Edith Lau

Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong

Summary Background Health authorities worldwide, especially in the Asia Pacific region, are seeking effective public-health interventions in the continuing epidemic of severe acute respiratory syndrome (SARS). We assessed the epidemiology of SARS in Hong Kong. Methods We included 1425 cases reported up to April 28, 2003. An integrated database was constructed from several sources containing information on epidemiological, demographic, and clinical variables. We estimated the key epidemiological distributions: infection to onset, onset to admission, admission to death, and admission to discharge. We measured associations between the estimated case fatality rate and patients’age and the time from onset to admission. Findings After the initial phase of exponential growth, the rate of confirmed cases fell to less than 20 per day by April 28. Public-health interventions included encouragement to report to hospital rapidly after the onset of clinical symptoms, contact tracing for confirmed and suspected cases, and quarantining, monitoring, and restricting the travel of contacts. The mean incubation period of the disease is estimated to be 6.4 days (95% Cl 5.2–7.7). The mean time from onset of clinical symptoms to admission to hospital varied between 3 and 5 days, with longer times earlier in the epidemic. The estimated case fatality rate was 13.2% (9.8–16.8) for patients younger than 60 years and 43.3% (35.2–52.4) for patients aged 60 years or older assuming a parametric γ distribution. A non-parametric method yielded estimates of 6.8% (4.0–9.6) and 55.0% (45.3–64.7), respectively. Case clusters have played an important part in the course of the epidemic. Interpretation Patients’age was strongly associated with outcome. The time between onset of symptoms and admission to hospital did not alter outcome, but shorter intervals will be important to the wider population by restricting the infectious period before patients are placed in quarantine. Published online May 7, 2003 http://image.thelancet.com/extras/03art4453web.pdf

Interim report and recommendations of the World Health Organization Task-Force for Osteoporosis.

Harry K. Genant (Chairman) , Cyrus Cooper (Rapporteur) , Gyula Poor (Rapporteur) , Ian Reid (Rapporteur) , George Ehrlich (Editor), J. Kanis (Editor), B. E. Christopher Nordin (Editor), Elizabet h Barrett-Connor , Dennis Black, J.-P. Bonjour, Bess Dawson-Hughes , Pierre D. Delmas, J. Dequeker , Sergio Ragi Eis, Carlo Gennari , Olaf Johnell , C. Conrad Johnston, Jr, Edith M. C. Lau, Uri A. Liberman, Robert Lindsay, Thomas John Martin, Basel Masri, Carlos A. Mautalen, Pierre J. Meunier, Paul D. Miller , Ambrish Mithal, Hirotoshi Morii , Socrates Papapoul os, Anthony Woolf, Wei Yu and Nikolai Khaltaev (WHO Secretariat) 30

The incidence of hip fracture in four Asian countries: the Asian Osteoporosis Study (AOS).

Abstract: The Asian Osteoporosis Study (AOS) is the first multicenter study to document and compare the incidence of hip fracture in four Asian countries. Hospital discharge data for the year 1997 were obtained for the Hong Kong SAR, Singapore, Malaysia and Thailand (Chiang Mai). The number of patients who were 50 years of age and older and who were discharged with a diagnosis of hip fracture (ICD9 820) was enumerated. The age-specific incidence rates were deduced and were directly adjusted to the US white population in 1989. The age-adjusted rates for men and women (per 100 000) are as follows: Hong Kong, 180 and 459; Singapore, 164 and 442; Malaysia, 88 and 218; Thailand, 114 and 289; compared with US White rates of 187 in men and 535 in women, published in 1989. We conclude that there is moderate variation in the incidence of hip fracture among Asian countries. The rates were highest in urbanized countries. With rapid economic development in Asia, hip fracture will prove to be a major public health challenge.

A meta-analysis of the association of fracture risk and body mass index in women.

Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20–105) years and follow up of 2.2 million person‐years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m2) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non‐obese women. Compared to a BMI of 25 kg/m2, the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m2 was 0.87 (95% confidence interval [CI], 0.85–0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09–1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored.

Associated factors and health impact of sarcopenia in older chinese men and women: a cross-sectional study.

