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1.
Vaccine ; 40(35): 5241-5247, 2022 08 19.
Article in English | MEDLINE | ID: mdl-35927133

ABSTRACT

BACKGROUND: The case fatality rate and the risk of complications due to pertussis is very high in infants. Asia has the second highest childhood pertussis burden. The study aimed to assess the prevalence, clinical complications, and mortality rates of pertussis disease requiring hospitalization among young infants in Malaysia. METHODS: The study was a one-year, hospital-based, multi-site surveillance of infants less than six months of age with symptoms consistent with pertussis and a cross-sectional analysis of their mothers for recent pertussis infection. Information was obtained from medical records and interviews with the parents. Pertussis diagnosis was confirmed for all infants through serum anti-PT titration test or PCR test. RESULTS: 441 possible cases of pertussis were included in this study. Of these, 12.7 % had laboratory confirmation of pertussis. Infants with confirmed pertussis had significantly higher rates of cyanosis (37.5 % vs 8.6 %; p < 0.0001) and apnea (12.5 % vs 3.9 %; p = 0.027) than test-negative infants. Most infants from both groups were in recovery/recovered at discharge. Those with confirmed pertussis had higher case fatality rate than test-negative cases (5.4 % vs 1.0 %; p = 0.094), but the difference did not reach significance. The majority of confirmed pertussis cases (89.3 %) occurred in infants too young to be fully vaccinated or under-vaccinated for their age. Both test-negative and confirmed pertussis resulted in work-day losses and incurred costs for both parents. CONCLUSIONS: A high pertussis disease burden persists in infants less than six months of age, especially among those un- and under-vaccinated. Maternal and complete, on-time infant vaccination is important to reduce disease burden.


Subject(s)
Whooping Cough , Child , Cross-Sectional Studies , Female , Hospitals , Humans , Infant , Malaysia/epidemiology , Pertussis Vaccine , Vaccination , Whooping Cough/prevention & control
2.
Clin Oncol (R Coll Radiol) ; 34(10): 630-641, 2022 10.
Article in English | MEDLINE | ID: mdl-35534398

ABSTRACT

AIMS: Radiotherapy with radiosensitisation offers opportunity for cure with organ preservation in muscle-invasive bladder cancer (MIBC). Treatment response assessment and follow-up are reliant on regular endoscopic evaluation of the retained bladder. In this study we aim to determine the role of diffusion-weighted magnetic resonance imaging (DWI) and apparent diffusion coefficient (ADC) analysis to assess bladder radiotherapy response. MATERIALS AND METHODS: Patients with T2-T4aN0-3M0 MIBC suitable for radical radiotherapy were recruited prospectively to an ethics approved protocol. Following transurethral resection of the bladder tumour and prior to any treatment, magnetic resonance imaging including DWI was performed on a 1.5T system using b values of 0, 100, 150, 250, 500, 750 s/mm2. DWI was repeated 3 months after completing radiotherapy. Cystoscopy and tumour site biopsy were undertaken following this. The response was dichotomised into response (0.9, P < 0.01). ΔADCall mean of 0.16 × 10-3 mm2/s and ΔADCb100 mean 0.12 × 10-3 mm2/s predicted radiotherapy response with sensitivity/specificity/positive predictive value/negative predictive value of 92.9%/100.0%/100.0%/75.0% and 89.3%/100.0%/100.0%/66.7%, respectively. CONCLUSIONS: Quantitative DWI analysis can successfully provide non-invasive assessment of bladder radiotherapy response. Multicentre validation is required before prospective testing to inform MIBC radiotherapy follow-up schedules and decision making.


Subject(s)
Urinary Bladder Neoplasms , Urinary Bladder , Diffusion Magnetic Resonance Imaging/methods , Humans , Magnetic Resonance Imaging , Prospective Studies , ROC Curve , Urinary Bladder/diagnostic imaging , Urinary Bladder Neoplasms/diagnostic imaging , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/radiotherapy
3.
Trop Biomed ; 38(1): 150-153, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33797539

