Sample size calculation and optimal design for regression-based norming of tests and questionnaires.

To prevent mistakes in psychological assessment, the precision of test norms is important. This can be achieved by drawing a large normative sample and using regression-based norming. Based on that norming method, a procedure for sample size planning to make inference on Z-scores and percentile rank scores is proposed. Sampling variance formulas for these norm statistics are derived and used to obtain the optimal design, that is, the optimal predictor distribution, for the normative sample, thereby maximizing precision of estimation. This is done under five regression models with a quantitative and a categorical predictor, differing in whether they allow for interaction and nonlinearity. Efficient robust designs are given in case of uncertainty about the regression model. Furthermore, formulas are provided to compute the normative sample size such that individuals' positions relative to the derived norms can be assessed with prespecified power and precision. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effects of galectin-3 protein on UVA-induced damage in retinal pigment epithelial cells.

Several inflammatory molecules have been suggested as biomarkers of age-related macular degeneration (AMD). Galectin-3 (Gal-3), which has been shown to have a protective role in corneal injury by promoting epithelial cells adhesion and migration to the extracellular matrix, is also highly expressed in the retinal pigment epithelium (RPE) of patients with AMD. This study evaluated the role of Gal-3 in an in vitro model of UVA-induced RPE damage, as a proof-of-concept. ARPE-19 cells (human RPE cell line), were incubated with Gal-3 at 0.5-2.5 µg/mL concentrations prior to UVA irradiation for 15, 30, and 45 min, which resulted in accumulated doses of 2.5, 5, and 7.5 J/cm2, respectively. After 24 h incubation, MTT and LDH assays, immunofluorescence, and ELISA were performed. UVA irradiation for 15, 30, and 45 min proved to reduce viability in 83%, 46%, and 11%, respectively. Based on the latter results, we chose the intermediate dose (5-J/cm2) for further analysis. Pretreatment with Gal-3 at concentrations > 1.5 µg/mL showed to increase the viability of UVA-irradiated cells (~ 75%) compared to untreated cells (64%). Increased levels of cleaved caspase 3, a marker of cell death, were detected in the ARPE cells after UVA irradiation with or without addition of exogenous Gal-3. The inhibitory effect of Gal-3 on UVA-induced cell damage was characterized by decreased ROS levels and increased p38 activation, as detected by fluorescence analysis. In conclusion, our study suggests a photoprotective effect of Gal-3 on RPE by reducing oxidative stress and increasing p38 activation.

Imputation of Missing Covariates in Randomized Controlled Trials with Continuous Outcomes: Simple, Unbiased and Efficient Methods.

The literature on dealing with missing covariates in nonrandomized studies advocates the use of sophisticated methods like multiple imputation (MI) and maximum likelihood (ML)-based approaches over simple methods. However, these methods are not necessarily optimal in terms of bias and efficiency of treatment effect estimation in randomized studies, where the covariate of interest (treatment group) is independent of all baseline (pre-randomization) covariates due to randomization. This has been shown in the literature, but only for missingness on a single baseline covariate. Here, we extend the situation to multiple baseline covariates with missingness and evaluate the performance of MI and ML compared with simple alternative methods under various missingness scenarios in RCTs with a quantitative outcome. We first derive asymptotic relative efficiencies of the simple methods under the missing completely at random (MCAR) scenario and then perform a simulation study for non-MCAR scenarios. Finally, a trial on chronic low back pain is used to illustrate the implementation of the methods. The results show that all simple methods give unbiased treatment effect estimation but with increased mean squared residual. It also turns out that mean imputation and the missing-indicator method are most efficient under all covariate missingness scenarios and perform at least as well as MI and LM in each scenario.

Effectiveness of an integrated multidisciplinary geriatric rehabilitation programme for older persons with stroke: a multicentre randomised controlled trial.

