We present a model for longitudinal measures of fetal weight as a function of gestational age. We use a linear mixed model, with a Box-Cox transformation of fetal weight values, and restricted cubic splines, in order to flexibly but parsimoniously model median fetal weight. We systematically compare our model to other proposed approaches. All proposed methods are shown to yield similar median estimates, as evidenced by overlapping pointwise confidence bands, except after 40 completed weeks, where our method seems to produce estimates more consistent with observed data. Sex-based stratification affects the estimates of the random effects variance-covariance structure, without significantly changing sex-specific fitted median values. We illustrate the benefits of including sex-gestational age interaction terms in the model over stratification. The comparison leads to the conclusion that the selection of a model for fetal weight for gestational age can be based on the specific goals and configuration of a given study without affecting the precision or value of median estimates for most gestational ages of interest.

The authors tested whether the relation between gestational weight gain (GWG) and 5 adverse pregnancy outcomes (small-for-gestational-age (SGA) birth, large-for-gestational-age (LGA) birth, spontaneous preterm birth, indicated preterm birth, and unplanned cesarean delivery) differed according to maternal race/ethnicity, smoking, parity, age, and/or height. They also evaluated whether GWG guidelines should be modified for special populations by studying GWG and risk of at least 1 adverse outcome within different subgroups. Data came from a cohort of 23,362 normal-weight mothers who delivered singletons at Magee-Womens Hospital in Pittsburgh, Pennsylvania (2003–2008). Adequacy of GWG was defined as observed GWG divided by recommended GWG. The synergy analysis found that the combination of smoking, black race/ethnicity, primiparity, or short height with poor GWG was associated with an excess risk of SGA birth, while high GWG combined with each of these characteristics diminished risk of LGA birth in comparison with the same GWG among the women's counterparts. Nevertheless, there were no significant or meaningful differences in the risk of at least 1 adverse outcome between the GWG recommended by the Institute of Medicine in 2009 and the GWG that minimized risk of the composite outcome. These findings do not support the tailoring of GWG guidelines on the basis of a mother's smoking status, race/ethnicity, parity, age, or height among normal-weight women.

Objective

To synthesise estimates of the prevalence of cessation attempts among adolescent smokers generally, and according to age and level of cigarette consumption.

Data sources

PubMed, ERIC, and PsychInfo databases and Internet searches of central data collection agencies.

Study selection

National population‐based studies published in English between 1990 and 2005 reporting the prevalence, frequency and/or duration of cessation attempts among smokers aged ⩾10 to <20 years.

Data extraction

Five reviewers determined inclusion criteria for full‐text reports. One reviewer extracted data on the design, population characteristics and results from the reports.

Data synthesis

In total, 52 studies conformed to the inclusion criteria. The marked heterogeneity that characterised the study populations and survey questions precluded a meta‐analysis. Among adolescent current smokers, the median 6‐month, 12‐month and lifetime cessation attempt prevalence was 58% (range: 22–73%), 68% (range 43–92%) and 71% (range 28–84%), respectively. More than half had made multiple attempts. Among smokers who had attempted cessation, the median prevalence of relapse was 34, 56, 89 and 92% within 1 week, 1 month, 6 months, and 1 year, respectively, following the longest attempt. Younger (age<16 years) and non‐daily smokers experienced a similar or higher prevalence of cessation attempts compared with older (age ⩾16 years) or daily smokers. Moreover, the prevalence of relapse by 6 months following the longest cessation attempt was similar across age and smoking frequency.

Conclusions

The high prevalence of cessation attempts and relapse among adolescent smokers extends to young adolescents and non‐daily smokers. Cessation surveillance, research and program development should be more inclusive of these subgroups.

According to the authors, time-modified confounding occurs when the causal relation between a time-fixed or time-varying confounder and the treatment or outcome changes over time. A key difference between previously described time-varying confounding and the proposed time-modified confounding is that, in the former, the values of the confounding variable change over time while, in the latter, the effects of the confounder change over time. Using marginal structural models, the authors propose an approach to account for time-modified confounding when the relation between the confounder and treatment is modified over time. An illustrative example and simulation show that, when time-modified confounding is present, a marginal structural model with inverse probability-of-treatment weights specified to account for time-modified confounding remains approximately unbiased with appropriate confidence limit coverage, while models that do not account for time-modified confounding are biased. Correct specification of the treatment model, including accounting for potential variation over time in confounding, is an important assumption of marginal structural models. When the effect of confounders on either the treatment or outcome changes over time, time-modified confounding should be considered.