ABSTRACT

Hand, foot, and mouth disease (HFMD) is a common childhood disease caused by enteroviruses. In 2018, a HFMD outbreak in Malaysia affected over 76,000 children. In this study, we used RT-qPCR and CODEHOP PCR to detect the causative agents in 89 clinically diagnosed HFMD patients in Kuala Lumpur and Selangor. Most (62.9%) of the children were below 3 years old. PCR with either assay detected enteroviruses in 84.2% (75/89) and CODEHOP PCR successfully typed 66.7% (50/75) of the enteroviruses. Sequencing of CODEHOP amplicons showed co-circulation of multiple enteroviruses with coxsackievirus A6 (CV-A6) and A16 as the predominant serotypes, but not the neurovirulent enterovirus A71. CV-A6 infection was more common in children less than 12 months old (p=0.01) and was more likely to cause vesicles in the gluteal area (p=0.01) compared to other enteroviruses. Establishing a robust identification method during HFMD outbreaks is important for patient management and public health responses.


Subject(s)
Enterovirus/isolation & purification , Hand, Foot and Mouth Disease/epidemiology , Child , Child, Preschool , Disease Outbreaks , Enterovirus/classification , Female , Hand, Foot and Mouth Disease/virology , Humans , Infant , Malaysia/epidemiology , Male , Serogroup
4.
Tropical Biomedicine ; : 150-153, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-886322

ABSTRACT

@#Hand, foot, and mouth disease (HFMD) is a common childhood disease caused by enteroviruses. In 2018, a HFMD outbreak in Malaysia affected over 76,000 children. In this study, we used RT-qPCR and CODEHOP PCR to detect the causative agents in 89 clinically diagnosed HFMD patients in Kuala Lumpur and Selangor. Most (62.9%) of the children were below 3 years old. PCR with either assay detected enteroviruses in 84.2% (75/89) and CODEHOP PCR successfully typed 66.7% (50/75) of the enteroviruses. Sequencing of CODEHOP amplicons showed co-circulation of multiple enteroviruses with coxsackievirus A6 (CV-A6) and A16 as the predominant serotypes, but not the neurovirulent enterovirus A71. CV-A6 infection was more common in children less than 12 months old (p=0.01) and was more likely to cause vesicles in the gluteal area (p=0.01) compared to other enteroviruses. Establishing a robust identification method during HFMD outbreaks is important for patient management and public health responses.

5.
J Chem Phys ; 153(16): 165101, 2020 Oct 28.
Article in English | MEDLINE | ID: mdl-33138431

ABSTRACT

Ultra-long-chain fatty acids (ULCFAs) are biosynthesized in the restricted tissues such as retina, testis, and skin. The conformation of a single ULCFA, in which the sn-1 unsaturated chain has 32 carbons, in three types of phospholipid bilayers is studied by molecular dynamics simulations. It is found that the ultra-long tail of the ULCFA flips between two leaflets and fluctuates among an elongation into the opposite leaflet, lies between two leaflets, and turns back. As the number ratio of lipids in the opposite leaflet increases, the ratio of the elongated shape linearly decreases in all three cases. Thus, ULCFAs can sense the density differences between the two leaflets and respond to these changes.


Subject(s)
Fatty Acids/chemistry , Lipid Bilayers/chemistry , Molecular Dynamics Simulation , Molecular Conformation , Phospholipids/chemistry
6.
Br J Dermatol ; 182(5): 1245-1252, 2020 05.
Article in English | MEDLINE | ID: mdl-31420964

ABSTRACT

BACKGROUND: Childhood atopic dermatitis can often have a negative impact on quality of life for affected children and their caregivers. The condition contributes to increased healthcare costs and can pose heavy economic burdens on healthcare systems and societies. OBJECTIVES: The objective of this study is to provide a comprehensive estimate of the economic burden of childhood atopic dermatitis in a Singaporean sample and to investigate associated factors. METHODS: This cross-sectional cost-of-illness study applied a societal perspective. Data was collected between December 2016 and December 2017 in Singapore. Caregivers to children below 16 years of age with a physician-confirmed diagnosis of atopic dermatitis were recruited and sociodemographics, clinical characteristics, health service utilization data and time spent on caregiving were collected from all eligible participants. RESULTS: The average annual cost per child with atopic dermatitis was estimated at U.S. dollars (USD) 7943 (mild USD 6651, moderate USD 7935 and severe USD 14 335) in 2017 prices. The major cost was for informal caregiving (46% of the total cost) followed by out-of-pocket expenses (37%). Healthcare utilization contributed to 17% of the total cost of which 43% was for medications. CONCLUSIONS: Childhood atopic dermatitis imposes substantial costs with a large proportion arising from informal caregiving and out-of-pocket expenses. The costs related to atopic dermatitis are also strongly related to disease severity. This information is important for policy makers and other health planners when considering how to better support affected families. What's already known about the topic? Childhood atopic dermatitis is a costly disease for society. However, comprehensive cost estimations are lacking. Previous cost studies are old, based on small sample sizes or are healthcare-setting specific. What does this study add? This study comprises a health economic evaluation assessing different levels of care and includes various categories of costs. The result showed that informal caregiving was the most prominent cost for children with atopic dermatitis.


