Concept: Statistical terminology
To determine the proportion of avoidable deaths (due to acts of omission and commission) in acute hospital trusts in England and to determine the association with the trust’s hospital-wide standardised mortality ratio assessed using the two commonly used methods - the hospital standardised mortality ratio (HSMR) and the summary hospital level mortality indicator (SHMI).
Objectives To evaluate the risk of all cause mortality associated with initiating compared with not initiating benzodiazepines in adults, and to address potential treatment barriers and confounding related to the use of a non-active comparator group.Design Retrospective cohort study.Setting Large de-identified US commercial healthcare database (Optum Clinformatics Datamart).Participants 1:1 high dimensional propensity score matched cohort of benzodiazepine initiators, and randomly selected benzodiazepine non-initiators with a medical visit within 14 days of the start of benzodiazepine treatment (n=1 252 988), between July 2004 and December 2013. To address treatment barriers and confounding, patients were required to have filled one or more prescriptions for any medication in the 90 days and 91-180 days before the index date (ie, the date of starting benzodiazepine treatment for initiators and the date of the selected medical visit for benzodiazepine non-initiators) and the high dimensional propensity score was estimated on the basis of more than 300 covariates.Main outcome measure All cause mortality, determined by linkage with the Social Security Administration Death Master File.Results Over a six month follow-up period, 5061 and 4691 deaths occurred among high dimensional propensity score matched benzodiazepine initiators versus non-initiators (9.3 v 9.4 events per 1000 person years; hazard ratio 1.00, 95% confidence interval 0.96 to 1.04). A 4% (95% confidence interval 1% to 8%) to 9% (2% to 7%) increase in mortality risk was observed associated with the start of benzodiazepine treatment for follow-ups of 12 and 48 months and in subgroups of younger patients and patients initiating short acting agents. In secondary analyses comparing 1:1 high dimensional propensity score matched patients initiating benzodiazepines with an active comparator, ie, patients starting treatment with selective serotonin reuptake inhibitor antidepressants, benzodiazepine use was associated with a 9% (95% confidence interval 3% to 16%) increased risk.Conclusions This large population based cohort study suggests either no increase or at most a minor increase in risk of all cause mortality associated with benzodiazepine initiation. If a detrimental effect exists, it is likely to be much smaller than previously stated and to have uncertain clinical relevance. Residual confounding likely explains at least part of the small increase in mortality risk observed in selected analyses.
- CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne
- Published over 7 years ago
BACKGROUND:Case reports indicate that the use of fluoroquinolones may lead to acute kidney injury. We studied the association between the use of oral fluoroquinolones and acute kidney injury, and we examined interaction with renin-angiotensin-system blockers. METHODS:We formed a nested cohort of men aged 40-85 enrolled in the United States IMS LifeLink Health Plan Claims Database between 2001 and 2011. We defined cases as men admitted to hospital for acute kidney injury, and controls were admitted to hospital with a different presenting diagnosis. Using risk-set sampling, we matched 10 controls to each case based on hospital admission, calendar time (within 6 wk), cohort entrance (within 6 wk) and age (within 5 yr). We used conditional logistic regression to assess the rate ratio (RR) for acute kidney injury with current, recent and past use of fluoroquinolones, adjusted by potential confounding variables. We repeated this analysis with amoxicillin and azithromycin as controls. We used a case-time-control design for our secondary analysis. RESULTS:We identified 1292 cases and 12 651 matched controls. Current fluoroquinolone use had a 2.18-fold (95% confidence interval [CI] 1.74-2.73) higher adjusted RR of acute kidney injury compared with no use. There was no association between acute kidney injury and recent (adjusted RR 0.87, 95% CI 0.66-1.16) or past (RR 0.86, 95% CI 0.66-1.12) use. The absolute in crease in acute kidney injury was 6.5 events per 10 000 person-years. We observed 1 additional case per 1529 patients given fluoroquinolones or per 3287 prescriptions dispensed. The dual use of fluoroquinolones and renin- angiotensin-system blockers had an RR of 4.46 (95% CI 2.84-6.99) for acute kidney injury. Our case-time-control analysis confirmed an increased risk of acute kidney injury with fluoroquinolone use (RR 2.16, 95% CI 1.52-3.18). The use of amoxicillin or azithro mycin was not associated with acute kidney injury. INTERPRETATION:We found a small, but significant, increased risk of acute kidney injury among men with the use of oral fluoroquinolones, as well as a significant interaction between the concomitant use of fluoroquinolones and renin- angiotensin-system blockers.
