Effects of dietary intake, appetite, and eating habits on dialysis and non-dialysis treatment days in hemodialysis patients: cross-sectional results from the HEMO study.

OBJECTIVE: To evaluate differences between dietary energy intake (DEI), dietary protein intake (DPI), appetite, dietary patterns, and eating habits during dialysis treatment days (DD) and non-dialysis treatment days (NDD) in 1,901 adults receiving maintenance hemodialysis who were enrolled in the baseline phase of the National Institutes of Health-sponsored Hemodialysis (HEMO) study. DESIGN: A cross-sectional analysis of participants at baseline (before randomization). SETTING: Fifteen clinical centers across the United States. MEASUREMENTS: DEI, DPI, and self-reported assessment of appetite, dietary patterns, and eating habits. RESULTS: For the entire study cohort, total mean (+/- SD) DEI (1,566 +/- 636 kcal/day) and weight-adjusted DEI (23.2 +/- 9.5 kcal/kg/day) were significantly higher (P <.0001) on NDD than on DD (1,488 +/- 620 kcal/day and 22.2 +/- 9.6 kcal/kg/day), respectively. Similarly, DPI was significantly higher (P <.0001) on NDD (65.0 +/- 29.0 g/day and 0.96 +/- 0.43 g/kg/day) than on DD (60.2 +/- 26.5 g/day and 0.90 +/- 0.41 g/kg/day). On DD and NDD, the mean weight-adjusted DEI for the entire cohort was less than the HEMO study standard of care (SOC) of > or =28 kcal/kg/day, whereas on NDD, several subgroups reported dietary protein intakes that were closer to the study's SOC. These included men, patients under 50 years of age, nonblack participants, those without diabetes, those with a normal or mild Index of Co-Existing Disease score, and those on dialysis for more than 5 years. Protein and energy intakes declined with worsening self-reported appetites in both DD and NDD after adjusting for other subgroup effects. CONCLUSION: Dietary energy and protein intakes of HEMO study participants were lower on DD than on NDD, and also lower than the SOC on both days, particularly with regard to energy intake. People receiving maintenance hemodialysis should be counseled to consume adequate amounts of energy and protein daily, especially on DD. Practitioners should monitor closely those patients who report poor appetite and should intervene appropriately.     

alpha-Galactosidase A deficiency in Dutch patients on dialysis: a critical appraisal of screening for Fabry disease.

INTRODUCTION: Fabry disease or alpha-galactosidase A (alpha-Gal A) deficiency is an X-linked lysosomal storage disorder that often leads to renal insufficiency in males and occasionally in females. The disease is rare, but its prevalence may be underestimated due to its variable clinical picture. Enzyme supplementation therapy with rHu-alphaGal A is currently available. Limited experience has so far shown that therapy may at best stabilize renal function. Despite these preliminary findings, much effort is being put into screening high-risk groups for undiagnosed alpha-Gal A deficiency. We studied the prevalence of alpha-Gal A deficiency in a Dutch dialysis cohort to establish possible underdiagnosis. We discuss the benefits of screening for Fabry disease. METHODS: Activity of alpha-Gal A in whole blood was measured in a group of 508 male Dutch dialysis patients. RESULTS: Of the 508 patients studied only one patient, already known with Fabry disease, had a alpha-Gal A deficiency, a prevalence of 0.22% (95 CI 0-1.1%). CONCLUSIONS: No undiagnosed Fabry patients were found, indicating that in our studied cohort there is no large-scale underestimation of its prevalence. Even though screening of dialysis patients for Fabry disease might identify patients who remain otherwise unrecognized, screening of high-risk populations for alpha-Gal A deficiency should be carried out with caution since long-term efficacy of treatment is currently unknown.     

New onset postoperative atrial fibrillation and early anticoagulation after cardiac surgery

Objectives. New onset postoperative atrial fibrillation (POAF) after cardiac surgery is associated with increased risk for thromboembolic complications. Compliance with anticoagulation treatment is prerequisite for successful outcome after POAF. We hypothesized that a disciplined anticoagulation protocol initiated instantly after POAF secures a long-term outcome. Design. A total of 519 consecutive patients undergoing cardiac surgery were retrospectively analyzed. Patients received anticoagulation using warfarin whenever POAF lasted longer than five min. Postoperative outcome including mortality, myocardial infarction and stroke were compared with patients on sinus rhythm (non-POAF). Results. Mean age of the study cohort was 64.3?±?9.0 years and median follow-up time was 76 months. There were 177 (34%) POAF and 342 (66%) non-POAF patients. At discharge, 144 (81%) POAF patients complied with warfarin, while 82 (24%) non-POAF patients received warfarin for non-rhythm causes (p?p?=?.03). After adjustment for comorbidities, major adverse clinical events (MACE)- including a combination of late cardiovascular mortality, myocardial infarction, stroke and late atrial fibrillation- was independently associated with POAF (OR 2.73, 95%CI 1.69-4.45, p?Conclusions. POAF after cardiac surgery was associated with high risk of MACE. Early anticoagulation may be justified in POAF patients to secure a long-term outcome after cardiac surgery.     

Association of 18 Confirmed Susceptibility Loci for Type 2 Diabetes With Indices of Insulin Release, Proinsulin Conversion, and Insulin Sensitivity in 5,327 Nondiabetic Finnish Men

OBJECTIVE

We investigated the effects of 18 confirmed type 2 diabetes risk single nucleotide polymorphisms (SNPs) on insulin sensitivity, insulin secretion, and conversion of proinsulin to insulin.

RESEARCH DESIGN AND METHODS

A total of 5,327 nondiabetic men (age 58 ± 7 years, BMI 27.0 ± 3.8 kg/m²) from a large population-based cohort were included. Oral glucose tolerance tests and genotyping of SNPs in or near PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, LOC387761, CDKN2B, IGF2BP2, CDKAL1, HNF1B, WFS1, JAZF1, CDC123, TSPAN8, THADA, ADAMTS9, NOTCH2, KCNQ1, and MTNR1B were performed. HNF1B rs757210 was excluded because of failure to achieve Hardy-Weinberg equilibrium.

RESULTS

Six SNPs (TCF7L2, SLC30A8, HHEX, CDKN2B, CDKAL1, and MTNR1B) were significantly (P < 6.9 × 10⁻⁴) and two SNPs (KCNJ11 and IGF2BP2) were nominally (P < 0.05) associated with early-phase insulin release (InsAUC_0–30/GluAUC_0–30), adjusted for age, BMI, and insulin sensitivity (Matsuda ISI). Combined effects of these eight SNPs reached −32% reduction in InsAUC_0–30/GluAUC_0–30 in carriers of ≥11 vs. ≤3 weighted risk alleles. Four SNPs (SLC30A8, HHEX, CDKAL1, and TCF7L2) were significantly or nominally associated with indexes of proinsulin conversion. Three SNPs (KCNJ11, HHEX, and TSPAN8) were nominally associated with Matsuda ISI (adjusted for age and BMI). The effect of HHEX on Matsuda ISI became significant after additional adjustment for InsAUC_0–30/GluAUC_0–30. Nine SNPs did not show any associations with examined traits.

CONCLUSIONS

Eight type 2 diabetes–related loci were significantly or nominally associated with impaired early-phase insulin release. Effects of SLC30A8, HHEX, CDKAL1, and TCF7L2 on insulin release could be partially explained by impaired proinsulin conversion. HHEX might influence both insulin release and insulin sensitivity.Impaired insulin secretion and insulin resistance, two main pathophysiological mechanisms leading to type 2 diabetes, have a significant genetic component (1). Recent studies have confirmed 20 genetic loci reproducibly associated with type 2 diabetes (2–13). Three were previously known (PPARG, KCNJ11, and TCF7L2), whereas 17 loci were recently discovered either by genome-wide association studies (SLC30A8, HHEX-IDE, LOC387761, CDKN2A/2B, IGF2BP2, CDKAL1, FTO, JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, THADA, ADAMTS9, NOTCH2, KCNQ1, and MTNR1B), or candidate gene approach (WFS1 and HNF1B). The mechanisms by which these genes contribute to the development of type 2 diabetes are not fully understood.PPARG is the only gene from the 20 confirmed loci previously associated with insulin sensitivity (14,15). Association with impaired β-cell function has been reported for 14 loci (KCNJ11, SLC30A8, HHEX-IDE, CDKN2A/2B, IGF2BP2, CDKAL1, TCF7L2, WFS1, HNF1B, JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, KCNQ1, and MTNR1B) (6,12,13,16–38). Although associations of variants in HHEX (16–22), CDKAL1 (6,21–26), TCF7L2 (22,27–30), and MTNR1B (13,31,32) with impaired insulin secretion seem to be consistent across different studies, information concerning other genes is limited (12,18–25,27,33–38). The mechanisms by which variants in these genes affect insulin secretion are unknown. However, a few recent studies suggested that variants in TCF7L2 (22,39–42), SLC30A8 (22), CDKAL1 (22), and MTNR1B (31) might influence insulin secretion by affecting the conversion of proinsulin to insulin. Variants of FTO have been shown to confer risk for type 2 diabetes through their association with obesity (7,16) and therefore were not included in this study.Large population-based studies can help to elucidate the underlying mechanisms by which single nucleotide polymorphisms (SNPs) of different risk genes predispose to type 2 diabetes. Therefore, we investigated confirmed type 2 diabetes–related loci for their associations with insulin sensitivity, insulin secretion, and conversion of proinsulin to insulin in a population-based sample of 5,327 nondiabetic Finnish men.     

Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background  

Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.     

Spontaneous rupture of a hepatic cystadenoma and cystadenocarcinoma: report of two cases

Hepatobiliary cystadenomas and cystadenocarcinomas are rare tumors. Differentiating between these tumors and benign hepatic cysts may be difficult. Because of their rarity, diagnosis is often delayed and may result in inaccurate treatment, resulting in unnecessary morbidity and mortality. The purpose of this report is to draw attention to these entities and their complications. We report on two cases with spontaneous rupture of hepatobiliary cystadenoma and cystadenocarcinoma cysts, initially treated as simple hepatic cysts by aspiration, or by aspiration combined with sclerotherapy. The spontaneous rupture of the cysts appeared years after the initial treatment of the cysts, leading in one case to a prolonged stay in an intensive care unit. In both cases, a formal liver resection was carried out and microscopic investigations revealed a mucinous cystadenocarcinoma and cystadenoma. In conclusion, although hepatobiliary cystadenomas and cystadenocarcinomas are rare findings, they should not be forgotten in the diagnostic workshop when examining patients with hepatic cysts. If hepatobiliary cystadenomas and cystadenocarcinomas cannot be excluded following radiological imaging, surgery is recommended.     

Adrenoceptor subtypes in the control of burn-induced plasma extravasation

Burn trauma is known to induce a significant rise in circulating catecholamine levels and despite catecholamines being potent endogenous vasoactive agents with known actions on microvascular permeability, their effect on burn edema has been poorly investigated. The present study in rats investigated the role and importance of adrenergic receptor subtypes in the regulation of basal capillary permeability in normal skin and hyperpermeability in partial- and full-thickness skin burns. Edema was quantified by spectrophotometric analysis of extravasated Evans blue-albumin. Evaluation was based on intravenous administration of the following adrenergic agonists and antagonists: l-phenylephrine (alpha(1)-receptor agonist), prazosin (alpha(1)-receptor antagonist), clonidine (alpha(2)-receptor agonist), yohimbine (alpha(2)-receptor antagonist), prenalterol (beta(1)-receptor agonist), terbutaline (beta(2)-receptor agonist), or propranolol (beta(1)- and beta(2)-receptor antagonist). Results showed increased capillary permeability in normal skin following administration of terbutaline (p<0.01) and yohimbine (p<0.01). In partial-thickness burns, clonidine significantly (p<0.05) reduced edema formation, whereas in full-thickness burns edema was significantly reduced by clonidine (p<0.05) and l-phenylephrine (p<0.01). In conclusion, the inhibition of postburn edema induced by stimulation of alpha(1)-receptors (l-phylephrine) and alpha(2)-receptors (clonidine) could be secondary to increased vascular resistance and reduced tissue perfusion pressure and/or suppressed inflammatory reaction in the burn injury. In the treatment of burn patients, clonidine is particularly interesting since the agent has previously been proven to induce potent analgesia in thermally injured.     

Multimethod Evaluation of Information and Communication Technologies in Health in the Context of Wicked Problems and Sociotechnical Theory

Objective

Few research designs look at the deep structure of complex social systems. We report the design and implementation of a multimethod evaluation model to assess the impact of computerized order entry systems on both the technical and social systems within a health care organization.

Design

We designed a multimethod evaluation model informed by sociotechnical theory and an appreciation of the nature of wicked problems. We mobilized this model to assess the impact of an electronic medication management system via a three-year program of research at a major academic hospital.

Measurements

Model components include measurements relating to three dimensions of system impact: safety and quality, organizational culture, and work and communication patterns.

Results

Application of the evaluation model required the development and testing of purpose-built measurement tools such as software to collect multidimensional work measurement data. The model applied established research methods including medication error audits and social network analysis. Design features of these tools and techniques are described, along with the practical challenges of their implementation. The distinctiveness of doing research within a unique paradigm of complex systems, explicating the wickedness and the dimensionality of sociotechnical theory, is articulated.

Conclusion

Designing an effective evaluation model requires a deep understanding of the nature and complexity of the problems that information technology interventions in health care are trying to address. Adopting a sociotechnical perspective for model generation improves our ability to develop evaluation models that are adaptive and sensitive to the characteristics of wicked problems and provides a strong theoretical basis from which to analyze and interpret findings.     

Contextual Implementation Model: A Framework for Assisting Clinical Information System Implementations

Objective

This paper presents a multiple perspectives model of clinical information system implementation, the Contextual Implementation Model (CIM). Although other implementation models have been developed, few are grounded in data and others fail to take adequate account of the clinical environment and users’ requirements.

Design

The CIM arose from qualitative data collected from four clinical units in two large Australian teaching hospitals. The aim of the study was to explore physicians’ test management work practices associated with the compulsory use of a hospital-wide, mandatory computerized provider order entry (CPOE) system.¹ The dataset consisted of non-participatory observations of physicians using CPOE (n=55 sessions) and interviews with health professionals (n=28) about test management work practices. Data were analyzed by two researchers independently using an iterative grounded approach.

Results

A core underlying theme of ‘contextual differences’ emerged which explained physicians’ use of the CPOE system in the sites. The CIM focuses attention on diversity at three contextual levels: the organizational level; the clinical or departmental level, and the individual level. