Different Methods of Balancing Covariates Leading to Different Effect Estimates in the Presence of Effect Modification

A number of covariate-balancing methods, based on the propensity score, are widely used to estimate treatment effects in observational studies. If the treatment effect varies with the propensity score, however, different methods can give very different answers. The authors illustrate this effect by using data from a United Kingdom–based registry of subjects treated with anti–tumor necrosis factor drugs for rheumatoid arthritis. Estimates of the effect of these drugs on mortality varied from a relative risk of 0.4 (95% confidence interval: 0.16, 0.91) to a relative risk of 1.3 (95% confidence interval: 0.8, 2.25), depending on the balancing method chosen. The authors show that these differences were due to a combination of an interaction between propensity score and treatment effect and to differences in weighting subjects with different propensity scores. Thus, the methods are being used to calculate average treatment effects in populations with very different distributions of effect-modifying variables, resulting in different overall estimates. This phenomenon highlights the importance of careful selection of the covariate-balancing method so that the overall estimate has a meaningful interpretation

Propensity scores in the presence of effect modification: A case study using the comparison of mortality on hemodialysis versus peritoneal dialysis

Purpose. To control for confounding bias from non-random treatment assignment in observational data, both traditional multivariable models and more recently propensity score approaches have been applied. Our aim was to compare a propensity score-stratified model with a traditional multivariable-adjusted model, specifically in estimating survival of hemodialysis (HD) versus peritoneal dialysis (PD) patients. Methods. Using the Dutch End-Stage Renal Disease Registry, we constructed a propensity score, predicting PD assignment from age, gender, primary renal disease, center of dialysis, and year of first renal replacement therapy. We developed two Cox proportional hazards regression models to estimate survival on PD relative to HD, a propensity score-stratified model stratifying on the propensity score and a multivariable-adjusted model, and tested several interaction terms in both models. Results. The propensity score performed well: it showed a reasonable fit, had a good c-statistic, calibrated well and balanced the covariates. The main-effects multivariable-adjusted model and the propensity score-stratified univariable Cox model resulted in similar relative mortality risk estimates of PD compared with HD (0.99 and 0.97, respectively) with fewer significant covariates in the propensity model. After introducing the missing interaction variables for effect modification in both models, the mortality risk estimates for both main effects and interactions remained comparable, but the propensity score model had nearly as many covariates because of the additional interaction variables. Conclusion. Although the propensity score performed well, it did not alter the treatment effect in the outcome model and lost its advantage of parsimony in the presence of effect modification

Dipeptidyl peptidase 4 inhibitors and risk of inflammatory bowel disease: Real-world evidence in U.S. Adults

OBJECTIVE A recent study raises concerns that dipeptidyl peptidase 4 inhibitors (DPP4i) are associated with increased risk of inflammatory bowel disease (IBD). We evaluated the association between new use of DPP4i and IBD risk compared with other secondline antihyperglycemics. RESEARCH DESIGN AND METHODS We implemented an active-comparator, new-user cohort design using two U.S. administrative claims databases for commercially insured (MarketScan) and older adult (Medicare fee-for-service, 20% random sample) patients from January 2007 to December 2016.We identified patients, aged ≥18 years, who initiated DPP4i versus sulfonylureas (SUs) or initiated DPP4i versus thiazolidinediones (TZDs) and were without prior diagnosis, treatment, or procedure for IBD. The primary outcome was incident IBD, defined by IBD diagnosis preceded by colonoscopy and biopsy and followed by IBD treatment. We performed propensity score weighting to control for measured baseline confounding, estimated adjusted hazard ratios (aHRs [95% CI]) using weighted Cox proportional hazards models, and used randomeffects meta-analysis models to pool aHRs across cohorts. RESULTS We identified 895,747 eligible patients initiating DPP4i, SU, or TZD; IBD incidence rates ranged from 11.6 to 32.3/100,000 person-years. Over a median treatment duration of 1.09-1.69 years, DPP4i were not associated with increased IBD risk across comparisons. The pooled aHRs for IBD were 0.82 (95% CI 0.41-1.61) when comparing DPP4i (n 5 161,612) to SU (n 5 310,550) and 0.76 (0.46-1.26) when comparing DPP4i (n 5 205,570) to TZD (n 5 87,543). CONCLUSIONS Our population-based cohort study of U.S. adults with diabetes suggests that shortterm DPP4i treatment does not increase IBD risk

Prevalence of psychosis in black ethnic minorities in Britain: analysis based on three national surveys

Purpose A considerable excess of psychosis in black ethnic minorities is apparent from clinical studies, in Britain, as in other developed economies with white majority populations. This excess is not so marked in population surveys. Equitable health service provision should be informed by the best estimates of the excess. We used national survey data to establish the difference in the prevalence of psychosis between black ethnic groups and the white majority in the British general population. Methods Analysis of the combined datasets (N = 26,091) from the British national mental health surveys of 1993, 2000 and 2007. Cases of psychosis were determined either by the use of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), or from a combination of screening items. We controlled for sex, age, social class, unemployment, design features and other putative confounders, using a Disease Risk Score. Results People from black ethnic minorities had an excess prevalence rate of psychosis compared with the white majority population. The OR, weighted for study design and response rate, was 2.72 (95 % CI 1.3–5.6, p = 0.002). This was marginally increased after controlling for potential confounders (OR = 2.90, 95 % CI 1.4–6.2, p = 0.006). Conclusions The excess of psychosis in black ethnic minority groups was similar to that in two previous British community surveys, and less than that based on clinical studies. Even so it confirms a considerable need for increased mental health service resources in areas with high proportions of black ethnic minority inhabitants

Clustering of antibiotic resistance of E. coli in couples: suggestion for a major role of conjugal transmission

BACKGROUND: Spread of antibiotic resistance in hospitals is a well-known problem, but studies investigating the importance of factors potentially related to the spread of resistant bacteria in outpatients are sparse. METHODS: Stool samples were obtained from 206 healthy couples in a community setting in Southern Germany in 2002–2003. E. coli was cultured and minimal inhibition concentrations were tested. Prevalences of E. coli resistance to commonly prescribed antibiotics according to potential risk factors were ascertained. RESULTS: Prevalences of ampicillin resistance were 15.7% and 19.4% for women and men, respectively. About ten percent and 15% of all isolates were resistant to cotrimoxazole and doxycycline, respectively. A partner carrying resistance was the main risk factor for being colonized with resistant E. coli. Odds ratios (95% CI) for ampicillin and cotrimoxazole resistance given carriage of resistant isolates by the partner were 6.9 (3.1–15.5) and 3.3 (1.5–18.0), respectively. CONCLUSION: Our data suggest that conjugal transmission may be more important for the spread of antibiotic resistance in the community setting than commonly suspected risk factors such as previous antibiotic intake or hospital contacts

Car drivers' road safety performance. A benchmark across 32 countries

The road safety performance of a country and the success of policy measures can be measured and monitored in different ways. In addition to the traditional road safety indicators based on the number of fatalities or injured people in road traffic crashes, complementary road safety performance indicators can be used in relation to vehicles, infrastructure, or road users' behaviour. The last-mentioned can be based on data from roadside surveys or from questionnaire surveys. However, results of such surveys are seldom comparable across countries due to differences in aims, scope, or methodology. This paper is based on the second edition of the E-Survey of Road Users' Attitudes (ESRA), an online survey carried out in 2018, and includes data from more than 35,000 road users across 32 countries. The objective is to present the main results of the ESRA survey regarding the four most important risky driving behaviours in traffic: driving under the influence (alcohol/drugs), speeding, mobile phone use while driving, and fatigued driving. The paper explores several aspects related to these behaviours as car driver, such as the self-declared behaviours, acceptability and risk perception, support for policy measures, and opinions on traffic rules and penalties. Results show that despite the high perception of risk and low acceptability of all the risky driving behaviours analysed, there is still a high percentage of car drivers who engage in risky behaviours in traffic in all the regions analysed. Speeding and the use of a mobile phone while driving were the most frequent self-declared behaviours. On the other hand, driving under the influence of alcohol or drugs was the least declared behaviour. Most respondents support policy measures to restrict risky behaviour in traffic and believe that traffic rules are not being checked regularly enough, and should be stricter. The ESRA survey proved to be a valuable source of information to understand the causes underlying road traffic crashes. It offers a unique database and provides policy makers and researchers with valuable insights into public perception of road safety

Comparative effectiveness and harms of antibiotics for outpatient diverticulitis two nationwide cohort studies

Background: Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin-clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for diverticulitis is uncertain. Objective: To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis. Design: Active-comparator, new-user, retrospective cohort studies. Setting: Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015). Participants: Immunocompetent adults with diverticulitis in the outpatient setting. Intervention: Metronidazole-with-fluoroquinolone or amoxicillin-clavulanate. Measurements: 1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery. Results: In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin-clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, -0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, -0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin-clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, -0.7 to 0.9]), 1-year urgent surgery risk (risk difference, -0.2 percentage points [CI, -0.6 to 0.1]), or 3-year elective surgery risk (risk difference, -0.3 percentage points [CI, -1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin-clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]). Limitation: Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed. Conclusion: Treating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes

Alcohol dehydrogenase 1B (ADH1B) genotype, alcohol consumption and breast cancer risk by age 50 years in a German case–control study

In a population-based study of 613 cases and 1082 controls, alcohol dehydrogenase 1B (ADH1B) genotype was not an independent risk factor for breast cancer, athough the possibility was raised that it modifies risk associated with high levels of alcohol consumption (OR 1.1, 95% confidence interval (CI) 0.8–1.6 for ADH1B*1/*1 genotype vs 0.2, 95% CI 0.1–1.0 for ADH1B*2 carriers)

Influenza Vaccine Effectiveness in the Elderly Based on Administrative Databases: Change in Immunization Habit as a Marker for Bias

Administrative databases provide efficient methods to estimate influenza vaccine effectiveness (IVE) against severe outcomes in the elderly but are prone to intractable bias. This study returns to one of the linked population databases by which IVE against hospitalization and death in the elderly was first assessed. We explore IVE across six more recent influenza seasons, including periods before, during, and after peak activity to identify potential markers for bias.Acute respiratory hospitalization and all-cause mortality were compared between immunized/non-immunized community-dwelling seniors ≥65 years through administrative databases in Manitoba, Canada between 2000-01 and 2005-06. IVE was compared during pre-season/influenza/post-season periods through logistic regression with multivariable adjustment (age/sex/income/residence/prior influenza or pneumococcal immunization/medical visits/comorbidity), stratification based on prior influenza immunization history, and propensity scores. Analysis during pre-season periods assessed baseline differences between immunized and unimmunized groups. The study population included ∼140,000 seniors, of whom 50-60% were immunized annually. Adjustment for key covariates and use of propensity scores consistently increased IVE. Estimates were paradoxically higher pre-season and for all-cause mortality vs. acute respiratory hospitalization. Stratified analysis showed that those twice consecutively and currently immunized were always at significantly lower hospitalization/mortality risk with odds ratios (OR) of 0.60 [95%CI0.48-0.75] and 0.58 [0.53-0.64] pre-season and 0.77 [0.69-0.86] and 0.71 [0.66-0.77] during influenza circulation, relative to the consistently unimmunized. Conversely, those forgoing immunization when twice previously immunized were always at significantly higher hospitalization/mortality risk with OR of 1.41 [1.14-1.73] and 2.45 [2.21-2.72] pre-season and 1.21 [1.03-1.43] and 1.78 [1.61-1.96] during influenza circulation.The most pronounced IVE estimates were paradoxically observed pre-season, indicating bias tending to over-estimate vaccine protection. Change in immunization habit from that of the prior two years may be a marker for this bias in administrative data sets; however, no analytic technique explored could adjust for its influence. Improved methods to achieve valid interpretation of protection in the elderly are needed

Dynamic 3D shape of the plantar surface of the foot using coded structured light:a technical report

The foot provides a crucial contribution to the balance and stability of the musculoskeletal system, and accurate foot measurements are important in applications such as designing custom insoles/footwear. With better understanding of the dynamic behavior of the foot, dynamic foot reconstruction techniques are surfacing as useful ways to properly measure the shape of the foot. This paper presents a novel design and implementation of a structured-light prototype system providing dense three dimensional (3D) measurements of the foot in motion. The input to the system is a video sequence of a foot during a single step; the output is a 3D reconstruction of the plantar surface of the foot for each frame of the input. Methods Engineering and clinical tests were carried out to test the accuracy and repeatability of the system. Accuracy experiments involved imaging a planar surface from different orientations and elevations and measuring the fitting errors of the data to a plane. Repeatability experiments were done using reconstructions from 27 different subjects, where for each one both right and left feet were reconstructed in static and dynamic conditions over two different days. Results The static accuracy of the system was found to be 0.3 mm with planar test objects. In tests with real feet, the system proved repeatable, with reconstruction differences between trials one week apart averaging 2.4 mm (static case) and 2.8 mm (dynamic case). Conclusion The results obtained in the experiments show positive accuracy and repeatability results when compared to current literature. The design also shows to be superior to the systems available in the literature in several factors. Further studies need to be done to quantify the reliability of the system in clinical environment