Expanded carrier screening using next-generation sequencing of 123 Hong Kong Chinese families: a pilot study.

INTRODUCTION: To determine the carrier frequency and common mutations of Mendelian variants in Chinese couples using next-generation sequencing (NGS). METHODS: Preconception expanded carrier testing using NGS was offered to women who attended the subfertility clinic. The test was then offered to the partners of women who had positive screening results. Carrier frequency was calculated, and the results of the NGS panel were compared with those of a target panel. RESULTS: One hundred twenty-three women and 20 of their partners were screened. Overall, 84 (58.7%) individuals were identified to be carriers of at least one disease, and 68 (47.6%) were carriers after excluding thalassaemias. The most common diseases found were GJB2-related DFNB1 nonsyndromic hearing loss and deafness (1 in 4), alpha-thalassaemia (1 in 7), beta-thalassaemia (1 in 14), 21-hydroxylase deficient congenital adrenal hyperplasia (1 in 13), Pendred's syndrome (1 in 36), Krabbe's disease (1 in 48), and spinal muscular atrophy (1 in 48). Of the 43 identified variants, 29 (67.4%) were not included in the American College of Medical Genetics and Genomics or American College of Obstetrics and Gynecology guidelines. Excluding three couples with alpha-thalassaemia, six at-risk couples were identified. CONCLUSION: The carrier frequency of the investigated members of the Chinese population was 58.7% overall and 47.6% after excluding thalassaemias. This frequency is higher than previously reported. Expanded carrier screening using NGS should be provided to Chinese people to improve the detection rate of carrier status and allow optimal pregnancy planning.

Improving the emergency department management of post-chemotherapy sepsis in haematological malignancy patients.

OBJECTIVE: To review the result of the implementation of treatment protocol for post-chemotherapy sepsis in haematological malignancy patients. DESIGN: Case series with internal comparison. SETTING: Accident and Emergency Department, Queen Elizabeth Hospital, Hong Kong. PATIENTS: Febrile patients presenting to the Accident and Emergency Department with underlying haematological malignancy and receiving chemotherapy within 1 month of Accident and Emergency Department visit between June 2011 and July 2012. Similar cases between June 2010 and May 2011 served as historical referents. MAIN OUTCOME MEASURES: The compliance rate among emergency physicians, the door-to-antibiotic time before and after implementation of the protocol, and the impact of the protocol on Accident and Emergency Department and hospital service. RESULTS: A total of 69 patients were enrolled in the study. Of these, 50 were managed with the treatment protocol while 19 patients were historical referents. Acute myeloid leukaemia was the most commonly encountered malignancy. Overall, 88% of the patients presented with sepsis syndrome. The mean door-to-antibiotic time of those managed with the treatment protocol was 47 minutes versus 300 minutes in the referent group. Overall, 86% of patients in the treatment group met the target door-to-antibiotic time of less than 1 hour. The mean lengths of stay in the emergency department (76 minutes vs 105 minutes) and hospital (11 days vs 15 days) were shorter in those managed with the treatment protocol versus the historical referents. CONCLUSION: Implementation of the protocol can effectively shorten the door-to-antibiotic time to meet the international standard of care in neutropenic sepsis patients. The compliance rate was also high. We proved that effective implementation of the protocol is feasible in a busy emergency department through excellent teamwork between nurses, pharmacists, and emergency physicians.

Effects of supercoiling on the sequence-specific photo-modification of DNA by a vanadium(V)-peroxo complex.

Sequence-specific photo-modification of DNA has been demonstrated, for the first time, in a vanadium(V)-peroxo complex, NH4[VO(O2)2(5,6-Me2phen)] (where 5,6-Me2phen = 5,6-dimethyl-1,10-phenanthroline). Using molecular cloning technique, a consensus sequence motif of 5'-G(A/G)TA(T/C)C was identified associated with the two specific photo-modification sites, 5'-ATC and 5'-TACC found on a plasmid DNA, pBluescript, by a modified Sanger sequencing technique. DNA supercoiling was shown to be a critical prerequisite for this observed sequence-specific photo-modification activity.

