Missing data and multiple imputation in clinical epidemiological research

Missing data are ubiquitous in clinical epidemiological research. Individuals with missing data may differ from those with no missing data in terms of the outcome of interest and prognosis in general. Missing data are often categorized into the following three types: missing completely at random (MCAR), missing at random (MAR), and missing not at random (MNAR). In clinical epidemiological research, missing data are seldom MCAR. Missing data can constitute considerable challenges in the analyses and interpretation of results and can potentially weaken the validity of results and conclusions. A number of methods have been developed for dealing with missing data. These include complete-case analyses, missing indicator method, single value imputation, and sensitivity analyses incorporating worst-case and best-case scenarios. If applied under the MCAR assumption, some of these methods can provide unbiased but often less precise estimates. Multiple imputation is an alternative method to deal with missing data, which accounts for the uncertainty associated with missing data. Multiple imputation is implemented in most statistical software under the MAR assumption and provides unbiased and valid estimates of associations based on information from the available data. The method affects not only the coefficient estimates for variables with missing data but also the estimates for other variables with no missing data

Combined endo-β-1,4-xylanase and α-L-arabinofuranosidase increases butyrate concentration during broiler cecal fermentation of maize glucurono-arabinoxylan

Solubilisation of prebiotic arabinoxylooligosaccharides from complex arabinoxylans in e.g. maize by xylanases may be increased by addition of auxiliary debranching enzymes. In this study, the hydrolysis and fermentation of maize fibre was investigated in vitro using a xylanase and an alpha-L-arabinofuranosidase. Combining the enzymes induced a higher (P < .001) xylose solubilisation and higher (P < .05) butyrate production during in vitro fermentation of maize fibre with cecal broiler inoculum compared to applying enzymes separately after 48 h. Subsequently, fibre degradation and fermentation was investigated in ROSS 308 broiler chickens supplemented with the enzyme combination to test the effects on gut morphology and microbiota composition along with performance. However, to address the relevance of combining the enzymes in vivo, further full factorial studies using individual enzymes at lower dosages are needed. Birds were fed a maize/soy based diet with 100 g/kg maize DDGS and 50 g/kg rapeseed meal. Enzymes supplementation increased (P < .001) body weight (+ 5.4%) and improved (P < .001) feed conversion ratio (-5.8%) after 29 days compared to control birds. Non-starch polysaccharide analysis and confocal microscopy of jejunum digesta visualised and confirmed solubilisation of the insoluble maize (glucurono)arabinoxylan. Birds receiving enzyme supplementation had increased (P < .001) duodenum villi length (+120 mu m) and reduced (P < .002) CD3 T-cell infiltration (-22.1%) after 29 days. Cecal butyrate levels were increased (P < .05) compared to controls. Although the microbiota composition was not significantly altered, numerical increases in cecal Ruminococcaceae and Lachnospiraceae genera were observed in birds supplemented with enzymes

Selective serotonin reuptake inhibitor use in hip fracture patients: a Danish nationwide prevalence study

BACKGROUND AND PURPOSE — Selective serotonin reuptake inhibitors (SSRIs) are often used in the elderly and are associated with adverse effects. Therefore, it is important to ascertain the prevalence of SSRI use in fragile and surgery-treated hip fracture patients. METHODS — This population-based prevalence study included Danish hip fracture patients aged ≥ 65 years operated in 2006–2016 (n = 68,607) and matched individuals from the background population (n = 343,020). Using Poisson regression, prevalence risk ratios (PRRs) with 95% confidence intervals (CIs) were estimated to compare hip fracture patients with the general population, and to estimate the association between hip fracture patient characteristics and SSRI prescriptions. RESULTS — The prevalence of SSRI use among hip fracture patients was 23% compared with 12% in the general population. During 2006–2016, the prevalence decreased from 26% to 18% among hip fracture patients and from 13% to 10% in the general population. Factors associated with SSRI use in hip fracture patients were age 75–84 years (PRR 1.18, CI 1.13–1.23), age ≥ 85 years (PRR 1.17, CI 1.11–1.22), female sex (PRR 1.13, CI 1.09–1.17), unmarried status (PRR 1.15, CI 1.11–1.19), living in a residential institution (PRR 2.30, CI 2.19–2.40), Charlson comorbidity index (CCI) score 1–2 (PRR 1.50, CI 1.45–1.55), CCI score 3+ (PRR 1.62, CI 1.55–1.69), and several medications. INTERPRETATION — The prevalence of SSRI use was high among hip fracture patients compared with the general population. Our data stress the importance of continued clinical awareness of frailty, comorbidity, and polypharmacy of hip fracture patients and the potentially adverse drug effects of SSRI treatment

