[Using artificial intelligence as an initial triage strategy in diabetic retinopathy screening program in China].

Objective: To investigate the diagnostic accuracy and efficiency of an artificial intelligence (AI) triaging model in a diabetic retinopathy (DR) screening program. Methods: A DR screening program was conducted in Kashi City and Kizilsu Kirghiz Autonomous Prefecture of the Xinjiang Uyur Autonomous Region from May to July 2018, and 8 005 patients with diabetes mellitus were included. Fundus images, one centered at optic disc and one centered at macula, were taken for both eyes. A previously validated AI algorithm was applied as the first step to identify the patients with all 4 images. If the images were classified as gradable and negative DR, an AI-generated report was immediately provided without sending to manual grading, and 1/3 of these patients were randomly sampled for manual grading and quality control (group A). For the patients with at least one image classified as ungradable or positive for any DR, all images were sent for manual grading (group B). Finally, 300 patients were randomly selected from group A and group B respectively for accuracy assessment, where the patients and their images were classified by a specialist panel for referral DR (pre-proliferative DR, or proliferative DR, and/or diabetic macular edema). Results: Among 8 005 patients for DR screening [including 3 220 males and 4 785 females, aged (58.3±10.6) years], after AI triaging, 5 267 (65.8%) potentially received reports from AI system and 2 738 (34.2%) required manual grading. In group A, the accuracy and specificity of AI classification and manual grading on referral DR were all 100%. In group B, the accuracy of AI and manual grading were 75.8% and 90.3%, respectively, while the sensitivity of AI and manual grading was 100% and 79.1%, respectively. Conclusion: AI alleviates 60% of the workload of manual grading without missing any referral patients with the aid of the current AI triaging model.

Sudden arrhythmia death syndrome in young victims: a five-year retrospective review and two-year prospective molecular autopsy study by next-generation sequencing and clinical evaluation of their first-degree relatives.

OBJECTIVE: Sudden arrhythmia death syndrome (SADS) accounts for about 30% of causes of sudden cardiac death (SCD) in young people. In Hong Kong, there are scarce data on SADS and a lack of experience in molecular autopsy. We aimed to investigate the value of molecular autopsy techniques for detecting SADS in an East Asian population. METHODS: This was a two-part study. First, we conducted a retrospective 5-year review of autopsies performed in public mortuaries on young SCD victims. Second, we conducted a prospective 2-year study combining conventional autopsy investigations, molecular autopsy, and cardiac evaluation of the first-degree relatives of SCD victims. A panel of 35 genes implicated in SADS was analysed by next-generation sequencing. RESULTS: There were 289 SCD victims included in the 5-year review. Coronary artery disease was the major cause of death (35%); 40% were structural heart diseases and 25% were unexplained. These unexplained cases could include SADS-related conditions. In the 2-year prospective study, 21 SCD victims were examined: 10% had arrhythmogenic right ventricular cardiomyopathy, 5% had hypertrophic cardiomyopathy, and 85% had negative autopsy. Genetic analysis showed 29% with positive heterozygous genetic variants; six variants were novel. One third of victims had history of syncope, and 14% had family history of SCD. More than half of the 11 first-degree relatives who underwent genetic testing carried related genetic variants, and 10% had SADS-related clinical features. CONCLUSION: This pilot feasibility study shows the value of incorporating cardiac evaluation of surviving relatives and next-generation sequencing molecular autopsy into conventional forensic investigations in diagnosing young SCD victims in East Asian populations. The interpretation of genetic variants in the context of SCD is complicated and we recommend its analysis and reporting by qualified pathologists.

Genetic basis of channelopathies and cardiomyopathies in Hong Kong Chinese patients: a 10-year regional laboratory experience.