Subject(s)
Dermatitis, Atopic , Child , Cost of Illness , Cross-Sectional Studies , Dermatitis, Atopic/epidemiology , Health Care Costs , Humans , Quality of Life , Singapore/epidemiology
7.
Br J Dermatol ; 182(2): 444-453, 2020 02.
Article in English | MEDLINE | ID: mdl-31179535

ABSTRACT

BACKGROUND: Eczema is a prevalent complex skin condition requiring active disease monitoring and personalized education. No studies have assessed the quality of apps that aim to support eczema self-management. OBJECTIVES: To evaluate the quality and comprehensiveness of English, Chinese and Spanish self-management eczema smartphone apps for patients and/or their caregivers. METHODS: A systematic assessment of eczema apps from July 2018 to November 2018. The assessment criteria were based on conformance with international eczema guidelines. The following domains were assessed: consistency and comprehensiveness of eczema-specific educational information; quality and comprehensiveness of eczema-specific tracking functions; compliance with health information best practice principles. RESULTS: In total, 98 apps were assessed: 82 (84%) provided educational information; 38 (39%) tracking functions; and 13 (13%) both. We found that 34% (28/82) of apps provided misleading information, particularly regarding aspects of treatment and disease progression of eczema. Only 15% (12/82) provided international guideline supported information on pharmacological therapies and 16% (13/82) on nonpharmacological therapies. Among 38 apps with a tracking function, 82% (31/38) measured specific symptoms, disease severity or current skin condition and 89% (34/38) helped users to record medication usage including application of topicals. Environmental or dietary allergens were recorded by 34% (13/38). None of the included apps complied with all criteria for educational information, tracking functions or health information principles. CONCLUSIONS: Eczema apps have not yet reached their potential. The large variance in quality of eczema apps highlights the need for quality assurance mechanisms for health apps and guidance for clinicians that would enable them to make personalized recommendations for patients and caregivers. What's already known about this topic? There is limited information about the quality of eczema self-management smartphone apps on the global market. What does this study add? This systematic assessment evaluated all English, Chinese and Spanish language apps that support eczema self-management. The majority did not conform with information in guidelines and insufficiently support evidence-based self-management. The large variance in the quality of eczema apps highlights the need for mechanisms to ensure app quality and to guide personalized app selection for patients, caregivers and doctors.


Subject(s)
Eczema , Mobile Applications , Self-Management , Eczema/therapy , Humans
8.
J Comp Pathol ; 173: 30-40, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31812171

ABSTRACT

The aim of this study was to investigate the expression of tumour endothelial marker 8 (TEM8) in canine mammary gland tumours (MGTs) by immunohistochemistry and to evaluate the association between tumour cell TEM8 expression and tumour histological features, histological grades and expression of luminal and basal/myoepithelial cell markers. TEM8 expression was detected in >60 % of neoplastic epithelial cells in all simple adenomas (n = 25), simple carcinomas (n = 43) and invasive micropapillary carcinomas (n = 5) studied. Six of the 18 solid carcinomas studied showed TEM8 expression in >60% of carcinoma cells present in solid structures and in 12 of the 18 solid carcinomas, <30% of the luminal structure-forming carcinoma cells showed TEM8 expression. TEM8 expression in the neoplastic cells was not associated with histological malignancy in canine MGTs. TEM8+ tumour cells frequently showed the luminal-like phenotype cytokeratin (CK)19+/p63-/α-smooth muscle actin (SMA)-, while most TEM8- tumour cells exhibited the basal-like phenotype CK19-/p63+/αSMA-. These findings indicate that TEM8 may be involved in maintaining the characteristics of luminal cells in canine MGTs and that TEM8 would be useful in identifying the type of neoplastic epithelial cell in MGTs.


