Tsan Yuk Hospital

There is increasing interest in utilizing novel markers of cardiovascular disease risk, and consequently, there is a need to assess the value of their use. This scientific statement reviews current concepts of risk evaluation and proposes standards for the critical appraisal of risk assessment methods. An adequate evaluation of a novel risk marker requires a sound research design, a representative at-risk population, and an adequate number of outcome events. Studies of a novel marker should report the degree to which it adds to the prognostic information provided by standard risk markers. No single statistical measure provides all the information needed to assess a novel marker, so measures of both discrimination and accuracy should be reported. The clinical value of a marker should be assessed by its effect on patient management and outcomes. In general, a novel risk marker should be evaluated in several phases, including initial proof of concept, prospective validation in independent populations, documentation of incremental information when added to standard risk markers, assessment of effects on patient management and outcomes, and ultimately, cost-effectiveness.

Obesity adversely affects cardiac function, increases the risk factors for coronary heart disease, and is an independent risk factor for cardiovascular disease. The risk of developing coronary heart disease is directly related to the concomitant burden of obesity-related risk factors. Modest weight loss can improve diastolic function and affect the entire cluster of coronary heart disease risk factors simultaneously. This statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism reviews the relationship between obesity and the cardiovascular system, evaluates the effect of weight loss on coronary heart disease risk factors and coronary heart disease, and provides practical weight management treatment guidelines for cardiovascular healthcare professionals. The data demonstrate that weight loss and physical activity can prevent and treat obesity-related coronary heart disease risk factors and should be considered a primary therapy for obese patients with cardiovascular disease.

OBJECTIVES: To validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling. DESIGN: Diagnostic accuracy validated against full karyotyping, using prospectively collected or archived maternal plasma samples. SETTING: Prenatal diagnostic units in Hong Kong, United Kingdom, and the Netherlands. PARTICIPANTS: 753 pregnant women at high risk for fetal trisomy 21 who underwent definitive diagnosis by full karyotyping, of whom 86 had a fetus with trisomy 21. Intervention Multiplexed massively parallel sequencing of DNA molecules in maternal plasma according to two protocols with different levels of sample throughput: 2-plex and 8-plex sequencing. MAIN OUTCOME MEASURES: Proportion of DNA molecules that originated from chromosome 21. A trisomy 21 fetus was diagnosed when the z score for the proportion of chromosome 21 DNA molecules was >3. Diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were calculated for trisomy 21 detection. RESULTS: Results were available from 753 pregnancies with the 8-plex sequencing protocol and from 314 pregnancies with the 2-plex protocol. The performance of the 2-plex protocol was superior to that of the 8-plex protocol. With the 2-plex protocol, trisomy 21 fetuses were detected at 100% sensitivity and 97.9% specificity, which resulted in a positive predictive value of 96.6% and negative predictive value of 100%. The 8-plex protocol detected 79.1% of the trisomy 21 fetuses and 98.9% specificity, giving a positive predictive value of 91.9% and negative predictive value of 96.9%. CONCLUSION: Multiplexed maternal plasma DNA sequencing analysis could be used to rule out fetal trisomy 21 among high risk pregnancies. If referrals for amniocentesis or chorionic villus sampling were based on the sequencing test results, about 98% of the invasive diagnostic procedures could be avoided.

Obesity is a major influence on the development and course of cardiovascular diseases and affects physical and social functioning and quality of life. The importance of effective interventions to reduce obesity and related health risks has increased in recent decades because the number of adults and children who are obese has reached epidemic proportions. To prevent the development of overweight and obesity throughout the life course, population-based strategies that improve social and physical environmental contexts for healthful eating and physical activity are essential. Population-based approaches to obesity prevention are complementary to clinical preventive strategies and also to treatment programs for those who are already obese. This American Heart Association scientific statement aims: 1) to raise awareness of the importance of undertaking population-based initiatives specifically geared to the prevention of excess weight gain in adults and children; 2) to describe considerations for undertaking obesity prevention overall and in key risk subgroups; 3) to differentiate environmental and policy approaches to obesity prevention from those used in clinical prevention and obesity treatment; 4) to identify potential targets of environmental and policy change using an ecological model that includes multiple layers of influences on eating and physical activity across multiple societal sectors; and 5) to highlight the spectrum of potentially relevant interventions and the nature of evidence needed to inform population-based approaches. The evidence-based experience for population-wide approaches to obesity prevention is highlighted.