INTRODUCTION: Hereditary channelopathies and cardiomyopathies are potentially lethal and are clinically and genetically heterogeneous, involving at least 90 genes. Genetic testing can provide an accurate diagnosis, guide treatment, and enable cascade screening. The genetic basis among the Hong Kong Chinese population is largely unknown. We aimed to report on 28 unrelated patients with positive genetic findings detected from January 2006 to December 2015. METHODS: Sanger sequencing was performed for 28 unrelated patients with a clinical diagnosis of channelopathies or cardiomyopathies, testing for the following genes: KCNQ1,KCNH2,KCNE1,KCNE2, and SCN5A, for long QT syndrome; SCN5A for Brugada syndrome; RYR2 for catecholaminergic polymorphic ventricular tachycardia; MYH7 and MYBPC3 for hypertrophic cardiomyopathy; LMNA for dilated cardiomyopathy; and PKP2 and DSP for arrhythmogenic right ventricular dysplasia/cardiomyopathy. RESULTS: There were 17 males and 11 females; their mean age at diagnosis was 39 years (range, 1-80 years). The major clinical presentations included syncope, palpitations, and abnormal electrocardiography findings. A family history was present in 13 (46%) patients. There were 26 different heterozygous mutations detected, of which six were novel-two in SCN5A (NM_198056.2:c.429del and c.2024-11T>A), two in MYBPC3 (NM_000256.3:c.906-22G>A and c.2105_2106del), and two in LMNA (NM_170707.3:c.73C>A and c.1209_1213dup). CONCLUSIONS: We have characterised the genetic heterogeneity in channelopathies and cardiomyopathies among Hong Kong Chinese patients in a 10-year case series. Correct interpretation of genetic findings is difficult and requires expertise and experience. Caution regarding issues of non-penetrance, variable expressivity, phenotype-genotype correlation, susceptibility risk, and digenic inheritance is necessary for genetic counselling and cascade screening.

Structure of a mouse submaxillary messenger RNA encoding epidermal growth factor and seven related proteins.

The structure of the messenger RNA (mRNA) encoding the precursor to mouse submaxillary epidermal growth factor (EGF) was determined from the sequence of a set of overlapping complementary DNA's (cDNA). The mRNA is unexpectedly large, about 4750 nucleotide bases, and predicts the sequence of preproEGF, a protein of 1217 amino acids (133,000 molecular weight). The EGF moiety (53 amino acids) is flanked by polypeptide segments of 976 and 188 amino acids at its amino and carboyxl termini, respectively. The amino terminal segment of the precursor contains seven peptides with sequences that are similar but not identical to EGF.

Subthreshold depression and cognitive impairment but not demented in stroke patients during their rehabilitation.

BACKGROUND: Subthreshold depression (sD) and cognitive impairment but not demented (CIND) in stroke patients are associated with poorer rehabilitative outcomes. Their diagnosis can easily be operationalized using validated scales. AIM: The aim of the study was to ascertain the prevalence of depressive symptoms and cognitive impairment in stroke patients during three crucial stages of the rehabilitative process, viz. upon admission, upon planned discharges from rehabilitation hospitals and at 6 months post-stroke, using validated scales like the Geriatric Depression Scale and Abbreviated Mental Test (recommended by the British Geriatric Society). Their baseline risk factors were also ascertained. RESULTS: On admission, the prevalence of depressive symptoms and cognitive impairment was 60% and 54% respectively. The prevalence upon planned discharges and 6 months post-stroke, respectively, of depressive symptoms was 38% and 34% and that of impaired cognition was 33% and 40%. Baseline independent correlates at 6 months post-stroke depressive symptoms were: recurrent stroke (OR 3.34); on admission cognitive impairment (OR 4.78) and ADL dependence (OR 5.28). And that of cognitive impairment were: increasing age (OR 8.07); post-stroke dysphagia (OR 4.58); on admission cognitive impairment (OR 23.95) and on admission depressive symptoms (OR 3.50). CONCLUSIONS: Continuous screening and appropriate intervention, especially at baseline, would significantly decrease the burden posed by stroke patients with such psychological impairments in the community.

Modeling fire-induced smoke spread and carbon monoxide transportation in a long channel: Fire Dynamics Simulator comparisons with measured data.