Selective serotonin reuptake inhibitor use and mortality, postoperative complications, and quality of care in hip fracture patients: a Danish nationwide cohort study

PURPOSE: To examine the association between selective serotonin reuptake inhibitor (SSRI) use and mortality, postoperative complications, and quality of in-hospital care in hip fracture patients. PATIENTS AND METHODS: The study was a nationwide cohort study based on individual-level linked, prospectively collected data from Danish population-based national registries covering all hospitals in Denmark. The health care system in Denmark is tax-funded, and all citizens have equal access to health care services. We included patients with first-time hospitalization due to hip fracture undergoing surgery from 2006–2016. We estimated the risk of 30-day mortality, any unplanned readmission, any reoperation, specific postoperative complications including cardiovascular events and major bleeding, and quality of in-hospital care using Cox and Poisson regression analyses comparing current and former SSRI users with non-users. RESULTS: In 68,487 hip fracture patients, 13,272 (19%) were current SSRI users, 2,777 (4%) were former SSRI users, and 52,438 (77%) were SSRI non-users. The 30-day mortality risk was 13% in current SSRI users (HR 1.16, 1.10–1.21) and 12% in former (HR 1.15, 1.04–1.27) compared with 10% in non-users. The HR for any unplanned readmission was 1.11 (1.02–1.20) in current and 1.13 (1.01–1.27) in former SSRI users and for any reoperation 1.21 (1.11–1.31) in current and 1.04 (0.84–1.28) in former SSRI users compared with non-users. The risk of venous thromboembolism, myocardial infarction, stroke, and bleeding were similar irrespective of SSRI use. No association between current and former SSRI use and quality of in-hospital care was found. CONCLUSION: In patients undergoing hip fracture surgery, 30-day mortality and overall readmission risk were elevated in both current and former SSRI users compared with non-users. Those currently using SSRI had a 26% increased reoperation risk compared with non-users. However, SSRI use was not associated with increased risk of other postoperative complications and lower quality of in-hospital care. A limitation of this study was the inability to control for potential confounding of social deprivation

MLVA Subtyping of Genovar E Chlamydia trachomatis Individualizes the Swedish Variant and Anorectal Isolates from Men who Have Sex with Men

This study describes a new multilocus variable number tandem-repeat (VNTR) analysis (MLVA) typing system for the discrimination of Chlamydia trachomatis genovar D to K isolates or specimens. We focused our MLVA scheme on genovar E which predominates in most populations worldwide. This system does not require culture and therefore can be performed directly on DNA extracted from positive clinical specimens. Our method was based on GeneScan analysis of five VNTR loci labelled with fluorescent dyes by multiplex PCR and capillary electrophoresis. This MLVA, called MLVA-5, was applied to a collection of 220 genovar E and 94 non-E genovar C. trachomatis isolates and specimens obtained from 251 patients and resulted in 38 MLVA-5 types. The genetic stability of the MLVA-5 scheme was assessed for results obtained both in vitro by serial passage culturing and in vivo using concomitant and sequential isolates and specimens. All anorectal genovar E isolates from men who have sex with men exhibited the same MLVA-5 type, suggesting clonal spread. In the same way, we confirmed the clonal origin of the Swedish new variant of C. trachomatis. The MLVA-5 assay was compared to three other molecular typing methods, ompA gene sequencing, multilocus sequence typing (MLST) and a previous MLVA method called MLVA-3, on 43 genovar E isolates. The discriminatory index was 0.913 for MLVA-5, 0.860 for MLST and 0.622 for MLVA-3. Among all of these genotyping methods, MLVA-5 displayed the highest discriminatory power and does not require a time-consuming sequencing step. The results indicate that MLVA-5 enables high-resolution molecular epidemiological characterisation of C. trachomatis genovars D to K infections directly from specimens

Type D personality is associated with increased metabolic syndrome prevalence and an unhealthy lifestyle in a cross-sectional Dutch community sample

