Polygenic risk assessment reveals pleiotropy between sarcoidosis and inflammatory disorders in the context of genetic ancestry.

Sarcoidosis is a complex disease of unknown etiology characterized by the presence of granulomatous inflammation. Though various immune system pathways have been implicated in disease, the relationship between the genetic determinants of sarcoidosis and other inflammatory disorders has not been characterized. Herein, we examined the degree of genetic pleiotropy common to sarcoidosis and other inflammatory disorders to identify shared pathways and disease systems pertinent to sarcoidosis onset. To achieve this, we quantify the association of common variant polygenic risk scores from nine complex inflammatory disorders with sarcoidosis risk. Enrichment analyses of genes implicated in pleiotropic associations were further used to elucidate candidate pathways. In European-Americans, we identify significant pleiotropy between risk of sarcoidosis and risk of asthma (R2=2.03%; P=8.89 × 10-9), celiac disease (R2=2.03%; P=8.21 × 10-9), primary biliary cirrhosis (R2=2.43%; P=2.01 × 10-10) and rheumatoid arthritis (R2=4.32%; P=2.50 × 10-17). These associations validate in African Americans only after accounting for the proportion of genome-wide European ancestry, where we demonstrate similar effects of polygenic risk for African-Americans with the highest levels of European ancestry. Variants and genes implicated in European-American pleiotropic associations were enriched for pathways involving interleukin-12, interleukin-27 and cell adhesion molecules, corroborating the hypothesized immunopathogenesis of disease.

Adaptive trials for tuberculosis: early reflections on theory and practice.

SETTING: Adaptive designs (ADs) have been proposed for anti-tuberculosis treatment trials. This call for innovation occurs against the backdrop of fundamental changes in the acceptable evidence base in anti-tuberculosis treatment. OBJECTIVE: To contextualise ADs for tuberculosis (TB) and explore early responses from those working in the field. DESIGN: In this qualitative study investigating processes of theoretical and practical change in randomised controlled trials, 24 interviews were conducted with professionals involved in AD trials, half of whom worked in the TB field. RESULTS: Clinical trialists working on AD trials in TB are positive about the efficiency these designs offer, but remain cautious about their suitability. In addition to technical concerns, informants discussed the challenges of implementing AD in developing countries, including limited regulatory capacity to evaluate proposals, investments needed in infrastructure and site capacity, and challenges regarding informed consent. Respondents identified funding, interdisciplinary communication and regulatory and policy responses as additional concerns potentially affecting the success of AD for TB. CONCLUSION: Empirical research is needed into patient experiences of AD, including informed consent. Further consideration of the contexts of innovation in trial design is needed. These are fundamental to the successful translation of theory into practice.

Effect of socioeconomic status on objectively measured physical activity.

BACKGROUND: A socioeconomic gradient in childhood obesity is known to be present by the age of school entry in the UK. The origin of this gradient is unclear at present, but must lie in socioeconomic differences in habitual physical activity, sedentary behaviour, or dietary intake. AIMS: To test the hypothesis that habitual physical activity and/or sedentary behaviour are associated with socioeconomic status (SES) in young Scottish children. METHODS: Observational study of 339 children (mean age 4.2 years, SD 0.3) in which habitual physical activity and sedentary behaviour were measured by accelerometry over six days (study 1). In a second study, 39 pairs of children of distinctly different SES (mean age 5.6 years, SD 0.3) were tested for differences in habitual physical activity and sedentary behaviour by accelerometry over seven days. RESULTS: In study 1, SES was not a significant factor in explaining the amount of time spent in physical activity or sedentary behaviour once gender and month of measurement were taken into account. In study 2, there were no significant differences in time spent in physical activity or sedentary behaviour between affluent and deprived groups. CONCLUSION: Results do not support the hypothesis that low SES in young Scottish children is associated with lower habitual physical activity or higher engagement in sedentary behaviour.

Nutritional status and energy expenditure in children pre-bone-marrow-transplant.