Infants who receive prolonged and exclusive breastfeeding grow more slowly during the first year of life than those who do not. However, infant feeding and growth are dynamic processes in which feeding may affect growth, and prior growth and size may also influence subsequent feeding decisions. The authors carried out an observational analysis of 17,046 Belarusian infants who were recruited between June 1996 and December 1997 and who participated in a cluster-randomized trial of a breastfeeding promotion intervention. To assess the effects of infant size on subsequent feeding, the authors restricted the analysis to infants breastfed (or exclusively breastfed) at the beginning of each follow-up interval and examined associations between weight or length at the beginning of the interval and weaning or discontinuation of exclusive breastfeeding by the end of the interval. Smaller size (especially weight for age) was strongly and statistically significantly associated with increased risks of subsequent weaning and of discontinuing exclusive breastfeeding (adjusted odds ratios = 1.2–1.6), especially between 2 and 6 months, even after adjusment for potential confounding factors and clustered measurement. The authors speculate that similar dynamic processes involving infant crying, other signs of hunger, and supplementation/weaning undermine causal inferences about the “effect” of prolonged and exclusive breastfeeding on slower infant growth.

Background: Health plans must prioritize disease management efforts to reduce hospitalization and mortality rates in heart failure patients.

Methods and Results: We developed a risk model to predict the 5-year risk of mortality or hospitalization for heart failure among patients at a large health maintenance organization. We identified 4696 patients who had an echocardiogram and a heart failure diagnosis from 1999 to 2004.

We observed a 56% five-year risk of hospitalization for heart failure or death (95% confidence interval, 54% to 58%). The hazard ratios for echocardiogram data contributed statistically significantly to the model, but echocardiogram findings did not improve our ability to predict risk accurately once we had accounted for demographic characteristics and clinical findings. A more complex model demonstrated a modest capacity to accurately predict risk. Our risk model discriminated the highest- and lowest-risk patients with limited success–the observed risk was 3 times higher in the highest risk quintile, compared with the lowest-risk quintile.

Conclusions: Using data available from electronic health records, we developed a series of risk-prediction models for poor outcomes in patients with heart failure. We found that a relatively simple model is as effective as a more complex model, but that all the models predict with only modest accuracy. Until better prediction variables are available for heart failure patients, our prediction model may be valuable for prioritizing centralized disease management program efforts by stratifying patients according to their absolute risk of poor outcomes.

That conditioning on a common effect of exposure and outcome may cause selection, or collider-stratification, bias is not intuitive. We provide two hypothetical examples to convey concepts underlying bias due to conditioning on a collider. In the first example, fever is a common effect of influenza and consumption of a tainted egg-salad sandwich. In the second example, case-status is a common effect of a genotype and an environmental factor. In both examples, conditioning on the common effect imparts an association between two otherwise independent variables; we call this selection bias.

The authors investigated variations in cognitive ability by gestational age among 13,824 children at age 6.5 years who were born at term with normal weight, using data from a prospective cohort recruited in 1996–1997 in Belarus. The mean differences in the Wechsler Abbreviated Scales of Intelligence were examined by gestational age in completed weeks and by fetal growth after controlling for maternal and family characteristics. Compared with the score for those born at 39–41 weeks, the full-scale intelligence quotient (IQ) score was 1.7 points (95% confidence interval (CI): −2.7, −0.7) lower in children born at 37 weeks and 0.4 points (95% CI: −1.1, 0.02) lower at 38 weeks after controlling for confounders. There was also a graded relation in postterm children: a 0.5-points (95% CI: −2.6, 1.6) lower score at 42 weeks and 6.0 points (95% CI: −15.1, 3.1) lower at 43 weeks. Compared with children born large for gestational age (>90th percentile), children born small for gestational age (<10th percentile) had the lowest IQ, followed by those at the 10th–50th percentile and those at the >50th–90th percentile. These findings suggest that, even among healthy children born at term, cognitive ability at age 6.5 years is lower in those born at 37 or 38 weeks and those with suboptimal fetal growth.

Our objective was to examine the association between HIV and HCV discordant infection status and the sharing of drug equipment by injection drug users (IDUs). IDUs were recruited from syringe exchange and methadone treatment programmes in Montreal, Canada. Characteristics of participants and their injecting partners were elicited using a structured questionnaire. Among 159 participants and 245 injecting partners, sharing of syringes and drug preparation equipment did not differ between concordant or discordant partners, although HIV-positive subjects did not share with HIV-negative injectors. Sharing of syringes was positively associated with discordant HIV status (OR = 1.85) and negatively with discordant HCV status (OR = 0.65), but both results were not statistically significant. Sharing of drug preparation equipment was positively associated with both discordant HIV (OR = 1.61) and HCV (OR = 1.18) status, but both results were non-significant. Factors such as large injecting networks, frequent mutual injections, younger age, and male gender were stronger predictors of equipment sharing. In conclusion, IDUs do not appear to discriminate drug equipment sharing partners based at least on their HCV infection status. The results warrant greater screening to raise awareness of infection status, post-test counselling to promote status disclosure among partners, and skill-building to avoid equipment sharing between discordant partners.

Overadjustment is defined inconsistently. This term is meant to describe control (eg, by regression adjustment, stratification, or restriction) for a variable that either increases net bias or decreases precision without affecting bias. We define overadjustment bias as control for an intermediate variable (or a descending proxy for an intermediate variable) on a causal path from exposure to outcome. We define unnecessary adjustment as control for a variable that does not affect bias of the causal relation between exposure and outcome but may affect its precision. We use causal diagrams and an empirical example (the effect of maternal smoking on neonatal mortality) to illustrate and clarify the definition of overadjustment bias, and to distinguish overadjustment bias from unnecessary adjustment. Using simulations, we quantify the amount of bias associated with overadjustment. Moreover, we show that this bias is based on a different causal structure from confounding or selection biases. Overadjustment bias is not a finite sample bias, while inefficiencies due to control for unnecessary variables are a function of sample size.

Summary

The ‘birthweight paradox’ describes the phenomenon whereby birthweight-specific mortality curves cross when stratified on other exposures, most notably cigarette smoking. The paradox has been noted widely in the literature and numerous explanations and corrections have been suggested. Recently, causal diagrams have been used to illustrate the possibility for collider-stratification bias in models adjusting for birthweight. When two variables share a common effect, stratification on the variable representing that effect induces a statistical relation between otherwise independent factors. This bias has been proposed to explain the birthweight paradox.

Causal diagrams may illustrate sources of bias, but are limited to describing qualitative effects. In this paper, we provide causal diagrams that illustrate the birthweight paradox and use a simulation study to quantify the collider-stratification bias under a range of circumstances. Considered circumstances include exposures with and without direct effects on neonatal mortality, as well as with and without indirect effects acting through birthweight on neonatal mortality. The results of these simulations illustrate that when the birthweight-mortality relation is subject to substantial uncontrolled confounding, the bias on estimates of effect adjusted for birthweight may be sufficient to yield opposite causal conclusions, i.e. a factor that poses increased risk appears protective. Effects on stratum-specific birthweight-mortality curves were considered to illustrate the connection between collider-stratification bias and the crossing of the curves. The simulations demonstrate the conditions necessary to give rise to empirical evidence of the paradox.

Summary

Investigators have long puzzled over the observation that low-birthweight babies of smokers tend to fare better than low-birthweight babies of non-smokers. Similar observations have been made with regard to factors other than smoking status, including socio-economic status, race and parity. Use of standardised birthweights, or birthweight z-scores, has been proposed as an approach to resolve the crossing of the curves that is the hallmark of the so-called birthweight paradox. In this paper, we utilise directed acyclic graphs, analytical proofs and an extensive simulation study to consider the use of z-scores of birthweight and their effect on statistical analysis. We illustrate the causal questions implied by inclusion of birthweight in statistical models, and illustrate the utility of models that include birthweight or z-scores to address those questions.

