Development and validation of the Rapid Positive Mental Health Instrument (R-PMHI) for measuring mental health outcomes in the population.

BACKGROUND: The multidimensional Positive Mental Health Instrument (PMHI) has 47 items and six subscales. This study aimed to develop and validate a short unidimensional version of the PMHI among Singapore's adult resident population. METHODS: Using pooled data from three earlier studies (n = 1050), PMHI items were reduced by Partial Credit Rasch Model (PCRM) runs in a random split-half sample, while psychometric properties of the resulting measure were tested through confirmatory factor analysis (CFA), item response theory-graded response model and internal consistency reliability in the other half. Its reliability, construct and concurrent validity, agreement with the original scale, floor and ceiling effect, and scale estimates were further investigated in an external representative general population sample (n = 1925). RESULTS: The average age of the participants was around 41 years. Four PCRM re-runs for item selection resulted in a 6-item unidimensional Rapid PMHI (R-PMHI). CFA confirmed the unidimensional structure of the R-PMHI in the internal (RMSEA = 0.075, CFI = 0.985, TLI = 0.974) and external (RMSEA = 0.051, CFI = 0.992, TLI = 0.987) validation samples. In the external validation sample, the R-PMHI met concurrent validity criteria, showing high agreement with the 47-item version with intra-class correlation coefficient of 0.872 (95% CI: 0.861 to 0.882) and low floor and ceiling effects. Weight-adjusted mean (SE, 95% CI) R-PMHI score in the population was 4.86 (0.2, 4.82-4.90). CONCLUSION: The unidimensional 6-item R-PMHI offers brevity over the original multidimensional measure while appropriately representing the positive mental health construct. Prospective studies are needed to assess its responsiveness and test-retest reliability.

Use of a Real-Time Locating System for Contact Tracing of Health Care Workers During the COVID-19 Pandemic at an Infectious Disease Center in Singapore: Validation Study.

BACKGROUND: In early 2020, coronavirus disease (COVID-19) emerged and spread by community and nosocomial transmission. Effective contact tracing of potentially exposed health care workers is crucial for the prevention and control of infectious disease outbreaks in the health care setting. OBJECTIVE: This study aimed to evaluate the comparative effectiveness of contact tracing during the COVID-19 pandemic through the real-time locating system (RTLS) and review of the electronic medical record (EMR) at the designated hospital for COVID-19 response in Singapore. METHODS: Over a 2-day study period, all admitted patients with COVID-19, their ward locations, and the health care workers rostered to each ward were identified to determine the total number of potential contacts between patients with COVID-19 and health care workers. The numbers of staff-patient contacts determined by EMR reviews, RTLS-based contact tracing, and a combination of both methods were evaluated. The use of EMR-based and RTLS-based contact tracing methods was further validated by comparing their sensitivity and specificity against self-reported staff-patient contacts by health care workers. RESULTS: Of 796 potential staff-patient contacts (between 17 patients and 162 staff members), 104 (13.1%) were identified by both the RTLS and EMR, 54 (6.8%) by the RTLS alone, and 99 (12.4%) by the EMR alone; 539 (67.7%) were not identified through either method. Compared to self-reported contacts, EMR reviews had a sensitivity of 47.2% and a specificity of 77.9%, while the RTLS had a sensitivity of 72.2% and a specificity of 87.7%. The highest sensitivity was obtained by including all contacts identified by either the RTLS or the EMR (sensitivity 77.8%, specificity 73.4%). CONCLUSIONS: RTLS-based contact tracing showed higher sensitivity and specificity than EMR review. Integration of both methods provided the best performance for rapid contact tracing, although technical adjustments to the RTLS and increasing user compliance with wearing of RTLS tags remain necessary.

Association of diabetes treatment with long-term glycemic patterns in patients with type 2 diabetes mellitus: A prospective cohort study.