The aims of this study were to establish the nutritional status of children pre-BMT and to determine whether predictive methods of assessing nutritional status and resting energy expenditure (REE) are accurate in this population. We analysed the body cell mass (BCM) (n=26) and REE (n=24) in children undergoing BMT. BCM was adjusted for height (BCM/HT(p)) and expressed as a Z score to represent nutritional status. To determine whether body mass index (BMI) was indicative of nutritional status in children undergoing BMT, BMI Z scores were compared to the reference method of BCM/HT(p) Z scores. Schofield predictive equations of basal metabolic rate (BMR) were compared to measured REE to evaluate the accuracy of the predictive equations. The mean BCM/HT(p) Z score for the subject population was -1.09+/-1.28. There was no significant relationship between BCM/HT(p) Z score and BMI Z score (r=0.34; P>0.05); however there was minimal difference between measured REE and predicted BMR (bias=-11+/-149 kcal/day). The results of this study demonstrate that children undergoing BMT may have suboptimal nutritional status and that BMI is not an accurate indication of nutritional status in this population. However, Schofield equations were found to be suitable for representing REE in children pre-BMT.

Total energy expenditure and physical activity in young Scottish children: mixed longitudinal study.

Childhood obesity has been attributed to a decline in total energy expenditure (TEE). We measured TEE, physical activity, and sedentary behaviour in a representative sample of young children from Glasgow, UK, at age 3 years (n=78), and we did a follow-up study at age 5 years (n=72). Mean physical activity level (TEE/resting energy expenditure) was 1.56 (SD 0.39) at age 3 years and 1.61 (0.22) at age 5 years. Median time in sedentary behaviour was 79% of monitored hours at age 3 years (IQR 74-84) and 76% (71-80) at age 5 years. Median time spent in moderate to vigorous physical activity represented only 2% of monitored hours at age 3 years (IQR 1-4) and 4% at age 5 years (2-6). Modern British children establish a sedentary lifestyle at an early age.

Energy intake by multiple pass 24 h recall and total energy expenditure: a comparison in a representative sample of 3-4-year-olds.

The accuracy of the multiple pass 24 h recall for assessment of habitual energy intake in pre-school children is unclear. The primary aim of this study was to assess its accuracy by comparison with measurement of total energy expenditure by doubly-labelled water in a representative sample of forty-one 3-4-year-olds. The recall method was well tolerated by subjects and was administered quickly and easily. However, it produced estimates of energy intake which significantly exceeded measures of total energy expenditure from doubly-labelled water, mean paired difference 660 kJ/d (P<0.01). Agreement between the two methods was poor at the individual level: limits of agreement 660+/-3018 kJ/d. Error and imprecision in both methods contribute to individual differences, but the present study suggests that the multiple pass 24 h recall does not provide accurate estimates of dietary energy intake in individual children.

Creating a balanced scorecard for a hospital system.

In 1999, hospitals in Ontario, Canada, collaborated with a university-based research team to develop a report on the relative performance of individual hospitals in Canada's most populated province. The researchers used the balanced-scorecard framework advocated by Kaplan and Norton. Indicators of performance were developed in four areas: clinical utilization and outcomes, patient satisfaction, system integration and change, and financial performance and condition. The process of selecting, calculating, and validating meaningful indicators of financial performance and condition is outlined. Lessons learned along the way are provided. These lessons may prove valuable to other finance researchers and practitioners who are engaged in performance measurement endeavors.

The burden of personality disorder: a district-based survey.