Smoke and toxic gases, such as carbon monoxide, are the most fatal factors in fires. This paper models fire-induced smoke spread and carbon monoxide transportation in an 88m long channel by Fire Dynamics Simulator (FDS) with large eddy simulation (LES). FDS is now a well-founded fire dynamics computational fluid dynamic (CFD) program, which was developed by National Institute of Standards and Technology (NIST). Two full scale experiments with fire sizes of 0.75 and 1.6MW were conducted in this channel to validate the program. The spread of the fire-induced smoke flow together with the smoke temperature distribution along the channel, and the carbon monoxide concentration at an assigned position were measured. The FDS simulation results were compared with experimental data with fairly good agreement demonstrated. The validation work is then extended to numerically study the carbon monoxide concentration distribution, both vertically and longitudinally, in this long channel. Results showed that carbon monoxide concentration increase linearly with the height above the floor and decreases exponentially with the distance away from the fire source.

High-copy suppression of glucose transport defects by HXT4 and regulatory elements in the promoters of the HXT genes in Saccharomyces cerevisiae.

HXT4, a new member of the hexose transporter (HXT) family in Saccharomyces cerevisiae was identified by its ability to suppress the snf3 mutation in multicopy. Multicopy HXT4 increases both high and low affinity glucose transport in snf3 strains and increases low and high transport in wild-type strains. Characterization of HXT4 led to the discovery of a new class of multicopy suppressors of glucose transport defects: regulatory elements in the promoters of the HXT genes. We have designated these sequences DDSEs (DNA sequence dependent suppressing element). Multicopy HXT4 and DDSEs in the HXT1, HXT2, HXT3 and HXT4 promoters were found to restore growth to snf3 and grr1 strains on low glucose media. The DDSE in the HXT4 promoter was refined to a 340-bp sequence 450 bp upstream of the HXT4 translational start. This region was found to contain an 183-amino acid open reading frame. Extensive analysis indicates that the DNA sequence itself and not the encoded protein is responsible for suppression. The promoters of SNF3 and of other glycolytic genes examined did not suppress snf3 in multicopy. Suppression of snf3 by DDSE is dependent on the presence of either HXT2 or HXT3.

Appropriate use of personal protective equipment among healthcare workers in public sector hospitals and primary healthcare polyclinics during the SARS outbreak in Singapore.

BACKGROUND: Singapore was affected by an outbreak of severe acute respiratory syndrome (SARS) from 25 February to 31 May 2003, with 238 probable cases and 33 deaths. AIMS: To study usage of personal protective equipment (PPE) among three groups of healthcare workers (HCWs: doctors, nurses, and administrative staff), to determine if the appropriate PPE were used by the different groups and to examine the factors that may determine inappropriate use. METHODS: A self-administered questionnaire survey of 14,554 HCWs in nine healthcare settings, which included tertiary care hospitals, community hospitals, and polyclinics, was carried out in May-July 2003. Only doctors, nurses, and clerical staff were selected for subsequent analysis. RESULTS: A total of 10 236 valid questionnaires were returned (70.3% response); 873 doctors, 4404 nurses, and 921 clerical staff were studied. A total of 32.5% of doctors, 48.7% of nurses, and 77.1% of the administrative staff agreed that paper and/or surgical masks were "useful in protecting from contracting SARS". Among this group, 23.6% of doctors and 42.3% of nurses reported working with SARS patients. The view that a paper and/or surgical mask was adequate protection against SARS was held by 33.3% of doctors and 55.9% of nurses working at the A&E unit, 30.5% of doctors and 49.4% of nurses from medical wards, and 27.5% of doctors and 37.1% of nurses from intensive care units. Factors which predicted for agreement that paper and/or surgical masks were protective against SARS, included HCW's job title, reported contact with SARS patients, area of work, and Impact Events Scale scores. CONCLUSION: A variety of factors determine appropriate use of personal protective equipment by HCWs in the face of a major SARS outbreak.

Kawasaki disease in Hong Kong, 1994 to 2000.

