Showing papers in "Emerging Themes in Epidemiology in 2015"

Applying the Bradford Hill criteria in the 21st century: how data integration has changed causal inference in molecular epidemiology.

Abstract: In 1965, Sir Austin Bradford Hill published nine “viewpoints” to help determine if observed epidemiologic associations are causal. Since then, the “Bradford Hill Criteria” have become the most frequently cited framework for causal inference in epidemiologic studies. However, when Hill published his causal guidelines—just 12 years after the double-helix model for DNA was first suggested and 25 years before the Human Genome Project began—disease causation was understood on a more elementary level than it is today. Advancements in genetics, molecular biology, toxicology, exposure science, and statistics have increased our analytical capabilities for exploring potential cause-and-effect relationships, and have resulted in a greater understanding of the complexity behind human disease onset and progression. These additional tools for causal inference necessitate a re-evaluation of how each Bradford Hill criterion should be interpreted when considering a variety of data types beyond classic epidemiology studies. Herein, we explore the implications of data integration on the interpretation and application of the criteria. Using examples of recently discovered exposure–response associations in human disease, we discuss novel ways by which researchers can apply and interpret the Bradford Hill criteria when considering data gathered using modern molecular techniques, such as epigenetics, biomarkers, mechanistic toxicology, and genotoxicology.

The impact of childhood vaccines on bacterial carriage in the nasopharynx: a longitudinal study

Abstract: Background: There is increasing evidence that childhood vaccines have effects that extend beyond their target disease. The objective of this study was to assess the effects of routine childhood vaccines on bacterial carriage in the nasopharynx. Methods: A cohort of children from rural Gambia was recruited at birth and followed up for one year. Nasopharyngeal swabs were taken immediately after birth, every two weeks for the first six months and then every other month. The presence of bacteria in the nasopharynx (Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus) was compared before and after the administration of DTP-Hib-HepB and measles-yellow fever vaccines. Results: A total of 1,779 nasopharyngeal swabs were collected from 136 children for whom vaccination data were available. The prevalence of bacterial carriage was high: 82.2% S. pneumoniae, 30.6%, S.aureus ,2 7.8%H. influenzae. Carriage of H. influenzae (OR =0.36; 95% CI: 0.13, 0.99) and S. pneumoniae (OR =0.25; 95% CI: 0.07, 0.90) were significantly reduced after measles-yellow fever vaccination; while DTP-Hib-HepB had no effect on bacterial carriage.

Sexually transmitted infections among female sex workers tested at STI clinics in the Netherlands, 2006-2013.

Abstract: Background Specialised sexually transmitted infection (STI) clinics in the Netherlands provide STI care for high-risk groups, including female sex workers (FSW), at the clinic and by outreach visiting commercial sex workplaces with a permit. The objective was to investigate the STI positivity rate and determinants of an STI diagnosis among FSW tested by STI clinics in the Netherlands.

Adjustment for physical activity in studies of sedentary behaviour.

Abstract: Sedentary behaviour (too much sitting, as distinct from too little exercise) has emerged as a potentially significant public health issue. Analytically, researchers have reported ‘independent’ associations between sedentary behaviour (SB) and a number of health outcomes by adjusting for physical activity (PA) (and other confounders), and conclude that SB is associated with the outcome even in those who are physically active. However, the logical rationale for why adjustments for PA are required is often not delineated, and as a consequence, PA has been conceptualised as a confounder, an intermediary, and an effect measure modifier—sometimes simultaneously—in studies of SB and health outcomes. This paper discusses the analytical assumptions underlying adjustment for PA in studies of SB and a given outcome, and considers the implications for associations between SB and health.