The increase in heart failure (HF) rates throughout the developed and developing regions of the world poses enormous challenges for caregivers, researchers, and policymakers. Therefore, prevention of this global scourge deserves high priority. Identifying and preventing the well-recognized illnesses that lead to HF, including hypertension and coronary heart disease, should be paramount among the approaches to prevent HF. Aggressive implementation of evidence-based management of risk factors for coronary heart disease should be at the core of HF prevention strategies. Questions currently in need of attention include how to identify and treat patients with asymptomatic left ventricular systolic dysfunction (Stage B HF) and how to prevent its development. The relationship of chronic kidney disease to HF and control of chronic kidney disease in prevention of HF need further investigation. Currently, we have limited understanding of the pathophysiological basis of HF in patients with preserved left ventricular systolic function and management techniques to prevent it. New developments in the field of biomarker identification have opened possibilities for the early detection of individuals at risk for developing HF (Stage A HF). Patient groups meriting special interest include the elderly, women, and ethnic/racial minorities. Future research ought to focus on obtaining a much better knowledge of genetics and HF, especially both genetic risk factors for development of HF and genetic markers as tools to guide prevention. Lastly, a national awareness campaign should be created and implemented to increase public awareness of HF and the importance of its prevention. Heightened public awareness will provide a platform for advocacy to create national research programs and healthcare policies dedicated to the prevention of HF.

Collectively, cardiovascular disease (including stroke), cancer, and diabetes account for approximately two thirds of all deaths in the United States and about 700 billion dollars in direct and indirect economic costs each year. Current approaches to health promotion and prevention of cardiovascular disease, cancer, and diabetes do not approach the potential of the existing state of knowledge. A concerted effort to increase application of public health and clinical interventions of known efficacy to reduce prevalence of tobacco use, poor diet, and insufficient physical activity-the major risk factors for these diseases-and to increase utilization of screening tests for their early detection could substantially reduce the human and economic cost of these diseases. In this article, the ACS, ADA, and AHA review strategies for the prevention and early detection of cancer, cardiovascular disease, and diabetes, as the beginning of a new collaboration among the three organizations. The goal of this joint venture is to stimulate substantial improvements in primary prevention and early detection through collaboration between key organizations, greater public awareness about healthy lifestyles, legislative action that results in more funding for and access to primary prevention programs and research, and reconsideration of the concept of the periodic medical checkup as an effective platform for prevention, early detection, and treatment.

Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due to the lack of data from a large sample set. We studied 392 pregnancies, among which 25 involved a trisomy 13 fetus and 37 involved a trisomy 18 fetus, by massively parallel sequencing. By using our previously reported standard z-score approach, we demonstrated that this approach could identify 36.0% and 73.0% of trisomy 13 and 18 at specificities of 92.4% and 97.2%, respectively. We aimed to improve the detection of trisomy 13 and 18 by using a non-repeat-masked reference human genome instead of a repeat-masked one to increase the number of aligned sequence reads for each sample. We then applied a bioinformatics approach to correct GC content bias in the sequencing data. With these measures, we detected all (25 out of 25) trisomy 13 fetuses at a specificity of 98.9% (261 out of 264 non-trisomy 13 cases), and 91.9% (34 out of 37) of the trisomy 18 fetuses at 98.0% specificity (247 out of 252 non-trisomy 18 cases). These data indicate that with appropriate bioinformatics analysis, noninvasive prenatal diagnosis of trisomy 13 and trisomy 18 by maternal plasma DNA sequencing is achievable.

HomeCirculationVol. 107, No. 4American Heart Association Guide for Improving Cardiovascular Health at the Community Level