OBJECTIVE: To describe the epidemiology, clinical characteristics, and management of Kawasaki disease in children in Hong Kong. DESIGN: Retrospective survey of medical records from July 1994 to June 1997, and prospective data collection from July 1997 to June 2000. SETTING: Hospitals with a paediatric unit in Hong Kong. PATIENTS: Patients diagnosed with Kawasaki disease between July 1994 and June 2000 in public hospitals in Hong Kong. MAIN OUTCOME MEASURES: Incidence of Kawasaki disease and coronary artery aneurysm rates. RESULTS: A total of 696 cases of Kawasaki disease were reported. There were 435 (62.5%) boys and 261 (37.5%) girls giving a male to female ratio of 1.7:1. The age ranged from 1 month to 15 years 5 months with a median of 1.7 years. Infants (<1 year) constituted the largest group of patients (223, 32.0%) and overall, 638 (91.7%) were younger than 5 years. Skin rash, conjunctivitis, and oral signs were among the principal clinical features present in over 80% of cases. Prominent cervical lymph nodes larger than 1.5 cm were less commonly found (24%). Coronary artery aneurysms or ectasia were present in 15.7% (109/696), 8.5% (59/696), and 5.0% (35/696) of patients at 2, 4, and 8 weeks, respectively. The incidence of Kawasaki disease per 100,000 children under 5 years was significantly higher in the prospective study period than in the retrospective period (39 vs 26, P<0.001). CONCLUSION: The incidence of Kawasaki disease is high in Hong Kong and is 39 per 100,000 children below 5 years of age. The coronary artery aneurysm prevalence is 5%. Intravenous gamma-globulin and high-dose aspirin is the mainstay of treatment.

A study on the prevalence of hepatitis B surface antigen among Chinese adult males in Singapore.

A study was conducted in Singapore on 8829 Chinese men aged 35 years or more to determine whether the prevalence of hepatitis B surface antigen (HBsAg) positivity is associated with the source from which the subjects were recruited, or with occupation as an indicator of socioeconomic status. The HBsAg prevalence rates were significantly different (p less than 0.0001) among the five source groups: 8.3% in healthy blood donors, 7.8 in other healthy subjects, 9.2 in non-hepatic outpatients, 10.3 in hospital non-hepatic patients who were not gravely ill, and 11.2 in hospital non-hepatic patients who were gravely ill. After statistical adjustment by multiple logistic regression for age and occupation, the odds ratio (using 'other healthy subjects' as the reference group) ranged from 0.98 (95% CL = 0.65-1.47) for healthy blood donors to 1.42 (95% CL = 0.95-2.12) for hospital non-hepatic patients who were gravely ill. The HBsAg prevalence rates were also significantly different (p less than 0.0001) among occupations: 8.5% in professional, technical and administrative personnel, 9.7 in clerical, sales and services personnel, 10.3 in agricultural and factory workers and unskilled labourers, and 10.5 among the unemployed and retired. After statistical adjustment for age and source groups, the odds ratio (using professional, technical and administrative subjects as the reference group) ranged from 1.07 (95% CL = 0.99-1.17) for the unemployed and retired subjects, to 1.19 (95% CL = 0.93-1.53) for agricultural and factory workers and unskilled labourers.

Photodynamic therapy of actinic keratosis with topical 5-aminolevulinic acid. A pilot dose-ranging study.

OBJECTIVE: To examine the safety and efficacy of photodynamic therapy using topical 5-aminolevulinic acid (ALA) and red light to treat actinic keratoses (AKs). DESIGN: Actinic keratoses were treated with topical ALA (concentrations of 0%, 10%, 20%, or 30%) under occlusion for 3 hours. Before photodynamic therapy, sites were examined for fluorescence. Sites were irradiated with an argon pumped dye laser (630 nm) at fluences of 10 to 150 J/cm2. SETTING: Academic medical center. PATIENTS: Forty patients with 6 clinically typical, previously untreated AKs per patient. MAIN OUTCOME MEASURE: Complete resolution and decrease in lesion area of the AK relative to baseline evaluated at weeks 1, 4, 8, and 16. RESULTS: Three hours after ALA administration, lesions showed moderate red fluorescence. Cutaneous phototoxic effects, localized erythema and edema, peaked at 72 hours. Patients experienced mild burning and stinging during light exposure. Eight weeks after a single treatment using 30% ALA, there was total clearing of 91% of lesions on the face and scalp and 45% of lesions, on the trunk and extremities. No significant differences were observed in clinical responses with treatment using 10%, 20%, or 30% ALA. All concentrations of ALA were more effective than treating AKs with vehicle and light. CONCLUSIONS: Topical photodynamic therapy with ALA is an effective treatment of typical AKs. Complete clearing of nonhypertrophic AKs can be achieved with 10%, 20%, or 30% ALA that is easily tolerated by the patient. Lesions on the face and scalp are more effectively treated than lesions on the trunk and extremities. Hypertrophic AKs did not respond effectively.

