Use of psychotropic medication and risk of road traffic crashes: a registry-based case-control study in Denmark, 1996-2018.

RATIONALE: Use of psychotropics is relatively prevalent amongst motor vehicle drivers because mobility is also important for persons suffering from psychiatric illness. However, medication side effects may increase the likelihood of being involved in traffic crashes. OBJECTIVES: This study aimed to assess the association between the use of four types of medication (antipsychotics, benzodiazepines and z-hypnotics, antidepressants and stimulants of ADHD treatment) and the risk of traffic crashes, in general, and single crashes subsequently. METHOD: We conducted a case-control study of data from 130,000 drivers involved in traffic crashes with personal injury and prescription data from all of Denmark during the period 1996-2018. RESULTS: For antipsychotics, we found odds ratios of 0.86 and 1.29 for traffic crashes and single crashes, respectively; for benzodiazepines and z-hypnotics, 1.29 and 2.49, respectively; for antidepressants, 1.30 and 2.25, respectively; and for stimulants of ADHD treatment, 1.62 and 1.95, respectively. All p values were below 0.001. CONCLUSIONS: Based on our results on twofold increased risks of single crashes and moderately increased risks in persons with ADHD, it might seem tempting to ban psychotropic medication in traffic. Conversely, we accept increased risks of traffic crashes in young drivers and in the physically disabled with special aids and, to some extent, with exposure to alcohol. In the end, it is the authorities who must review the evidence and decide whether to prohibit (some types of) psychotropic medication in traffic. Finally, underlying disease and not the drug may increase the risk of being involved in a traffic crash.

Single-bicycle crashes: An in-depth analysis of self-reported crashes and estimation of attributable hospital cost.

Cyclists' awareness of their risk of single-bicycle crashes is limited. Thus, knowledge of the most common contributory factors of single-bicycle crashes is required. Similarly, single-bicycle crashes and their costs to society are under-recognized by the public. The aim of this study was to conduct an analysis of single-bicycle crashes occurring in a cohort of cyclists in Denmark and supplement it with estimation of some attributable costs of single-bicycle crashes among all injured cyclists during one year treated in a hospital or emergency room in Denmark. We conducted a one-year follow-up of 6,793 active cyclists (mean age: 45.8 years) encountering 349 single-bicycle crashes (single-bicycle crash rate: 55 per 1,000 person-years). An in-depth analysis of the crashes suggested that daily winter road maintenance is crucial in colder climates and that the current cyclist infrastructure design gives rise to many single-bicycle crashes. Further analysis of the co-occurrence of the factors contributing to the crashes indicated that when the weather is warmer, the factors pertaining to the individual cyclist (and not the road authorities) dominate. The risk of sustaining a more severe injury (i.e. other than light bruises) once in a single-bicycle crash was 18 %. However, for cyclists above 50 years, this risk doubled compared with their younger counterparts, wholly due to a 4.7 times higher risk during the warm season. Among cyclists treated in hospital or emergency room, we estimated the attributable hospital cost of single-bicycle crashes at €1,701 and the attributable cost of municipality care at €417 in the first year after the injury (2019 prices). In cyclists aged 18-60 years and treated in hospital or emergency room, the estimated attributable risk of sickness benefit was 5.2 percentage points in the first year after the injury. We concluded that to increase cyclist safety, the road authorities should improve winter road maintenance and redesign cyclist infrastructure.

An in-depth analysis of self-reported cycling injuries in single and multiparty bicycle crashes in Denmark.

INTRODUCTION: Cycling is one of the main forms of transportation in Denmark. However, while the number of traffic crash fatalities in the country has decreased over the past decade, the frequency of cyclists killed or seriously injured has increased. The high rate of serious injuries and fatalities associated with cycling emphasizes the increasing need for mitigating the severity of such crashes. METHOD: This study conducted an in-depth analysis of cyclist injury severity resulting from single and multiparty bicycle-involved crashes. Detailed information was collected using self-reporting data undertaken in Denmark for a 12-month period between 1 November 2012 and 31 October 2013. Separate multilevel logistic (MLL) regression models were applied to estimate cyclist injury severity for single and multiparty crashes. The goodness-of-fit measures favored the MLL models over the standard logistic models, capturing the intercorrelation among bicycle crashes that occurred in the same geographical area. RESULTS: The results also showed that single bicycle-involved crashes resulted in more serious outcomes when compared to multiparty crashes. For both single and multiparty bicycle crash categories, non-urban areas were associated with more serious injury outcomes. For the single crashes, wet surface condition, autumn and summer seasons, evening and night periods, non-adverse weather conditions, cyclists aged between 45 and 64 years, male sex, riding for the purpose of work or educational activities, and bicycles with light turned-off were associated with severe injuries. For the multiparty crashes, intersections, bicycle paths, non-winter season, not being employed or retired, lower personal car ownership, and race bicycles were directly related to severe injury consequences. Practical Applications: The findings of this study demonstrated that the best way to promote cycling safety is the combination of improving the design and maintenance of cycling facilities, encouraging safe cycling behavior, and intensifying enforcement efforts.