Background: Sarcopenia is increasingly being recognized as a feature of frailty in old age and is associated with unfavorable health outcomes in Western populations. Little is known about sarcopenia among Asian elderly populations. Objectives: The study was undertaken to study the association between sarcopenia and common chronic illnesses, lifestyle factors, psychosocial well-being and physical performance. Methods: 4,000 community-dwelling Chinese elderly ≧65 years were recruited. Medical illnesses, cigarette smoking, alcohol consumption, physical activity level and psychosocial well-being scores were recorded. Physical performance measured included grip strength, timed chair-stands, stride length and a timed 6-meter walk. Muscle mass was measured using dual-energy X-ray absorptiometry. Relationships between appendicular skeletal muscle mass (ASM/ht2) and multiple variables were analyzed using uni- and multivariate analyses. Results: Mean ASM/ht2 was 7.19 and 6.05 kg/m2 in men and women respectively. Older age, cigarette smoking, chronic lung disease, atherosclerosis, underweight, and physical inactivity were associated with low adjusted ASM, which was in turn associated with poorer physical well-being in men. After adjustment to age, lower appendicular muscle mass was associated with weaker grip strength in both sexes. In men, lower limb tests (chair-stands, walking speed and step length) were not related to ASM, while in women, lower muscle mass was not associated with poorer lower limb muscle performance. Conclusions: Sarcopenia in community-dwelling older Chinese men and women was associated with cigarette smoking, chronic illnesses, underweight, physical inactivity, poorer well-being and upper limb physical performance.

The Reproducibility and Usefulness of the Oral Glucose Tolerance Test in Screening for Diabetes and other Cardiovascular Risk Factors

We examined the reproducibility of oral glucose tolerance tests (OGTT) using the World Health Organization criterion in 212 Chinese subjects (male 149, female 63) who underwent two 75 g OGTTs within a 6-week period. The overall reproducibility was 65.6% (139/212) of which 74 subjects had normal glucose tolerance, 24 had diabetes and 41 had impaired glucose tolerance (IGT) on two occasions. The subjects were divided into three groups [group 1: normal OGTTs on both occasions (n = 74); group 2: one abnormal OGTT (either diabetes or IGT (n = 51); group 3: 2 abnormal OGTTs (n = 87)]. Subjects in group 1 were younger, had lower blood pressure, body mass index (BMI), waist-to-hip ratio (WHR), fasting and 2 h plasma insulin levels, triglyceride, very — low density lipoprotein and apolipoprotein-B concentrations than both groups 2 and 3. Group 2 had similar characteristics as group 3 except for a lower glycated haemoglobin (HbA1c), fasting and 2 h plasma glucose during the two OGTTs. With receiver operating characteristic curve (ROC) analysis, a HbA1c. of 5.3% gave an optimal sensitivity of 70.7% and specificity of 74.3% to predict diabetes as defined by a 2h plasma glucose value ≥ 11.1 mmol/L in the first OGTT. Of the 212 subjects, 73 had HbA1c ≥ 5.3%. The reproducibility of OGTT was 56.2% for these 73 subjects. With ROC analysis, a BMI of 25 kg/m2 gave an optimal sensitivity of 53.7% and specificity of 56.7% to predict diabetes. For the 36 subjects with BMI ≥ 25 kg/m2, the reproducibility of OGTT was 58.3%. Similarly, for the 140 subjects with WHR ≥ 0.9, the reproducibility of OGTT was 57.9%. These findings confirmed the poor reproducibility of OGTT which was not improved even amongst subjects with high HbA1c, BMI or WHR. Furthermore, subjects with one abnormal OGTT, whether reproducible or not, had a higher cardiovascular risk profile compared to subjects who had two normal OGTTs.

Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial

IMPORTANCE Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor. OBJECTIVE To determine the efficacy and safety of abaloparatide, 80 μg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture. DESIGN, SETTING, AND PARTICIPANTS The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤-2.0 and >-5.0 or without fracture criteria and a T score ≤-3.0 and >-5.0 could enroll. INTERVENTIONS Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 μg (n = 824); or open-label teriparatide, 20 μg (n = 818) for 18 months. MAIN OUTCOMES AND MEASURES Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants. RESULTS Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], −2.96 [95%CI, −5.12 to −0.87]; P = .006). [table: see text]. CONCLUSIONS AND RELEVANCE Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01343004.

The effects of calcium supplementation and exercise on bone density in elderly Chinese women.