<p>Abstract</p> <p>Background</p> <p>People with Type D-Distressed-personality have a general tendency towards increased negative affectivity (NA), while at the same time inhibiting these emotions in social situations (SI). Type D personality is associated with an increased risk of adverse outcomes in patients with cardiovascular disease. Whether Type D personality is a cardiovascular risk factor in healthy populations remains to be investigated. In the present study, the relations between Type D personality and classical cardiovascular risk factors, i.e. metabolic syndrome and lifestyle were investigated in a Dutch community sample.</p> <p>Methods</p> <p>In a cross-sectional study 1592 participants were included, aged 20-80 years. Metabolic syndrome was defined by self-report, following the International Diabetes Federation-IDF-guidelines including an increased waist circumference, dyslipidemia, hypertension, and diabetes. In addition lifestyle factors smoking, alcohol use, exercise and dietary habits were examined. Metabolic syndrome prevalence was stratified by Type D personality (a high score on both NA and SI), lifestyle and confounders age, gender, having a partner, higher education level, cardiac history, family history of cardiovascular disease.</p> <p>Results</p> <p>Metabolic syndrome was more prevalent in persons with a Type D personality (13% vs. 6%). Persons with Type D personality made poorer lifestyle choices, adhered less to the physical activity norm (OR = 1.5, 95%CI = 1.1-2.0, <it>p </it>= .02), had a less varied diet (OR = 0.50, 95%CI = 0.40-0.70, <it>p </it>< .0005), and were less likely to restrict their fat intake (OR = 0.70, 95%CI = 0.50-0.90, <it>p </it>= .01). Type D personality was related to a twofold increased risk of metabolic syndrome (OR = 2.2, 95%CI = 1.2-4.0, <it>p </it>= .011), independent of lifestyle factors and confounders.</p> <p>Conclusions</p> <p>Type D personality is related to an increased prevalence of metabolic syndrome and unhealthy lifestyle, which suggests both behavioral and biological vulnerability for development of cardiovascular disorders and diabetes.</p

Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion

The personality traits of neuroticism and extraversion are predictive of a number of social and behavioural outcomes and psychiatric disorders. Twin and family studies have reported moderate heritability estimates for both traits. Few associations have been reported between genetic variants and neuroticism/extraversion, but hardly any have been replicated. Moreover, the ones that have been replicated explain only a small proportion of the heritability (<∼2%). Using genome-wide single-nucleotide polymorphism (SNP) data from ∼12 000 unrelated individuals we estimated the proportion of phenotypic variance explained by variants in linkage disequilibrium with common SNPs as 0.06 (s.e.=0.03) for neuroticism and 0.12 (s.e.=0.03) for extraversion. In an additional series of analyses in a family-based sample, we show that while for both traits ∼45% of the phenotypic variance can be explained by pedigree data (that is, expected genetic similarity) one third of this can be explained by SNP data (that is, realized genetic similarity). A part of the so-called ‘missing heritability' has now been accounted for, but some of the reported heritability is still unexplained. Possible explanations for the remaining missing heritability are that: (i) rare variants that are not captured by common SNPs on current genotype platforms make a major contribution; and/ or (ii) the estimates of narrow sense heritability from twin and family studies are biased upwards, for example, by not properly accounting for nonadditive genetic factors and/or (common) environmental factors

A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder

Background Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. Methods We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls). Results Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98–1.06], p = .28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11–1.18], p = 1.5E-15). Conclusions Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence

Use of complementary and alternative medicine at Norwegian and Danish hospitals

<p>Abstract</p> <p>Background</p> <p>Several studies have found that a high proportion of the population in western countries use complementary and alternative medicine (CAM). However, little is known about whether CAM is offered in hospitals. The aim of this study was to describe to what extent CAM is offered in Norwegian and Danish hospitals and investigate possible changes in Norway since 2001.</p> <p>Methods</p> <p>A one-page questionnaire was sent to all included hospitals in both countries. The questionnaire was sent to the person responsible for the clinical activity, typically the medical director. 99 hospitals in the authority (85%) in Norway and 126 in Denmark (97%) responded. Given contact persons were interviewed.</p> <p>Results</p> <p>CAM is presently offered in about 50% of Norwegian hospitals and one-third of Danish hospitals. In Norway CAM was offered in 50 hospitals, 40 of which involved acupuncture. 19 hospitals gave other alternative therapies like biofeedback, hypnosis, cupping, ear-acupuncture, herbal medicine, art therapy, homeopathy, reflexology, thought field therapy, gestalt therapy, aromatherapy, tai chi, acupressure, yoga, pilates and other. 9 hospitals offered more than one therapy form. In Denmark 38 hospitals offered acupuncture and one Eye Movement Desensitization and Reprocessing Light Therapy. The most commonly reported reason for offering CAM was scientific evidence in Denmark. In Norway it was the interest of a hospital employee, except for acupuncture where the introduction is more often initiated by the leadership and is more based on scientific evidence of effect. All persons (except one) responsible for the alternative treatment had a medical or allied health professional background and their education/training in CAM treatment varied substantially.</p> <p>Conclusions</p> <p>The extent of CAM being offered has increased substantially in Norway during the first decade of the 21^stcentury. This might indicate a shift in attitude regarding CAM within the conventional health care system.</p