The construct validity of the Child Health Utility 9D-DK instrument.

BACKGROUND: Relative to their application with adults there is currently little information about the application of preference-based health-related quality of life (HRQL) instruments among populations of young people. The Child Health Utility 9D (CHU9D) is a paediatric-specific generic preference-based HRQL instrument, recently translated and linguistically validated into Danish (CHU9D-DK). The purpose of this study was to investigate the construct validity of the CHU9D-DK in a sample of Danish high school students. METHODS: All students attending a Danish High School were invited to participate in a web-based survey in January 2018 (N = 272). The survey included the CHU9D-DK, the young adult version of the Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales (PedsQL), self-reported health status, presence/absence of disability/chronic diseases, life satisfaction, and socio-economic questions. CHU9D-DK utility scores were generated by employing the two scoring algorithms developed from adults in the UK and adolescents in Australia, respectively. Internal consistency, reliability and construct validity of the CHU9D-DK instrument were investigated. RESULTS: Two hundred and twenty-eight (84%) students consented to participate and completed the survey. The mean ± (standard deviation) values of the CHU9D-DK utilities were 0.84 (0.11) when the UK adult algorithm was applied and 0.70 (0.22), when the Australian adolescent algorithm was applied. The mean PedsQL score was 82.32 (13.14). The CHU9D-DK showed good internal consistency reliability (Cronbach's alpha = 0.803). Higher levels of health status and life satisfaction were significantly associated with higher CHU9D-DK utility scores regardless of which scoring algorithm was applied (p-values < 0.001). Students living with a disability/chronic disease exhibited significantly lower utility scores relative to their healthy peers (p-values < 0.05). Higher socio-economic status (approximated by financial situation and frequency of family vacations) was also associated with higher utility scores (p-values < 0.005). CONCLUSION: The CHU9D-DK demonstrated good psychometric performance overall and shows potential as a valid and reliable instrument for assessing the HRQL of Danish young people. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03391999, Registered 15 October 2017.

Does a tow-bar increase the risk of neck injury in rear-end collisions?

INTRODUCTION: Does a tow-bar increase the risk of neck injury in the struck car in a rear-end collision? The rear part of a modern car has collision zones that are rendered nonoperational when the car is equipped with a tow-bar. Past crash tests have shown that a car's acceleration was higher in a car equipped with a tow-bar and also that a dummy placed in a car with a tow-bar had higher peak acceleration in the lower neck area. METHOD: This study aimed to investigate the association between the risk of neck injury in drivers and passengers, and the presence of a registered tow-bar on the struck car in a rear-end collision. We performed a merger of police reports, the National Hospital Discharge Registry, and the National Registry of Motor Vehicles in Denmark. We identified 9,370 drivers and passengers of whom 1,519 were diagnosed with neck injury within the first year after the collision. We found a statistically insignificant 5% decrease in the risk of neck injury in the occupants of the struck car when a tow-bar was fitted compared to when it was not fitted (hazard ratio=0.95; 95% confidence level=0.85-1.05; p=0.32). The result was controlled for gender, age, and the seat of the occupant. Several other collision and car characteristics and demographic information on the drivers and passengers were evaluated as confounders but were not statistically significant. CONCLUSIONS: The present study may serve as valuable input for a meta-analysis on the effect of a tow-bar because negative results are necessary in order to avoid publication bias.

Randomized trials and self-reported accidents as a method to study safety-enhancing measures for cyclists-two case studies.

A large number of studies show that high visibility in traffic is important in the struggle of getting the attention from other road users and thus an important safety factor. Cyclists have a much higher risk of being killed or injured in a traffic accident than car drivers so for them high visibility is particularly important. A number of studies have examined the effect of high visibility, such as reflective clothing, but most studies have been primitive, the data limited and the results very uncertain. In this paper we describe the safety impact of increased visibility of cyclists through two randomised controlled trials: permanent running lights on bicycles and a yellow bicycle jacket, respectively. The effect of running lights was studied through a trial where the lights were mounted to 1,845 bicycles and 2,000 others comprised a control group. The bicycle accidents were recorded every two month in a year through self-reporting on the Internet. Participants were asked to report all cycling accidents independently of severity to avoid differences between participants as regards to which accidents were reported. They reported a total of 255 accidents i.e. 7 accidents per 100 cyclists. The results showed that the incidence rate for multiparty bicycle accidents with personal injury was 47% lower for cyclists with permanent running light. The difference is statistically significant at the 5% level. The effect of a yellow bicycle jacket was examined through a trial with 6,800 volunteer cyclists. The half of the group received a bicycle jacket and the other half comprised a control group. Both groups reported every month all their bicycle accidents independently of severity on the Internet. They reported a total of 694 accidents i.e. 10 accidents per 100 cyclists. The treatment group was asked each month if they carried the jacket on their last cycling trip. The results showed that on a random day the treatment group carried the jacket or other fluorescent cycling garment on 77% of their cycle trips. The incidence rate for multiparty accidents with personal injury was 38% lower than the control group. The difference is statistically significant at the 5% level. The trials were not blind and it seems that the lack of blinding has influenced the level of the groups accident reporting. To address this bias we used a correction factor formed by the difference in the number of single accidents of the two groups. The experiences with self-reporting of accidents via a web based questionnaire sent by e-mail with one respective two month intervals were very good; in both trials more than 80% answered all questionnaires whereas less than 2% did not answer, and the quality of the self-reported accident was considered high.

Unannounced versus announced hospital surveys: a nationwide cluster-randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of unannounced versus announced surveys in detecting non-compliance with accreditation standards in public hospitals. DESIGN: A nationwide cluster-randomized controlled trial. SETTING AND PARTICIPANTS: All public hospitals in Denmark were invited. Twenty-three hospitals (77%) (3 university hospitals, 5 psychiatric hospitals and 15 general hospitals) agreed to participate. INTERVENTION: Twelve hospitals were randomized to receive unannounced surveys (intervention group) and eleven hospitals to receive announced surveys (control group). We hypothesized that the hospitals receiving the unannounced surveys would reveal a higher degree of non-compliance with accreditation standards than the hospitals receiving announced surveys. Nine surveyors trained and employed by the Danish Institute for Quality and Accreditation in Healthcare (IKAS) were randomized into teams and conducted all surveys. MAIN OUTCOME MEASURE: The outcome was the surveyors' assessment of the hospitals' level of compliance with 113 performance indicators-an abbreviated set of the Danish Healthcare Quality Programme (DDKM) version 2, covering organizational standards, patient pathway standards and patient safety standards. Compliance with performance indicators was analyzed using binomial regression analysis with bootstrapped robust standard errors. RESULTS: In all, 16 202 measurements were acceptable for data analysis. The risk of observing non-compliance with performance indicators for the intervention group compared with the control group was statistically insignificant (risk difference (RD) = -0.6 percentage points [-2.51-1.31], P = 0.54). A converged analysis of the six patient safety critical standards, requiring 100% compliance to gain accreditation status revealed no statistically significant difference (RD = -0.78 percentage points [-4.01-2.44], P = 0.99). CONCLUSIONS: Unannounced hospital surveys were not more effective than announced surveys in detecting quality problems in Danish hospitals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02348567, https://clinicaltrials.gov/ct2/show/NCT02348567?term=NCT02348567.

Run charts revisited: a simulation study of run chart rules for detection of non-random variation in health care processes.

BACKGROUND: A run chart is a line graph of a measure plotted over time with the median as a horizontal line. The main purpose of the run chart is to identify process improvement or degradation, which may be detected by statistical tests for non-random patterns in the data sequence. METHODS: We studied the sensitivity to shifts and linear drifts in simulated processes using the shift, crossings and trend rules for detecting non-random variation in run charts. RESULTS: The shift and crossings rules are effective in detecting shifts and drifts in process centre over time while keeping the false signal rate constant around 5% and independent of the number of data points in the chart. The trend rule is virtually useless for detection of linear drift over time, the purpose it was intended for.

Perinatal markers of estrogen exposure and risk of testicular cancer: follow-up of 1,333,873 Danish males born between 1950 and 2002.

OBJECTIVE: To examine whether indicators of an increased prenatal estrogen exposure correlate with risk of testicular cancer. METHODS: This nationwide follow-up study was conducted by linking data on prenatal exposures obtained from medical and birth records for information on incident testicular cancer cases identified from the Danish Cancer Registry. The study population included all boys born between 1950 and 2002 and alive in April 1968 or later with restriction to sons of mothers born after 1935 and alive in April 1968. RESULTS: A total of 2,151 incident testicular cancer cases were identified in 29 million person-years at risk. Men born with a high birth weight (>4,150 g) had an increased risk of testicular cancer [incidence rate ratio (IRR) = 1.6 (95% CI: 1.0, 2.4)]. Having a twin sister was associated with reduced risk [IRR = 0.5 (95% CI: 0.2, 1.1)], and the IRR for sons of mothers suffering from preeclampsia indicated a low risk [IRR = 0.6 (95% CI: 0.2, 2.0)], although none of these estimates were statistically significant. Increasing sib order and preterm birth was not associated with decreased risk. PRINCIPAL CONCLUSIONS: Results provide no strong evidence for the hypothesis.