OBJECTIVE: The purpose of this study was to determine whether end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc), as a single measurement or in combination with serum total bilirubin (STB) measurements, can predict the development of hyperbilirubinemia during the first 7 days of life. METHODS: From 9 multinational clinical sites, 1370 neonates completed this cohort study from February 20, 1998, through February 22, 1999. Measurements of both ETCOc and STB were performed at 30 +/- 6 hours of life; STB also was measured at 96 +/- 12 hours and subsequently following a flow diagram based on a table of hours of age-specific STB. An infant was defined as hyperbilirubinemic if the hours of age-specific STB was greater than or equal to the 95th percentile as defined by the table at any time during the study. RESULTS: A total of 120 (8.8%) of the enrolled infants became hyperbilirubinemic. Mean STB in breastfed infants was 8.92 +/- 4.37 mg/dL at 96 hours versus 7.63 +/- 3.58 mg/dL in those fed formula only. The mean ETCOc at 30 +/- 6 hours for the total population was 1.48 +/- 0.49 ppm, whereas those of nonhyperbilirubinemic and hyperbilirubinemic infants were 1.45 +/- 0.47 ppm and 1.81 +/- 0.59 ppm, respectively. Seventy-six percent (92 of 120) of hyperbilirubinemic infants had ETCOc greater than the population mean. An ETCOc greater than the population mean at 30 +/- 6 hours yielded a 13.0% positive predictive value (PPV) and a 95.8% negative predictive value (NPV) for STB >/=95th percentile. When infants with STB >95th percentile at <36 hours of age were excluded, the STB at 30 +/- 6 hours yielded a 16.7% PPV and a 98.1% NPV for STB >75th percentile. The combination of these 2 measurements at 30 +/- 6 hours (either ETCOc more than the population mean or STB >75th percentile) had a 6.4% PPV with a 99.0% NPV. Conclusions. This prospective cohort study supports previous observations that measuring STB before discharge may provide some assistance in predicting an infant's risk for developing hyperbilirubinemia. The addition of an ETCOc measurement provides insight into the processes that contribute to the condition but does not materially improve the predictive ability of an hours of age-specific STB in this study population. The combination of STB and ETCOc as early as 30 +/- 6 hours may identify infants with increased bilirubin production (eg, hemolysis) or decreased elimination (conjugation defects) as well as infants who require early follow-up after discharge for jaundice or other clinical problems such as late anemia. Depending on the incidence of hyperbilirubinemia within an institution, the criteria for decision making should vary according to its unique population.

HomeCirculationVol. 110, No. 25CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease

Atherosclerotic cardiovascular disease (CVD) is a major health problem in the United States and around the world. Evidence accumulated over decades convincingly demonstrates that family history in a parent or a sibling is associated with atherosclerotic CVD, manifested as coronary heart disease, stroke, and/or peripheral arterial disease. Although there are several mendelian disorders that contribute to CVD, most common forms of CVD are believed to be multifactorial and to result from many genes, each with a relatively small effect working alone or in combination with modifier genes and/or environmental factors. The identification and the characterization of these genes and their modifiers would enhance prediction of CVD risk and improve prevention, treatment, and quality of care. This scientific statement describes the approaches researchers are using to advance understanding of the genetic basis of CVD and details the current state of knowledge regarding the genetics of myocardial infarction, atherosclerotic CVD, hypercholesterolemia, and hypertension. Current areas of interest and investigation--including gene-environment interaction, pharmacogenetics, and genetic counseling--are also discussed. The statement concludes with a list of specific recommendations intended to help incorporate usable knowledge into current clinical and public health practice, foster and guide future research, and prepare both researchers and practitioners for the changes likely to occur as molecular genetics moves from the laboratory to clinic.

OBJECTIVE: To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy? METHODS: Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question. We performed analyses using traditional frequentist statistical and Bayesian approaches, including random-effects Bayesian network meta-analyses. RESULTS: Our results suggest that: 1) There is a modest but significant improvement in systolic BP in randomized controlled trials of self-measured BP versus usual care at 6 but not 12 months, and for selected patients and their providers self-measured BP may be a helpful adjunct to routine office care. 2) systolic BP lowering to a target of <130 mm Hg may reduce the risk of several important outcomes including risk of myocardial infarction, stroke, heart failure, and major cardiovascular events. No class of medications (ie, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta blockers) was significantly better than thiazides and thiazide-like diuretics as a first-line therapy for any outcome.

Objective To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy? Methods Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question. We performed analyses using traditional frequentist statistical and Bayesian approaches, including random-effects Bayesian network meta-analyses. Results Our results suggest that: 1) There is a modest but significant improvement in systolic BP in randomized controlled trials of self-measured BP versus usual care at 6 but not 12 months, and for selected patients and their providers self-measured BP may be a helpful adjunct to routine office care. 2) systolic BP lowering to a target of &lt;130 mm Hg may reduce the risk of several important outcomes including risk of myocardial infarction, stroke, heart failure, and major cardiovascular events. No class of medications (ie, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta blockers) was significantly better than thiazides and thiazide-like diuretics as a first-line therapy for any outcome.