AIM: This study aimed to analyze diabetes treatment and treatment changes in association with long-term glycemic patterns in an Asian population with diabetes. MATERIALS AND METHODS: This was a prospective cohort study of 6218 patients with type 2 diabetes managed in public primary care clinics in Singapore. Clinical data from 2011 to 2016 were extracted from electronic medical records, including serial HbA1c measurements and dispensed antidiabetic medication records. Patterns of longitudinal HbA1c trajectories were identified using latent class growth analysis, and patients' annual treatment plans were compared between subgroups with different HbA1c patterns. RESULTS: We identified four distinct HbA1c patterns. Eighty-one percent of patients were classified in the low-stable group, where monotherapy and dual therapy with oral agents were the most common treatments. We also identified three groups with poorer control, with moderate-stable (14%), moderate-increase (3%), and high-decrease (2%) HbA1c patterns. Insulin treatment was most prevalent in these groups, with 61% to 72% of subjects receiving insulin treatment in 2016. More than 60% of subjects in poorer control groups had experienced treatment intensification during follow-up. Addition of multiple insulin injections was the most common intensification in moderate-increase and high-decrease groups. CONCLUSIONS: Treatment reflected and was appropriate to the extent of dysglycemia in this population. A small group of patients had deteriorating glycemic control, in spite of being treated with multiple insulin injections, suggesting non-response or non-adherence to treatment. Further investigation is needed to identify reasons for the deteriorating control observed and design effective interventions for these patients.

Longitudinal trends in HbA1c patterns and association with outcomes: A systematic review.

BACKGROUND: This study aimed to review studies that identified patterns of longitudinal HbA1c trends in patients with diabetes and to summarize factors and outcomes associated with distinct trajectory patterns. METHODS: PubMed and Web of Science were systematically searched for studies examining HbA1c trends among patients with diabetes from database inception through September 2017. Articles were included if they met the following inclusion criteria: (a) longitudinal study of subjects with diabetes only, (b) use of serial measurements of HbA1c , and (c) analysis of the trend of HbA1c using group-based trajectory approaches. RESULTS: Twenty studies were included, 11 on type 1 diabetes and 9 on type 2 diabetes. These studies identified 2 to 6 HbA1c trajectory patterns. The most commonly identified patterns included stable HbA1c around 7.0% and at levels between 8.0% and 9.9%, which usually captured the HbA1c pattern among the majority of subjects in the study population. Unstable patterns identified included increasing HbA1c trend, decreasing HbA1c trend, and non-linear patterns. These patterns were associated with differential risk of disease outcomes, over and beyond single-point HbA1c measures. Age, gender, ethnicity, diabetes duration, disease management frequency, cardiovascular risk factors, insulin treatment, family environment, and psychosocial factors were the most frequently reported factors associated with membership of specific HbA1c pattern groups. CONCLUSION: Common patterns of longitudinal HbA1c trends were identified despite heterogeneity among the studies. A better understanding of what underlies these different patterns may provide opportunities to tailor therapies and care for these patients to reduce adverse outcomes.

Psychometric properties and population norms of the positive mental health instrument in a representative multi-ethnic Asian population.

BACKGROUND: Measures of mental well-being and positive mental health (PMH) have been largely developed and used in Western populations, however, data on representative Asian communities are lacking. Using data from a population sample, this study sought to establish psychometric properties and norms of the PMH Instrument (PMH-I), a measure of positive mental health developed in Singapore. METHODS: We conducted a nationally representative survey among 1925 adults aged 18-79 years of Chinese, Malay, Indian or other ethnicity. Participants reported socio-demographic characteristics and completed the PMH-I along with measures of health-related quality of life (HRQoL) and psychological distress. Construct validity of the PMH-I was assessed using confirmatory factor analysis and concurrent validity was tested through correlation with other psychological measures. Normative PMH values and differences in population subgroups were estimated. RESULTS: The six-factor-higher-order structure of the PMH-I comprising six subscales of general coping, emotional support, spirituality, interpersonal skills, personal growth and autonomy and global affect was confirmed. Concurrent validity was shown through significant positive correlation of the total PMH score and its subscales with HRQoL and an inverse correlation with psychological distress. Weighted age, gender and ethnicity-specific norms were derived for the Singapore population. Total PMH was significantly higher in participants aged over 40 years as compared with 18-29 year olds and in non-Chinese ethnic groups as compared with Chinese. These differences were observed for all PMH-I subscales, with the exception of emotional support and interpersonal skills score differences by age. In contrast, gender, marital status, and education level were significantly associated with some of the subscales, but not with total PMH. CONCLUSIONS: These results support the psychometric properties of the PMH-I in a multi-ethnic Asian population sample. The generalizable population-based norms support the application of the PMH-I for measuring mental health and assessing its determinants within the Singapore general population.

Adequacy of public health communications on H7N9 and MERS in Singapore: insights from a community based cross-sectional study.

BACKGROUND: Singapore remains vulnerable to worldwide epidemics due to high air traffic with other countries This study aims to measure the public's awareness of the Middle East Respiratory Syndrome (MERS) and Avian Influenza A (H7N9), identify population groups who are uninformed or misinformed about the diseases, understand their choice of outbreak information source, and assess the effectiveness of communication channels in Singapore. METHODS: A cross-sectional study, comprising of face-to-face interviews, was conducted between June and December 2013 to assess the public's awareness and knowledge of MERS and H7N9, including their choice of information source. Respondents were randomly selected and recruited from 3 existing cohort studies. An opportunistic sampling approach was also used to recruit new participants or members in the same household through referrals from existing participants. RESULTS: Out of 2969 participants, 53.2% and 79.4% were not aware of H7N9 and MERS respectively. Participants who were older and better educated were most likely to hear about the diseases. The mean total knowledge score was 9.2 (S.D ± 2.3) out of 20, and 5.9 (S.D ± 1.2) out of 10 for H7N9 and MERS respectively. Participants who were Chinese, more educated and older had better knowledge of the diseases. Television and radio were the primary sources of outbreak information regardless of socio-demographic factors. CONCLUSION: Heightening education of infectious outbreaks through appropriate media to the young and less educated could increase awareness.

Epidemiology and Relative Severity of Influenza Subtypes in Singapore in the Post-Pandemic Period from 2009 to 2010.

BACKGROUND: After 2009, pandemic influenza A(H1N1) [A(H1N1)pdm09] cocirculated with A(H3N2) and B in Singapore. METHODS: A cohort of 760 participants contributed demographic data and up to 4 blood samples each from October 2009 to September 2010. We compared epidemiology of the 3 subtypes and investigated evidence for heterotypic immunity through multivariable logistic regression using a generalized estimating equation. To examine age-related differences in severity between subtypes, we used LOESS (locally weighted smoothing) plots of hospitalization to infection ratios and explored birth cohort effects referencing the pandemic years (1957; 1968). RESULTS: Having more household members aged 5-19 years and frequent public transport use increased risk of infection, while preexisting antibodies against the same subtype (odds ratio [OR], 0.61; P = .002) and previous influenza infection against heterotypic infections (OR, 0.32; P = .045) were protective. A(H1N1)pdm09 severity peaked in those born around 1957, while A(H3N2) severity was least in the youngest individuals and increased until it surpassed A(H1N1)pdm09 in those born in 1952 or earlier. Further analysis showed that severity of A(H1N1)pdm09 was less than that for A(H3N2) in those born in 1956 or earlier (P = .021) and vice versa for those born in 1968 or later (P < .001), with no difference in those born between 1957 and 1967 (P = .632). CONCLUSIONS: Our findings suggest that childhood exposures had long-term impact on immune responses consistent with the theory of antigenic sin. This, plus observations on short-term cross-protection, have implications for vaccination and influenza epidemic and pandemic mitigation strategies.

Insights into the genetic structure and diversity of 38 South Asian Indians from deep whole-genome sequencing.

South Asia possesses a significant amount of genetic diversity due to considerable intergroup differences in culture and language. There have been numerous reports on the genetic structure of Asian Indians, although these have mostly relied on genotyping microarrays or targeted sequencing of the mitochondria and Y chromosomes. Asian Indians in Singapore are primarily descendants of immigrants from Dravidian-language-speaking states in south India, and 38 individuals from the general population underwent deep whole-genome sequencing with a target coverage of 30X as part of the Singapore Sequencing Indian Project (SSIP). The genetic structure and diversity of these samples were compared against samples from the Singapore Sequencing Malay Project and populations in Phase 1 of the 1,000 Genomes Project (1 KGP). SSIP samples exhibited greater intra-population genetic diversity and possessed higher heterozygous-to-homozygous genotype ratio than other Asian populations. When compared against a panel of well-defined Asian Indians, the genetic makeup of the SSIP samples was closely related to South Indians. However, even though the SSIP samples clustered distinctly from the Europeans in the global population structure analysis with autosomal SNPs, eight samples were assigned to mitochondrial haplogroups that were predominantly present in Europeans and possessed higher European admixture than the remaining samples. An analysis of the relative relatedness between SSIP with two archaic hominins (Denisovan, Neanderthal) identified higher ancient admixture in East Asian populations than in SSIP. The data resource for these samples is publicly available and is expected to serve as a valuable complement to the South Asian samples in Phase 3 of 1 KGP.

Using peer review to distribute group work marks equitably between medical students.

BACKGROUND: Although peer assessment has been used for evaluating performance of medical students and practicing doctors, it has not been studied as a method to distribute a common group work mark equitably to medical students working in large groups where tutors cannot observe all students constantly. METHODS: The authors developed and evaluated a mathematical formulation whereby a common group mark could be distributed among group members using peer assessment of individual contributions to group work, maintaining inter-group variation in group work scores. This was motivated by community health projects undertaken by large groups of year four medical students at the National University of Singapore, and the new and old formulations are presented via application to 263 students in seven groups of 36 to 40 during the academic year 2012/2013. RESULTS: This novel formulation produced a less clustered mark distribution that rewarded students who contributed more to their team. Although collusion among some members to form a voting alliance and 'personal vendettas' were potential problems, the former was not detected and the latter had little impact on the overall grade a student received when working in a large group. The majority of students thought the new formulation was fairer. CONCLUSIONS: The new formulation is easy to implement and arguably awards grades more equitably in modules where group work is a major component.

The impact of breast cancer-specific birth cohort effects among younger and older Chinese populations.

Historically low breast cancer incidence rates among Asian women have risen worldwide; purportedly due to the adoption of a "Western" life style among younger generations (i.e., the more recent birth cohorts). However, no study has simultaneously compared birth cohort effects between both younger and older women in different Asian and Western populations. Using cancer registry data from rural and urban China, Singapore and the United States (1990-2008), we estimated age-standardized incidence rates (ASR), annual percentage change (EAPC) in the ASR, net drifts, birth cohort specific incidence rates and cohort rate ratios (CRR). Younger (30-49 years, 1943-1977 birth cohorts) and older women (50-79 years; 1913-1957 birth cohorts) were assessed separately. CRRs among Chinese populations were estimated using birth cohort specific rates with US non-Hispanic white women (NHW) serving as the reference population with an assigned CRR of 1.0. We observed higher EAPCs and net drifts among those Chinese populations with lower ASRs. Similarly, we observed the most rapidly increasing cohort-specific incidence rates among those Chinese populations with the lowest baseline CRRs. Both trends were more significant among older than younger women. Average CRRs were 0.06-0.44 among older and 0.18-0.81 among younger women. Rapidly rising cohort specific rates have narrowed the historic disparity between Chinese and US NHW breast cancer populations particularly in regions with the lowest baseline rates and among older women. Future analytic studies are needed to investigate risk factors accounting for the rapid increase of breast cancer among older and younger women separately in Asian populations.

Predicting HLA alleles from high-resolution SNP data in three Southeast Asian populations.

The major histocompatibility complex (MHC) containing the classical human leukocyte antigen (HLA) Class I and Class II genes is among the most polymorphic and diverse regions in the human genome. Despite the clinical importance of identifying the HLA types, very few databases jointly characterize densely genotyped single nucleotide polymorphisms (SNPs) and HLA alleles in the same samples. To date, the HapMap presents the only public resource that provides a SNP reference panel for predicting HLA alleles, constructed with four collections of individuals of north-western European, northern Han Chinese, cosmopolitan Japanese and Yoruba Nigerian ancestry. Owing to complex patterns of linkage disequilibrium in this region, it is unclear whether the HapMap reference panels can be appropriately utilized for other populations. Here, we describe a public resource for the Singapore Genome Variation Project with: (i) dense genotyping across ∼ 9000 SNPs in the MHC; (ii) four-digit HLA typing for eight Class I and Class II loci, in 96 southern Han Chinese, 89 Southeast Asian Malays and 83 Tamil Indians. This resource provides population estimates of the frequencies of HLA alleles at these eight loci in the three population groups, particularly for HLA-DPA1 and HLA-DPB1 that were not assayed in HapMap. Comparing between population-specific reference panels and a cosmopolitan panel created from all four HapMap populations, we demonstrate that more accurate imputation is obtained with population-specific panels than with the cosmopolitan panel, especially for the Malays and Indians but even when imputing between northern and southern Han Chinese. As with SNP imputation, common HLA alleles were imputed with greater accuracy than low-frequency variants.

Deep whole-genome sequencing of 100 southeast Asian Malays.

Whole-genome sequencing across multiple samples in a population provides an unprecedented opportunity for comprehensively characterizing the polymorphic variants in the population. Although the 1000 Genomes Project (1KGP) has offered brief insights into the value of population-level sequencing, the low coverage has compromised the ability to confidently detect rare and low-frequency variants. In addition, the composition of populations in the 1KGP is not complete, despite the fact that the study design has been extended to more than 2,500 samples from more than 20 population groups. The Malays are one of the Austronesian groups predominantly present in Southeast Asia and Oceania, and the Singapore Sequencing Malay Project (SSMP) aims to perform deep whole-genome sequencing of 100 healthy Malays. By sequencing at a minimum of 30× coverage, we have illustrated the higher sensitivity at detecting low-frequency and rare variants and the ability to investigate the presence of hotspots of functional mutations. Compared to the low-pass sequencing in the 1KGP, the deeper coverage allows more functional variants to be identified for each person. A comparison of the fidelity of genotype imputation of Malays indicated that a population-specific reference panel, such as the SSMP, outperforms a cosmopolitan panel with larger number of individuals for common SNPs. For lower-frequency (<5%) markers, a larger number of individuals might have to be whole-genome sequenced so that the accuracy currently afforded by the 1KGP can be achieved. The SSMP data are expected to be the benchmark for evaluating the value of deep population-level sequencing versus low-pass sequencing, especially in populations that are poorly represented in population-genetics studies.

Evaluation of Equations for Predicting 24-Hour Urinary Sodium Excretion from Casual Urine Samples in Asian Adults.

BACKGROUND: The collection of 24-h urine samples for the estimation of sodium intake is burdensome, and the utility of spot urine samples in Southeast Asian populations is unclear. OBJECTIVE: We aimed to assess the validity of prediction equations with the use of spot urine concentrations. METHODS: A sample of 144 Singapore residents of Chinese, Malay, and Indian ethnicity aged 18-79 y were recruited from the Singapore Health 2 Study conducted in 2014. Participants collected urine for 24 h in multiple small bottles on a single day. To determine the optimal collection time for a spot urine sample, a 1-mL sample was taken from a random bottle collected in the morning, afternoon, and evening. Published equations and a newly derived equation were used to predict 24-h sodium excretion from spot urine samples. RESULTS: The mean ± SD concentration of sodium from the 24-h urine sample was 125 ± 53.4 mmol/d, which is equivalent to 7.2 ± 3.1 g salt. Bland-Altman plots showed good agreement at the group level between estimated and actual 24-h sodium excretion, with biases for the morning period of -3.5 mmol (95% CI: -14.8, 7.8 mmol; new equation) and 1.46 mmol (95% CI: -10.0, 13.0 mmol; Intersalt equation). A larger bias of 25.7 mmol (95% CI: 12.2, 39.3 mmol) was observed for the Tanaka equation in the morning period. The prediction accuracy did not differ significantly for spot urine samples collected at different times of the day or at a random time of day (P = 0.11-0.76). CONCLUSION: This study suggests that the application of both our own newly derived equation and the Intersalt equation to spot urine concentrations may be useful in predicting group means for 24-h sodium excretion in urban Asian populations.

Prevalence of sleep-disordered breathing in a multiethnic Asian population in Singapore: A community-based study.

BACKGROUND AND OBJECTIVE: Limited data exist on the prevalence variation in sleep-disordered breathing (SDB) across different Asian ethnicities. This population study aimed to estimate the prevalence of SDB in Singapore, a multiethnic nation, and to quantify the prevalence variation among Chinese, Malays and Indians. METHODS: The Singapore Health Study 2012 was a cross-sectional population study conducted on adults aged 21-79 years. Among 2329 participants who completed baseline examination, a sample of 242 subjects completed home-based sleep testing with an Embletta device (type 3 monitor). Moderate-to-severe SDB, defined as an apnoea-hypopnoea index (AHI) of ≥15 events/h, was used to estimate prevalence. RESULTS: The weighted estimates of the population prevalence of moderate-to-severe SDB and sleep apnoea syndrome were 30.5% and 18.1%, respectively. Of subjects with AHI ≥15, 91.0% were previously undiagnosed. Moderate-to-severe SDB prevalence varied across the Chinese (32.1%), Malays (33.8%) and Indians (16.5%). The mean body mass index (BMI) was lowest in Chinese (23.3 kg/m(2) ) and highest among Malays (26.0 kg/m(2) ) and Indians (25.4 kg/m(2) ). Compared with Chinese, Indians had lower odds of moderate-to-severe SDB after adjustment for age, sex and BMI (odds ratio 0.82, 95% CI: 0.70-0.96, P = 0.02). CONCLUSION: Sleep-disordered breathing is prevalent but mostly undiagnosed among Asians in Singapore. There was a lower prevalence of SDB among Indians compared with Chinese that remained after adjustment for age, sex and BMI. Strategies are needed to optimize diagnosis and recognize ethnic differences in SDB prevalence.

Reproductive factors, adiposity, breastfeeding and their associations with ovarian cancer in an Asian cohort.

PURPOSE: The aim of this study was to assess associations of breastfeeding, adiposity and reproductive risk factors with ovarian cancer risk in a Singaporean population. In addition to the main analysis, interaction effects of parity on other risk factors were examined. METHODS: A retrospective cohort consisting of 28,201 women with 107 incident ovarian cancers in up to 17 years of follow-up from the Singapore Breast Cancer Screening Project (1994-1997) was studied. Hazard ratios (HRs) for risk factors were estimated using Cox proportional hazards models. RESULTS: Body mass index and breastfeeding were found to have no statistical significant association with ovarian cancer risk. Gravidity was inversely associated with ovarian cancer risk [each pregnancy, adjusted HR 0.89, 95% confidence interval (CI) 0.81, 0.97], while results for parity were very similar (per delivery, HR 0.89, 95% CI 0.81, 0.98). Each additional year of ovulatory period was found to increase ovarian cancer risk by 2% (HR 1.02, 95% CI 1.00, 1.04). Each year increase in total duration of oral contraceptive use reduced ovarian cancer risk by 6% (HR 0.94, 95% CI 0.85, 1.02). CONCLUSIONS: Parity, gravidity and shorter ovulatory period were associated with lower ovarian cancer risk. Breastfeeding and body mass index were not associated with ovarian cancer risk, while increased duration of oral contraceptive use resulted in borderline risk reduction. No significant evidence was found to suggest that parity had an interaction effect on any risk factor.

The Pittsburgh Sleep Quality Index in a multi-ethnic Asian population contains a three-factor structure.

PURPOSE: The Pittsburgh Sleep Quality Index (PSQI) is a widely used measure for assessing sleep impairment. Although it was developed as a unidimensional instrument, there is much debate that it contains multidimensional latent constructs. We examined the dimensionality of the underlying factor structure of PSQI in Singapore, a rapidly industrialising Asian country with multi-ethnicities representing the Chinese, Malays and Indians. METHODS: The PSQI was administered through an interviewer-based questionnaire in two separate population-based cross-sectional surveys. An explanatory factor analysis (EFA) was first used to explore the underlying construct of the PSQI in both studies. Then, a confirmatory factor analysis (CFA) was conducted to evaluate an optimal factor model by comparing against other possible models identified in EFA. RESULTS: There are three correlated yet distinguishable factors that account for an individual's sleep experience from the same best-fit model obtained in both studies: perceived sleep quality, daily disturbances and sleep efficiency. Our three-factor structure of PSQI is superior to the originally intended unidimensional model. Our model also shows the best-fit indices when compared to the previously reported single-factor, two-factor and three-factor (by Cole et al.) models in a multi-ethnic Asian population. CONCLUSION: There is strong evidence that the PSQI contains a three-factor rather than a unidimensional structure in a multi-ethnic Asian population. Scoring the PSQI along their multidimensional perspectives may provide a more accurate understanding of the relationship between sleep impairment and health conditions rather than using a single global score.

Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO).

While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 control who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17-1.45) for all histological types combined, 1.26 (95% CI: 1.10-1.44) for adenocarcinoma, 1.41 (95% CI: 0.99-1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89-2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62-5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for nonsmall cell lung cancers (OR=2.11, 95% CI: 1.11-4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention.

Rate of decline of antibody titers to pandemic influenza A (H1N1-2009) by hemagglutination inhibition and virus microneutralization assays in a cohort of seroconverting adults in Singapore.

BACKGROUND: The rate of decline of antibody titers to influenza following infection can affect results of serological surveys, and may explain re-infection and recurrent epidemics by the same strain. METHODS: We followed up a cohort who seroconverted on hemagglutination inhibition (HI) antibody titers (≥ 4-fold increase) to pandemic influenza A(H1N1)pdm09 during a seroincidence study in 2009. Along with the pre-epidemic sample, and the sample from 2009 with the highest HI titer between August and October 2009 (A), two additional blood samples obtained in April 2010 and September 2010 (B and C) were assayed for antibodies to A(H1N1)pdm09 by both HI and virus microneutralization (MN) assays. We analyzed pair-wise mean-fold change in titers and the proportion with HI titers ≥ 40 and MN ≥ 160 (which correlated with a HI titer of 40 in our assays) at the 3 time-points following seroconversion. RESULTS: A total of 67 participants contributed 3 samples each. From the highest HI titer in 2009 to the last sample in 2010, 2 participants showed increase in titers (by HI and MN), while 63 (94%) and 49 (73%) had reduction in HI and MN titers, respectively. Titers by both assays decreased significantly; while 70.8% and 72.3% of subjects had titers of ≥ 40 and 160 by HI and MN in 2009, these percentages decreased to 13.9% and 36.9% by September 2010. In 6 participants aged 55 years and older, the decrease was significantly greater than in those aged below 55, so that none of the elderly had HI titers ≥ 40 nor MN titers ≥ 160 by the final sample. Due to this decline in titers, only 23 (35%) of the 65 participants who seroconverted on HI in sample A were found to seroconvert between the pre-epidemic sample and sample C, compared to 53 (90%) of the 59 who seroconverted on MN on Sample A. CONCLUSIONS: We observed marked reduction in titers 1 year after seroconversion by HI, and to a lesser extent by MN. Our findings have implications for re-infections, recurrent epidemics, vaccination strategies, and for cohort studies measuring infection rates by seroconversion.

Frequency of atlantoaxial calcium pyrophosphate dihydrate deposition at CT.

PURPOSE: To determine (a) the prevalence of atlantoaxial calcium pyrophosphate dihydrate (CPPD) crystal deposition in a population of patients undergoing computed tomography (CT) for acute trauma and (b) the association between atlantoaxial CPPD crystal deposition and retro-odontoid soft-tissue thickness. MATERIALS AND METHODS: This HIPAA-compliant study was approved by the institutional review board, and the requirement to obtain informed consent was waived. In 513 consecutive patients, CT scans of the cervical spine obtained for acute trauma were retrospectively reviewed for the presence of atlantoaxial CPPD crystal deposition, and the maximal thickness of the retro-odontoid soft tissues was measured. The relationships among imaging findings, age, and sex were assessed with the t test, the χ(2) test, Spearman correlation, and logistic and linear regression models as appropriate. RESULTS: The overall prevalence of atlantoaxial CPPD crystal deposition was 12.5% (64 of 513 patients), and prevalence increased with age (P < .0001, logistic regression coefficient). In patients aged 60 years and older, the prevalence of CPPD crystal deposition was 34% (58 of 170 patients). In patients aged 80 years and older, the prevalence of CPPD crystal deposition was 49% (37 of 75 patients). There was a positive correlation between age and retro-odontoid soft-tissue thickness (Spearman ρ = 0.48, P < .0001). The mean retro-odontoid soft-tissue thickness in patients with CPPD crystal deposition was greater than that in patients without CPPD crystal deposition (3.4 mm vs 2.2 mm, respectively; P < .0001, t test). CONCLUSION: CPPD crystal deposition in the cervical spine is seen with a higher prevalence than previously reported. CPPD crystal deposition shows a positive correlation with age and retro-odontoid soft-tissue thickening.

Lifetime and twelve-month prevalence of heavy-drinking in Singapore: results from a representative cross-sectional study.

BACKGROUND: The study aimed to establish the prevalence of heavy drinking, evaluate correlations between heavy drinking and socio-demographic factors, physical and psychiatric conditions, and assess the impact of heavy drinking on quality of life and days of work-loss. METHODS: Data from a nationally-representative cross-sectional sample were used. The sample comprised 6616 community-dwelling Singaporeans & Singapore Permanent Residents. The main instruments used were the World Mental Health Composite International Diagnostic Interview and EuroQol 5D. Heavy drinking was defined as consumption of 4 or more drinks, or 5 or more drinks in a day in women and men respectively. RESULTS: 12.6% of all adult Singapore residents reported heavy drinking in the last 12 months, and 15.9% reported lifetime heavy-drinking. Strong gender, ethnic, age and income differences were seen. Heavy drinking was positively associated with major depression, the presence of any mood disorder, and with chronic pain. It was also strongly associated with alcohol dependence, alcohol abuse, and nicotine dependence. Heavy-drinkers reported lower quality of life compared to non-heavy drinkers, measured using the EuroQol 5D Visual Analogue Scale. CONCLUSIONS: Singapore has a relatively high prevalence of 12-month heavy drinking of 12.6%, and lifetime heavy drinking of 15.9%. Heavy drinking was positively associated with both physical and mental health conditions, and with declines in quality of life. Continued monitoring of heavy drinking behavior and sustained efforts to mitigate the risks associated with heavy drinking is needed.