Prenatal risk factors for cutaneous malignant melanoma: follow-up of 2,594,783 Danes born from 1950 to 2002.

The incidence of cutaneous malignant melanoma has increased in young adults, specifically in Denmark. In this study, we examined the risk of cutaneous malignant melanoma in relation to prenatal markers of hormone levels and to family-related risk factors. The study was based on a follow-up of 2,594,783 Danes born from 1950 to 2002. Occurrence of possible hormone-related cancers among family members and indicators of abnormal prenatal hormone levels were not associated with cutaneous malignant melanoma risk, whereas family size and mother's age at first birth were significant risk factors for cutaneous malignant melanoma in offspring.

Correcting for selection using frailty models.

Chronic diseases are roughly speaking lifelong transitions between the states: relapse and recovery. The long-term pattern of recurrent times-to-relapse can be investigated with routine register data on hospital admissions. The relapses become readmissions to hospital, and the time spent in hospital are gaps between subsequent times-at-risk. However, problems of selection and dependent censoring arise because the calendar period of observation is limited and the study population likely to be heterogeneous. We will theoretically verify that an assumption of conditional independence of all times-at-risk and gaps, given the latent individual frailty level, allows for consistent inference in the shared frailty model. Using simulation studies, we also investigate cases where gaps (and/or staggered entry) are informative for the individual frailty. We found that the use of the shared frailty model can be extended to situations, where gaps are dependent on the frailty, but short compared to the distribution of the times-to-relapse. Our motivating example deals with the course of schizophrenia. We analysed routine register data on readmissions in almost 9000 persons with the disorder. Marginal survival curves of time-to-first-readmission, time-to-second-readmission, etc. were estimated in the shared frailty model. Based on the schizophrenia literature, the conclusion of our analysis was rather surprising: one of a stable course of disorder.

Socioeconomic status and use of postmenopausal hormone replacement therapy among Danish women.

BACKGROUND: Observational studies on hormone replacement therapy (HRT) have shown cardioprotective effects that have not been replicated in randomized controlled trials, perhaps due to unaccounted confounding by socioeconomic factors. To resolve this discrepancy, we examined the association between socioeconomic status (SES) and HRT use in a large population of Danish postmenopausal women. METHODS: We conducted a register-based cross-sectional study based on all women aged 40 or more with a permanent address in the North Jutland County, Denmark on 1 January 1999 (n = 122 584). The women were classified according to SES through the Prevention Registry at Statistics Denmark. Through the Pharmaco-epidemiological Prescription Database, we identified all reimbursed HRT prescriptions in North Jutland County for women aged 40 or more in the study population during 1999. We calculated 1-year prevalence proportions of HRT use for all socioeconomic groups. Between-group comparisons were made by log-risk analysis with adjustment for age. RESULTS: The estimated overall user-prevalence of HRT in 1999 among Danish postmenopausal women was 14.9%[95% confidence interval (CI) 14.7-15.1]. No substantial socioeconomic gradient was found in the study. The adjusted relative prevalence proportions (RPPs) varied between 0.90 and 1.14 among the different groups when using salaried employees, basic level, as the reference group. CONCLUSIONS: Our findings suggest that recent observational studies on the use of hormone replacement therapy among women in Denmark may not have suffered from strong confounding by socioeconomic status.

Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status.

Research suggests that heredity and early fetal development play a causal role in autism. This case-control study explored the association between perinatal factors, parental psychiatric history, socioeconomic status, and risk of autism. The study was nested within a cohort of all children born in Denmark after 1972 and at risk of being diagnosed with autism until December 1999. Prospectively recorded data were obtained from nationwide registries in Denmark. Cases totaled 698 children with a diagnosis of autism; each case was individually matched by gender, birth year, and age to 25 controls. Analyses by conditional logistic regression produced risk ratios and 95% confidence intervals. Adjusted analyses showed that the risk of autism was associated with breech presentation (risk ratio (RR) = 1.63, 95% confidence interval (CI): 1.18, 2.26), low Apgar score at 5 minutes (RR = 1.89, 95% CI: 1.10, 3.27), gestational age at birth <35 weeks (RR = 2.45, 95% CI: 1.55, 3.86), and parental psychiatric history (schizophrenia-like psychosis: RR = 3.44, 95% CI: 1.48, 7.95; affective disorder: RR = 2.91, 95% CI: 1.65, 5.14). Analyses showed no statistically significant association between risk of autism and weight for gestational age, parity, number of antenatal visits, parental age, or socioeconomic status. Results suggest that prenatal environmental factors and parental psychopathology are associated with the risk of autism. These factors seem to act independently.