Both analytically and through a simulation study we show that neither birthweight nor z-score adjustment may be used for effect decomposition. The z-score approach yields an unbiased estimate of the total effect, even when collider-stratification would adversely impact estimates from birthweight-adjusted models; however, the total effect could have been estimated more directly with an unadjusted model. The use of z-scores does not add additional information beyond the use of unadjusted models. Thus, the ability of z-scores to successfully resolve the paradoxical crossing of mortality curves is due to an alteration in the causal parameter being estimated (total effect), rather than adjustment for confounding or effect decomposition or other factors.

Michael S Kramer and colleagues suggest that double clustering might explain the negative results of some cluster randomised trials and describe some strategies for avoiding the problem

Contemporary fetal growth standards are created by using theoretical properties (percentiles) of birth weight (for gestational age) distributions. The authors used a clinically relevant, outcome-based methodology to determine if separate fetal growth standards are required for singletons and twins. All singleton and twin livebirths between 36 and 42 weeks’ gestation in the United States (1995–2002) were included, after exclusions for missing information and other factors (n = 17,811,922). A birth weight range was identified, at each gestational age, over which serious neonatal morbidity and neonatal mortality rates were lowest. Among singleton males at 40 weeks, serious neonatal morbidity/mortality rates were lowest between 3,012 g (95% confidence interval (CI): 3,008, 3,018) and 3,978 g (95% CI: 3,976, 3,980). The low end of this optimal birth weight range for females was 37 g (95% CI: 21, 53) less. The low optimal birth weight was 152 g (95% CI: 121, 183) less for twins compared with singletons. No differences were observed in low optimal birth weight by period (1999–2002 vs. 1995–1998), but small differences were observed for maternal education, race, parity, age, and smoking status. Patterns of birth weight-specific serious neonatal morbidity/neonatal mortality support the need for plurality-specific fetal growth standards.

Secondary syringe exchange (SSE) refers to the exchange of sterile syringes between injection drug users (IDUs). To date there has been limited examination of SSE in relation to the social networks of IDUs. This study aimed to identify characteristics of drug injecting networks associated with the receipt of syringes through SSE. Active IDUs were recruited from syringe exchange and methadone treatment programs in Montreal, Canada, between April 2004 and January 2005. Information on each participant and on their drug-injecting networks was elicited using a structured, interviewer-administered questionnaire. Subjects’ network characteristics were examined in relation to SSE using regression models with generalized estimating equations. Of 218 participants, 126 were SSE recipients with 186 IDUs in their injecting networks. The 92 non-recipients reported 188 network IDUs. Networks of SSE recipients and non-recipients were similar with regard to network size and demographics of network members. In multivariate analyses adjusted for age and gender, SSE recipients were more likely than non-recipients to self-report being HIV-positive (OR = 3.56 [1.54–8.23]); require or provide help with injecting (OR = 3.74 [2.01–6.95]); have a social network member who is a sexual partner (OR = 1.90 [1.11–3.24]), who currently attends a syringe exchange or methadone program (OR = 2.33 [1.16–4.70]), injects daily (OR = 1.77 [1.11–2.84]), and shares syringes with the subject (OR = 2.24 [1.13–4.46]). SSE is associated with several injection-related risk factors that could be used to help focus public health interventions for risk reduction. Since SSE offers an opportunity for the dissemination of important prevention messages, SSE-based networks should be used to improve public health interventions. This approach can optimize the benefits of SSE while minimizing the potential risks associated with the practice of secondary exchange.

Background

The objective of most biomedical research is to determine an unbiased estimate of effect for an exposure on an outcome, i.e. to make causal inferences about the exposure. Recent developments in epidemiology have shown that traditional methods of identifying confounding and adjusting for confounding may be inadequate.

Discussion

The traditional methods of adjusting for "potential confounders" may introduce conditional associations and bias rather than minimize it. Although previous published articles have discussed the role of the causal directed acyclic graph approach (DAGs) with respect to confounding, many clinical problems require complicated DAGs and therefore investigators may continue to use traditional practices because they do not have the tools necessary to properly use the DAG approach. The purpose of this manuscript is to demonstrate a simple 6-step approach to the use of DAGs, and also to explain why the method works from a conceptual point of view.

