Female adiposity and time-to-pregnancy: a multiethnic prospective cohort.

STUDY QUESTION: Are higher overall and central adiposity associated with reduced fecundability, measured by time-to-pregnancy (TTP), in Asian women? SUMMARY ANSWER: Higher overall adiposity, but not central adiposity, was associated with longer TTP in Asian women. WHAT IS KNOWN ALREADY: High body mass index (BMI) has been associated with a longer TTP, although the associations of body composition and distribution with TTP are less clear. There are no previous studies of TTP in Asian women, who have a relatively higher percentage of body fat and abdominal fat at relatively lower BMI. STUDY DESIGN, SIZE, DURATION: Prospective preconception cohort using data from 477 Asian (Chinese, Malay and Indian) women who were planning to conceive and enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) study, 2015-2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women's mean age was 30.7 years. Overall adiposity was assessed by BMI, sum of 4-site skinfold thicknesses (SFT) and total body fat percentage (TBF%, measured using air displacement plethysmography); central adiposity was assessed by waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and A body Shape Index (ABSI). Pregnancy occurring within one year from recruitment was ascertained by ultrasonography. Those who did not conceive within one year of recruitment, were lost to follow-up, or initiated fertility treatment were censored. TTP was measured in cycles. Discrete-time proportional hazards models were used to estimate the fecundability ratio (FR) and 95% confidence interval (CI) for each anthropometric measure in association with fecundability, adjusting for confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to women with a normal BMI of 18.5-22.9 kg/m2, women with higher BMI of 23-27.4 and ≥27.5 kg/m2 showed lower FR of 0.66 (95% CI 0.45, 0.97) and 0.53 (0.31, 0.89), respectively. Compared to women in the lowest quartile of SFT (25-52.9 mm), those in the highest quartile of ≥90.1 mm showed lower FR of 0.58 (95% CI 0.36, 0.95). Compared to women in the lowest quartile of TBF% (13.6-27.2%), those in the upper two quartiles of 33.0-39.7% and ≥39.8% showed lower FR of 0.56 (95% CI 0.32, 0.98) and 0.43 (0.24, 0.80), respectively. Association of high BMI with reduced fecundability was particularly evident among nulliparous women. Measures of central adiposity (WC, WHR, WHtR, ABSI) were not associated with fecundability. LIMITATIONS REASONS FOR CAUTION: Small sample size could restrict power of analysis.The analysis was confined to planned pregnancies, which could limit generalizability of findings to non-planned pregnancies, estimated at around 44% in Singapore. Information on the date of last menstrual period for each month was not available, hence the accuracy of self-reported menstrual cycle length could not be validated, potentially introducing error into TTP estimation. Measures of exposures and covariates such as cycle length were not performed repeatedly over time; cycle length might have changed during the period before getting pregnant. WIDER IMPLICATIONS OF THE FINDINGS: Other than using BMI as the surrogate measure of body fat, we provide additional evidence showing that higher amounts of subcutaneous fat that based on the measure of SFT at the sites of biceps, triceps, suprailiac and subscapular, and TBF% are associated with longer TTP. Achieving optimal weight and reducing total percentage body fat may be a potential intervention target to improve female fertility. The null results observed between central adiposity and TTP requires confirmation in further studies. STUDY FUNDING/COMPETING INTEREST(S): This research is supported by Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council, (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. Y.S.C., K.M.G., F.Y. and Y.S.L. have received reimbursement to speak at conferences sponsored by companies selling nutritional products. Y.S.C., K.M.G. and S.Y.C. are part of an academic consortium that has received research funding from Abbott, Nutrition, Nestle and Danone. Other authors declared no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Effect of 12-month intervention with lipid-based nutrient supplement on the physical activity of Malawian toddlers: a randomised, controlled trial.

