Latency and time-dependent exposure in a case-control study

Detailed historical data are elicited often from subjects in retrospective studies, yielding time-dependent measures of exposures. Investigation of a hypothesized period of latency can be made by examining disease/exposure relationships in multiple time windows, either along the age or time-before diagnosis axes. We suggest splitting the data into many time intervals and separately fitting regression models tothe available data in each interval. Covariances between estimated coefficients from different intervals are empirically estimated, and used for assessing variability of specified functions of the time-specific coefficients. Alternative methods of interval formation and their consequences are discussed. We apply these methods to a French case-control study of oral contraceptive use and cervical cancer incidence, and compare the results to those of standard analyses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29651/1/0000740.pd

Parametric frailty models for clustered data with arbitrary censoring: application to effect of male circumcision on HPV clearance

Background In epidemiological studies, subjects are often followed for a period during which study outcomes are measured at selected time points, such as by diagnostic testing performed on biological samples collected at each visit. Although test results may indicate the presence or absence of a disease or condition, they cannot provide information on when exactly it occurred. Such study designs generate arbitrarily censored time-to-event data, which can include left, interval and right censoring. Adding to this complexity, the data may be clustered such that observations within the same cluster are not independent, such as time to recovery of an infectious disease of family or community members. This data structure is observed when evaluating circumcision\u27s effect on clearance of penile high risk human papillomavirus (HR-HPV) infections using data collected from the male circumcision(MC) trial conducted in Rakai, Uganda, where the multiple infections within individual and HPV testings performed at trial follow-up visits gave rise to the clustered data with arbitrary censoring. Methods We describe the use of parametric proportional hazards frailty models and accelerated failure time frailty models to examine the relationship between explanatory variables and the survival outcomes that are subject to arbitrary censoring, while accounting for the correlation within clusters. Standard software such as SAS can be used for parameter estimation. Results Circumcision\u27s effect on HPV infection was a secondary end point in the Rakai MC trial, and HPV genotyping was conducted for penile samples of a subset of trial participants collected at enrollment, 6, 12 and 24-month follow up visits. At enrollment, 36.7% intervention arm men (immediate circumcision) and 36.6% control arm men (delayed circumcision at 2 years) were infected with HR-HPV, with the number of infections per man being 1-5. The proposed models were used to examine whether MC facilitated clearance of the prevalent infections. Results show that clearance of multiple infections within each man is highly correlated, and clearance was 60% faster if a man was circumcised. Conclusions Parametric frailty models provide viable ways to study the relationship between exposure variables and clustered survival outcome that is subject to arbitrary censoring, as is often observed in HPV epidemiology studies

Alcohol and traffic safety: A sensitivity analysis of data from composite sources

Risk factors associated with single-vehicle driver fatalities are explored in a sensitivity analysis of data from composite sources. Information on fatalities was taken from the Federal Accident Reporting System data base for 1976-1981. Characteristics of the driving population were given by the 1973 National Roadside Breath Testing Survey (Wolfe 1974). Using Bayes theorem and logistic regression analysis, the effect of changing driver characteristics on the probability of a fatality was explored. The method used is proposed for a case-control study in which the controls may not accurately represent the population from which the cases were drawn. Risk factors identified are generally in agreement with previous reports.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28061/1/0000500.pd

Bartlett correction factors in logistic regression models

Bartlett correction factors for likelihood ratio tests of parameters in conditional and unconditional logistic regression models are calculated. The resulting tests are compared to the Wald, likelihood ratio, and score tests, and a test proposed by Moolgavkar and Venzon in Modern Statistical Methods in Chronic Disease Epidemiology. (Wiley, New York, 1986).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31011/1/0000686.pd

Risk factors and case management of acute diarrhoea in North Gondar zone, Ethiopia

In Ethiopia, evidence is lacking about maternal care-taking and environmental risk factors that contribute to acute diarrhoea and the case management of diarrhoea. The aim of this study was to identify the risk factors and to understand the management of acute diarrhoea. A pretested structured questionnaire was used for interviewing mothers of 440 children in a prospective, matched, case-control study at the University of Gondar Referral and Teaching Hospital in Gondar, Ethiopia. Results of multivariate analysis demonstrated that children who were breastfed and not completely weaned and mothers who were farmers were protective factors; risk factors for diarrhoea included sharing drinking-water and introducing supplemental foods. Children presented with acute diarrhoea for 3.9 days with 4.3 stools per day. Mothers usually did not increase breastmilk and other fluids during diarrhoea episodes and generally did not take children with diarrhoea to traditional healers. Incorporating messages about the prevention and treatment of acute diarrhoea into child-health interventions will help reduce morbidity and mortality associated with this disease

Cluster randomized controlled trial analysis at the cluster level: The clan command.