A review of the safety and efficacy of acarbose in diabetes mellitus.

Acarbose is a novel oral anti-hyperglycemic agent approved for the treatment of noninsulin-dependent diabetes mellitus. It inhibits alpha-glucosidases in the small intestine, an action that delays the digestion and absorption of complex carbohydrates. Subsequently, there is a smaller rise in the postprandial plasma glucose levels and an overall decrease in the glycosylated hemoglobin by 0.5-1.0%. Potential advantages of acarbose include a greater effectiveness in controlling postprandial hyperglycemia, a low risk of hypoglycemia, and a possible delay in initiating insulin therapy. Acarbose can potentiate the hypoglycemic effects of sulfonylureas or insulin. It has not been associated with weight gain and hyperinsulinemia, both of which can occur with sulfonylureas or insulin. Gastrointestinal adverse effects are common with acarbose, and may decrease with continued treatment. Although rare, elevated serum transaminase levels have been reported.

Decreased formation of aqueous humour in insulin-dependent diabetic patients.

The rate of aqueous humour formation was measured by fluorophotometry in 34 insulin-dependent diabetic patients and 12 non-diabetic controls to determine whether or not aqueous flow in diabetics differed from that of normal controls, and whether or not aqueous flow among diabetics was correlated with the stage of retinopathy. Diabetic patients were divided into three groups based on the degree of retinopathy; group I without retinopathy, group II with minimal to moderate non-proliferative retinopathy, and group III with proliferative retinopathy. Aqueous flow (mean, SD) in diabetic patients was: 1.55 (0.32) microliter/min in group I, 1.51 (0.47) microliter/min in group II, and 1.26 (0.39) microliter/min in group III. No statistically significant difference was found among these three diabetic groups. Aqueous flow in the non-diabetic controls was 2.18 (0.40) microliter/min, and this was statistically significantly greater than in each of the diabetic groups. Intraocular pressure, age, duration of diabetes, haemoglobin A1C, and blood glucose levels had no significant effect on aqueous flow in diabetic patients.

Knowledge and concerns of newly diagnosed NIDDM patients in Singapore.

This paper describes the findings of a questionnaire survey of the knowledge and concern of 152 newly diagnosed NIDDM patients presenting at the Government Polyclinic (primary health care centre). This study is part of a project on outpatient diabetic care in Singapore. It was found that 23.7% of the subjects had no education and 51.3% had only primary school education. More than eighty percent of the subjects understood the importance of diet control and weight control in their condition. More than half of the subjects, 61% of males and 52.7% of females were aware that diabetes could not be cured and that once diabetes is controlled, that medication cannot be stopped and that one must still take the medication even if one feels well. Less than 30% knew about the interpretation of blood and urine sugar findings. The two major concerns amongst the subjects were complications and the need for long-term medication. These findings will be incorporated into the next phase of the project where a health education programme for NIDDM patients will be developed and evaluated.

Jervell-Lange Nielsen syndrome in a Pakistani family.

Congenital long QT syndrome is a rare hereditary disease that is related to the dysfunction of ion channels in cardiac cells. We report on a very rare case of its autosomal recessive form--the Jervell-Lange Nielsen syndrome--in a Pakistani family, which was diagnosed after the incidental finding of bradycardia in a newborn baby girl. We discuss the range of presentations in neonates; the importance of strong suspicion of the syndrome and family screening; the use of the diagnostic criteria and genetic tests; and the different management strategies.