BACKGROUND: Almost half of the stroke patients admitted to geriatric rehabilitation has persisting problems after discharge. Currently, there is no evidence based geriatric rehabilitation programme available for older stroke patients, combining inpatient rehabilitation with adequate ambulatory aftercare in the community. Therefore, we developed an integrated multidisciplinary rehabilitation programme that includes aftercare for older persons with stroke. We evaluated the effectiveness of this newly developed rehabilitation programme in comparison to usual care. METHODS: A multicentre randomised controlled trial was conducted in eight geriatric rehabilitation stroke units and their collaborating partners in primary care. The study population involved stroke patients and their informal caregivers who were aged 65 or over, living in the community before admission to geriatric rehabilitation, and expected to be able to return home after discharge. The programme consisted of three modules: inpatient neurorehabilitation, home-based self-management training, and stroke education. For patients, daily activity (FAI) was assessed as primary outcome and functional dependence (Katz-15), perceived quality of life (SSQoL) and social participation (IPA) as secondary outcomes. Additionally, among informal caregivers perceived care burden (self-rated burden VAS), objective care burden (Erasmus iBMG), and quality of life (CarerQol), were assessed as secondary outcomes. RESULTS: In total 190 patients and 172 informal caregivers were included. Mean age of the patients in the intervention group was 78.9 years (SD = 7.0) and in the usual care group 79.0 years (SD = 6.5). Significant favourable effects for the programme were observed for the subscale autonomy outdoors of the IPA (- 2.15, P = .047, and for the informal caregivers perceived care burden (1.23, P = .048. For the primary outcome daily activity and the other secondary outcomes, no significant effects were observed. CONCLUSION: The integrated multidisciplinary programme had no effect on daily activity of older stroke patients. However, patients participating in the programme had a higher level of perceived autonomy of outdoor activities and their informal caregivers perceived a lower care burden. The programme might be promising in providing adequate (after) care, although adaptation of the programme is recommended to increase its feasibility and improve its effects. TRIAL REGISTRATION: Current Controlled Trials ISRCTN62286281 . Registered 19-3-2010.

Imputation of missing covariate in randomized controlled trials with a continuous outcome: Scoping review and new results.

In this article, we first review the literature on dealing with missing values on a covariate in randomized studies and summarize what has been done and what is lacking to date. We then investigate the situation with a continuous outcome and a missing binary covariate in more details through simulations, comparing the performance of multiple imputation (MI) with various simple alternative methods. This is finally extended to the case of time-to-event outcome. The simulations consider five different missingness scenarios: missing completely at random (MCAR), at random (MAR) with missingness depending only on the treatment, and missing not at random (MNAR) with missingness depending on the covariate itself (MNAR1), missingness depending on both the treatment and covariate (MNAR2), and missingness depending on the treatment, covariate and their interaction (MNAR3). Here, we distinguish two different cases: (1) when the covariate is measured before randomization (best practice), where only MCAR and MNAR1 are plausible, and (2) when it is measured after randomization but before treatment (which sometimes occurs in nonpharmaceutical research), where the other three missingness mechanisms can also occur. The proposed methods are compared based on the treatment effect estimate and its standard error. The simulation results suggest that the patterns of results are very similar for all missingness scenarios in case (1) and also in case (2) except for MNAR3. Furthermore, in each scenario for continuous outcome, there is at least one simple method that performs at least as well as MI, while for time-to-event outcome MI is best.

Two receptor-like protein kinases, MUSTACHES and MUSTACHES-LIKE, regulate lateral root development in Arabidopsis thaliana.

Receptor-like protein kinases (RLKs) play key roles in regulating plant growth, development and stress adaptations. There are at least 610 RLKs (including receptor-like cytoplasmic kinases) in Arabidopsis. The functions of the majority of RLKs have not yet been determined. We previously generated promoter::GUS transgenic plants for all leucine-rich repeat (LRR)-RLKs in Arabidopsis and analyzed their expression patterns during various developmental stages. We found the expression of two LRR-RLKs, MUSTACHES (MUS) and MUSTACHES-LIKE (MUL), are overlapped in lateral root primordia. Independent mutants, mus-3 mul-1 and mus-4 mul-2, show a significantly decreased emerged lateral root phenotype. Our analyses indicate that the defects of the double mutant occur mainly at stage I of lateral root development. Exogenous application of auxin can dramatically enhance the transcription of MUS, which is largely dependent on AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19. MUS and MUL are inactive kinases in vitro but are phosphorylated in planta, possibly by an unknown kinase. The kinase activity of MUS is dispensable for its function in lateral root development. Many cell wall related genes are down regulated in mus-3 mul-1. In conclusion, we identified MUS and MUL, two kinase-inactive RLKs, in controlling the early development of lateral root primordia likely via regulating cell wall synthesis and remodeling.