Subject(s)
Adenocarcinoma/veterinary , Adenoma/veterinary , Dog Diseases/pathology , Mammary Neoplasms, Animal/pathology , Receptors, Peptide/biosynthesis , Animals , Biomarkers, Tumor/analysis , Dog Diseases/metabolism , Dogs , Female , Mammary Neoplasms, Animal/metabolism , Receptors, Peptide/analysis
9.
Med J Malaysia ; 74(4): 333-334, 2019 08.
Article in English | MEDLINE | ID: mdl-31424044

ABSTRACT

Although post-stroke shoulder pain is a common medical complication among the stroke population, pseudotumor deltoideus which is non-malignant is rarely seen. This case report demonstrates a thorough history, physical examination followed by the relevant investigations are essential when managing a common post-stroke complication. We postulate that pseudotumor deltoideus is likely a pre-existing asymptomatic variant in our patient before the stroke and has presented symptomatically after the stroke due to the associated neurological and musculoskeletal impairments. As post-stroke shoulder pain is associated with unfavourable outcomes, it is important to recognise the underlying causes of post-stroke shoulder pain early and institute prompt appropriate treatment.


Subject(s)
Deltoid Muscle/abnormalities , Shoulder Pain/etiology , Stroke Rehabilitation , Stroke/complications , Humans , Male , Middle Aged
10.
Allergy ; 73(10): 1964-1978, 2018 10.
Article in English | MEDLINE | ID: mdl-29869791

ABSTRACT

United airways disease (UAD) is the concept that the upper and lower airways, which are anatomically and immunologically related, form a single organ. According to this concept, upper and lower airway diseases are frequently comorbid because they reflect manifestations of a single underlying disease at different sites of the respiratory tract. Allergic asthma-allergic rhinitis is the archetypal UAD, but emerging data indicate that UAD is a heterogeneous condition and consists of multiple phenotypes (observable clinical characteristics) and endotypes (pathobiologic mechanisms). The UAD paradigm also extends to myriad sinonasal diseases (eg, chronic rhinosinusitis with or without nasal polyps) and lower airway diseases (eg, bronchiectasis, chronic obstructive pulmonary disease). Here, we review currently known phenoendotypes of UAD and propose a "treatable traits" approach for the classification and management of UAD, wherein pathophysiological mechanisms and factors contributing to disease are identified and targeted for treatment. Treatable traits in UAD can be analyzed according to a framework comprising airway inflammation (eosinophilic, neutrophilic), impaired airway mucosal defense (impaired mucociliary clearance, antibody deficiency), and exogenous cofactors (allergic sensitizers, tobacco smoke, microbes). Appreciation of treatable traits is necessary in advancing the effort to deliver precise treatments and achieve better outcomes in patients with UAD.


Subject(s)
Precision Medicine/methods , Respiratory Tract Diseases/therapy , Comorbidity , Disease Management , Respiratory Tract Diseases/classification , Respiratory Tract Diseases/epidemiology
11.
Clin Exp Allergy ; 48(6): 650-662, 2018 06.
Article in English | MEDLINE | ID: mdl-29676834

ABSTRACT

BACKGROUND: Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. OBJECTIVE: To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. METHODS: The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18-88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. RESULTS: At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non-severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma-related quality of life and symptoms of depression or anxiety (P < .01). CONCLUSION AND CLINICAL RELEVANCE: Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age.