Summary

Using the simple 6-step DAG approach to confounding and selection bias discussed is likely to reduce the degree of bias for the effect estimate in the chosen statistical model.

Background

Discrepancies between the conclusions of different meta-analyses (quantitative syntheses of systematic reviews) are often ascribed to methodological differences. The objective of this study was to determine the discordance in interpretations when meta-analysts are presented with identical data.

Methods

We searched the literature for all randomized clinical trials (RCT) and review articles on the efficacy of intravenous magnesium in the early post-myocardial infarction period. We organized the articles chronologically and grouped them in packages. The first package included the first RCT, and a summary of the review articles published prior to first RCT. The second package contained the second and third RCT, a meta-analysis based on the data, and a summary of all review articles published prior to the third RCT. Similar packages were created for the 5th RCT, 10th RCT, 20th RCT and 23rd RCT (all articles). We presented the packages one at a time to eight different reviewers and asked them to answer three clinical questions after each package based solely on the information provided. The clinical questions included whether 1) they believed magnesium is now proven beneficial, 2) they believed magnesium will eventually be proven to be beneficial, and 3) they would recommend its use at this time.

Results

There was considerable disagreement among the reviewers for each package, and for each question. The discrepancies increased when the heterogeneity of the data increased. In addition, some reviewers became more sceptical of the effectiveness of magnesium over time, and some reviewers became less sceptical.

Conclusion

The interpretation of the results of systematic reviews with meta-analyses includes a subjective component that can lead to discordant conclusions that are independent of the methodology used to obtain or analyse the data.

Background

Interpregnancy interval (IPI), marital status, and neighborhood are independently associated with birth outcomes. The joint contribution of these exposures has not been evaluated. We tested for effect modification between IPI and marriage, controlling for neighborhood.

Methods

We analyzed a cohort of 98,330 live births in Montréal, Canada from 1997–2001 to assess IPI and marital status in relation to small for gestational age (SGA) birth. Births were categorized as subsequent-born with short (<12 months), intermediate (12–35 months), or long (36+ months) IPI, or as firstborn. The data had a 2-level hierarchical structure, with births nested in 49 neighborhoods. We used multilevel logistic regression to obtain adjusted effect estimates.

Results

Marital status modified the association between IPI and SGA birth. Being unmarried relative to married was associated with SGA birth for all IPI categories, particularly for subsequent births with short (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.31–1.95) and intermediate (OR 1.48, 95% CI 1.26–1.74) IPIs. Subsequent births had a lower likelihood of SGA birth than firstborns. Intermediate IPIs were more protective for married (OR 0.50, 95% CI 0.47–0.54) than unmarried mothers (OR 0.65, 95% CI 0.56–0.76).

Conclusion

Being unmarried increases the likelihood of SGA birth as the IPI shortens, and the protective effect of intermediate IPIs is reduced in unmarried mothers. Marital status should be considered in recommending particular IPIs as an intervention to improve birth outcomes.

After publication it was brought to our attention that the information for one of the variables in Table 1 was incorrect (Weiss, O'Loughlin et al. International Journal of Behavioral Nutrition and Physical Activity 2007, 4:2). The variable in question is "Use of a neighborhood facility for activity". In the first column, the first row should read "yes", and the second row, "no". In the second column, the first row should read 25.8 (41) and the second row, 41.3 (152).

Unadjusted and adjusted Odds Ratios for potential predictors of becoming inactive [1].

aBody Mass Index

* Not included in final model

Background

Obesity in North America is now endemic, and increased understanding of the determinants of physical inactivity is critical. This analysis identified predictors of declines in physical activity over 5 years among adults in low-income, inner-city neighbourhoods.

Methods

Data on leisure time physical activity were collected in telephone interviews in 1992 and 1997 from 765 adults (47% of baseline respondents), as part of the evaluation of a community-based cardiovascular disease risk reduction program.

Results

One-third of 527 participants who were physically active at baseline, were inactive in 1997. Predictors of becoming inactive included female sex (OR = 1.63 95% CI (1.09, 2.43)), older age (1.02 (1.01, 1.04)), higher BMI (1.57 (1.03, 2.40)), poor self-rated health (1.39 (1.05, 1.84)), lower self-efficacy for physical activity (1.46 (1.00, 2.14)), and not using a neighborhood facility for physical activity (1.61 (1.02, 2.14)).