A population-based study on the association between parental occupations and some common birth defects in singapore (1994-1998).

We sought to study the association between some common birth defects and parental occupations. The live births and congenital malformation born between January 1994 and December 1998 were obtained from the Singapore National Registry of Births and Deaths (the National Birth Defect Registry). The prevalence of overall birth defects among Singapore live births during the study period is 13.9 per 1,000 live births. The most frequent single coding defects were "bulbus cordis anomalies and anomalies of cardiac septal closure (BCA)," "congenital anomalies of urinary system (CUS)," "cleft palate and cleft lip (CPL)," and "certain congenital musculoskeletal deformities (CMD)." Using the "Legislators, Senior Officers & Managers" as reference and adjusting for possible confounders, there were significant associations for: (1) paternal "clerical workers" (adjusted RR 2.25) with the BCA; (2) maternal "professionals" with CUS (adjusted risk ratio [RR] 3.58); (3) paternal "production craftsmen and related workers" with both the BCA (adjusted RR 2.04), and the CMD (adjusted RR 2.83); (4) paternal "plant and machine operators and assemblers" with the BCA (adjusted RR 2.49), and the CUS (adjusted RR 5.19), and the CMD (adjusted RR 3.01). Paternal rather than maternal exposure might be more important in the causation of some common birth defects in Singapore.

Low birth weight in relation to parental occupations-a population-based registry in Singapore (1994-1998).

OBJECTIVES: To study the association between parental occupation and low birth weight (LBW) in infants born in Singapore between 1994 and 1998. Other factors that may be related to LBW were also investigated. METHODS: A retrospective study. Information was obtained from the Singapore National Registry of Births and Deaths on parental occupations for live births between 1 January 1994 to 31 December 1998. Parental date of birth, ethnic group, and highest educational qualification were also obtained. The associations between these factors and the occurrence of LBW was assessed using descriptive statistics and logistic regression analysis. RESULTS: A total 208,360 live births were studied. Analyses were restricted to singleton births > or =37th week gestation (total of 189,064). No significant differences in LBW risk were found for the different maternal occupational groups, compared with a referent group ("legislators, senior officers, and managers"). However, fathers who were "not working" (OR=2.04; 1.57-2.65), "not classifiable by occupation" (OR=1.34; 1.09-1.65), and "cleaners, laborers, and related workers" (OR=1.32; 1.12-1.55) had the highest risk of LBW infants when compared with "legislators, senior officers, and managers," after adjustment for maternal occupation, ethnic group, educational level and age, paternal educational level, infant gestational age, sex, and birth order. CONCLUSION: Certain paternal occupational groups appear to be associated with a higher risk of having LBW infants. This may be linked to socioeconomic status and possible work-related factors. Future studies of pregnancy outcomes should not ignore the potential contributions of fathers.

Parental occupations and other risk factors associated with nonchromosomal single, chromosomal single, and multiple birth defects: a population-based study in Singapore from 1994 to 1998.