Subject(s)
Absenteeism , Asthma/epidemiology , Efficiency , Quality of Life , Workplace , Activities of Daily Living , Adult , Aged , Asthma/diagnosis , Asthma/etiology , Female , Humans , Male , Middle Aged , Registries , Severity of Illness Index , Surveys and Questionnaires
12.
Soft Matter ; 14(8): 1397-1407, 2018 Feb 21.
Article in English | MEDLINE | ID: mdl-29383371

ABSTRACT

Shape transformations of flat bilayer membranes and vesicles induced by hydrolysis and condensation reactions of amphiphilic molecules are studied using coarse-grained molecular dynamics simulations. The hydrolysis and condensation reactions result in the formation and dissociation of amphiphilic molecules, respectively. Asymmetric reactions between the inner and outer leaflets of a vesicle can transport amphiphilic molecules between the leaflets. It is found that the resulting area difference between the two leaflets induces bilayer sheet protrusion (BP) and budding at low reduced volumes of the vesicles, whereas BP only occurs at high reduced volumes. The probabilities of these two types of transformations depend on the shear viscosity of the surrounding fluids compared to the membrane as well as the reaction rates. A higher surrounding fluid viscosity leads to more BP formation. The inhomogeneous spatial distribution of the hydrophobic reaction products forms the nuclei of BP formation, and faster diffusion of the products enhances BP formation. Our results suggest that adjustment of the viscosity is important to control membrane shape transformations in experiments.

13.
Nat Commun ; 9(1): 479, 2018 02 02.
Article in English | MEDLINE | ID: mdl-29396479

ABSTRACT

Nano-structured silicon is an attractive alternative anode material to conventional graphite in lithium-ion batteries. However, the anode designs with higher silicon concentrations remain to be commercialized despite recent remarkable progress. One of the most critical issues is the fundamental understanding of the lithium-silicon Coulombic efficiency. Particularly, this is the key to resolve subtle yet accumulatively significant alterations of Coulombic efficiency by various paths of lithium-silicon processes over cycles. Here, we provide quantitative and qualitative insight into how the irreversible behaviors are altered by the processes under amorphous volume changes and hysteretic amorphous-crystalline phase transformations. Repeated latter transformations over cycles, typically featured as a degradation factor, can govern the reversibility behaviors, improving the irreversibility and eventually minimizing cumulative irreversible lithium consumption. This is clearly different from repeated amorphous volume changes with different lithiation depths. The mechanism behind the correlations is elucidated by electrochemical and structural probing.

15.
Oncogene ; 37(1): 28-38, 2018 01 04.
Article in English | MEDLINE | ID: mdl-28846105

ABSTRACT

C-reactive protein (CRP) is an acute phase protein synthesized upon the inflammatory responses, associated with breast cancer. The process of tumor cell invasion and metastasis involves the adherence of cells to the extracellular matrix via integrin as a receptor for matrix molecules. The present study investigated the role of CRP in the adhesive phenotype of breast cells and the underlying mechanisms. Here, we first showed that CRP induces adhesion of MCF10A human breast epithelial cells through the activation of integrin α2 signaling. Expression of integrin α2 was induced by CRP in which transcription factors c-fos and SP1 may be involved. Binding of CRP with integrin α2 leads to the activation of focal adhesion kinase (FAK), paxillin and ERKs. CRP also binds to an Fcγ receptor Fcγ receptor I (FcγRI), and induces activation of paxillin, FAK and ERKs. Integrin α2 and FAK have crucial roles in the adhesive and invasive phenotypes as well as MMP-9 upregulation induced by CRP in MCF10A cells. Treatment with an inflammatory lipid sphingosine-1-phosphate induced CRP, which may be secreted and exert an autocrine effect by binding to FcγRI and integrin α2. Involvement of CRP in adhesion, invasion, anchorage-independent growth and upregulation of integrin α2, paxillin and FAK was observed in MDA-MB-231 triple-negative human breast cancer (TNBC) cells. Using an in vivo invasion model and an orthotopic mouse tumor model with MDA-MB-231 cells, we showed that CRP has an important role in intravasation and tumor growth in vivo, demonstrating the in vivo relevance of our in vitro results. The present study elucidates a critical molecular basis between CRP, integrin α2 and FcγRI pathways in MCF10A breast cells and MDA-MB-231 TNBC cells, thereby providing useful information on CRP-induced aggressiveness of breast cells in the inflammatory microenvironment.