Patients with a clinical diagnosis of personality disorder (PD) often suffer prolonged distress. They are a considerable burden on psychiatric services and they are experienced as difficult to manage by their keyworkers. This paper describes the creation of a community-based case register of patients suffering from PD. It explores the relationship between psychological distress, personality dysfunction, service utilisation and keyworker stress. Mental Health workers were asked to identify those patients on their caseload whose primary problem was PD. This list provided the basis for the case register. Patients completed the revised Personality Diagnostic Questionnaire IV (PDQ 4); the General Health Questionnaire (GHQ); and the Beck Depression Inventory - 21 item (BDI). A brief, semi-structured interview was conducted by Community Psychiatric Nurses to estimate service utilisation and keyworker stress. The mean GHQ was 14.58; the mean BDI score was 28.22. The mean number of PDs per patient was 4.5. One quarter of patients (21/80) had been admitted at least once to a psychiatric ward in the previous year and 17% (13/80) had presented to casualty at least once in the previous two months. 57% of the patients had weekly or more contacts with a helping agency. The number of PD diagnoses per patient as measured by the PDQ 4 was not found to be predictive of stress experienced by CPNs, whereas high BDI and GHQ scores were strongly correlated. Similarly, the number of admissions to a psychiatric ward was associated with high BDI and GHQ scores but not with number of PDs per patient. It is feasible to establish a case register of all patients in the district with PD. There are high levels of depression and distress amongst patients with PD being treated as outpatients. Service utilisation and keyworker stress are not predicted by number of PDs per patient but are strongly associated with distress as measured by the GHQ and BDI. The implications of these findings are discussed.

Cost-effective post-exposure prevention of poison ivy dermatitis.

BACKGROUND: Poison ivy (toxicodendron) dermatitis is the most common allergic contact dermatitis in the USA. No studies have shown an effect of washing after a short period of time for the prevention of binding of urushiol to the skin. Objective To evaluate the efficacy of three different modes of postcontact prevention using a surfactant (Dial ultra dishwashing soap), an oil-removing compound (Goop), and chemical inactivation (a commercial product Tecnu). METHODS: A consented, unsponsored, volunteer experimental study on medical students from the University of Missouri School of Medicine, Kansas City. Each subject served as his/her own control, comparing four 2.5-cm exposed squares on the inner aspect of the forearm, three of which were treated and one untreated. RESULTS: Comparisons between the different agents were nonsignificant with P > 0.05. Each treatment, however, was significantly improved over the untreated control. CONCLUSIONS: Our study showed 70%, 61.8%, and 56. 4% protection with Tecnu, Goop, and Dial, respectively, when compared to the positive control, or to the possible maximum response, with a cost per ounce (in a local drug and automotive store) of $1.25, $0.07, and $0.07, respectively, for a decrease in protection that is nonsignificant.

Developing guidelines for allocating catheterization laboratory resources: lessons from an Ontario Consensus Panel. Consensus Panel on Cardiac Catheterization Laboratory Services in Ontario and the Steering Committee of the Cardiac Care Network of Ontario.

In March 1997, the Ontario Ministry of Health asked the Cardiac Care Network of Ontario (CCN) to develop guidelines for allocating cardiac catheterization laboratory resources. A consensus panel of providers and planners used findings from the literature and expert opinion to recommend guidelines for the operation of cardiac catheterization laboratories and criteria to be considered when allocating additional cardiac catheterization laboratory resources. This article summarizes the consensus panel's major findings that may be of value to other jurisdictions, including need identification, clinical practice, system issues, location criteria and cost considerations. The article reflects the advice given to the Ontario Ministry of Health by the CCN and is not an official position paper of the Canadian Cardiovascular Society.

Creating corporate advantage.

What differentiates truly great corporate strategies from the merely adequate? How can executives at the corporate level create tangible advantage for their businesses that makes the whole more than the sum of the parts? This article presents a comprehensive framework for value creation in the multibusiness company. It addresses the most fundamental questions of corporate strategy: What businesses should a company be in? How should it coordinate activities across businesses? What role should the corporate office play? How should the corporation measure and control performance? Through detailed case studies of Tyco International, Sharp, the Newell Company, and Saatchi and Saatchi, the authors demonstrate that the answers to all those questions are driven largely by the nature of a company's special resources--its assets, skills, and capabilities. These range along a continuum from the highly specialized at one end to the very general at the other. A corporation's location on the continuum constrains the set of businesses it should compete in and limits its choices about the design of its organization. Applying the framework, the authors point out the common mistakes that result from misaligned corporate strategies. Companies mistakenly enter businesses based on similarities in products rather than the resources that contribute to competitive advantage in each business. Instead of tailoring organizational structures and systems to the needs of a particular strategy, they create plain-vanilla corporate offices and infrastructures. The company examples demonstrate that one size does not fit all. One can find great corporate strategies all along the continuum.