OBJECTIVE: The purpose of this study was to evaluate the association between the prevalence of birth defects among maternal and paternal occupation groups in Singapore for live births between January 1, 1994, and December 31, 1998, and to determine whether there are certain demographic risk factors and maternal and/or paternal occupation groups that are associated with an increased risk for birth defects versus chromosomal single birth defect, nonchromosomal single birth defect, and multiple birth defects. STUDY DESIGN: This was a retrospective study. Information on live births (Singapore National Registry of Births and Deaths) and birth defect cases (National Birth Defects Register) were studied. Other information included the mother's date of birth, ethnic group, highest educational qualification, and the occupation of the mother and the father. Cox regression analysis was used to determine whether certain demographic and occupational factors were associated with the three groups of birth defects. RESULTS: Of a total of 237,755 live births, there were 3276 birth defect cases (nonchromosomal single birth defect, 1869 cases; chromosomal single birth defect, 197 cases; and multiple birth defects, 1210 cases). Increased risks for all types of birth defects were observed with advancing gestational age. Occurrence of nonchromosomal single birth defect and multiple birth defects were significantly higher for multiple births compared to singleton births. Significant associations were found with the use of "legislators, senior officers, and managers" as reference: Maternal occupation of "cleaners, laborers, and related workers" with chromosomal single birth defect anomalies (adjusted risk ratio, 4.86; 95% CI, 1.07-22.14); paternal occupation of "plant and machine operators and assemblers" (adjusted risk ratio, 1.50; 95% CI, 1.14-1.98) with nonchromosomal single birth defect; "production craftsmen and related workers" and "cleaners and laborers and related workers" with nonchromosomal single birth defect (adjusted risk ratio, 1.42; 95% CI, 1.10-1.82; and adjusted risk ratio, 1.43; 95% CI, 1.07-1.91 respectively); and multiple birth defects (adjusted risk ratio, 1.42; 95% CI, 1.03-1.94; and adjusted risk ratio, 1.47; 95% CI, 1.03-2.09, respectively). CONCLUSION: Maternal delivery age is an important risk factor for all birth defects. Mothers and fathers who work as "cleaners and laborers and related workers" appear to have a higher risk of giving birth to children with chromosomal single birth defect and nonchromosomal single birth defect and multiple birth defects, respectively. Further in-depth study would be needed to confirm these observations.

Prevalence of birth defects and parental work in Singapore live births from 1994 to 1998: a population-based study.

The aims of the study were to assess the prevalence of birth defects (BDs) among different occupational groups and non-working parents, and to identify possible risk factors associated with BDs in Singapore live births born between 1 January 1994 and 31 December 1998. To do this, information on live births (from the Singapore National Registry of Births and Deaths) and BD cases [from the National Birth Defects Register (NBDR)] was obtained from 1 January 1994 to 31 December 1998. There were a total of 237 755 live births in Singapore between 1 January 1994 and 31 December 1998. Over the same period, 3293 cases of BDs were reported to the NBDR, giving an overall rate of 13.9 per 1000 live births. A downward trend with time was noted. Of the live born with BDs in this series, 36.7% presented with multiple anomalies. The overall occurrence of malformation (per 1000 live births) among working versus non-working mothers was 13.4 versus 14.2, respectively, and 13.8 for working fathers compared with 16.8 for non-working fathers. Parents in the occupational group 'Legislators, Senior Officers & Managers' had the lowest prevalence rates of congenital anomalies (9.4 per 1000 for mothers and 10.3 per 1000 for fathers), while the 'Agricultural & Fishery Workers' had the highest rates (40.0 per 1000 for mothers and 23.4 per 1000 for fathers). However, the very small number of workers in this latter group makes the rate unreliable. The prevalence of BDs in Singapore is comparable to those in other countries. Parental work per se is not correlated with BDs.

Study on musculoskeletal complaints involving the back, neck and upper limbs.

OBJECTIVE & METHODS: A mail questionnaire survey was conducted among designated factory doctors (DFDs) to determine the nature and extent of musculoskeletal aches/pains in patients attending their clinics over one working week. Information was recorded for all patients aged 15 years and above presenting with aches or pains in the back, neck or upper limbs, as the main complaint or as one of the presenting symptoms. RESULTS: For the 155 doctors participating in the survey, the total attendance of patients aged 15 years and above during the study period was 35,010. Of these, 3.9% presented with the symptoms studied and 1.8% had work-related complaints. The commonest site affected was the back (55.7%), followed by the neck (21.4%) and shoulders (19.2%). A higher proportion of males than females had back complaints with the reverse for complaints involving hands/wrists and arms/forearms. 82.3% of the affected were employed, 60.3% being production workers, compared to 33.3% professional/office workers and 6.4% service workers. Of the patients who were working, 51.3% had work-related symptoms and 54.4% were given medical leave. Production workers had the highest proportion with work-related symptoms while service workers had the highest proportion given medical leave. The "medical certificate rate" was highest for back symptoms -57.6%, while work-related symptoms was highest for complaints involving hands/wrists. CONCLUSION: The study findings are consistent with those of a 1993 morbidity survey of outpatients in Singapore and indicate that the prevalence of work-related musculoskeletal aches/pains is not high.

