Methotrexate polyglutamates as a potential marker of adherence to long-term therapy in children with juvenile idiopathic arthritis and juvenile dermatomyositis:an observational, cross-sectional study

Introduction: Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of adherence to MTX is important. The present study demonstrates the feasibility of using methotrexate polyglutamates (MTXPGs) as a biomarker to measure adherence to MTX treatment in children with JIA and JDM. Methods: Data were collected prospectively from a cohort of 48 children (median age 11.5 years) who received oral or subcutaneous (SC) MTX therapy for JIA or JDM. Dried blood spot samples were obtained from children by finger pick at the clinic or via self- or parent-led sampling at home, and they were analysed to determine the variability in MTXPG concentrations and assess adherence to MTX therapy. Results: Wide fluctuations in MTXPG total concentrations (>2.0-fold variations) were found in 17 patients receiving stable weekly doses of MTX, which is indicative of nonadherence or partial adherence to MTX therapy. Age (P = 0.026) and route of administration (P = 0.005) were the most important predictors of nonadherence to MTX treatment. In addition, the study showed that MTX dose and route of administration were significantly associated with variations in the distribution of MTXPG subtypes. Higher doses and SC administration of MTX produced higher levels of total MTXPGs and selective accumulation of longer-chain MTXPGs (P < 0.001 and P < 0.0001, respectively). Conclusions: Nonadherence to MTX therapy is a significant problem in children with JIA and JDM. The present study suggests that patients with inadequate adherence and/or intolerance to oral MTX may benefit from SC administration of the drug. The clinical utility of MTXPG levels to monitor and optimise adherence to MTX in children has been demonstrated. Trial registration: ISRCTN Registry identifier: ISRCTN93945409. Registered 2 December 2011.

Factors associated with high anticholinergic burden in aging adults with intellectual disabilities:a cross-sectional study

Background: Anticholinergic (AC) medications are associated with cognitive and functional decline in older people, with risk of adverse outcomes increasing with increasing AC exposure. Older people with intellectual disabilities are at increased risk of high AC exposure owing to higher prevalence of multimorbidity, particularly psychiatric morbidities. Objectives: The aims of this study were to determine individual’s AC exposure using the AC cognitive burden (ACB) scale, identify therapeutic classes contributing to burden and determine clinical and demographic factors associated with two levels of AC exposure (ACB score 1–4, ACB 5+). Methods: Cross-sectional (self-report/proxy report)medication data were drawn from Wave 1 of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing, a study on ageing of 753nationally representative people with ID aged over40 randomly selected from the National Intellectual Disability Database. Medication data were available for 736 (98%). Each individual’s cumulative AC exposure was calculated using the ACB. Multinomiallogistic regression was performed identifying clinical and demographic factors associated with ACB score1–4, and ACB 5+. Results: In the eligible population of 736 participants(mean (±SD) age 54.1 (±8.8) years,55% female), 522(70.9%) were exposed to an ACB medicine (ACB 1+); 214 (29%) had an ACB score of 5+; mean total ACB score= 4.5 (±3.0). Antipsychotics accounted for35.6% of the cumulative ACB score. Age over 65yearswas associated with increased likelihood of both levels of AC exposure (ACB 1–4—adjusted OR 3.28; 95%CI 1.49–7.25, ACB 5+—adjusted OR 3.08; 95%CI1.21–7.63) and having a mental health condition(ACB 1–4—adjusted OR 9.79; 95%CI 5.63–17.02, ACB 5+—adjusted OR 23.74; 95%CI 12.29–45.83). Conclusions: Using a simple cumulative measure proved an effective means to capture total burden and established that AC exposure was high and associated with older age and mental health morbidity. This highlights need for comprehensive medication reviews for older people with intellectual disabilities.

