AIM: To study the relationship between genetic risk of beta cell dysfunction, young onset age and glycaemic progression in individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: 1385 T2D outpatients were included in cross-sectional sub-study and 730 insulin-naïve outpatients were followed for 3 years in prospective sub-study. Genetic risk score (GRS) was derived from 24 beta cell dysfunction-related single nucleotide polymorphisms, with lower and upper 25 percentiles defined as low and high genetic risk. Glycaemic progression was defined as requirement for sustained insulin therapy. RESULTS: 388 participants in cross-sectional and 128 in prospective sub-study experienced glycaemic progression. Young onset age (T2D diagnosis below 40 year-old) was associated with high risk of glycaemic progression as compared to usual-onset counterparts (adjusted OR 1.64 [95% CI 1.14-2.36], and 2.92 [95% CI 1.76-4.87] in cross-sectional and prospective sub-study, respectively). As compared to those with intermediate risk, a low GRS was associated with lower risk for glycaemic progression (adjusted OR 0.72 [95% CI 0.49-1.06], and 0.51 [95% CI 0.29-0.90]) whereas a high GRS was not significantly associated with glycaemic progression. Notably, the association of young-onset T2D with high risk of glycaemic progression was independent of known clinical risk factors and beta cell dysfunction GRS (P interaction > 0.10). CONCLUSION: Young onset age and low genetic risk of beta cell dysfunction are independently associated with risk of glycaemic progression. Our data do not support that genetic risk modulates the risk of glycaemic progression in individuals with young-onset T2D.

Are skin equipment for assessing childhood eczema any good?

AIM: Symptomatology and severity of atopic dermatitis (AD) can be objectively measured with equipment. This study aimed to compare skin measurements and investigate their correlations with various clinical severity scores. METHODS: Skin hydration (SH), transepidermal water loss (TEWL), pH, erythema, pigmentation, and ITA (individual typology angle) were measured (using Delfin, Courage + Khazaka, and Mettler Toledo equipment), and correlated with Patient-Oriented Eczema Measure (POEM, a short-term subjective-symptom score), Scoring Atopic Dermatitis (SCORAD, a short-term subjective-symptom and objective-sign score), Nottingham Eczema Severity Score (NESS, a long-term subjective-symptom score), Children Dermatology Life Quality Index (CDLQI, a short-term subjective-symptom score) with Spearman's rho coefficient. RESULTS: 80 sets of clinical scores from eczema patients (mean age: 10.8 ± 4.9 years; 44.6% male) were evaluated. The POEM, objective SCORAD, CDLQI correlated well with each other. Skin pH ranged from 4.3 to 7.0 (mean 5.7 ± 0.61). Skin pH was correlated with Objective SCORAD components, including area (rho = 0.269, p = .036), erythema (rho = 0.302, p = .018), and lichenification (rho = 0.365, p = .026) and with the usage frequency of topical antibiotics. Skin pH was also correlated with other skin measurements, including SH (Delfin equipment: rho = -0.38, p < .001). SH and TEWL as measured by Delfin equipment correlated better with a number of symptoms and signs than Courage + Khazaka equipment. Other clinical measurements including erythema, melanin, and skin color did not demonstrate strong correlations with clinical symptom scores. CONCLUSION: Skin pH (using Mettler Toledo), SH, and TEWL (using Delfin equipment) correlated well with various clinical symptomatology scores. Less acidic pH appears to be associated with worse clinical scores of symptomatology, and increase usage of topical antibiotics, These findings not only support the supplementary usage of equipment in aiding objective documentation of clinical symptomatology in eczema therapeutic research but also the advocacy of maintaining more acidic skin and avoiding alkaline soap and emollient products.

Microarray analysis of multiple candidate genes and associated plasma proteins for nephropathy secondary to type 2 diabetes among Chinese individuals.

AIMS/HYPOTHESIS: Evolving research suggests that common and rare alleles jointly constitute the genetic landscape of complex disease. We studied the association between 43 pathway-related candidate genes with 'intermediate phenotype' (i.e. corresponding plasma protein) and diabetic nephropathy in a customised microarray of 1,536 SNPs. METHODS: In this case-control study of type 2 diabetic Chinese individuals with and without diabetic nephropathy, cases (n = 545) were defined on the basis of a spot urinary albumin/creatinine ratio (ACR) > 113 mg/mmol; the value for controls (n = 503) was ACR < 3.3 mg/mmol. Genotyping was performed using Illumina GoldenGate assay. RESULTS: No single nucleotide polymorphism (SNP) remained significant in single locus analysis after correction for multiple testing. Therefore, we explored the best approximately 1% SNPs. Of these 13 SNPs, four clustered to a 5' end NADPH oxidase homologue 4 (NOX4) haplotype (GGCC frequency = 0.776) with estimated OR for diabetic nephropathy of 2.05 (95% CI 1.04-4.06) (heterozygous) and 2.48 (1.27-4.83) (homozygous) (p = 0.0055). The haplotype was correlated with plasma Cu/Zn superoxide dismutase (SOD) concentration, suggesting increased oxidative burden. Endothelin-1 SNP (rs1476046G>A, frequency = 0.252) was correlated with plasma C-terminal pro-endothelin-1 concentrations with an estimated OR for diabetic nephropathy of (heterozygous) 1.26 (0.96-1.66) and (homozygous) 1.87 (1.13-3.12) (p = 0.0072). Nitric oxide synthase 1 (NOS1) 5' haplotype (TGTC frequency = 0.38) also revealed a suggestive association with diabetic nephropathy: heterozygous 1.26 (0.95-1.67), homozygous 1.57 (1.04-2.35) (p = 0.0073). A rare NADPH oxidase homologue 1 (NOX1)-coding non-synonymous SNP (Arg315His, frequency = 0.006) was found exclusively among cases. CONCLUSIONS/INTERPRETATION: Our preliminary observations suggest that common haplotypes from NOX4 and endothelin-1 SNP correlated with plasma Cu/Zn SOD and C-terminal pro-endothelin-1 concentrations, respectively, and might have conferred diabetic nephropathy susceptibility. Common NOS1 and rare NOX1 variants also revealed a suggestive association with diabetic nephropathy. Future studies to validate our observation are needed.

Pilot Studies on Two Complementary Bath Products for Atopic Dermatitis Children: Pine-Tar and Tea.

Background: Few standardized bath product clinical trials were performed for atopic dermatitis patients. Pine-tar and green tea extracts are plant-derived products that have been described as having anti-allergic effects which may reduce AD disease severity. Methods: The efficacy of two complementary bath products was studied and compared. Efficacy and acceptability of the bath products were measured by patient general acceptability of treatment (GAT: very, good, fair or poor), disease severity (SCORAD: SCoring Atopic Dermatitis), quality of life (CDLQI: Children Dermatology Life Quality Index), and pertinent clinical parameters were measured before and after four weeks of treatment. Sample size calculations for further clinical trials were performed. In one group, nine AD patients were subjected to bathing with a pine-tar bath oil for 10⁻15 min daily for four weeks. In another group, 20 AD subjects bathed with a teabag containing green tea extracts for four weeks. Results: Significant improvements in clinical- and patient-orientated parameters were found in the pine-tar bathing group, but not the tea-bag bathing group. Both groups reported very good/good GAT on the studied products. Teabag bathing was considered not efficacious for further clinical trials. Conclusions: The pilot studies provided preliminary data on the efficacy of pine tar bath oil. We do not document a significant efficacy for bathing with tea extracts. Bathing with pine-tar is potentially a complementary topical treatment with good patient acceptance and adherence, but further evidence-based research for its recommendations is needed.

Testing the Actions of a Multi-action Emollient: Patient's Acceptability Determines Product Efficacy.

AIM: Eczema or Atopic Dermatitis (AD) is associated with itch, sleep disturbance, impaired life quality, reduced skin hydration, impaired epidermal barrier function and colonization by Staphylococcus aureus (SA). We investigated an emollient with claimed multi-actions on barrier repair, antihistaminergic and antimicrobial effects. METHODS: Consecutive AD patients were recruited. Swabs and cultures from eczematous areas, disease severity (SCOring Atopic Dermatitis score: SCORAD), quality-of-life (Children Dermatology Life Quality Index, CDLQI), Skin Hydration (SH), and Transepidermal Water Loss (TEWL) were obtained before and 4-week following usage of the emollient. Global or General Acceptability of Treatment (GAT) was obtained (as very good, good, fair or poor). RESULTS: 30 AD patients were recruited. 73% reported "very good" or "good", whereas 27% reported "fair" or "poor" GAT of the emollient. Following the use of the multi-action emollient, area affected, disease intensity and severity significantly improved, especially in the very good/good group (p=0.006-0.035). There was no significant improvement of itch or sleep scores, quality of life, SH, TEWL, S. aureus colonization status, or use of topical treatments. When compared with the historical data of another product, there was no statistical difference between the two creams. CONCLUSION: The emollient is acceptable in nearly three-quarter of AD patients. Patients that accept the moisturizer have less area affected, disease intensity and severity than the non-accepting counterparts following its usage. Despite claim for multi-action, there were no appreciable quality-oflife, anti-itch, skin barrier, and anti-microbial effects.