A SAS procedure for exact probability testing of difference between sample and population proportion.

Statistical testing of the hypothesis that the proportion of subjects in a defined population having a certain attribute (proportion of "positives" in a population, P) is equal to some specified value (P0) is frequently encountered in biomedical research. For example, a study might be carried out to statistically test whether the postoperative wound infection rate in patients having undergone an operation with a "new" surgical procedure is 20%, the same value that has been observed for the "established" surgical procedure. The significance test for this hypothesis (e.g., test H0: P = 0.20 against HA: P not equal to 0.20) is usually based on the normal theory approximation method. However, when the sample size is "small", especially if P0 is close to 0 or 1, the normal theory method can yield grossly unreliable results. In contrast, the significance test based on the exact binomial probability procedure always yields reliable results. A computer program coded in SAS is described herein to perform this exact probability test procedure.

A survey of the feline leukaemia virus in Singapore.

In this survey for the presence of the feline leukaemia virus (FeLV) in the Singapore domestic cat population, the sera of two different groups of unvaccinated mainly short haired cats which were over 6 months old were sampled. The FeLV enzyme-linked immunoadsorbent assay (ELISA) diagnostic test kit was used to detect the presence of the FeLV group specific (gs) antigens in the blood of cats. Of the 345 clinically healthy cats surveyed, 34 sera (9.9%) were found to be positive and of the group of 123 cats with clinical signs such as chronic wasting, marked by anaemia, anorexia and lethargy, 33 sera (26.8%) were found to be positive. From the time of diagnosis of a viraemia, 70% of cats will die within 20 months. The results are therefore indicative that annually a small proportion of cats in the local environment will die from a FeLV infection. This survey reflects the natural distribution of an infectious oncovirus in a susceptible host population which is unaffected by any control programme to interfere with the normal sequence of events of host virus interactions.

Health and morbidity profiles of older adults in Singapore and their health care needs.

Before setting up the first Senior Citizens' Health Care Centre (SCHCC), a survey was done to establish the health and morbidity profiles of older adults in the community and their health care needs. Community volunteers personally interviewed 1,697 persons aged 55 years and above, living in three areas in Singapore. The response rate was 75%. The respondents' general characteristics, the prevalence rate of chronic diseases, their functional and mobility status, utilisation of the health services and how the chronic diseases affected their activities of daily living (ADL) were studied. Among the respondents, 2.1% required nursing care, 4.2% were unable to climb stairs, and 23.3% were on long-term medications. As compared to the younger age groups, those 75 years and above reported more difficulties with mobility (semi-ambulant 6.5%, bedridden 1.8%), more needed assistance in ADL (bathing 4.8%, toiletting 4.7%, dressing 3.0%, and feeding 2.4%) and a higher percentage required nursing care (3.6%). Services that would benefit the frail elderly are reported in this paper.

Awareness and acceptance of hepatitis B vaccination in Clementi, Singapore.

Hepatitis B Virus infection, a public health problem in Singapore, can be effectively controlled by vaccination. This paper reports on a study conducted in 1988/89 to ascertain the awareness and uptake rate of Hepatitis B vaccination. A list of children born between November 1986 and May 1987 in the catchmen zone of the Clementi Maternal and Child Health (MCH) Clinic was obtained. Out of a total of 257 children, 226 (87.9%) responded to our study in May 1988 which was part of a larger community health survey carried out by a group of medical students. The vaccination uptake rate was 23%. The awareness of the parents on Hepatitis B virus infection and vaccination was assessed using a standardised questionnaire. About two-thirds were aware of the main modes of Hepatitis B transmission, 46.5% were aware of the long-term consequences of Hepatitis B infection and 6.6% thought that the vaccine was not safe from serious side effects. A follow-up survey of the respondents was carried out in August 1989. The Hepatitis B vaccination uptake had increased to 48.3%. The immunisation status showed a correlation with the ethnic group, father's occupation and awareness score of respondents. The more than two-fold increase in uptake rate can be attributed to a reduction in the cost of Hepatitis B vaccination and a vigorous nation-wide education programme during the preceding year.