OBJECTIVE: To study the incidence of domestic violence in pregnant women attending the antenatal clinic of a local teaching hospital. STUDY DESIGN: All pregnant women attending their first antenatal clinic in Tsan Yuk Hospital between 11th August and 3rd November, 1998 were interviewed by a designated research nurse (Y.Y.J.L.) using a standard questionnaire (Abuse Assessment Screen) to detect the incidence of domestic violence, the nature of violence, the frequency of violence and the perpetrator of abuse. Demographic factors of the abused group were compared with those of the non-abused group using student's t-test and chi-square test. RESULTS: Pregnant women (631) were interviewed; 113 of them (17.9%) had a history of abuse; 99 women (15.7%) had been abused in the last year; 27 of them (4.3%) had been abused during their current pregnancy; 59 women (9.4%) had been sexually abused in the last year. The husband was the perpetrator in the majority of cases. The nature of violence during pregnancy was mainly psychological in the form of threats of abuse without any physical injury. Risk factors included unplanned pregnancy (P = 0.002) and women with husbands/partners who were unemployed or manual workers (P < 0.05). Unexpectedly, domestic violence occurred more commonly in permanent local residents rather than new immigrants (P < 0.05). CONCLUSION: This is probably the first study on the incidence of domestic violence in pregnant women in a Chinese community. The incidence is comparable to that from American studies. Routine screening with structured questions during the antenatal visits is necessary in order to identify the abused women so as to prevent potential trauma and to interrupt existing abuse.

A retrospective review was performed on the obstetric outcome of teenage pregnancies delivered in 1 year in a tertiary centre. The results were compared with the rest of the obstetric population in the same hospital in the same year. The teenage mothers (n = 194) had increased incidence of sexually transmitted diseases (5.2 versus 1.0%, P < 0.05), and preterm labour (13.0 versus 7.0%, P < 0.01), but decreased incidence of gestational glucose intolerance (3.1 versus 11.4%, P < 0.001), when compared with the non-teenage mothers (n = 4914). There was no difference in the types of labour, while the incidence of Caesarean section was lower (4.1 versus 12.6%, P < 0.001) in the teenage mothers. Although the incidence of low birthweight was higher in the teenage mothers (13.5 versus 6.5%, P < 0.001), there was no significant difference in the mean birthweight, gestation at delivery, incidence of total preterm delivery, or perinatal mortality or morbidity. The results indicate that the major risk associated with teenage pregnancies is preterm labour, but the perinatal outcome is favourable. The good results accomplished in our centre could be attributed to the free and readily available prenatal care and the quality of support from the family or welfare agencies that are involved with the care of teenage mothers.

AIM: To determine whether non-anaemic women with gestational diabetes mellitus (GDM) diagnosed in third trimester pregnancy have evidence of increased iron stores compared with matched non-diabetic controls. METHODS: In a prospective study, women who had antenatal booking before 20 weeks' gestation and without anaemia or diabetes mellitus were recruited at the time of the oral glucose tolerance test (OGTT) at 28-31 weeks' gestation for the study of serum ferritin, iron and transferrin concentrations. The results were blinded to the managing obstetricians. After delivery, the records were reviewed. The cases diagnosed as GDM were compared with a control group (two controls for each index case matched for parity) selected at random from the at-risk but nondiabetic cases. RESULTS: GDM was diagnosed in 97 of the 401 women recruited. Compared with the 194 controls, there was no difference in the weight, body mass index, booking and third trimester haemoglobin, or third trimester red cell indices, but concentrations of serum ferritin, iron, transferrin saturation, and the post-natal haemoglobin were significantly higher. On multiple regression analysis, maternal BMI and the log-transformed ferritin concentration remained significant determinants of the OGTT 2-h glucose value. CONCLUSION: The results suggest an association between increased iron stores and glucose intolerance at the third trimester in non-anaemic women. The role of iron excess in the pathogenesis of GDM needs to be examined.

OBJECTIVE: To investigate the effectiveness of oral misoprostol as a cervical priming agent for patients presenting with pre-labor rupture of membranes at term. METHODS: Eighty patients presenting with pre-labor rupture of membranes at term were randomized to receive either 200 micrograms of misoprostol or 50 mg of vitamin B6 orally 1 hour after admission. Labor was induced with intravenous oxytocin infusion 12 hours after oral medication if the patient did not go into labor. We compared the induction rate, duration of labor, mode of delivery, and leaking-to-delivery interval in the two groups. RESULTS: The cervical score was significantly improved and the induction rate was also reduced in the misoprostol group when compared with the control group. The interval from recruitment to onset of labor, duration of labor, and the interval from recruitment to delivery were significantly shorter in the misoprostol group. The mode of delivery and the perinatal outcome were similar for the two groups. CONCLUSION: Oral misoprostol is an effective agent for cervical priming and labor induction in patients with pre-labor rupture of membranes at term.