Emollient Acceptability in Childhood Atopic Dermatitis: Not All Emollients are Equal.

BACKGROUND: Eczema or Atopic Dermatitis (AD) is a common chronic relapsing skin disease associated with impaired quality of life. Regular usage of moisturizer/emollient is the mainstay of management but acceptability of emollient is often suboptimal. We investigated if emollient acceptability is influenced by various clinical factors in AD. METHODS: A survey on frequency of emollient usage, brands, clinical factors including disease severity (Nottingham Eczema Severity Score, NESS), quality of life (Children Dermatology Life Quality Index, CDLQI), Transpidermal Water Loss (TEWL), and Skin Hydration (SH) was performed. Acceptability was classified as very good, good, fair or poor. RESULTS: We evaluated 128 AD patients. NESS correlated with CDLQI and the treatment domain of CDLQI. Emollient usage is elementary for AD treatment. 89.1% of patients reported that doctor's recommendation was the major source of advice when choosing an emollient. Aqueous cream (AQ) and petroleum-derived products were among the commonly used emollients. More aqueous cream users reported fair/poor acceptability (p=0.017) and lower SH (p<0.05). Linear regression showed that patients who thought their emollient as fair or poor were currently using AQ (p=0.003), their emollient not recommended by a doctor (p=0.035), with more severe disease (p=0.04), and had lower emollient usage in winter (p=0.05). CONCLUSION: Physicians play a pivotal role in assisting patients to select an emollient that they will accept and use consistently. The studied emollients are generally acceptable by over 80% patients. However, aqueous cream is least acceptable by patients, making it the least favorable emollient to recommend to patients.

Determinants for asthma control, quality of life and use of complementary and alternative medicine in asthmatic pediatric patients in four cities.

BACKGROUND: Asthma is a significant chronic health problem worldwide. Management aims at disease control by reducing functional impairment and exacerbations and improving quality of life (QoL). We report a multi-center study to survey asthma control and QoL in four cities in the Pearl River Delta. METHODS: The conjoint survey involved ten Hong Kong pediatric hospitals/units, two Shenzhen hospitals, two Macau hospitals, and two Guangzhou hospitals on asthma control (using Asthma Control Test) and QoL (Pediatric Allergic Disease Quality of Life Questionnaire, PADQLQ). Acceptability of a treatment is graded as very good/good/fair/poor. RESULTS: Good asthma control was only reported in 80% subjects in Hong Kong, but higher in sister cities (85-94%, P < 0.001). Allergic rhinitis, "incense burning", and "smoker in family" were prevalent among the four cities. Logistic regression showed better control of asthma was associated with better PADQLQ (B = - 0.029, P < 0.001), better acceptability of bronchodilator (B = - 1.488, P = 0.025), negatively with "smoker in family" (B = - 0.83, P = 0.015) and various PADQLQ domains. Conversely, worse PADQLQ was associated with allergic rhinitis severity (B = 4.77, P < 0.001), poor control of asthma (B = 7.56, P < 0.001), increased frequency of traditional Chinese medicine use (B = 1.7, P < 0.05), increased frequency of bronchodilator usage (B = 1.05, P < 0.05), "smoker in family" (B = 4.05, P < 0.05), and incense burning at home (B = 3.9, P < 0.05). CONCLUSIONS: There are some clinical and cultural differences among the four southern Chinese cities within the Guangdong province. This study identifies potentially modifiable environmental and treatment factors associated with poor asthma control and QoL for health-care interventions. Having a smoker in the family is independently associated with poor asthma control and QoL.

Niacin affects cell adhesion molecules and plasminogen activator inhibitor-1 in HepG2 cells.