Subject(s)
Breast Neoplasms/pathology , C-Reactive Protein/metabolism , Cell Adhesion , Integrin alpha2/metabolism , Receptors, IgG/metabolism , Animals , Breast/cytology , Breast/pathology , Breast Neoplasms/genetics , C-Reactive Protein/genetics , Cell Line, Tumor , Cell Movement , Disease Progression , Female , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Integrin alpha2/genetics , Mice , Mice, Inbred BALB C , Mice, Nude , RNA, Small Interfering/metabolism , Receptors, IgG/genetics , Signal Transduction/genetics , Up-Regulation , Xenograft Model Antitumor Assays
16.
J Biol Chem ; 292(29): 12054-12064, 2017 07 21.
Article in English | MEDLINE | ID: mdl-28578316

ABSTRACT

Docosahexaenoic acid (DHA) has essential roles in photoreceptor cells in the retina and is therefore crucial to healthy vision. Although the influence of dietary DHA on visual acuity is well known and the retina has an abundance of DHA-containing phospholipids (PL-DHA), the mechanisms associated with DHA's effects on visual function are unknown. We previously identified lysophosphatidic acid acyltransferase 3 (LPAAT3) as a PL-DHA biosynthetic enzyme. Here, using comprehensive phospholipid analyses and imaging mass spectroscopy, we found that LPAAT3 is expressed in the inner segment of photoreceptor cells and that PL-DHA disappears from the outer segment in the LPAAT3-knock-out mice. Dynamic light-scattering analysis of liposomes and molecular dynamics simulations revealed that the physical characteristics of DHA reduced membrane-bending rigidity. Following loss of PL-DHA, LPAAT3-knock-out mice exhibited abnormalities in the retinal layers, such as incomplete elongation of the outer segment and decreased thickness of the outer nuclear layers and impaired visual function, as well as disordered disc morphology in photoreceptor cells. Our results indicate that PL-DHA contributes to visual function by maintaining the disc shape in photoreceptor cells and that this is a function of DHA in the retina. This study thus provides the reason why DHA is required for visual acuity and may help inform approaches for overcoming retinal disorders associated with DHA deficiency or dysfunction.


Subject(s)
Acyltransferases/metabolism , Docosahexaenoic Acids/metabolism , Photoreceptor Cells, Vertebrate/metabolism , Vision Disorders/metabolism , Acyltransferases/genetics , Animals , Biomarkers/metabolism , Crosses, Genetic , Docosahexaenoic Acids/analysis , Docosahexaenoic Acids/chemistry , Electroretinography , Liposomes , Membrane Fluidity , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Electron, Transmission , Molecular Dynamics Simulation , Multimodal Imaging , Optical Imaging , Phospholipids/chemistry , Phospholipids/metabolism , Photoreceptor Cells, Vertebrate/pathology , Photoreceptor Cells, Vertebrate/ultrastructure , Physical Phenomena , Retina/metabolism , Retina/pathology , Retina/ultrastructure , Retinal Photoreceptor Cell Outer Segment/metabolism , Retinal Photoreceptor Cell Outer Segment/pathology , Retinal Photoreceptor Cell Outer Segment/ultrastructure , Vision Disorders/pathology
17.
Allergy ; 72(9): 1398-1405, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28295424

ABSTRACT

BACKGROUND: Assessing future risk of exacerbations is an important component of asthma management. Existing studies have investigated short- but not long-term risk. Problematic asthma patients with unfavorable long-term disease trajectory and persistently frequent severe exacerbations need to be identified early to guide treatment. AIM: To identify distinct trajectories of severe exacerbation rates among "problematic asthma" patients and develop a risk score to predict the most unfavorable trajectory. METHODS: Severe exacerbation rates over five years for 177 "problematic asthma" patients presenting to a specialist asthma clinic were tracked. Distinct trajectories of severe exacerbation rates were identified using group-based trajectory modeling. Baseline predictors of trajectory were identified and used to develop a clinical risk score for predicting the most unfavorable trajectory. RESULTS: Three distinct trajectories were found: 58.5% had rare intermittent severe exacerbations ("infrequent"), 32.0% had frequent severe exacerbations at baseline but improved subsequently ("nonpersistently frequent"), and 9.5% exhibited persistently frequent severe exacerbations, with the highest incidence of near-fatal asthma ("persistently frequent"). A clinical risk score composed of ≥2 severe exacerbations in the past year (+2 points), history of near-fatal asthma (+1 point), body mass index ≥25kg/m2 (+1 point), obstructive sleep apnea (+1 point), gastroesophageal reflux (+1 point), and depression (+1 point) was predictive of the "persistently frequent" trajectory (area under the receiver operating characteristic curve: 0.84, sensitivity 72.2%, specificity 81.1% using cutoff ≥3 points). The trajectories and clinical risk score had excellent performance in an independent validation cohort. CONCLUSIONS: Patients with problematic asthma follow distinct illness trajectories over a period of five years. We have derived and validated a clinical risk score that accurately identifies patients who will have persistently frequent severe exacerbations in the future.