It is common to present multiple adjusted effect estimates from a single model in a single table. For example, a table might show odds ratios for one or more exposures and also for several confounders from a single logistic regression. This can lead to mistaken interpretations of these estimates. We use causal diagrams to display the sources of the problems. Presentation of exposure and confounder effect estimates from a single model may lead to several interpretative difficulties, inviting confusion of direct-effect estimates with total-effect estimates for covariates in the model. These effect estimates may also be confounded even though the effect estimate for the main exposure is not confounded. Interpretation of these effect estimates is further complicated by heterogeneity (variation, modification) of the exposure effect measure across covariate levels. We offer suggestions to limit potential misunderstandings when multiple effect estimates are presented, including precise distinction between total and direct effect measures from a single model, and use of multiple models tailored to yield total-effect estimates for covariates.
Objectives To study the association between maternal use of antidepressants during pregnancy and autism spectrum disorder (ASD) in offspring.Design Observational prospective cohort study with regression methods, propensity score matching, sibling controls, and negative control comparison.Setting Stockholm County, Sweden.Participants 254 610 individuals aged 4-17, including 5378 with autism, living in Stockholm County in 2001-11 who were born to mothers who did not take antidepressants and did not have any psychiatric disorder, mothers who took antidepressants during pregnancy, or mothers with psychiatric disorders who did not take antidepressants during pregnancy. Maternal antidepressant use was recorded during first antenatal interview or determined from prescription records.Main outcome measure Offspring diagnosis of autism spectrum disorder, with and without intellectual disability.Results Of the 3342 children exposed to antidepressants during pregnancy, 4.1% (n=136) had a diagnosis of autism compared with a 2.9% prevalence (n=353) in 12 325 children not exposed to antidepressants whose mothers had a history of a psychiatric disorder (adjusted odds ratio 1.45, 95% confidence interval 1.13 to 1.85). Propensity score analysis led to similar results. The results of a sibling control analysis were in the same direction, although with wider confidence intervals. In a negative control comparison, there was no evidence of any increased risk of autism in children whose fathers were prescribed antidepressants during the mothers' pregnancy (1.13, 0.68 to 1.88). In all analyses, the risk increase concerned only autism without intellectual disability.Conclusions The association between antidepressant use during pregnancy and autism, particularly autism without intellectual disability, might not solely be a byproduct of confounding. Study of the potential underlying biological mechanisms could help the understanding of modifiable mechanisms in the aetiology of autism. Importantly, the absolute risk of autism was small, and, hypothetically, if no pregnant women took antidepressants, the number of cases that could potentially be prevented would be small.
Objectives. We examined the relationship between levels of household firearm ownership, as measured directly and by a proxy-the percentage of suicides committed with a firearm-and age-adjusted firearm homicide rates at the state level. Methods. We conducted a negative binomial regression analysis of panel data from the Centers for Disease Control and Prevention’s Web-Based Injury Statistics Query and Reporting Systems database on gun ownership and firearm homicide rates across all 50 states during 1981 to 2010. We determined fixed effects for year, accounted for clustering within states with generalized estimating equations, and controlled for potential state-level confounders. Results. Gun ownership was a significant predictor of firearm homicide rates (incidence rate ratio = 1.009; 95% confidence interval = 1.004, 1.014). This model indicated that for each percentage point increase in gun ownership, the firearm homicide rate increased by 0.9%. Conclusions. We observed a robust correlation between higher levels of gun ownership and higher firearm homicide rates. Although we could not determine causation, we found that states with higher rates of gun ownership had disproportionately large numbers of deaths from firearm-related homicides. (Am J Public Health. Published online ahead of print September 12, 2013: e1-e8. doi:10.2105/AJPH.2013.301409).
Background The role of bracing in patients with adolescent idiopathic scoliosis who are at risk for curve progression and eventual surgery is controversial. Methods We conducted a multicenter study that included patients with typical indications for bracing due to their age, skeletal immaturity, and degree of scoliosis. Both a randomized cohort and a preference cohort were enrolled. Of 242 patients included in the analysis, 116 were randomly assigned to bracing or observation, and 126 chose between bracing and observation. Patients in the bracing group were instructed to wear the brace at least 18 hours per day. The primary outcomes were curve progression to 50 degrees or more (treatment failure) and skeletal maturity without this degree of curve progression (treatment success). Results The trial was stopped early owing to the efficacy of bracing. In an analysis that included both the randomized and preference cohorts, the rate of treatment success was 72% after bracing, as compared with 48% after observation (propensity-score-adjusted odds ratio for treatment success, 1.93; 95% confidence interval [CI], 1.08 to 3.46). In the intention-to-treat analysis, the rate of treatment success was 75% among patients randomly assigned to bracing, as compared with 42% among those randomly assigned to observation (odds ratio, 4.11; 95% CI, 1.85 to 9.16). There was a significant positive association between hours of brace wear and rate of treatment success (P<0.001). Conclusions Bracing significantly decreased the progression of high-risk curves to the threshold for surgery in patients with adolescent idiopathic scoliosis. The benefit increased with longer hours of brace wear. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and others; BRAIST ClinicalTrials.gov number, NCT00448448 .).