BACKGROUND: Beyond lipid-modifying actions, niacin lowers the risk of atherothrombotic events by lowering prothrombotic factors like fibrinogen. Plasminogen activator inhibitor type 1 (PAI-1) is a potential factor for atherogenesis and thrombosis, increased in acute myocardial infarctions and restenosis after angioplasty. Cell adhesion molecules (CAM) mediate adhesion, recruitment and migration of white blood cells through vascular surfaces, an essential process in atherogenesis. ICAM-1 is a significant predictor of future coronary events. Whether niacin affects ICAM-1 expression is unknown. We studied the effects of niacin on PAI-1 and CAM using HepG2 cells. METHODS: HepG2 cells were cultured in DMEM until 90% confluent. After serum starvation, cells were exposed to DME/F12 containing niacin. Transforming growth factor-beta (TGF-beta) was added directly to cell media. Cell lysate and conditioned media were collected for measurement of PAI-1 by ELISA. For measurement of ICAM, cells were treated with tumor necrosis factor-alpha (TNF-alpha) instead. The effect of niacin on mRNA expression of ICAM-1 was studied using RT-PCR. RESULTS: Niacin reduced the TGF-beta-induced rise by 30% to 55% (p=0.002). The differences in degree of PAI-1 reduction, between different niacin concentrations, were not statistically significant. Niacin reduced TNF-alpha-induced rise in ICAM-1 levels by 66% to 89% (p<0.0001), but did not significantly affect TNF-alpha-induced rise in PECAM-1. Semiquantitative RT-PCR analysis showed that reduced TNF-alpha-induced rise in ICAM-1 mRNA expression significantly by 17% (p=0.001). CONCLUSIONS: Treatment with niacin suppressed PAI-1 and ICAM-1 levels in HepG2 cells. Further studies to understand the mechanistic pathways of this suppression, could further explain benefits of niacin in prevention of atherosclerotic disease, and offer therapeutic avenues against the rising burden of atherothrombotic disease.

Patients with low levels of high-density lipoprotein cholesterol: to treat or not to treat?

Clinical evidence indicates that a low level of high-density lipoprotein cholesterol (HDL-C) is a major risk of atherosclerosis. Raising HDL-C reduces this risk significantly, making HDL-C levels an important target of treatment for dyslipidaemia, especially in pre-existent atherosclerosis. HDL-C is protective against atherosclerosis, largely due to its function of reverse cholesterol transport. Additionally, some important roles include fibrinolysis, antioxidant functions, and reduction of platelet aggregability. A number of agents potentially modify HDL favourably. Niacin is the most potent HDL-C raising agent currently available in clinical practice, followed by fibrates. CETP inhibitors show greater HDL-C rising, but are still used in trial settings only. HDL mimetic agents are another group of agents that offer much promise. Clinical outcome data are awaited for these newer therapeutic agents.

Causes of isolated prolonged activated partial thromboplastin time in an acute care general hospital.

INTRODUCTION: To determine the causes of isolated prolonged activated partial thromboplastin time (APTT) in an acute care general hospital setting so as to rationalise fresh frozen plasma usage. METHODS: A prospective study of consecutive patients with isolated prolonged APTT presenting to our hospital between February 2002 and January 2004 was performed. All patients had normal prothrombin time and thrombin time. For all patients, an initial 50:50 correction with plasma was done and a standard panel of tests was performed. These included detection of lupus anticoagulant using two different sensitive tests; measurement of coagulant factors VIII (FVIII), IX, XI and XII, which are involved in the intrinsic arm of haemostasis; von Willebrand factor antigen (vWF:Ag) levels and for those with FVIII levels less than 10 percent, an inhibitor assay using the Nijmegen modification of the Bethesda method. RESULTS: 177 patients were included in the study. The cohort was typical of an acute care general hospital patient population in Singapore in terms of age, sex and racial distribution. The most common cause of an isolated prolonged APTT in our study was the presence of lupus anticoagulant (53.1 percent of cases). In 31.6 percent of cases, obvious cause could be detected after our panel of tests. These patients mostly had mildly prolonged APTT that could be both correctable and non-correctable by normal plasma. Prolonged APTT due to factor deficiency was relatively rare with those that may potentially cause haemorrhagic problems only accounting for 4.5 percent of cases. CONCLUSION: Our study suggests that most of the causes of isolated prolonged APTT do not lead to haemorrhagic complications. In fact, in a majority, it may signify an underlying thrombophilic condition. As a result, prolongation of APTT should be fully investigated and correction with fresh frozen plasma should be used only when appropriate.