Subject(s)
Asthma/epidemiology , Disease Progression , Severity of Illness Index , Adult , Aged , Asthma/diagnosis , Female , Humans , Longitudinal Studies , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , ROC Curve , Risk , Risk Assessment , Risk Factors , Time Factors
18.
Bone Marrow Transplant ; 52(3): 363-371, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27797364

ABSTRACT

The refined disease risk index (DRI) is a powerful prognostic model based solely on the disease type and stage for predicting survival outcomes of various hematological malignancies after allogeneic transplant. Here, we analyzed our series of 690 patients transplanted over the past 15 years, and showed that besides overall survival (OS), the refined DRI is also able to segregate event-free survival and relapse mortality in our cohort of largely Southeast Asian patients with a long and complete follow-up. Stratification by refined DRI remains statistically significant even when broken down by specific diseases each with a smaller number of patients, as well as for a small subset of patients younger than 18 years old, providing a robust model for prognostication. Multivariable analysis shows that refined DRI, age, year of transplant and donor type are independent risk factors for OS. We further demonstrated here that prognostication for a given patient with a specific disease can be made more discriminating by integrating independent risk factors such as age and donor type with the refined DRI. The future development of prognostic system incorporating the refined DRI with patient- and transplant-related risk factors will provide a more precise estimate of transplant outcome.


Subject(s)
Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Tissue Donors , Adult , Age Factors , Allografts , Disease-Free Survival , Female , Humans , Male , Middle Aged , Risk Assessment , Risk Factors , Survival Rate
19.
Trop Biomed ; 34(1): 240-248, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-33593003

ABSTRACT

Hand, foot and mouth disease (HFMD) is a childhood illness, commonly caused by enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). In recent years, unusual HFMD outbreaks caused by coxsackievirus A6 (CV-A6) have been reported. From May 2012 to September 2013, enteroviruses were detected in 25 HFMD patients in University Malaya Medical Centre, Kuala Lumpur, Malaysia. The predominant serotypes were EV-A71 (48%) and CV-A6 (48%), followed by CV-A16 (4%). CV-A6 patients (mean age, 2.1) were significantly younger than EV-A71 patients (mean age, 3.3). There were no significant differences observed in clinical features between EV-A71 and CV-A6 patients. Since enteroviruses are difficult to differentiate clinically, the conserved 5' untranslated region (5' UTR) was used to identify enterovirus serotypes. Phylogenetic analysis of 5' UTR showed distinct clustering of viruses as EV-A71, CV-A16 and CV-A6. Further genotyping with capsid genes showed that all the EVA71 sequences belonged to subgenotype B5, while the CV-A16 sequence belonged to subgenotype B2b. CV-A6 sequences were clustered into genotypes D1 and D2, with recent isolates from Seri Kembangan, Malaysia and China. In summary, 59.5% of HFMD cases in our centre in 2012-2013 were caused by EV-A71, CV-A16 and the newly emerging CV-A6. This study also demonstrated that 5' UTR is suitable for preliminary identification of enteroviruses during HFMD outbreaks, but specific capsid genes such as VP1 and VP4/VP2 are required for further genotyping. Apart from measures to control the spread of the virus during an outbreak of HFMD, identification of EV-A71 as the etiological agent is important as EV-A71 is a major cause of severe neurological complications and potentially fatal.

20.
Phys Rev E ; 94(5-1): 053304, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27967021

ABSTRACT

Microscopic stress fields are widely used in molecular simulations to understand mechanical behavior. Recently, decomposition methods of multibody forces to central force pairs between the interacting particles have been proposed. Here, we introduce a force center of a three-body potential and propose different force decompositions that also satisfy the conservation of translational and angular momentum. We compare the force decompositions by stress-distribution magnitude and discuss their difference in the stress profile of a bilayer membrane by using coarse-grained and atomistic molecular dynamics simulations.

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