Conclusion

These results highlight the fact that a variety of variables play a role in determining activity level, from demographic variables such as age and sex, to psychosocial and environmental variables. In addition, these results highlight the important role that other health-related variables may play in predicting physical activity level, in particular the observed association between baseline BMI and the increased risk of becoming inactive over time. Lastly, these results demonstrate the need for multi-component interventions in low-income communities, which target a range of issues, from psychosocial factors, to features of the physical environment.

Background

Search filters or hedges play an important role in evidence-based medicine but their development depends on the availability of a "gold standard" – a reference standard against which to establish the performance of the filter. We demonstrate the feasibility of using relative recall of included studies from multiple systematic reviews to validate methodological search filters as an alternative to validation against a gold standard formed through hand searching.

Methods

We identified 105 Cochrane reviews that used the Highly Sensitive Search Strategy (HSSS), included randomized or quasi-randomized controlled trials, and reported their included studies. We measured the ability of two published and one novel variant of the HSSS to retrieve the MEDLINE-index studies included in these reviews.

Results

The systematic reviews were comprehensive in their searches. 72% of included primary studies were indexed in MEDLINE. Relative recall of the three strategies ranged from .98 to .91 across all reviews and more comprehensive strategies showed higher recall.

Conclusion

An approach using relative recall instead of a hand searching gold standard proved feasible and produced recall figures that were congruent with previously published figures for the HSSS. This technique would permit validation of a methodological filter using a collection of approximately 100 studies of the chosen design drawn from the included studies of multiple systematic reviews that used comprehensive search strategies.

Background

Most electronic search efforts directed at identifying primary studies for inclusion in systematic reviews rely on the optimal Boolean search features of search interfaces such as DIALOG® and Ovid™. Our objective is to test the ability of an Ultraseek® search engine to rank MEDLINE® records of the included studies of Cochrane reviews within the top half of all the records retrieved by the Boolean MEDLINE search used by the reviewers.

Methods

Collections were created using the MEDLINE bibliographic records of included and excluded studies listed in the review and all records retrieved by the MEDLINE search. Records were converted to individual HTML files. Collections of records were indexed and searched through a statistical search engine, Ultraseek, using review-specific search terms. Our data sources, systematic reviews published in the Cochrane library, were included if they reported using at least one phase of the Cochrane Highly Sensitive Search Strategy (HSSS), provided citations for both included and excluded studies and conducted a meta-analysis using a binary outcome measure. Reviews were selected if they yielded between 1000–6000 records when the MEDLINE search strategy was replicated.

Results

Nine Cochrane reviews were included. Included studies within the Cochrane reviews were found within the first 500 retrieved studies more often than would be expected by chance. Across all reviews, recall of included studies into the top 500 was 0.70. There was no statistically significant difference in ranking when comparing included studies with just the subset of excluded studies listed as excluded in the published review.

Conclusion

The relevance ranking provided by the search engine was better than expected by chance and shows promise for the preliminary evaluation of large results from Boolean searches. A statistical search engine does not appear to be able to make fine discriminations concerning the relevance of bibliographic records that have been pre-screened by systematic reviewers.

Background

Little information exists on the impact of highly active antiretroviral therapy (HAART) on health-care provision in South Africa despite increasing scale-up of access to HAART and gradual reduction in HAART prices.

Methods and Findings

Use and cost of services for 265 HIV-infected adults without AIDS (World Health Organization [WHO] stage 1, 2, or 3) and 27 with AIDS (WHO stage 4) receiving HAART between 1995 and 2000 in Cape Town were compared with HIV-infected controls matched for baseline WHO stage, CD4 count, age, and socioeconomic status, who did not receive antiretroviral therapy (ART; No-ART group). Costs of service provision (January 2004 prices, US$1 = 7.6 Rand) included local unit costs, and two scenarios for HAART prices for WHO recommended first-line regimens: scenario 1 used current South African public-sector ART drug prices of $730 per patient-year (PPY), whereas scenario 2 was based on the anticipated public-sector price for locally manufactured drug of $181 PPY. All analyses are presented in terms of patients without AIDS and patients with AIDS.