The Control of Cell Expansion, Cell Division, and Vascular Development by Brassinosteroids: A Historical Perspective.

Steroid hormones are important signaling molecules in plants and animals. The plant steroid hormone brassinosteroids were first isolated and characterized in the 1970s and have been studied since then for their functions in plant growth. Treatment of plants or plant cells with brassinosteroids revealed they play important roles during diverse developmental processes, including control of cell expansion, cell division, and vascular differentiation. Molecular genetic studies, primarily in Arabidopsis thaliana, but increasingly in many other plants, have identified many genes involved in brassinosteroid biosynthesis and responses. Here we review the roles of brassinosteroids in cell expansion, cell division, and vascular differentiation, comparing the early physiological studies with more recent results of the analysis of mutants in brassinosteroid biosynthesis and signaling genes. A few representative examples of other molecular pathways that share developmental roles with brassinosteroids are described, including pathways that share functional overlap or response components with the brassinosteroid pathway. We conclude by briefly discussing the origin and conservation of brassinosteroid signaling.

Factors associated with successful home discharge after inpatient rehabilitation in frail older stroke patients.

BACKGROUND: Stroke is a highly prevalent disease among older people and can have a major impact on daily functioning and quality of life. When community-dwelling older people are hospitalized due to stroke, discharge to an intermediate care facility for geriatric rehabilitation is indicated when return to the previous living situation is expected but not yet possible. However, a substantial proportion is still unable to return home after discharge and has to be admitted to a residential care setting. This study aims to identify which factors are associated with home discharge after inpatient rehabilitation among frail and multimorbid older stroke patients. METHODS: This study is a longitudinal cohort study among 92 community-dwelling stroke patients aged 65 years or over. All patients were admitted to one of eight participating intermediate care facilities for geriatric rehabilitation, under the expectation to return home after rehabilitation. We examined whether 16 potentially relevant factors (age; sex; household situation before admission; stroke history; cardiovascular disorders; diabetes mellitus; multimorbidity; cognitive disability; neglect; apraxia; dysphagia; urinary and bowel incontinence; emotional problems; sitting balance; daily activity level; and independence in activities of daily living) measured at admission were associated with discharge to the former living situation. Logistic regression analysis was used for statistical analysis. RESULTS: Mean age of the patients was 79.0 years (SD 6.4) and 51.1% was female. A total of 71 patients (77.1%) were discharged to the former living situation within 6 months after the start of geriatric rehabilitation. Of the 16 factors analysed, only a higher level of independence in activities of daily living at admission was significantly associated with home discharge. CONCLUSIONS: Our study shows that the vast majority of previously identified factors predicting home discharge among stroke patients, could not predict home discharge among a group of frail and multimorbid older persons admitted to geriatric rehabilitation. Only a higher level of independence in activities of daily living at admission was significantly related to home discharge. Additional insight in other factors that might predict home discharge after geriatric rehabilitation among this specific group of frail older stroke patients, is needed. TRIAL REGISTRATION: ISRCTN ISRCTN62286281. Registered 19-3-2010.

SERK Receptor-like Kinases Control Division Patterns of Vascular Precursors and Ground Tissue Stem Cells during Embryo Development in Arabidopsis.