Sickness absence in private sector establishments in Singapore.

AIM: A study was conducted in June 1995 to determine the current level of sickness absence in Singapore. METHOD: The questionnaire survey was part of a larger labour market survey conducted quarterly by the Ministry of Labour, and covered 3,553 private sector establishments employing 25 or more employees. RESULTS: Overall, 14.4% of the 628,477 employees took sick leave, while the percentage of working days lost due to sick leave, excluding maternity leave, was 1.1%. An average of 3.2 days of medical leave were taken per person per year. Industry specific characteristics seemed to have more influence on sickness absence than establishment size, employee's sex and occupation (viz, professional versus clerical versus production staff), number of hours worked and overtime work. Over 60% of the establishments, particularly larger companies and those in manufacturing, implemented measures to control sickness absence, most commonly counselling, disciplinary procedures and attendance allowance or bonus. Over 13% monitored sickness absence using computerised records. CONCLUSION: Comparing with overseas sickness absence (lost time) rates, the rates observed in this study do not appear high.

Maximal respiratory pressures in adult Chinese, Malays and Indians.

Maximal static inspiratory and expiratory mouth pressures (PI,max and PE,max, respectively) enable the noninvasive measurement of global respiratory muscle strength. The aim of this study was primarily to obtain normal values of PI,max and PE,max for adult Chinese, Malays and Indians and, secondarily, to study their effect on lung volumes in these subjects. Four hundred and fifty two healthy subjects (221 Chinese, 111 Malays, 120 Indians) were recruited. Measurements of PI,max from residual volume (RV), PE,max from total lung capacity (TLC) and forced vital capacity (FVC) were obtained in the seated position. There were significant ethnic differences in PI,max and PE,max measurements obtained in males, and FVC measurements in both males and females. Chinese males had higher PI,max values (mean (+/-SD) 88.7+/-32.5 cmH2O) and higher PE,max values (113.4+/-41.5) than Malay males (PI,max 74.0+/-22.7 cmH2O, PE,max 94.7+/-23.4 cmH2O). Chinese males had higher PE,max than Indian males (PI,max = 83.7+/-30.0 cmH2O, PE,max 98.4+/-29.2 cmH2O). There were no significant differences among Chinese females (PI,max 53.6+/-2.3 cmH2O, PE,max 68.3+/-24.0 cmH2O), Malay females (PI,max 50.7+/-18.3 cmH2O, PE,max 63.6+/-21.6 cmH2O) and Indian females (PI,max 50.0+/-15.2 cmH2O, PE,max 60.7+/-20.4 cmH2O). In both sexes, the Chinese had a higher FVC compared with Malays and Indians. After adjusting for age, height and weight, race was still a determinant for PE,max in males, and FVC in both sexes. The FVC only correlated weakly with PI,max and PE,max in both sexes. Ethnic differences in respiratory muscle strength, and lung volumes, occur among Asians. However, respiratory muscle strength does not explain the differences in lung volumes in healthy Asian subjects.

Calibration and validity of an eccentric photorefractor.

A new graphical calibration method was developed to convert the photorefractive reflex into refractive error. With this graphical method, the refractive error can be obtained for pupil sizes and for photorefractive reflex sizes which have not been precalibrated. In the conventional method, the refractive error associated with non-precalibrated pupil and reflex sizes is obtained by interpolating between neighbouring precalibrated points. This introduces error because the relationship between refractive error and pupil and reflex size is not linear. Three hundred and sixty-one children aged between 36 and 65 months were clinically examined and photorefracted. The refractive error obtained using retinoscopy and the eccentric photorefractor agreed well with each other, although the photorefractor tended to under-estimate refractive error. Using the referral criteria developed by Chan, O.Y.C. and Edwards, L.M. (Refraction referral criteria for Hong Kong Chinese Children. Ophthal. Physiol. Opt. 14, 259-256, 1994), the photorefractor had a sensitivity of 74.6% and a specificity of 96.4%. All the under-referred cases were borderline, having just failed the referral criteria. All the cases with hyperopia of > + 2.0 D, astigmatism of > 1.25 D and visual acuity of worse than 6/18 were identified.