Asian American individuals make up the fastest growing racial and ethnic group in the United States. Despite the substantial variability that exists in type 2 diabetes and atherosclerotic cardiovascular disease risk among the different subgroups of Asian Americans, the current literature, when available, often fails to examine these subgroups individually. The purpose of this scientific statement is to summarize the latest disaggregated data, when possible, on Asian American demographics, prevalence, biological mechanisms, genetics, health behaviors, acculturation and lifestyle interventions, pharmacological therapy, complementary alternative interventions, and their impact on type 2 diabetes and atherosclerotic cardiovascular disease. On the basis of available evidence to date, we noted that the prevalences of type 2 diabetes and stroke mortality are higher in all Asian American subgroups compared with non-Hispanic White adults. Data also showed that atherosclerotic cardiovascular disease risk is highest among South Asian and Filipino adults but lowest among Chinese, Japanese, and Korean adults. This scientific statement discusses the biological pathway of type 2 diabetes and the possible role of genetics in type 2 diabetes and atherosclerotic cardiovascular disease among Asian American adults. Challenges to provide evidence-based recommendations included the limited data on Asian American adults in risk prediction models, national surveillance surveys, and clinical trials, leading to significant research disparities in this population. The large disparity within this population is a call for action to the public health and clinical health care community, for whom opportunities for the inclusion of the Asian American subgroups should be a priority. Future studies of atherosclerotic cardiovascular disease risk in Asian American adults need to be adequately powered, to incorporate multiple Asian ancestries, and to include multigenerational cohorts. With advances in epidemiology and data analysis and the availability of larger, representative cohorts, furthering refining the Pooled Cohort Equations, in addition to enhancers, would allow better risk estimation in segments of the population. Last, this scientific statement provides individual- and community-level intervention suggestions for health care professionals who interact with the Asian American population.

A prospective observational study was performed on 488 women with haemoglobin >/=10 g/dl at booking to examine the relationship between serum ferritin concentration quartiles at 28-30 weeks gestation with maternal characteristics, pregnancy complications and infant outcome. While there was no difference in the maternal characteristics or gestational age, the infant size decreased significantly and progressively from the lowest to the highest quartile. Despite a significant difference in the incidence of multiparous women, there was no difference in the incidence of most complications except for prelabour rupture of the membranes and infant admission to the neonatal unit. Compared with the other three quartiles, the highest quartile was associated with increased risk for preterm delivery and neonatal asphyxia, while the lowest quartile was associated with decreased risk of pre-eclampsia, prelabour rupture of the membranes, and infant admission to the neonatal unit. Overall, ferritin quartiles were correlated with other parameters of iron status and red cell indices, and ferritin concentration was inversely correlated with infant birthweight. Our findings suggested that maternal ferritin concentration is primarily a reflection of maternal iron status, and a high level is associated with unfavourable outcome. The rationale of routine iron supplementation in non-anaemic women needs to be re-examined.

Three undifferentiated nasopharyngeal carcinoma (NPC) tumour lines were successfully established from fresh biopsy material injected s.c. into athymic mice and passaged for many generations. These xenografts were found to be free of infiltrating lymphoid cells and remained undifferentiated up to passage 30. They were designated NPC/HK2117 (Xeno-1), NPC/HK1915 (Xeno-2) and NPC/HK1530 (Xeno-3), respectively. Passage 16 from Xeno-1, passage 1 from Xeno-2 and passage 14 from Xeno-3 were studied cytogenetically using G-banding with the trypsin-Giemsa method. Two xenografts were hyperdiploid with chromosome modal numbers ranging from 49 to 76, and one was hypodiploid with modal numbers ranging from 28 to 38. Five marker chromosomes have been identified with involvement of chromosomes 1, 3, 11, 12 and 17. Marker chromosomes derived from chromosomes 12q, 1q and 3q were consistent in one of the 2 xenografts successfully G-banded, and chromosomes 12, 11 and 17 were consistent in another. Three out of the 6 markers involve 12q13----qter. An abnormal chromosome 3 with most of the p arm deleted was also observed.