During embryo development, the vascular precursors and ground tissue stem cells divide to renew themselves and produce the vascular tissue, endodermal cells, and cortical cells. However, the molecular mechanisms regulating division of these stem cells have remained largely elusive. In this study, we show that loss of function of SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) genes results in aberrant embryo development. Fewer cortical, endodermal, and vascular cells are generated in the embryos of serk1 serk2 bak1 triple mutants. WUSCHEL-RELATED HOMEOBOX 5 (WOX5) is ectopically expressed in vascular cells of serk1 serk2 bak1 embryos. The first transverse division of vascular precursors in mid-globular embryos and second asymmetric division of ground tissue stem cells in early-heart embryos are abnormally altered to a longitudinal division. The embryo defects can be partially rescued by constitutively activated mitogen-activated protein kinase (MAPK) kinase kinase YODA (YDA) and MAPK kinase MKK5. Taken together, our results reveal that SERK-mediated signals regulate division patterns of vascular precursors and ground tissue stem cells, likely via the YDA-MKK4/5 cascade, during embryo development.

Air pollution during New Year's fireworks and daily mortality in the Netherlands.

Short-term exposure to air pollution has been associated with cardiovascular and respiratory mortality and morbidity. Little is known about associations between air pollution caused by firework events and daily mortality. We investigated whether particulate matter from fireworks during New Year's celebrations was associated with daily mortality. We analyzed the celebrations of the years 1995-2012. PM10 concentrations increased dramatically during the firework events. Countrywide, the daily average PM10 concentrations from 27-30 December was 29 µg/m3 and increased during the first hour of the New Year by 277 µg/m3. In the more densely populated areas of the Netherlands the increase was even steeper, 598 µg/m3 in the first hour of the New Year. No consistent associations were found using linear regression models between PM10 concentrations during the first six hours of 1 January and daily mortality in the general population. Yet, using a case-crossover analysis firework-days and PM10 concentrations were associated with daily mortality. Therefore, in light of the contradictory results obtained with the different statistical analyses, we recommend further epidemiological research on the health effects of exposure to firework emissions.

Professional and family caregivers' attitudes towards involuntary treatment in community-dwelling people with dementia.

AIMS: The aim of this study was to gain insight into professional and family caregivers' attitudes towards involuntary treatment in community-dwelling people with dementia (PwD). BACKGROUND: The number of PwD with complex care needs living at home is increasing rapidly. In some situations, caregivers provide care against the will of PwD, referred to as involuntary treatment, which includes non-consensual care, psychotropic medication and physical restraints. DESIGN: A cross-sectional study. METHODS: A total of 228 professional (nursing staff, general practitioners (GPs) and other healthcare professionals such as physical therapists and psychologists) and 77 family caregivers of PwD completed the Maastricht Attitude Questionnaire-Home Care. This questionnaire measures attitudes towards involuntary treatment and perceived restrictiveness of and experienced discomfort in using involuntary treatment. Data were collected in the Netherlands between June and November 2016. RESULTS: Family caregivers and GPs had more positive attitudes towards involuntary treatment than nursing staff and other healthcare professionals, indicating that they are more accepting of involuntary treatment. A more positive attitude was associated with higher perceived caregiver burden and being a family caregiver. Family caregivers and GPs found the use of involuntary treatment less restrictive and indicated feeling more comfortable when using these measures. CONCLUSION: It is important to account for the differences in attitudes and foster dialogue among professional and family caregivers to find common ground about alternatives to involuntary treatment. These results will inform the development of an intervention that aims to prevent involuntary treatment in home care.

Relative efficiencies of two-stage sampling schemes for mean estimation in multilevel populations when cluster size is informative.

In multilevel populations, there are two types of population means of an outcome variable ie, the average of all individual outcomes ignoring cluster membership and the average of cluster-specific means. To estimate the first mean, individuals can be sampled directly with simple random sampling or with two-stage sampling (TSS), that is, sampling clusters first, and then individuals within the sampled clusters. When cluster size varies in the population, three TSS schemes can be considered, ie, sampling clusters with probability proportional to cluster size and then sampling the same number of individuals per cluster; sampling clusters with equal probability and then sampling the same percentage of individuals per cluster; and sampling clusters with equal probability and then sampling the same number of individuals per cluster. Unbiased estimation of the average of all individual outcomes is discussed under each sampling scheme assuming cluster size to be informative. Furthermore, the three TSS schemes are compared in terms of efficiency with each other and with simple random sampling under the constraint of a fixed total sample size. The relative efficiency of the sampling schemes is shown to vary across different cluster size distributions. However, sampling clusters with probability proportional to size is the most efficient TSS scheme for many cluster size distributions. Model-based and design-based inference are compared and are shown to give similar results. The results are applied to the distribution of high school size in Italy and the distribution of patient list size for general practices in England.