Physical activity is beneficial for children's well-being. The effect of dietary supplementation on children's physical activity in food-insecure areas remains little studied. We examined the effects of a lipid-based nutrient supplement (LNS) on children's objectively measured physical activity in a randomised, controlled, outcome-assessor-blinded trial. Mothers of the children received one capsule daily of Fe-folic acid (IFA), one capsule containing eighteen micronutrients (MMN) or one 20 g sachet of LNS (containing twenty-two MMN, protein, carbohydrates, essential fatty acids and 494 kJ (118 kcal)) during pregnancy and for 6 months thereafter. Children in the IFA and MMN groups received no supplementation, and these groups were collapsed into a single control group; children in the LNS group received 20 g LNS from 6 to 18 months. We measured physical activity with accelerometers over 1 week at 18 months. The main outcome was mean vector magnitude counts/15 s. Of the 728 children at the beginning of child intervention at 6 months, 570 (78 %) provided sufficient data for analysis. The mean accelerometer counts for the 190 children in the LNS group and for the 380 children in the control group were 303 (sd 59) and 301 (sd 56), respectively (P for difference=0·65). LNS, given to mothers during pregnancy and 6 months postpartum and to their infants from 6 to 18 months of age, did not increase physical activity among 18-month-old children.

Understanding domains of health-related quality of life concerns of Singapore Chinese patients with advanced cancer: a qualitative analysis.

PURPOSE: Quality of life concerns in patients with advanced diseases might be different from other patients and are shaped by sociocultural context. The objective of this qualitative study was to identify domains and themes of health-related quality of life (HRQoL) that Chinese patients with advanced cancer in Singapore considered relevant and important. METHODS: English- and Chinese-speaking patients with advanced solid cancer were recruited from a tertiary cancer center and a community-based hospice for in-depth interview or focused group discussion. Thematic analysis was used to identify subthemes, themes, and domains from the transcripts. RESULTS: Forty-six ethnic Chinese (aged 26-86, 48% male) participated in the study. Six domains of HRQoL concerns were identified: pain and suffering, physical health, social health, mental health, financial well-being, and spiritual health. Pain and suffering are not limited to the physical domain, reflecting the multidimensional nature of this concept. Pain and suffering must also be understood within the cultural context. Healthcare relations (i.e., social health), existential well-being and religious well-being (i.e., spiritual health), and suffering (i.e., pain and suffering) are not fully captured in the existing HRQoL instruments. In addition, financial issues and the practice of secrecy in interpersonal relationships emerged as unique features possibly arising from our sociocultural context and healthcare financing landscape. CONCLUSION: Socioculturally specific issues not measured by the existing HRQoL instruments for use in patients with advanced cancers or terminal diseases were found in our study. These are non-physical pain and suffering, meaning of illness, meaning of death, financial issues, and practice of secrecy in interpersonal relationships.

The Functional Living Index-Cancer is a reliable and valid instrument in Chinese cancer patients.

PURPOSE: To evaluate the linguistic and psychometric properties of the Functional Living Index-Cancer (FLIC) in assessing the quality of life of Chinese cancer patients. METHODS: The English FLIC was translated into Traditional Chinese by the standard forward-backward procedure. After cognitive debriefing, a Traditional Chinese FLIC was administered to 500 cancer patients in a major public hospital in Hong Kong. Of which, 200 were invited to complete the questionnaire in 2 weeks. To identify a scale structure appropriate to Chinese, exploratory and confirmatory factor analyses were performed on two randomly split halves of the sample. RESULTS: We identified five scales of the Traditional Chinese FLIC which assess the physical, psychological, hardship, nausea and social aspects. These five scales and the overall scale demonstrated satisfactory fit and had the alpha coefficient ranged from 0.68 to 0.92. The intra-class correlation coefficient ranged from 0.67 to 0.88. In addition, all FLIC scales were negatively associated with the Eastern Cooperative Oncology Group performance status and, also except for the psychological scale, had lower scores in patients who were treated by chemotherapy. CONCLUSIONS: The Traditional Chinese FLIC is an appropriate health indicator for Chinese cancer patients.

Feasibility and validity of the ActiGraph GT3X accelerometer in measuring physical activity of Malawian toddlers.