Use of Homeostatic Model Assessment Indexes for the Identification of Metabolic Syndrome and Insulin Resistance among Cuban-Americans: A Cross Sectional Study

Aim: to determine cut off points for The Homeostatic Model Assessment Index 1 and 2 (HOMA-1 and HOMA-2) for identifying insulin resistance and metabolic syndrome among a Cuban-American population. Study Design: Cross sectional. Place and Duration of Study: Florida International University, Robert Stempel School of Public Health and Social Work, Department of Dietetics and Nutrition, Miami, FL from July 2010 to December 2011. Methodology: Subjects without diabetes residing in South Florida were enrolled (N=146, aged 37 to 83 years). The HOMA1-IR and HOMA2-IR 90th percentile in the healthy group (n=75) was used as the cut-off point for insulin resistance. A ROC curve was constructed to determine the cut-off point for metabolic syndrome. Results: HOMA1-IR was associated with BMI, central obesity, and triglycerides (P3.95 and >2.20 and for metabolic syndrome were >2.98 (63.4% sensitivity and 73.3% specificity) and >1.55 (60.6% sensitivity and 66.7% specificity), respectively. Conclusion: HOMA cut-off points may be used as a screening tool to identify insulin resistance and metabolic syndrome among Cuban-Americans living in South Florida.

A Cross-Generational Analysis of Spanish-to-English Lexico-Semantic Phenomena in Emerging Miami English

Sociolinguists have documented the substrate influence of various languages on the formation of dialects in numerous ethnic-regional setting throughout the United States. This literature shows that while phonological and grammatical influences from other languages may be instantiated as durable dialect features, lexical phenomena often fade over time as ethnolinguistic communities assimilate with contiguous dialect groups. In preliminary investigations of emerging Miami Latino English, we have observed that lexical forms based on Spanish lexical forms are not only ubiquitous among the speech of the first generation Cuban Americans but also of the second. Examples, observed in field work, casual observation, and studied formally in an experimental context include the following: “get down from the car,” which derives from the Spanish equivalent, bajar del carro instead of “get out of the car”. The translation task administered to thirty-one participants showed a variety lexical phenomena are still maintained at equal or higher frequencies.

Appendix A. Microfocus X-ray Computed Tomography cross-sectional images of Joergensenium arcticum Ikenoue, Dumitrica and Bjørklund n. sp.

Radiolarians in the Arctic Ocean have been studied lately in both plankton and sediment trap samples in the Chukchi Sea area. These studies have shed light on new radiolarian taxa, especially within the order Entactinaria, including two new species of Joergensenium, Joergensenium arcticum from the western Arctic Ocean, so far restricted to the Pacific Winter Water in the Chukchi Sea, and Joergensenium clevei hitherto found in the northern part of the Norwegian Sea south of the Fram Strait. The taxonomic position of the order Entactinaria is discussed and the genus Joergensenium has been emended. We have also observed in detail the internal structure of J. arcticum using Microfocus X-ray Computed Tomography and have utilized three-dimensional imaging for the first time in a species description.

Variations in hip shape are associated with radiographic knee osteoarthritis : cross-sectional and longitudinal analyses of the Johnston County Osteoarthritis Project

Funding was provided in part by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) K23 AR061406 (Nelson); US National Institutes of Health (NIH)/NIAMS P60AR30701 (Jordan/Renner/Schwartz); US Centers for Disease Control/Association of Schools of Public Health S043 and S3486 (Jordan/Renner); K24-AR04884, P50-AR063043, and P50-AR060752 (Lane); and NIH/National Center for Advancing Translational Sciences KL2TR001109 (Golightly).

Variations in hip shape are associated with radiographic knee osteoarthritis : cross-sectional and longitudinal analyses of the Johnston County Osteoarthritis Project

Funding was provided in part by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) K23 AR061406 (Nelson); US National Institutes of Health (NIH)/NIAMS P60AR30701 (Jordan/Renner/Schwartz); US Centers for Disease Control/Association of Schools of Public Health S043 and S3486 (Jordan/Renner); K24-AR04884, P50-AR063043, and P50-AR060752 (Lane); and NIH/National Center for Advancing Translational Sciences KL2TR001109 (Golightly).

Non-prescription medicine misuse, abuse and dependence : a cross-sectional survey of the UK general population

This study was supported by the Society of the Study of Addiction in the form of a PhD studentship awarded to NF.