Charging for intensive care using direct nursing hours as the cost marker.

The hypothesis that direct nursing hours correlate with the cost of a patient stay in intensive care was tested. One hundred and thirty-nine patients were studied and the data collected included: (a) direct nursing hours applied to each patient; (b) a daily TISS score: (c) a detailed costing of each patient (all costs are shown in N.Z.$). There was a strong correlation between the direct nursing hours and the total cost per patient (r2 = 0.98) (total cost = 54 x direct nursing hours + 344). Also a strong correlation existed between the total TISS scores and the total costs per patient (r2 = 0.96) (total cost = 67.13 x TISS). Direct nursing hours offer a relatively simple and logical method of allocating costs per patient.

A written guideline implementation can lead to reductions in laboratory testing in an intensive care unit.

The impact of developing guidelines for laboratory testing in an Intensive Care Unit (ICU) was examined. Targeted blood tests were recorded on fifty cardiac surgery and fifty general intensive care patients retrospectively. Following the introduction of guidelines, the study was repeated with prospective data collection. Comparison of the samples before and after the intervention showed a 25.9% reduction in all blood tests and a 17.1% reduction in arterial blood gases in the post cardiac surgery group. In general ICU patients, the drop in all tests was 16.6% and in arterial blood gases 21.9%. The cost saving from the cardiac surgery sample was N.Z.$3,637 and general ICU N.Z.$3,166, giving a sum total of N.Z.$6,803 in 100 patients. The potential cost savings for the annual admissions of 1,200 patients is N.Z.$81,636. This study shows that written guidelines can bring about major cost reduction in the short-term.

An SDI program for distributing funding opportunities using electronic mail.

As the competition for funding increases, the need to make researchers aware of all available funding is becoming more acute. The solution presented here is a Selective Dissemination of Information (SDI) service which electronically mails funding information that matches a researcher's keywords. The keywords are part of extensive faculty profiles that make up a Faculty Expertise database. The funding information comes from the Sponsored Programs Information Network (SPIN) database. The software enables researchers to learn about appropriate funding opportunities without spending time actively searching for them.

Caring and nursing's metaparadigm: can they survive the era of managed care?

Considering the growing power of third-party payers to control the length and methods of treatment, the authors summarize alternative treatment models of providing care. These models are evaluated within the context of nursing's metaparadigm. Clinical examples are provided to illustrate how focusing on client strengths and alternative solutions differs from more traditional approaches to treatment.

Personal response systems in the United States.

In summation, although Personal Response Systems are relatively new in the marketplace they have made tremendous inroads over the past fifteen years. The next decade presents some difficult problems for this country in terms of its aging population and the delivery of quality, cost effective health care to all who need it. In light of these problems, the PRS industry can offer viable solutions-solutions for the U.S. health care system in helping to control and reduce the cost of health care delivery; solutions for industry in attempting to meet their employee health care needs; solutions for families who are coping with the strains of eldercare; and most important, solutions for many people who, regardless of age, could not live independently without a Personal Response System.

Improving access to pediatric health care in Mississippi.

Working under the Mississippi Postneonatal Death Impact Project, the Mississippi Chapter of the American Academy of Pediatrics, in conjunction with the State Department of Health, helped improve access to pediatric health care in Mississippi. This was accomplished by developing a statewide telephone information and referral service (telephone case management), enlisting primary care physicians to treat a limited number of children without specific compensation and staging a public awareness campaign. System barriers encountered were identified and interagency coordination and cooperation suggested. This effort could be easily replicated and expanded.