AIM: To test the feasibility and validity of the ActiGraph GT3X accelerometer in measuring physical activity of rural Malawian toddlers. METHODS: Fifty-six children aged 16.0-18.5 months wore the accelerometer on their right hip for 7 days. We analysed days with a minimum of 600 min of wear time, excluding night time and periods when the unit registered zero for 20 consecutive minutes. The first and last days were excluded as they were incomplete. Accelerometer counts were compared with coded free play video recordings to define median accelerometer counts for sedentary, light, moderate and vigorous activity. Count cut points were defined for moderate to vigorous physical activity, with predictive validity assessed using a second set of video recordings. RESULTS: Median wear time was 797 min/day, with 79% of participants completing at least four eligible days. Accelerometer counts were significantly higher for observed moderate to vigorous physical activity, than lighter activity, with cut points of 208 counts/15 sec for vector magnitude and 35 counts/15 sec for vertical axis, showing sensitivity of 94.2% and 84.1% and specificity of 90.9% and 84.6%, respectively. CONCLUSION: The accelerometer proved a feasible and valid method of assessing physical activity among Malawian toddlers.

A simple approach to the estimation of incidence rate difference.

The incidence rate difference (IRD) is a parameter of interest in many medical studies. For example, in vaccine studies, it is interpreted as the vaccine-attributable reduction in disease incidence. This is an important parameter, because it shows the public health impact of an intervention. The IRD is difficult to estimate for various reasons, especially when there are quantitative covariates or the duration of follow-up is variable. In this paper, the authors propose an approach based on weighted least-squares regression for estimating the IRD. It is very easy to implement because it boils down to performing ordinary least-squares regression analysis of transformed variables. Furthermore, if the outcome events are repeatable, the authors propose that data on all events be analyzed instead of first events only. Four versions of the Huber-White robust standard error are considered for statistical inference. Simulation studies are used to examine the performance of the proposed method. In a variety of scenarios simulated, the method provides an unbiased estimate for the IRD, and the empirical coverage proportion of the 95% confidence interval is very close to the nominal level. The method is illustrated with data from a vaccine trial carried out in the Gambia in 2001-2004.

Spatial analysis of tuberculosis in an urban west African setting: is there evidence of clustering?

OBJECTIVES: To describe the pattern of tuberculosis (TB) occurrence in Greater Banjul, The Gambia with Geographical Information Systems (GIS) and Spatial Scan Statistics (SaTScan) and to determine whether there is significant TB case clustering. METHODS: In Greater Banjul, where 80% of all Gambian TB cases arise, all patients with TB registered at chest clinics between March 2007 and February 2008 were asked to participate. Demographic, clinical characteristics and GPS co-ordinates for the residence of each consenting TB case were recorded. A spatial scan statistic was used to identify purely spatial and space-time clusters of tuberculosis among permanent residents. RESULTS: Of 1145 recruited patients with TB, 84% were permanent residents with 88% living in 37 settlements that had complete maps available down to settlement level. Significant high- and low-rate spatial and space-time clusters were identified in two districts. The most likely cluster of high rate from both the purely spatial analysis and the retrospective space-time analysis were from the same geographical area. A significant secondary cluster was also identified in one of the densely populated areas of the study region. CONCLUSIONS: There is evidence of significant clustering of TB cases in Greater Banjul, The Gambia. Systematic use of cluster detection techniques for regular TB surveillance in The Gambia may aid effective deployment of resources. However, passive case detection dictates that community-based active case detection and risk factor surveys would help confirm the presence of true clusters and their causes.

Continuation of linear growth failure and its association with cognitive ability are not dependent on initial length-for-age: a longitudinal study from 6 months to 11 years of age.

AIM: To examine linear growth and its association with cognitive ability at age 11 years among full-term singletons with varying degree of stunting or without stunting at age 6 months. METHODS: A total of 1516 Filipino term-born singletons were followed bimonthly from age 6 to 24 months and took cognitive and academic achievement tests at 11 years. The tests were factor-analysed to give a summary cognitive ability score. Linear regression was used to examine associations and adjust for covariates. RESULTS: Mean height-for-age Z-score (HAZ) was -1.0 at age 6 months and -2.4 at 24 months. HAZ at 6 months, change in HAZ from 6 to 24 months and change in HAZ from 24 months to 11 years were positively associated with cognitive ability at 11 years (each p < 0.001). The association was seen in all categories of HAZ at 6 months. CONCLUSION: In this setting where linear growth retardation was common, association between linear growth after age 6 months and cognitive ability in adolescence was not dependent on initial HAZ. Prevention of growth stunting may benefit all children regardless of their initial HAZ.