InternationaL cross-sectIonAl and longItudinal assessment on aSthma cONtrol in European adult patients : the LIAISON study protocol

The study is funded by Chiesi Farmaceutici S.p.A., Parma, Italy

Association of anticholinergic burden with adverse effects in older people with intellectual disabilities:an observational cross-sectional study

BACKGROUND: No studies to date have investigated cumulative anticholinergic exposure and its effects in adults with intellectual disabilities. AIMS: To determine the cumulative exposure to anticholinergics and the factors associated with high exposure. METHOD: A modified Anticholinergic Cognitive Burden (ACB) scale score was calculated for a representative cohort of 736 people over 40 years old with intellectual disabilities, and associations with demographic and clinical factors assessed. RESULTS: Age over 65 years was associated with higher exposure (ACB 1-4 odds ratio (OR) = 3.28, 95% CI 1.49-7.28, ACB 5+ OR = 3.08, 95% CI 1.20-7.63), as was a mental health condition (ACB 1-4 OR = 9.79, 95% CI 5.63-17.02, ACB 5+ OR = 23.74, 95% CI 12.29-45.83). Daytime drowsiness was associated with higher ACB (P<0.001) and chronic constipation reported more frequently (26.6% ACB 5+ v. 7.5% ACB 0, P<0.001). CONCLUSIONS: Older people with intellectual disabilities and with mental health conditions were exposed to high anticholinergic burden. This was associated with daytime dozing and constipation.

Fluid resuscitation practice patterns in intensive care units of the USA: a cross-sectional survey of critical care physicians.

BACKGROUND: Fluid resuscitation is a cornerstone of intensive care treatment, yet there is a lack of agreement on how various types of fluids should be used in critically ill patients with different disease states. Therefore, our goal was to investigate the practice patterns of fluid utilization for resuscitation of adult patients in intensive care units (ICUs) within the USA. METHODS: We conducted a cross-sectional online survey of 502 physicians practicing in medical and surgical ICUs. Survey questions were designed to assess clinical decision-making processes for 3 types of patients who need volume expansion: (1) not bleeding and not septic, (2) bleeding but not septic, (3) requiring resuscitation for sepsis. First-choice fluid used in fluid boluses for these 3 patient types was requested from the respondents. Descriptive statistics were performed using a Kruskal-Wallis test to evaluate differences among the physician groups. Follow-up tests, including t tests, were conducted to evaluate differences between ICU types, hospital settings, and bolus volume. RESULTS: Fluid resuscitation varied with respect to preferences for the factors to determine volume status and preferences for fluid types. The 3 most frequently preferred volume indicators were blood pressure, urine output, and central venous pressure. Regardless of the patient type, the most preferred fluid type was crystalloid, followed by 5 % albumin and then 6 % hydroxyethyl starches (HES) 450/0.70 and 6 % HES 600/0.75. Surprisingly, up to 10 % of physicians still chose HES as the first choice of fluid for resuscitation in sepsis. The clinical specialty and the practice setting of the treating physicians also influenced fluid choices. CONCLUSIONS: Practice patterns of fluid resuscitation varied in the USA, depending on patient characteristics, clinical specialties, and practice settings of the treating physicians.

Gaussian Process Kernels for Cross-Spectrum Analysis in Electrophysiological Time Series

Multi-output Gaussian processes provide a convenient framework for multi-task problems. An illustrative and motivating example of a multi-task problem is multi-region electrophysiological time-series data, where experimentalists are interested in both power and phase coherence between channels. Recently, the spectral mixture (SM) kernel was proposed to model the spectral density of a single task in a Gaussian process framework. This work develops a novel covariance kernel for multiple outputs, called the cross-spectral mixture (CSM) kernel. This new, flexible kernel represents both the power and phase relationship between multiple observation channels. The expressive capabilities of the CSM kernel are demonstrated through implementation of 1) a Bayesian hidden Markov model, where the emission distribution is a multi-output Gaussian process with a CSM covariance kernel, and 2) a Gaussian process factor analysis model, where factor scores represent the utilization of cross-spectral neural circuits. Results are presented for measured multi-region electrophysiological data.