The effectiveness of an integrated care pathway in geriatric rehabilitation among older patients with complex health problems and their informal caregivers: a prospective cohort study.

BACKGROUND: To improve continuity and coordination of care in geriatric rehabilitation, an integrated care pathway was developed and implemented in The Netherlands. The purpose of this study was to assess the effects of this pathway on patients and informal caregivers. METHODS: Two cohorts of patients and their informal caregivers were prospectively recruited before implementation of the pathway (2011-2012) and after implementation of the pathway (2013-2014). Primary outcome measures were dependence in activities of daily living in patients (KATZ-15) and self-rated burden among informal caregivers (SRB-VAS). Secondary outcome measures were the frequency of performing extended daily activities, social participation, psychological well-being, quality of life and discharge location (patients) and quality of life and objective care burden (informal caregivers). Outcomes were measured at baseline, after three and after nine months. RESULTS: No effect was shown on the KATZ-15 after three and nine months. However, a larger percentage of patients were discharged home in the care pathway cohort (83% vs 58.1% after three months and 88.6% vs 67.4% after nine months; p = 0.004). Furthermore, after three months, patients from the care pathway cohort performed more extended daily activities (p = 0.014) and informal caregivers experienced a lower self-rated burden (p = 0.05). After nine months, these effects disappeared. No differences were found for the other outcome measures. CONCLUSIONS: Due to the positive effects of the integrated care pathway, we are inclined to recommend implementing the care pathway in regular care. To have longer lasting effects among patients and informal caregivers, we suggest actively disseminating information about the pathway to primary care providers who are currently still unaware of its content. TRIAL REGISTRATION: ISRCTN90000867 (date of registration: 07-04-2016).

The use of involuntary treatment among older adults with cognitive impairment receiving nursing care at home: A cross-sectional study.

BACKGROUND: Respect for inherent dignity and individual autonomy is a basic principle in health care. However, several studies indicate that care-dependent older adults with a cognitive impairment, receiving nursing care at home, are at risk of care without their consent, referred to as 'involuntary treatment'. This includes the application of physical restraints (e.g. measures to prevent leaving bed or chair), psychotropic drugs (e.g. antidepressants, sedatives) and non-consensual care (e.g. forced hygiene, hiding medication). Research about involuntary treatment is scarce and only recently first studies have been conducted. OBJECTIVE: To investigate 1) the prevalence of involuntary treatment, 2) associated factors and 3) who requests and applies their use among older adults with cognitive impairment receiving nursing care at home. DESIGN: Cross- sectional study. SETTING: Homes of older adults receiving nursing care from district nurses in the eastern part of Belgium. PARTICIPANTS: Data were collected from 1194 randomly selected older adults with cognitive impairments receiving nursing care at home (mean age 83; 67% female). METHOD: District nurses completed an online questionnaire for each selected older adult in their caseload. Involuntary treatment was measured using a questionnaire identifying use of physical restraints, psychotropic medication and non-consensual care. In addition who requests involuntary treatment and who applies it was examined. Older adults sociodemographic characteristics, diagnosis of dementia, activities of daily living (ADL), cognitive status and informal caregiver burden were assessed. RESULTS: Involuntary treatment was used in 52% (95%; CI 49-55) of the total sample. Non-consensual care was most often used (73%; 95% CI 70-77), followed by psychotropic drugs (43%; 95% CI 39-47) and physical restraints (38%; 95% CI 35-42). The use of involuntary treatment was associated with dependency for activities of daily life (OR 1.50; 95% CI 1.33-1.69), cognitive impairment (1.39; 95% CI 1.25-1.55), informal caregiver burden (OR 1.05; 95% CI 1.01-1.10) and aging (OR 0.97; 95% CI 0.95-0.99). Informal caregivers (71%), followed by general practitioners (47%) most frequently requested the use of involuntary treatment, and nurses (81%) mostly applied it. CONCLUSION: In Belgium, involuntary treatment is often used in older adults with a cognitive impairment receiving nursing care at home. The implication of this study for clinical practice is that it confirms the need to develop an approach to prevent and reduce it. Further research is needed to plan and develop such an approach, in order to prevent and reduce the use of involuntary treatment.