Health of female shiftworkers in Singapore.

More than 200,000 persons in Singapore work shifts. Over half of these shiftworkers are females. With the continued emphasis on capital-intensive industries and growing demand for "round-the-clock" services, shiftwork is increasingly an economic necessity for more and more industries and a way of life for many Singaporeans. It is generally accepted that about 20% of those who start shiftwork may find it difficult to continue in such work, usually for social rather than medical reasons. For those who continue on shiftwork, concerns have been raised regarding possible health effects, such as increased incidence of digestive disorders and ulcers, chronic fatigue and cardiovascular disorders. In the case of female shiftworkers, there is also the concern that the added responsibilities of looking after the home and young children may further aggravate sleep problems associated with shiftwork, thus adversely affecting their health. So far, our own studies of female electronics workers on 8-hour as well as 12-hour shift schedules indicate no serious long-term health effects. The study subjects had been employed in such work for at least over a year, some as long as 17 years and 6 years, respectively. Except for complaints of sleep problems and tiredness among some rotating shiftworkers, no significant differences in symptom prevalence, blood pressure or sickness absence were found between the shift and day workers. While the findings are reassuring, further studies may be needed to determine if preventive measures can be taken to minimise the common complaints of sleep problems and tiredness, particularly among rotating shiftworkers.

Urinary beta 2- and alpha 1-microglobulin levels in normal subjects in Singapore.

Differing normal values for urinary beta 2-microglobulin have been reported for different countries. In this study, we have attempted to establish the urinary beta 2- and alpha 1-microglobulin levels of apparently healthy subjects in Singapore. Urine samples collected from 271 subjects were analysed. The subjects ranged from 19 to 62 years old, with a mean age of 36.8 years. The majority (84.5%) were non-smokers. Urine samples with a pH level < 5.5 were excluded from the analysis. The urinary beta 2- and alpha 1-microglobulin values followed log normal distributions. Their 95th percentiles were 288 micrograms/g creatinine and 7.35 mg/g creatinine, respectively. Statistically significant differences were found between sexes and ethnic groups for urinary beta 2-microglobulin values. Both alpha 1- and beta 2-microglobulin values increased significantly with age. Smokers had significantly higher urinary alpha 1-microglobulin values.

Refraction referral criteria for Hong Kong Chinese preschool children.

The major types of ametropia and visual problems for Hong Kong Chinese and Caucasian children are different. Consequently, the referral criteria developed for Caucasian children may not be applicable to Hong Kong children. Results of our study suggested that the referral criteria for Hong Kong children should be set as hyperopia of > or = +2.0 D, myopia of > or = 1.0 D, astigmatism of > or = 1.0 D and anisometropia of > or = 1.25 D. Sensitivity using only these criteria for abnormal refraction in identifying children with amblyopia, esotropia, exotropia and subnormal vision (< 6/12) was respectively 100%, 84.6%, 45.2% and 95.7%. The overall sensitivity for the identification of visual problems was 86.1% and the overall specificity was 76%. If a cover test or a Hirschberg test was introduced into the screening battery so that all the strabismic cases were identified. the overall sensitivity would increase to 98.6%.

Comparison of cycloplegic and noncycloplegic retinoscopy in Chinese pre-school children.