For patients without AIDS, the mean number of inpatient days PPY was 1.08 (95% confidence interval [CI]: 0.97–1.19) for the HAART group versus 3.73 (95% CI: 3.55–3.97) for the No-ART group, and 8.71 (95% CI: 8.40–9.03) versus 4.35 (95% CI: 4.12–5.61), respectively, for mean number of outpatient visits PPY. Average service provision PPY was $950 for the No-ART group versus $1,342 and $793 PPY for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per life-year gained (LYG) was $1,622 for scenario 1 and $675 for scenario 2. For patients with AIDS, mean inpatients days PPY was 2.04 (95% CI: 1.63–2.52) for the HAART versus 15.36 (95% CI: 13.97–16.85) for the No-ART group. Mean outpatient visits PPY was 7.62 (95% CI: 6.81–8.49) compared with 6.60 (95% CI: 5.69–7.62) respectively. Average service provision PPY was $3,520 for the No-ART group versus $1,513 and $964 for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per LYG was cost saving for both scenarios. In a sensitivity analysis based on the lower (25%) and upper (75%) interquartile range survival percentiles, the incremental cost per LYG ranged from $1,557 to $1,772 for the group without AIDS and from cost saving to $111 for patients with AIDS.

Conclusion

HAART is a cost-effective intervention in South Africa, and cost saving when HAART prices are further reduced. Our estimates, however, were based on direct costs, and as such the actual cost saving might have been underestimated if indirect costs were also included.

Healthcare costs for HIV-infected South African adults on HAART compared with costs for HIV-infected controls not on HAART. Authors conclude HAART is cost effective.

Objective To determine the effect of helmets on the risk of head and neck injuries in skiers and snowboarders.

Design Matched case-control and case crossover study.

Setting 19 ski areas in Quebec, Canada, November 2001 to April 2002.

Participants 1082 skiers and snowboarders (cases) with head and neck injuries reported by the ski patrol and 3295 skiers and snowboarders (controls) with non-head or non-neck injuries matched to cases at each hill.

Main outcome measures Estimates of matched odds ratios for the effect of helmet use on the risk of any head or neck injury and for people requiring evacuation by ambulance.

Results The adjusted odds ratio for helmet use in participants with any head injury was 0.71 (95% confidence interval 0.55 to 0.92), indicating a 29% reduction in the risk of head injury. For participants who required evacuation by ambulance for head injuries, the adjusted odds ratio for helmet use was 0.44 (0.24 to 0.81). Similar results occurred with the case crossover design (odds ratio 0.43, 0.09 to 1.83). The adjusted odds ratio for helmet use for participants with any neck injury was 0.62 (0.33 to 1.19) and for participants who required evacuation by ambulance for neck injuries it was 1.29 (0.41 to 4.04).

Conclusions Helmets protect skiers and snowboarders against head injuries. We cannot rule out the possibility of an increased risk of neck injury with helmet use, but the estimates on which this assumption is based are imprecise.

Background

Epidemiological studies of exposures that vary with time require an additional level of methodological complexity to account for the time-dependence of exposure. This study compares a nested case-control approach for the study of time-dependent exposure with cohort analysis using Cox regression including time-dependent covariates.

Methods

A cohort of 1340 subjects with four fixed and seven time-dependent covariates was used for this study. Nested case-control analyses were repeated 100 times for each of 4, 8, 16, 32, and 64 controls per case, and point estimates were compared to those obtained using Cox regression on the full cohort. Computational efficiencies were evaluated by comparing central processing unit times required for analysis of the cohort at sizes 1, 2, 4, 8, 16, and 32 times its initial size.

Results

Nested case-control analyses yielded results that were similar to results of Cox regression on the full cohort. Cox regression was found to be 125 times slower than the nested case-control approach (using four controls per case).

Conclusions

The nested case-control approach is a useful alternative for cohort analysis when studying time-dependent exposures. Its superior computational efficiency may be particularly useful when studying rare outcomes in databases, where the ability to analyze larger sample sizes can improve the power of the study.