Nurses' knowledge of advance directives and perceived confidence in end-of-life care: a cross-sectional study in five countries

Nurses' knowledge regarding advance directives may affect their administration and completion in end-of-life care. Confidence among nurses is a barrier to the provision of quality end-of-life care. This study investigated nurses' knowledge of advance directives and perceived confidence in end-of-life care, in Hong Kong, Ireland, Israel, Italy and the USA using a cross-sectional descriptive design (n = 1089). In all countries, older nurses and those who had more professional experience felt more confident managing patients' symptoms at end-of-life and more comfortable stopping preventive medications at end-of-life. Nurses in the USA reported that they have more knowledge and experience of advance directives compared with other countries. In addition, they reported the highest levels of confidence and comfort in dealing with end-of-life care. Although legislation for advance directives does not yet exist in Ireland, nurses reported high levels of confidence in end-of-life care.

The association between parental attitudes and alcohol consumption and adolescent alcohol consumption in Southern Ireland: a cross-sectional study

Background: Alcohol plays a complex role in society. A recent study showed that over half of Irish adults drink hazardously. Adolescents report increased levels of alcohol consumption. Previous research has inferred the influence of the parent on their adolescent. Thus, the aim of the current study was to investigate the association between adolescent alcohol consumption and their parent’s consumption pattern and attitude toward alcohol use in Southern Ireland. Methods: A cross-sectional survey was undertaken in November 2014. This involved distributing a survey to adolescents (n = 982) in their final two years of second level education and at least one of their parents from a local electorate area in Southern Ireland. This survey included: alcohol use, self- reported height and weight, smoking status, mental health and well-being along with attitudinal questions. Chi-square tests and multivariate logistic regression were utilised. Results: A 37 % response rate was achieved. Over one-third (34.2 %) of adolescents and 47 % of parents surveyed reported hazardous drinking. Over 90 % of parents disagreed with allowing their adolescent to get drunk and rejected the idea that getting drunk is part of having fun as an adolescent. The majority (79.5 %) of parents surveyed believed that their alcohol consumption pattern set a good example for their adolescent. Multivariate logistic regression highlights the association between adolescent hazardous alcohol consumption and hazardous drinking by the father. Furthermore either parent permitting their adolescent to drink alcohol on special occasions was associated with hazardous alcohol consumption in the adolescent. Conclusion: The findings of this research notes a liberal attitude to alcohol and increased levels of consumption by the parent are linked to hazardous adolescent drinking behaviour. Future action plans aimed at combatting adolescent hazardous alcohol consumption should also be aimed at tackling parents’ attitudes towards and consumption of alcohol.

THE EFFECT OF PREECLAMPSIA ON RENAL FUNCTION: CROSS-SECTIONAL STUDIES OF POSTPARTUM PREECLAMPTICS AND WOMEN WHO WERE DESTINED TO DEVELOP PREECLAMPSIA

Preeclampsia (PE) is a pregnancy complication that is new-onset of hypertension and proteinuria after 20 weeks of gestation. However, subclinical renal dysfunction may be apparent earlier in gestation prior to the clinical presentation of PE. Although the maternal syndrome of PE resolves early postpartum, women with a history of PE are at higher risk of renal dysfunction later in life. Mineral metabolism, such as phosphate balance is heavily dependent on renal function, yet, phosphate handling in women with a history of PE is largely unknown. To investigate whether women with a history of PE would exhibit changes in phosphate metabolism compared to healthy parous women, phosphate loading test was used. Women with or without a history of PE, who were 6 months to 5 years postpartum, were recruited for this study. Blood and urine samples were collected before and after the oral dosing of 500mg phosphate solution. Biochemical markers of phosphate metabolism and renal function were evaluated. In order to assess the difference in renal function alteration between first trimester women who were or were not destined to develop PE, plasma cystatin C concentration was analysed. After phosphate loading, women with a history of PE had significantly elevated serum phosphate at both 1- and 2-hour, while controls had higher urine phosphate:urine creatinine excretion ratio at 1-hour than women with a history of PE. Women with a history of PE had no changes in intact parathyroid hormone (iPTH) concentration throughout the study period, whereas controls had elevated iPTH at 1-hour from baseline. In terms of renal function in the first trimester, there was no difference in plasma cystatin C concentration between women who were or were not destined to develop PE. The elevation of serum phosphate in women with a history of PE could be due to the delay in phosphate excretion. Prolong elevation of serum phosphate can have serious consequences later in life. Thus, oral phosphate challenge may serve as a useful method of early screening for altered phosphate metabolism and renal function.