Three estimates of the association between linear growth failure and cognitive ability.

OBJECTIVES: To compare three estimators of association between growth stunting as measured by height-for-age Z-score and cognitive ability in children, and to examine the extent statistical adjustment for covariates is useful for removing confounding due to socio-economic status. METHODS: Three estimators, namely random-effects, within- and between-cluster estimators, for panel data were used to estimate the association in a survey of 1105 pairs of siblings who were assessed for anthropometry and cognition. Furthermore, a 'combined' model was formulated to simultaneously provide the within- and between-cluster estimates. RESULTS: Random-effects and between-cluster estimators showed strong association between linear growth and cognitive ability, even after adjustment for a range of socio-economic variables. In contrast, the within-cluster estimator showed a much more modest association: For every increase of one Z-score in linear growth, cognitive ability increased by about 0.08 standard deviation (P < 0.001). The combined model verified that the between-cluster estimate was significantly larger than the within-cluster estimate (P = 0.004). CONCLUSION: Residual confounding by socio-economic situations may explain a substantial proportion of the observed association between linear growth and cognition in studies that attempt to control the confounding by means of multivariable regression analysis. The within-cluster estimator provides more convincing and modest results about the strength of association.

Long-term morbidity from severe pneumonia in early childhood in The Gambia, West Africa: a follow-up study.

OBJECTIVE: To assess long-term outcomes in severe early childhood pneumonia in The Gambia. DESIGN: Observational cohort study of children hospitalised with severe pneumonia between 1992 and 1994 compared to age, sex, and neighbourhood-matched controls on measures of current general and pulmonary health. RESULTS: Of 83 children successfully traced, 68 of the 69 alive at follow-up agreed to participate. Thirteen per cent of cases and 4% of controls had lung disease clinically or on spirometry. Another 16 (13%) participants had abnormal spirometry but did not meet the American Thoracic Society technical criteria (formally 'inconclusive'). Odds ratios of lung disease among childhood pneumonia cases were 2.93 (95%CI 0.69-12.48, P = 0.1468) with inconclusives omitted; 2.53 (95%CI 0.61-10.59, P = 0.2033) with inconclusives included as normal; and 2.83 (95%CI 1.09-7.36, P = 0.0334) with inconclusives included as lung disease. Among deceased cases, most deaths were reported within weeks of discharge, suggesting a possible connection between admission and subsequent death. CONCLUSION: These African data, while not conclusive, add to previous data suggesting a link between severe early childhood pneumonia and later chronic lung disease. While larger-scale research is needed, increased awareness of possible long-term morbidity in children with severe pneumonia is warranted to limit its impact and optimise long-term health.

Computerized administration of health-related quality of life instruments compared to interviewer administration may reduce sample size requirements in clinical research: a pilot randomized controlled trial among rheumatology patients.