A randomized controlled trial was carried out to determine whether calcium supplementation and load-bearing exercise can increase or maintain bone mass in the elderly. Fifty Chinese women, aged 62–92 years, living in a hostel for the elderly in Hong Kong were randomized to enter one of four treatment groups: (I) calcium supplementation of 800 mg (as calcium lactate gluconate) daily; (II) load-bearing exercise four times a week plus a daily placebo tablet; (III) calcium supplementation daily and load-bearing exercise four times a week; (IV) a placebo tablet daily. The interventions went on for 10 months. The bone mineral density (BMD) was measured at three sites in the hip (femoral neck, Wards triangle and intertrochanteric area) and the L2–4 level of the spine. The percentage change in BMD in 10 months was used as the main outcome measurement. The parathyroid hormone level and indices of bone metabolism were also measured before and after 10 months of intervention.The BMD at Wards triangle and the intertrochanteric area increased significantly in subjects on calcium supplement (p<0.05), but there was no significant change at the spine and femoral neck. Exercise had no effect on bone loss at any site. However, the results of two-way analysis of variance showed a significant joint effect of calcium supplements and exercise at the femoral neck (p<0.05), but not at the other sites. The parathyroid hormone levels fell significantly in subjects on calcium supplements (p<0.01).Calcium supplement in the form of calcium lactate gluconate was adequately absorbed in elderly Chinese women with a calcium intake of less than 300 mg per day. It was effective in reducing bone loss at the hip, and there may be interaction effects with exercise in maintaining bone density.

Risk factors for hip fracture in Asian men and women : the Asian osteoporosis study

The objectives of the Asian Osteoporosis Study (AOS) were to determine risk factors for hip fracture in men and women in four Asian countries, that is, Singapore, Malaysia, Thailand, and the Philippines. A total of 451 men and 725 women (aged 50 years and over) with hip fractures were compared with an equal number of community controls. A standardized questionnaire was administered by interview. The following relative risks (RRs) were found in women and men by multiple logistic regression: dietary calcium intake < 498 mg/day, 2.0 for women (95% CI, 1.5–2.8) and 1.5 for men (95% CI, 1.0–2.2); no load bearing activity in the immediate past, 2.0 for women (95% CI, 1.4–2.7) and 3.4 for men (95% CI, 2.3–5.1); no vigorous sport activities in young adulthood, 7.2 for women (95% CI, 4.0–13.0) and 2.4 for men (95% CI, 1.6–3.6); cigarette smoking, 1.5 for men (95% CI, 1.0–2.1); alcohol consumption 7 days a week, 2.9 for women (95% CI, 1.0–8.6) and 1.9 for men (95% CI, 1.1–3.2); fell twice or more in the last 12 months, 3.0 for women (95% CI, 1.8–4.8) and 3.4 for men (95% CI, 1.8–6.6); a history of fractures after 50 years of age, 1.8 for women (95% CI, 1.1–2.9) and 3.0 for men (95% CI, 1.6–5.6); a history of stroke, 3.8 for women (95% CI, 2.0–7.1) and 3.6 for men (95% CI, 1.8–7.1); use of sedatives, 2.5 for women (95% CI, 1.0–6.3) and 3.0 for men (95% CI, 1.0–9.7); and use of thyroid drugs, 7.1 for women (95% CI, 2.0–25.9) and 11.8 for men (95% CI, 1.3–106.0). Women who were 1.56 m or taller had an RR of 2.0 (95% CI, 1.3–3.0) for hip fracture and men who were 1.69 m or taller had an RR of 1.9 (95% CI, 1.2–3.1) for hip fracture. Based on these findings, primary preventive programs for hip fracture could be planned in Asia.

Milk Supplementation of the Diet of Postmenopausal Chinese Women on a Low Calcium Intake Retards Bone Loss

The Chinese diet is low in calcium (less than 500 mg/day on average), and previous observational studies have suggested an association between a low calcium intake and risk of hip and vertebral fracture. In this study, we randomly assigned 200 postmenopausal Chinese women (age range, 55–59 years) to receive 50 g of milk powder containing 800 mg of calcium per day or to a control group. The following are the mean percentage changes (and SEs) in height and bone mineral density (BMD) over 24 months: for height, −0.1 ± 0.2 cm in the milk supplementation group and −0.2 ± 0.1 cm in the control group; for BMD at the total hip, −0.06 ± 0.22% in the milk supplementation group and −0.88 ± 0.26% in the control group; for BMD at the spine (L1−L4), −0.56 ± 0.29% in the milk supplementation group and −1.5 ± 0.29% in the control group; for total body BMD, −0.32 ± 0.16% in the milk supplementation group and −1.2 ± 0.19% in the control group (p < 0.05 by analysis of covariance [ANCOVA] for repeated measures for height and BMD at all sites). The milk supplementation group had less loss in terms of both height and BMD than the control group (p < 0.05 by ANCOVA for repeated measures). Serum parathyroid hormone (PTH) concentration was lower and serum 25‐hyroxyvitamin D [25(OH)D] level was higher in the milk supplementation group than the control group at 12 months (p < 0.05 by paired t‐test). We conclude that supplementing the diet of postmenopausal Chinese women with high calcium milk powder retards bone loss.