Twenty-seven Hong Kong Chinese children, aged 3 to 5 1/2 years, were recruited in this study to evaluate the relation between refractive error as measured retinoscopically before and after cycloplegia using cyclopentolate 1%. The noncycloplegic spherical refractive error of these children ranged from -0.75 to +2.50 D and approximately 98% of the Hong Kong pre-school children have a manifest spherical error within this range. The cycloplegic refractive error can be approximated by multiplying the spherical component of the manifest error by 1.45 and adding +0.39 D to the product, while keeping the astigmatic power and axis unchanged. Cyclopentolate 1% requires more time to produce mydriasis and cycloplegia in eyes with heavily pigmented irides; however, its final effect on refractive error is apparently independent of iris pigmentation and depends on the amount of spherical refractive error present.

Blood cadmium levels in non-occupationally exposed adult subjects in Singapore.

Cadmium concentrations in whole blood were measured in subjects with no occupational exposure to cadmium. The study covered 128 males and 150 females from the three main ethnic groups in Singapore (namely Chinese, Malays and Indians). The geometric means (GM) of blood cadmium (CdB) levels of non-smoking males and females were 0.21 microgram/l and 0.26 microgram/l, respectively. Smokers had higher GM CdB levels than non-smokers. Significant ethnic differences were observed in both sexes, with Indian males having the highest GM CdB level of 0.48 microgram/l. Among the females, the Chinese had the highest GM CdB level: 0.33 microgram/l. Differences in dietary habits may have contributed to the observed ethnic differences in blood cadmium levels.

Pulmonary function in healthy Chinese, Malay and Indian adults in Singapore.

Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR), single-breath diffusion capacity measurements (effective alveolar volume (VA), carbon monoxide transfer factor (DLCO) and transfer coefficient (KCO)) were determined in 452 healthy Singaporean adults (277 males and 175 females) aged 20-70 years. The ratio of Chinese, Malay and Indian subjects was 5:2:3 in both sexes. Age, height and weight in the males were all significantly correlated with FEV1, FVC, DLCO, VA and PEFR. However, for females, only age and height were significantly correlated with the studied lung function parameters. Significant ethnic differences were observed for most of the pulmonary functions (except KCO and PEFR) among the Chinese, Malays and Indians for both males and females. The predicted FEV1 and FVC values (specific age and height) for both sexes were highest among the Chinese followed by the Malays than Indians, in that order. Regression equations, with age and height as independent variables, were derived for males and females in each ethnic group to predict normal pulmonary function for the Singapore Chinese, Malay and Indian populations. The predicted values of various pulmonary function measurements obtained from these regression equations for subjects of specified age (30 years) and height (165 cm for men, 155 cm for women) were compared with those reported in other studies. Differences were observed among the different races.

Study on the health of female electronics workers on 12 hour shifts.

Health complaints, blood pressure, sleep and sickness absence experience were studied in 308 female electronics workers employed for at least one year on 12 h shifts--253 on permanent and 55 on rotating schedules. Seventy-five 8 h day workers acted as controls. There were no significant differences in symptom prevalence between the controls and 12 h shift workers, except for complaints of tiredness, with a higher proportion of the rotating shift group also having headaches. No significant differences in prevalence of hypertension were noted. Although subjects on the night shift had shorter sleep than controls and 12h day workers, only the group on rotating schedule had a higher proportion of workers who did not sleep well compared to the controls. Sickness absence was not increased in the 12 h shift groups when compared to the controls. The results indicate no serious health problems among workers on 12 h shift for over a year.

Refractive errors in Hong Kong Chinese pre-school children.

Five hundred and seventy Chinese children aged between 36 and 65 months were recruited for refractive examination. The results show that both the spherical and cylindrical components of the refractive error tend to decrease with increasing age, although the changes were not statistically significant. The results of the present study, together with those of earlier studies carried out on Hong Kong Chinese children of different ages, show a pattern in the change of refractive errors in local children during the first 17 years of life. The combined results show that the average spherical refractive error decreases rapidly in hyperopic power during the 1st and the 6th to the 10th years of life; the astigmatic power decreases rapidly in the 1st year of life and remains thereafter rather constant until the age of 17 years.