This is the first detailed study of the relation between cesarean birth and child cognitive development. We measure differences in child cognitive performance at 4 to 9 years of age between cesarean-born and vaginally-born children (n = 3,666) participating in the Longitudinal Study of Australian Children (LSAC). LSAC is a nationally representative birth cohort surveyed biennially. Using multivariate regression, we control for a large range of confounders related to perinatal risk factors and the socio-economic advantage associated with cesarean-born children. Across several measures, we find that cesarean-born children perform significantly below vaginally-born children, by up to a tenth of a standard deviation in national numeracy test scores at age 8-9. Estimates from a low-risk sub-sample and lower-bound analysis suggest that the relation is not spuriously related to unobserved confounding. Lower rates of breastfeeding and adverse child and maternal health outcomes that are associated with cesarean birth are found to explain less than a third of the cognitive gap, which points to the importance of other mechanisms such as disturbed gut microbiota. The findings underline the need for a precautionary approach in responding to requests for a planned cesarean when there are no apparent elevated risks from vaginal birth.
Poor sanitation remains a major public health concern linked to several important health outcomes; emerging evidence indicates a link to childhood stunting. In India over half of the population defecates in the open; the prevalence of stunting remains very high. Recently published data on levels of stunting in 112 districts of India provide an opportunity to explore the relationship between levels of open defecation and stunting within this population. We conducted an ecological regression analysis to assess the association between the prevalence of open defecation and stunting after adjustment for potential confounding factors. Data from the 2011 HUNGaMA survey was used for the outcome of interest, stunting; data from the 2011 Indian Census for the same districts was used for the exposure of interest, open defecation. After adjustment for various potential confounding factors - including socio-economic status, maternal education and calorie availability - a 10 percent increase in open defecation was associated with a 0.7 percentage point increase in both stunting and severe stunting. Differences in open defecation can statistically account for 35 to 55 percent of the average difference in stunting between districts identified as low-performing and high-performing in the HUNGaMA data. In addition, using a Monte Carlo simulation, we explored the effect on statistical power of the common practice of dichotomizing continuous height data into binary stunting indicators. Our simulation showed that dichotomization of height sacrifices statistical power, suggesting that our estimate of the association between open defecation and stunting may be a lower bound. Whilst our analysis is ecological and therefore vulnerable to residual confounding, these findings use the most recently collected large-scale data from India to add to a growing body of suggestive evidence for an effect of poor sanitation on human growth. New intervention studies, currently underway, may shed more light on this important issue.
- Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine
- Published over 7 years ago
Abstract Background and Objective: Until 2010, newborns at our institution were bathed in the nursery at approximately 2 hours of life. In May 2010, infant baths were delayed until at least 12 hours of life. Infants are now bathed in the hospital room with parents' participation and are placed skin-to-skin immediately after the bath. This study explored whether delaying the newborn’s first bath correlates with increased in-hospital breastfeeding rates at our Baby-Friendly, urban safety-net hospital. Subjects and Methods: We performed a retrospective chart review comparing in-hospital breastfeeding rates during the 6 months before and the 6 months after the bath was delayed. Results: Of the infants, 702 met inclusion criteria. Before the bath was delayed, infants were bathed at an average of 2.4 hours of life. Afterward, infants were bathed at an average of 13.5 hours of life. In-hospital exclusive breastfeeding rates increased from 32.7% to 40.2% (p<0.05) after the bath was delayed. Multivariate logistic regression analysis showed that infants born after implementation of delayed bathing had odds of exclusive breastfeeding 39% greater than infants born prior to the intervention (adjusted odds ratio [AOR]=1.39; 95% confidence interval [CI] 1.02, 1.91) and 59% greater odds of near-exclusive breastfeeding (AOR=1.59; 95% CI 1.18, 2.15). The odds of breastfeeding initiation were 166% greater for infants born after the intervention than for infants born before the intervention (AOR=2.66; 95% CI 1.29, 5.46). Conclusions: In our cohort, a delayed newborn bath was associated with increased likelihood of breastfeeding initiation and with increased in-hospital breastfeeding rates.