OBJECTIVES: Computerized health-related quality of life (HRQoL) administration may facilitate clinical trials incorporating HRQoL assessment in rheumatology patients by reducing sample size requirements. We tested this hypothesis in a pilot randomized controlled trial. METHODS: Chinese-speaking adult rheumatology outpatients were randomized to computerized (PC) or interviewer (IA) administration of the EQ-5D (utility & VAS), Health Utilities Index (HUI2 & HUI3) and Family Functioning Measure (FFM). We compared measurement variability (i.e., variance) between PC and IA for each instrument before (Levene's test) and after adjusting for the effects of age, gender and education (multivariable modeling) and computed the variance ratio (VR) for PC over IA. RESULTS: In 138 patients (mean age: 48), the mean (SD) time for administration was similar for PC (n = 67) and IA (n = 71) at 17.7 (7.94) versus 17.3 minutes (7.49), respectively. More subjects expressed a preference for PC (n = 21) over IA (n = 13). Mean HRQoL scores were not significantly different for PC versus IA except for higher VAS scores with IA (difference -7.7, 95% CI -14.0 to 1.3, p = 0.018). Variances and adjusted VR were smaller with PC for the EQ-5D (adjusted VR 0.34, 95% CI 0.18 to 0.65), HUI3 (0.49, 0.27 to 0.89) and FFM (0.95, 0.61 to 1.46), but larger for the HUI2 (1.30, 0.67 to 2.55) and VAS (1.05, 0.55 to 2.00). CONCLUSION: The reduced variability in 3 of 5 instruments and good acceptance of computerized HRQoL assessment, if confirmed in larger studies, may lead to smaller sample size requirements, with potential reductions in cost and recruitment time for clinical trials and cohort studies.

Acceptance of prophylactic surgery and chemoprevention of cancer in Singapore - a survey.

INTRODUCTION: In addition to surveillance practices, chemoprevention and prophylactic surgery can reduce the risk of cancer in individuals at high risk. Sociocultural factors may have a role to play in such decision making. Little is known regarding the factors that play a role in decision making in Singapore. MATERIALS AND METHODS: One hundred and two individuals at normal risk completed a questionnaire on the concept of chemoprevention and prophylactic surgery. The results were analysed using the convenience sampling method. RESULTS: Participants were mostly Chinese (94.1%). More than 90% of the respondents answered the section on prophylactic surgery and chemoprevention. Thirty-eight individuals (41.3%) would not consider prophylactic surgery, while 42 (45.7%) would not consider prophylactic surgery now but might consider it in the future. Twenty-five individuals (26.9%) would not consider chemoprevention by taking a medication, 57% would not consider it now but might in the future. CONCLUSION: A cross-sectional public view suggests that medical prophylaxis is likely to be more acceptable to the general public compared to surgical prophylaxis.

Risk perception is affected by modes of risk presentation among Singaporeans.

INTRODUCTION: Not much is known about how Singaporeans perceive and react to risk presentation. There is no consensus on whether the European Union guidelines for describing the risk of side effects are valid. This study investigated the effect of different modes of risk presentation on how Singaporeans perceive and react to medical risk. Furthermore, we investigated the practical usage of qualitative phrases, the European Union's adjectives in particular, in describing levels of risk. MATERIALS AND METHODS: A hypothetical situation about the risk of side effects of an influenza vaccine was presented in either a probability format (i.e., 5%; n = 42) or a frequency format (i.e., 1 out of 20; n = 43). The 2 versions of questionnaire were handed out in an alternate order to a convenience sample of 47 healthcare professionals and 38 university students. RESULTS: Respondents presented with a "5% risk" were more likely to describe the risk as "uncommon" or "rare", as compared to respondents presented with a risk of "one out of twenty" (P <0.01). Furthermore, the former showed more willingness to accept the influenza vaccine described in the hypothetical situation than in the latter, but this was not statistically different (67% versus 54%; P >0.1). CONCLUSIONS: Modes of risk presentation affect how people perceive risk, even among people who are highly educated.

Concurrent chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the oesophagus: a single centre experience.

INTRODUCTION: Data on combined modality treatment for locally advanced squamous cell carcinoma of the oesophagus involving Asian patients are limited. MATERIALS AND METHODS: A retrospective study of 56 consecutive patients with this condition treated with concurrent chemoradiotherapy followed by surgery in a single tertiary institution in Singapore was performed. RESULTS: The median overall survival of the entire cohort was 14.1 months [95% confidence interval (CI); range, 8.6 to 19.6 months]. In patients who underwent successful oesophagectomy after chemoradiotherapy (n = 17), the median survival was 27.8 months compared to 9.8 months for those who did not have surgery (n = 39) (P = 0.046, log-rank test). The median time to first relapse for the entire cohort was 16.1 months (95% CI, 7.7 to 24.5 months). The time to first relapse was 23.9 months in the subgroup of patients with successful surgery and 12.1 months in the group which did not (P = 0.147, log-rank test). The high proportion of patients who were medically unfit for surgery or declined surgery may have conferred a selection bias. CONCLUSION: Concurrent chemoradiotherapy followed by surgery is feasible in selected patients. The benefit of adding of surgery to chemoradiotherapy is still controversial and we await the results of randomised controlled trials comparing chemoradiotherapy with surgery versus chemoradiotherapy alone.

