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.

Sleep-wake patterns and subjective sleep quality of day and night workers: interaction between napping and main sleep episodes.

Five hundred and ninety-three women electronics workers were studied to determine if there was any association between their subjective sleep quality and their sleep patterns. They were 108 day workers, 107 permanent night workers, 216 workers on weekly phase-advance (night/afternoon/morning), and 162 workers on two-weekly phase-delay (morning/afternoon/night) rotating shift schedules. The study was part of a larger survey on night workers involving a self-administered questionnaire. The proportion of nappers was higher in night workers than in day, morning, and afternoon shift workers. Nappers had shorter main sleep, but their total sleep duration was generally the same as that of nonnappers. Compared to nonnappers, a higher proportion of day and morning shift workers who napped did not sleep well. Permanent night workers, with the highest proportion of nappers, had more workers sleeping well than rotating night workers. Subjects who slept well were those with longer total and main sleep and generally started the main sleep earlier. The results indicate a relationship between subjective sleep quality, sleep length, main sleep start, and napping behavior. Whether this relationship is causal is difficult to establish as sleep quality may also reflect the general health status, and this may result in differences in sleep behavior.

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.

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.

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.

Shiftwork in Singapore.

In 1985, over 94,000 persons were engaged in shiftwork. With the continued emphasis on capital-intensive industries and growing demand for "round-the-clock" services, shiftwork is increasingly becoming an economic necessity in many industries in Singapore. A survey in 1991 confirmed this trend. The study covered 4,996 private sector establishments employing 25 or more paid employees. 34.4% of the establishments had shiftworkers. In terms of employees, 32% or 206,965 employees were working shifts. While the 8-hour shift schedule was still the predominant pattern, there was a ten-fold increase in the number of 12-hour shiftworkers. A trend towards permanent shift schedules was also noted. It was interesting that the proportion of shiftworkers doing nightwork decreased to 36.9% from 45.1% in 1985. The health implications of shiftwork have been widely reported. So far, our own studies indicate no serious long-term health effects among shiftworkers. However, further studies are needed to determine if preventive measures can be taken to minimise the common complaints of sleep problems and tiredness, particularly among rotating shiftworkers.

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.

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.

Leptospirosis risk in public cleansing and sewer workers.

The degree of leptospirosis risk was investigated in 80 sewer and 120 public cleansing workers. They were interviewed and their serum samples tested for the presence of leptospiral antibodies by the sensitised erythrocyte lysis (SEL) test. Another 100 control subjects matched by sex, age and ethnic group were similarly studied. The study subjects had higher seroprevalence than the controls--over six times higher for SEL titres of greater than 1:100 and over 1.5 times for titres of greater than 1:25. The highest seroprevalence was found in workers cleaning wet markets and food centres. There was no significant correlation between the prevalence of positive titres and symptom prevalence or hospitalisation. Five of the study subjects (all sewer workers) gave a history of jaundice.

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.

Respiratory function in cadmium battery workers--a follow-up study.

The lung function status of workers in a cadmium-nickel battery factory was re-examined 3 years after an initial study which showed a mild restrictive effect. During this period, further measures were taken to reduce the cadmium exposure. Of the 44 'original' cadmium-exposed workers, 17 were still exposed to cadmium. Another 13 were transferred to non-cadmium work at least 6 months and 14 left the company at least 1 year before the present study. Blood and urine cadmium concentrations were considerably lower than previously, consistent with the decreased cadmium-in-air levels. The total lung capacity increased both in the workers who were still exposed to cadmium and those who ceased exposure. The latter group also had increased vital capacity and forced expiratory volume in one second. The prevalence of respiratory symptoms decreased particularly in the workers who were no longer exposed to cadmium.

Study on workers exposed to cadmium in alkaline storage battery manufacturing and PVC compounding.

The extent of cadmium exposure was studied in a cadmium-nickel battery factory and 8 PVC factories using cadmium stabilisers in the compounding of PVC. A total of 101 cadmium-exposed workers and 21 control subjects matched by sex, age, ethnic group and smoking history was investigated. Blood and urine cadmium levels were considerably elevated in the battery workers but were not raised in the PVC workers. These findings were consistent with the results of cadmium-in-air assessments. Among the female battery workers, urine cadmium excretion increased significantly with employment time. There was good correlation between blood and urine cadmium levels among the female subjects. A significant association between blood cadmium levels and prevalence of chest pain was also noted among the females. No low molecular weight proteinuria was detected, but two female battery workers had slight albuminuria and one male PVC worker had glucosuria but had abnormal GTT results.