Satellite-aided survey sampling and implementation in low- and middle-income contexts: a low-cost/low-tech alternative

Abstract: The increasing availability of online maps, satellite imagery, and digital technology can ease common constraints of survey sampling in low- and middle-income countries. However, existing approaches require specialised software and user skills, professional GPS equipment, and/or commercial data sources; they tend to neglect spatial sampling considerations when using satellite maps; and they continue to face implementation challenges analogous to conventional survey implementation methods. This paper presents an alternative way of utilising satellite maps and digital aides that aims to address these challenges. The case studies of two rural household surveys in Rajasthan (India) and Gansu (China) compare conventional survey sampling and implementation techniques with the use of online map services such as Google, Bing, and HERE maps. Modern yet basic digital technology can be integrated into the processes of preparing, implementing, and monitoring a rural household survey. Satellite-aided systematic random sampling enhanced the spatial representativeness of the village samples and entailed savings of approximately £4000 compared to conventional household listing, while reducing the duration of the main survey by at least 25 %. This low-cost/low-tech satellite-aided survey sampling approach can be useful for student researchers and resource-constrained research projects operating in low- and middle-income contexts with high survey implementation costs. While achieving transparent and efficient survey implementation at low costs, researchers aiming to adopt a similar process should be aware of the locational, technical, and logistical requirements as well as the methodological challenges of this strategy.

County-level hurricane exposure and birth rates: application of difference-in-differences analysis for confounding control

Abstract: Epidemiological analyses of aggregated data are often used to evaluate theoretical health effects of natural disasters. Such analyses are susceptible to confounding by unmeasured differences between the exposed and unexposed populations. To demonstrate the difference-in-difference method our population included all recorded Florida live births that reached 20 weeks gestation and conceived after the first hurricane of 2004 or in 2003 (when no hurricanes made landfall). Hurricane exposure was categorized using ≥74 mile per hour hurricane wind speed as well as a 60 km spatial buffer based on weather data from the National Oceanic and Atmospheric Administration. The effect of exposure was quantified as live birth rate differences and 95 % confidence intervals [RD (95 % CI)]. To illustrate sensitivity of the results, the difference-in-differences estimates were compared to general linear models adjusted for census-level covariates. This analysis demonstrates difference-in-differences as a method to control for time-invariant confounders investigating hurricane exposure on live birth rates. Difference-in-differences analysis yielded consistently null associations across exposure metrics and hurricanes for the post hurricane rate difference between exposed and unexposed areas (e.g., Hurricane Ivan for 60 km spatial buffer [−0.02 births/1000 individuals (−0.51, 0.47)]. In contrast, general linear models suggested a positive association between hurricane exposure and birth rate [Hurricane Ivan for 60 km spatial buffer (2.80 births/1000 individuals (1.94, 3.67)] but not all models. Ecological studies of associations between environmental exposures and health are susceptible to confounding due to unmeasured population attributes. Here we demonstrate an accessible method of control for time-invariant confounders for future research.

Bayesian models as a unified approach to estimate relative risk (or prevalence ratio) in binary and polytomous outcomes

Abstract: Disadvantages have already been pointed out on the use of odds ratio (OR) as a measure of association for designs such as cohort and cross sectional studies, for which relative risk (RR) or prevalence ratio (PR) are preferable. The model that directly estimates RR or PR and correctly specifies the distribution of the outcome as binomial is the log-binomial model, however, convergence problems occur very often. Robust Poisson regression also estimates these measures but it can produce probabilities greater than 1. In this paper, the use of Bayesian approach to solve the problem of convergence of the log-binomial model is illustrated. Furthermore, the method is extended to incorporate dependent data, as in cluster clinical trials and studies with multilevel design, and also to analyse polytomous outcomes. Comparisons between methods are made by analysing four data sets. In all cases analysed, it was observed that Bayesian methods are capable of estimating the measures of interest, always within the correct parametric space of probabilities.

What's more general than a whole population?

Abstract: Statistical inference is commonly said to be inapplicable to complete population studies, such as censuses, due to the absence of sampling variability. Nevertheless, in recent years, studies of whole populations, e.g., all cases of a certain cancer in a given country, have become more common, and often report p values and confidence intervals regardless of such concerns. With reference to the social science literature, the current paper explores the circumstances under which statistical inference can be meaningful for such studies. It concludes that its use implicitly requires a target population which is wider than the whole population studied — for example future cases, or a supranational geographic region — and that the validity of such statistical analysis depends on the generalizability of the whole to the target population.

Pilgrims and MERS-CoV: what's the risk?

Abstract: The risk of Middle East Respiratory Syndrome Coronavirus spreading globally is worrying, given the annual mass gathering of the Hajj and the year-long influx of pilgrims undertaking the Umrah. Based on the incidence in Saudi Arabia since June 2012, the most likely scenario given recent pilgrim numbers is estimated to be one case per Hajj, and three Umrah pilgrims per year, but which could plausibly reach seven and ten pilgrims respectively. In addition to the 2015 Hajj, national surveillance systems should be on the alert for the low but long-lasting risk of infected pilgrims returning from the Umrah throughout the year.

High-frequency use of corrections, health, and social services, and association with mental illness and substance use

Abstract: A subgroup of individuals becomes entrenched in a “revolving door” involving corrections, health, and social welfare services. Little research has investigated the numbers of people that are in frequent contact with multiple public agencies, the costs associated with these encounters, or the characteristics of the people concerned. The present study used linked administrative data to examine offenders who were also very frequent users of health and social services. We investigated the magnitude and distribution of costs attributable to different categories of service for those in the top 10 % of sentences to either community or custodial settings. We hypothesized that the members of these subgroups would be significantly more likely to have substance use and other mental disorders than other members of the offender population. Data were linked across agencies responsible for services to the entire population of British Columbia spanning justice, health, and income assistance. Individuals were eligible for inclusion in the study if they were sentenced at least once in the Vancouver Provincial Court between 2003 and 2012. We examined the subset of participants who fell within the top 10 % of sentences and at least two of the following service categories: community physician services; hospital days; pharmaceutical costs; or income assistance between 2007 and 2012. We examined two groups of offenders separately (those in the top ten percent sentenced to community supervision or to custody) due to differences in time at risk and availability to receive community-based services. From more than 14,000 offenders sentenced in Vancouver’s Downtown Eastside, very High Frequency service users associated with community (n = 216) and custody (n = 107) sentences incurred average attributable public service costs of $168,000 and $247,000 respectively over a 5-year period of observation. Health-related costs for both groups were over $80,000 per person, primarily associated with hospital admissions. Across both groups, 99 % had been diagnosed with at least one mental disorder and over 80 % had co-occurring substance use and another mental disorder. A subset of offenders with concurrent psychiatric disorders receives extremely high levels of service from health, social welfare, and justice sectors in close temporal succession. Members of this subpopulation require targeted supports in order to produce positive outcomes and prevent the perpetuation of a costly and ineffective revolving door.

Socioeconomic disadvantage in childhood as a predictor of excessive gestational weight gain and obesity in midlife adulthood

Abstract: Background Lower childhood socioeconomic position is associated with greater risk of adult obesity among women, but not men. Pregnancy-related weight changes may contribute to this gender difference. The objectives of this study were to determine the associations between: 1. childhood socioeconomic disadvantage and midlife obesity; 2. excessive gestational weight gain (GWG) and midlife obesity; and 3. childhood socioeconomic disadvantage and excessive GWG, among a representative sample of childbearing women.

Vulnerability of Brazilian municipalities to hantavirus infections based on multi-criteria decision analysis.

Abstract: Hantavirus infection is an emerging zoonosis transmitted by wild rodents. In Brazil, high case-fatality rates among humans infected with hantavirus are of serious concern to public health authorities. Appropriate preventive measures partly depend on reliable knowledge about the geographical distribution of this disease. Incidence of hantavirus infections in Brazil (1993–2013) was analyzed. Epidemiological, socioeconomic, and demographic indicators were also used to classify cities’ vulnerability to disease by means of multi-criteria decision analysis (MCDA). From 1993 to 2013, 1752 cases of hantavirus were registered in 16 Brazilian states. The highest incidence of hantavirus was observed in the states of Mato Grosso (0.57/100,000) and Santa Catarina (0.13/100,000). Based on MCDA analysis, municipalities in the southern, southeastern, and midwestern regions of Brazil can be classified as highly vulnerable. Most municipalities in northern and northeastern Brazil were classified as having low vulnerability to hantavirus cardiopulmonary syndrome. Although most human infections by hantavirus registered in Brazil occurred in the southern region of the country, a greater vulnerability to hantavirus was found in the Brazilian Midwest. This result reflects the need to strengthen surveillance where the disease has thus far gone unreported.

Development of an international scale of socio-economic position based on household assets

Abstract: The importance of studying associations between socio-economic position and health has often been highlighted. Previous studies have linked the prevalence and severity of lung disease with national wealth and with socio-economic position within some countries but there has been no systematic evaluation of the association between lung function and poverty at the individual level on a global scale. The BOLD study has collected data on lung function for individuals in a wide range of countries, however a barrier to relating this to personal socio-economic position is the need for a suitable measure to compare individuals within and between countries. In this paper we test a method for assessing socio-economic position based on the scalability of a set of durable assets (Mokken scaling), and compare its usefulness across countries of varying gross national income per capita. Ten out of 15 candidate asset questions included in the questionnaire were found to form a Mokken type scale closely associated with GNI per capita (Spearman’s rank rs = 0.91, p = 0.002). The same set of assets conformed to a scale in 7 out of the 8 countries, the remaining country being Saudi Arabia where most respondents owned most of the assets. There was good consistency in the rank ordering of ownership of the assets in the different countries (Cronbach’s alpha = 0.96). Scores on the Mokken scale were highly correlated with scores developed using principal component analysis (rs = 0.977). Mokken scaling is a potentially valuable tool for uncovering links between disease and socio-economic position within and between countries. It provides an alternative to currently used methods such as principal component analysis for combining personal asset data to give an indication of individuals’ relative wealth. Relative strengths of the Mokken scale method were considered to be ease of interpretation, adaptability for comparison with other datasets, and reliability of imputation for even quite large proportions of missing values.

Quantitatively evaluating the effect of social barriers: a case-control study of family members' opposition and women's intention to use contraception in Pakistan.

Abstract: Background Uptake of family planning services in Pakistan has remained slow over the past decade despite a rapid increase in availability and awareness, indicating that social barriers may be preventing uptake. Social barriers such as opposition by family members have largely been studied qualitatively; there is a lack of quantitative evidence about the effect of different family members’ opposition on women’s intention to use contraceptives. The objective of this study was to quantitatively evaluate the effect of family members’ opposition to family planning on intention to use contraception amongst poor women in Pakistan who have physical access to family planning services.

Design and implementation of a sexual health intervention for migrant construction workers situated in Shanghai, China

Abstract: China’s growing population of internal migrants has exceeded 236 million. Driven by rapid development and urbanization, this extreme population mobility creates opportunities for transmission of HIV and sexually-transmitted infections (STI). Large numbers of rural migrants flock to megacities such as Shanghai in search of employment. Although migrants constitute a key population at heightened risk of acquiring HIV or an STI, there is a lack of easily accessible sexual health services available for them. In response, we designed a short, inexpensive sexual health intervention that sought to improve HIV and STI knowledge, while reducing stigma, risky sexual behaviour, and sexual transmission of HIV and STI among migrant construction workers (MCW) situated in Shanghai, China. We implemented a three-armed, community-randomized trial spread across three administrative districts of Shanghai. The low-intensity intervention included educational pamphlets. The medium-intensity intervention included pamphlets, posters, and videos. The high-intensity intervention added group and individual counselling sessions. Across 18 construction sites, 1871 MCW were allocated at baseline to receive one intervention condition. Among baseline participants, 1304 workers were retained at 3-months, and 1013 workers were retained at 6-months, representing a total of 579 person-years of follow-up. All workers, regardless of participation, had access to informational materials even if they did not participate in the evaluation. Overall outputs included: 2284 pamphlets distributed, 720 posters displayed, 672 h of video shown, 376 participants accessed group counselling, and 61 participants attended individual counselling sessions. A multivariable analysis of participation found that men (aOR = 2.2; 95 % CI 1.1, 4.1; p = 0.036), workers situated in Huangpu district (aOR = 5.0; 95 % CI 2.6, 9.5; p < 0.001), and those with a middle school education (aOR = 1.9; 95 % CI 1.2, 3.0; p = 0.01) were more likely to have participated in intervention activities. A brief educational intervention that prioritized ease of delivery to a highly mobile workforce was feasible and easily accessed by participants. Routine implementation of sexual health interventions in workplaces that employ migrant labour have the potential to make important contributions toward improving HIV and STI outcomes among migrant workers in China’s largest cities.

A reference relative time-scale as an alternative to chronological age for cohorts with long follow-up

Abstract: Epidemiologists have debated the appropriate time-scale for cohort survival studies; chronological age or time-on-study being two such time-scales. Importantly, assessment of risk factors may depend on the choice of time-scale. Recently, chronological or attained age has gained support but a case can be made for a ‘reference relative time-scale’ as an alternative which circumvents difficulties that arise with this and other scales. The reference relative time of an individual participant is the integral of a reference population hazard function between time of entry and time of exit of the individual. The objective here is to describe the reference relative time-scale, illustrate its use, make comparison with attained age by simulation and explain its relationship to modern and traditional epidemiologic methods. A comparison was made between two models; a stratified Cox model with age as the time-scale versus an un-stratified Cox model using the reference relative time-scale. The illustrative comparison used a UK cohort of cotton workers, with differing ages at entry to the study, with accrual over a time period and with long follow-up. Additionally, exponential and Weibull models were fitted since the reference relative time-scale analysis need not be restricted to the Cox model. A simulation study showed that analysis using the reference relative time-scale and analysis using chronological age had very similar power to detect a significant risk factor and both were equally unbiased. Further, the analysis using the reference relative time-scale supported fully-parametric survival modelling and allowed percentile predictions and mortality curves to be constructed. The reference relative time-scale was a viable alternative to chronological age, led to simplification of the modelling process and possessed the defined features of a good time-scale as defined in reliability theory. The reference relative time-scale has several interpretations and provides a unifying concept that links contemporary approaches in survival and reliability analysis to the traditional epidemiologic methods of Poisson regression and standardised mortality ratios. The community of practitioners has not previously made this connection.

Is uncertainty in complex disease epidemiology resolvable

Abstract: The imposed limitations on what we can know about nature have been long recognized. Yet in the field of epidemiology a futile search for lifestyle-related risk factors for common chronic diseases continues unabated. This has led to the production of a growing body of evidence about potential lifestyle risk factors that tend to be marginal, contradictory, irreproducible, or hard to interpret. While epidemiologists are calling for a more refined methodology, I argue that our limitation in studying complex diseases is insurmountable. This is because the study of lifestyle-related small risks requires accurate measurement of multiple behaviors-exposures over a long period of time. It is also because in complex systems such as population’s health, the effect of rich interactions between its parts cannot be predicted based on traditional causal models of epidemiology. Within complex systems, understanding the interactions between system components can be more important than the contribution of each to disease risk.