Guidelines for multiple imputations in repeated measurements with time-dependent covariates: a case study.

OBJECTIVES: We provide guidelines for handling the most common missing data problems in repeated measurements in observational studies and deal with practicalities in producing imputations when there are many partly missing time-varying variables and repeated measurements. STUDY DESIGN AND SETTING: The Maastricht Study on long-term dementia care environments was used as a case study. The data contain 84 momentary assessments for each of 115 participants. A continuous outcome and several time-varying covariates were involved containing missing observations varying from 4% to 25% per time point. A multiple imputation procedure is advocated with restrictions imposed on the relation within and between partially missing variables over time. RESULTS: Multiple imputation is a better approach to deal with missing observations in both outcome and independent variables. Furthermore, using the statistical package R-MICE, it is possible to deal with the limitations of current statistical software in imputation of missing observations in more complex data. CONCLUSION: In observational studies, the direct likelihood approach (i.e., the standard longitudinal data methods) is sufficient to obtain valid inferences in the presence of missing data only in the outcome. In contrast, multiple imputation is required when dealing with partly missing time-varying covariates and repeated measurements.

Where there's smoke, there's fire: focal points for risk communication.

Large fires involving hazardous materials are often characterized by failing crisis communication. In this study, we compared opinions of experts regarding the risks of major fires to lay beliefs using a mental models approach. Amongst lay people this revealed relevant knowledge gaps and beliefs in opposition to those held by experts. While, experts considered the chance of getting cancer from inhaling smoke from a chemical fire extremely small, most lay people thought that even at a great distance, the chance of getting cancer to be large. To improve crisis communication about risk in a case of large chemical fires, and reduce the potential for messages to be misunderstood, distrusted or dismissed, we recommend a clarification of cancer risk in communications about public health emergencies such as chemical fires, for which lay people equate even small exposures to carcinogenic chemicals make one more likely to get cancer later in life.

A Common Pathway of Root Growth Control and Response to CLE Peptides Through Two Receptor Kinases in Arabidopsis.

Cell-cell communication is essential for plants to integrate developmental programs with external cues that affect their growth. Recent advances in plant signaling have uncovered similar molecular mechanisms in shoot, root, and vascular meristem signaling that involve receptor-like kinases and small, secreted peptides. Here, we report that the receptor-like kinases TOAD2/RPK2 and RPK1 regulate root growth by controlling cell proliferation and affecting meristem size. Two types of developmental alterations were observed upon exogenous CLE peptide application. The first type was detected in all plants treated, and comprise increased proliferative activity of cells in the stem cell niche and a delay of progression in differentiation of daughter cells. The second type was changes specific to the genotypes that are sensitive to CLE-driven root meristem inhibition and include a large decrease in the occurrence of cell divisions in longitudinal files, correlating with shorter meristems and cessation of root growth. The root meristems of toad2/rpk2 mutant plants are insensitive to the inhibitory effect of CLE17 peptide treatment, consistent with TOAD2/RPK2 function as a receptor for CLE peptides. In addition, a strong reduction in the expression of RPK1 protein upon CLE treatment, dependent on TOAD2/RPK2, suggests that these two RLKs mediate CLE signaling in a common pathway to control root growth.

Promoting Functional Activity Among Nursing Home Residents: A Cross-Sectional Study on Barriers Experienced by Nursing Staff.

OBJECTIVE: To obtain insight into (a) the prevalence of nursing staff-experienced barriers regarding the promotion of functional activity among nursing home residents, and (b) the association between these barriers and nursing staff-perceived promotion of functional activity. METHOD: Barriers experienced by 368 nurses from 41 nursing homes in the Netherlands were measured with the MAastrIcht Nurses Activity INventory (MAINtAIN)-barriers; perceived promotion of functional activities was measured with the MAINtAIN-behaviors. Descriptive statistics and hierarchical linear regression analyses were performed. RESULTS: Most often experienced barriers were staffing levels, capabilities of residents, and availability of resources. Barriers that were most strongly associated with the promotion of functional activity were communication within the team, (a lack of) referral to responsibilities, and care routines. DISCUSSION: Barriers that are most often experienced among nursing staff are not necessarily the barriers that are most strongly associated with nursing staff-perceived promotion of functional activity.

A total-population multigenerational family clustering study of autoimmune diseases in obsessive-compulsive disorder and Tourette's/chronic tic disorders.

The association between obsessive-compulsive disorder (OCD) and Tourette's/chronic tic disorders (TD/CTD) with autoimmune diseases (ADs) is uncertain. In this nationwide study, we sought to clarify the patterns of comorbidity and familial clustering of a broad range of ADs in individuals with OCD, individuals with TD/CTD and their biological relatives. From a birth cohort of 7 465 455 individuals born in Sweden between 1940 and 2007, we identified 30 082 OCD and 7279 TD/CTD cases in the National Patient Register and followed them up to 31 December 2013. The risk of 40 ADs was evaluated in individuals with OCD, individuals with TD/CTD and their first- (siblings, mothers, fathers), second- (half siblings) and third-degree (cousins) relatives, compared with population controls. Individuals with OCD and TD/CTD had increased comorbidity with any AD (43% and 36%, respectively) and many individual ADs. The risk of any AD and several individual ADs was consistently higher among first-degree relatives than among second- and third-degree relatives of OCD and TD/CTD probands. The risk of ADs was very similar in mothers, fathers and siblings of OCD probands, whereas it tended to be higher in mothers and fathers of TD/CTD probands (compared with siblings). The results suggest a familial link between ADs in general (that is, not limited to Streptococcus-related conditions) and both OCD and TD/CTD. Additional mother-specific factors, such as the placental transmission of antibodies, cannot be fully ruled out, particularly in TD/CTD.

Troponin I and T in relation to cardiac injury detected with electrocardiography in a population-based cohort - The Maastricht Study.

Interest in high-sensitivity cardiac troponin I(hs-cTnI) and T(hs-cTnT) has expanded from acute cardiac care to cardiovascular disease(CVD) risk stratification. Whether hs-cTnI and hs-cTnT are interchangeable in the ambulant setting is largely unexplored. Cardiac injury is a mechanism that may underlie the associations between troponin levels and mortality in the general population. In the population-based Maastricht Study, we assessed the correlation and concordance between hs-cTnI and hs-cTnT. Multiple regression analyses were conducted to assess the association of hs-cTnI and hs-cTnT with electrocardiographic (ECG) changes indicative of cardiac abnormalities. In 3016 eligible individuals(mean age,60 ± 8years;50.6%,men) we found a modest correlation between hs-cTnI and hs-cTnT(r = 0.585). After multiple adjustment, the association with ECG changes indicative of cardiac abnormalities was similar for both hs-cTn assays(OR,hs-cTnI:1.72,95%CI:1.40-2.10;OR,hs-cTnT:1.60,95%CI:1.22-2.11). The concordance of dichotomized hs-cTnI and hs-cTnT was κ = 0.397(≥sex-specific 75th percentile). Isolated high levels of hs-cTnI were associated with ECG changes indicative of cardiac abnormalities(OR:1.93,95%CI:1.01-3.68), whereas isolated high levels of hs-cTnT were not(OR:1.07,95%CI:0.49-2.31). In conclusion, there is a moderate correlation and limited concordance between hs-cTnI and hs-cTnT under non-acute conditions. These data suggest that associations of hs-cTnI and hs-cTnT with cardiac injury detected by ECG are driven by different mechanisms. This information may benefit future development of CVD risk stratification algorithms.