Effect of 12-month intervention with lipid-based nutrient supplements on physical activity of 18-month-old Malawian children: a randomised, controlled trial.

BACKGROUND/OBJECTIVES: This study measured the effects of dietary supplementation with lipid-based nutrient supplements (LNSs) on 18-month-old children's physical activity. SUBJECTS/METHODS: In a randomised, controlled, outcome-assessor blinded trial 1932 six-month-old children from Malawi received one of five interventions daily from 6-18 months of age: 10-g milk-LNS, 20-g milk-LNS, 20-g non-milk-LNS, 40-g milk-LNS or 40-g non-milk-LNS, or received no intervention in the same period (control). The control group received delayed intervention with corn-soy blend from 18-30 months. Physical activity was measured over 1 week by ActiGraph GT3X+ accelerometer at 18 months. Main outcome was mean vector magnitude accelerometer counts/15 s. Analyses were restricted to children with valid accelerometer data on at least 4 days with minimum 6 h of wearing time per day. RESULTS: Of the 1435 children recruited to this substudy, 1053 provided sufficient data for analysis. The mean (s.d.) vector magnitude accelerometer counts in the total sample were 307 (64). The difference (95% CI) in mean accelerometer counts, compared with the control group, was 8 (-6 to 21, P=0.258) in 10-g milk-LNS, 3 (-11 to 17, P=0.715) in 20-g milk-LNS, 5 (-8 to 19, P=0.445) in 20-g non-milk-LNS, 10 (-3 to 23, P=0.148) in 40-g milk-LNS and 2 (-12 to 16, P=0.760) in 40-g non-milk-LNS groups. CONCLUSIONS: Provision of 10-40 g doses of LNS daily for 12 months did not increase physical activity of Malawian toddlers.

Adjustment for selection bias in cohort studies: an application of a probit model with selectivity to life course epidemiology.

Sample attrition is potentially a source of bias in cohort studies. The outcome may not be observed in a considerable proportion of the subjects. This article proposes the application of a probit model with sample selection to handle the problem. Two equations are simultaneously estimated and their error terms allowed to correlate: one regressing an observed outcome on a set of baseline variables, another regressing the probability of the outcome being observed upon a set of (perhaps the same) baseline variables. The method was applied to a study of a birth cohort, half of whose members were interviewed again at age 26. Baseline variables were observed for all the subjects included. The focus was on the association between birth weight and mental health in adults. The probit model with sample selection revealed a stronger and more significant (P = 0.037) relation between birth weight and mental health than an ordinary probit regression model (P = 0.170). Interpretation and practical considerations are discussed.

Marital status and mortality in British women: a longitudinal study.

BACKGROUND: Most previous studies on marital status and mortality did not adjust for the effect of 'marital selection'. Little research has been done about the relation between marital status and mortality in British women, with the exception of research on bereavement. METHODS: Subjects consisted of women aged > or = 35 in a longitudinal study of a nationally representative sample. Marital status and covariates were enumerated at a baseline interview in 1984/85 and a follow-up interview in 1991/92. Death data up to May 1997 were obtained from the National Health Service Central Register. Cox regression was used to estimate hazard ratios (HR) for the single, divorced and widowed states in relation to the married state. RESULTS: Having adjusted for age and martial selection factors, being single (HR = 1.45) was significantly associated with higher all-cause mortality. Being divorced and being widowed showed no excess mortality risk (each HR = 1.09). CONCLUSIONS: Being single was associated with higher mortality. A causal interpretation is plausible. Being divorced and being widowed were not associated with higher mortality.