In this article, we introduce a new command, clan, that conducts a cluster-level analysis of cluster randomized trials. The command simplifies adjusting for individual- and cluster-level covariates and can also account for a stratified design. It can be used to analyze a continuous, binary, or rate outcome

Taenia solium Cysticercosis Hotspots Surrounding Tapeworm Carriers: Clustering on Human Seroprevalence but Not on Seizures

Cysticercosis is a parasitic disease caused by the tapeworm Taenia solium, common in areas with limited sanitation or with migration from these populations. The adult parasite is hosted in the human intestine and releases large numbers of eggs with the feces. Human beings sometimes ingest eggs due to poor hygiene, and then eggs sometimes lodge on the brain and after a few years can cause intense headaches and seizures. During a study in seven rural communities in Peru, individuals exposed to T. solium eggs were often tightly clustered at the homes or immediate surrounding of the carriers of the adult parasite. However, no aggregation of cases of seizures was found near carriers. It appears that seizures do not cluster around carriers because several years pass between exposure to T. solium eggs and the onset of seizures. During these years the adult parasite has probably died or people had moved within or even outside their communities. Therefore, only a partial understanding of the epidemiology of cysticercosis is gained by studying seizures cases

Mobile phone-delivered reminders and incentives to improve childhood immunisation coverage and timeliness in Kenya (M-SIMU): a cluster randomised controlled trial

Background As mobile phone access continues to expand globally, opportunities exist to leverage these technologies to support demand for immunisation services and improve vaccine coverage. We aimed to assess whether short message service (SMS) reminders and monetary incentives can improve immunisation uptake in Kenya. Methods In this cluster-randomised controlled trial, villages were randomly and evenly allocated to four groups: control, SMS only, SMS plus a 75 Kenya Shilling (KES) incentive, and SMS plus 200 KES (85 KES = USD$1). Caregivers were eligible if they had a child younger than 5 weeks who had not yet received a first dose of pentavalent vaccine. Participants in the intervention groups received SMS reminders before scheduled pentavalent and measles immunisation visits. Participants in incentive groups, additionally, received money if their child was timely immunised (immunisation within 2 weeks of the due date). Caregivers and interviewers were not masked. The proportion of fully immunised children (receiving BCG, three doses of polio vaccine, three doses of pentavalent vaccine, and measles vaccine) by 12 months of age constituted the primary outcome and was analysed with logbinomial regression and General Estimating Equations to account for correlation within clusters. This trial is registered with ClinicalTrials.gov, number NCT01878435. Findings Between Oct 14, 2013, and Oct 17, 2014, we enrolled 2018 caregivers and their infants from 152 villages into the following four groups: control (n=489), SMS only (n=476), SMS plus 75 KES (n=562), and SMS plus 200 KES (n=491). Overall, 1375 (86%) of 1600 children who were successfully followed up achieved the primary outcome, full immunisation by 12 months of age (296 [82%] of 360 control participants, 332 [86%] of 388 SMS only participants, 383 [86%] of 446 SMS plus 75 KES participants, and 364 [90%] of 406 SMS plus 200 KES participants). Children in the SMS plus 200 KES group were significantly more likely to achieve full immunisation at 12 months of age (relative risk 1·09, 95% CI 1·02–1·16, p=0·014) than children in the control group. Interpretation In a setting with high baseline immunisation coverage levels, SMS reminders coupled with incentives significantly improved immunisation coverage and timeliness. Given that global immunisation coverage levels have stagnated around 85%, the use of incentives might be one option to reach the remaining 15%

Effects of improved complementary feeding and improved water, sanitation and hygiene on early child development among HIV-exposed children: substudy of a cluster randomised trial in rural Zimbabwe.

Introduction: HIV-exposed uninfected children may be at risk of poor neurodevelopment. We aimed to test the impact of improved infant and young child feeding (IYCF) and improved water, sanitation and hygiene (WASH) on early child development (ECD) outcomes. Methods: Sanitation Hygiene Infant Nutrition Efficacy was a cluster randomised 2×2 factorial trial in rural Zimbabwe ClinicalTrials.gov NCT01824940). Pregnant women were eligible if they lived in study clusters allocated to standard-of-care (SOC; 52 clusters); IYCF (20 g small-quantity lipid-based nutrient supplement/day from 6 to 18 months, complementary feeding counselling; 53 clusters); WASH (pit latrine, 2 hand-washing stations, liquid soap, chlorine, play space, hygiene counselling; 53 clusters) or IYCF +WASH (53 clusters). Participants and fieldworkers were not blinded. ECD was assessed at 24 months using the Malawi Developmental Assessment Tool (MDAT; assessing motor, cognitive, language and social skills); MacArthur Bates Communication Development Inventory (assessing vocabulary and grammar); A-not-B test (assessing object permanence) and a self-control task. Intention-to-treat analyses were stratified by maternal HIV status. Results: Compared with SOC, children randomised to combined IYCF +WASH had higher total MDAT scores (mean difference +4.6; 95% CI 1.9 to 7.2) and MacArthur Bates vocabulary scores (+8.5 words; 95% CI 3.7 to 13.3), but there was no evidence of effects from IYCF or WASH alone. There was no evidence that that any intervention impacted object permanence or self-control. Conclusions: Combining IYCF and WASH interventions significantly improved motor, language and cognitive development in HIV-exposed children. Trial registration number: NCT01824940