Children and youth with ‘unspecified injury to the head’: implications for traumatic brain injury research and surveillance

Abstract: The case definition for traumatic brain injury (TBI) often includes ‘unspecified injury to the head’ diagnostic codes. However, research has shown that the inclusion of these codes leads to false positives. As such, it is important to determine the degree to which inclusion of these codes affect the overall numbers and profiles of the TBI population. The objective of this paper was to profile and compare the demographic and clinical characteristics, intention and mechanism of injury, and discharge disposition of hospitalized children and youth aged 19 years and under using (1) an inclusive TBI case definition that included ‘unspecified injury to the head’ diagnostic codes, (2) a restricted TBI case definition that excluded ‘unspecified injury to the head ‘diagnostic codes, and (3) the ‘unspecified injury to the head’ only case definition. The National Ambulatory Care Reporting System and the Discharge Abstract Database from Ontario, Canada, were used to identify cases between fiscal years 2003/04 and 2009/10. The rate of TBI episodes of care using the inclusive case definition for TBI (2,667.2 per 100,000) was 1.65 times higher than that of the restricted case definition (1,613.3 per 100,000). ‘Unspecified injury to the head’ diagnostic codes made up of 39.5 % of all cases identified with the inclusive case definition. Exclusion of ‘unspecified injury to the head’ diagnostic code in the TBI case definition resulted in a significantly higher proportion of patients in the intensive care units (p < .0001; 18.5 % vs. 22.2 %) and discharged to a non-home setting (p < .0001; 9.9 % vs. 11.6 %). Inclusion of ‘unspecified injury to the head’ diagnostic codes resulted in significant changes in numbers, healthcare use, and causes of TBI. Careful consideration of the inclusion of ‘unspecified injury to the head’ diagnostic codes in the case definition of TBI for the children and youth population is important, as it has implications for the numbers used for policy, resource allocation, prevention, and planning of healthcare services. This paper can inform future work on reaching consensus on the diagnostic codes for defining TBI in children and youth.

Assessing bias in administrative database studies of RotaTeq vaccine completion due to exclusion of subjects with incomplete follow-up.

Abstract: RotaTeq® pentavalent human rotavirus vaccine (RV5) is effective against rotavirus illness and rotavirus-related hospitalizations and death. Effectiveness depends on adherence to the dosing schedule, which includes 3 doses at ages 2, 4 and 6 months. Two studies have used automated claims databases to estimate the proportion of vaccinated infants who complete the dosing schedule, but excluded from analysis vaccinated infants who were not enrolled in the database for a sufficient period to observe all 3 doses. Restricting study populations based on duration of follow-up can introduce bias if a large number of subjects are excluded due to insufficient follow-up, and if their outcomes differ from subjects who are included. To address the possibility that exclusions may have been extensive and led to biased estimates of completion rates, we conducted a claims database analysis in the HealthCore Integrated Research DatabaseSM to evaluate the proportion of rotavirus vaccinated infants who completed the 3 dose series of RV5. We evaluated potential error introduced by restricting analyses to infants with complete follow-up by estimating completion rates among infants with complete follow-up, and using Kaplan-Meier analyses to estimate completion rates including infants with incomplete follow-up. The inclusion criterion requiring continuous enrollment for the first year of life resulted in only 108,533 (40%) of 233,143 vaccinated infants from 2006–2012 being included in the analysis. After relaxing inclusion criteria, we were able to include 86% of vaccinated infants. The estimated completion rate among infants with continuous enrollment from birth through the first year of life was 78.1% (95% confidence limits [CLs] 77.8%, 78.3%), and among the expanded population the estimated completion rate was 77.4% (95% CLs 77.2%, 77.6%). These results indicate that most infants were not followed in the database through the first year of life, but the impact of excluding infants with incomplete follow-up was negligible when assessing RV5 completion rates for this commercially insured population. Nonetheless, to increase the size of study populations and reduce the potential for bias, it is preferable to include subjects with incomplete follow-up in automated database analyses, and adopt more robust approaches to defining and analyzing study populations that account for missing data.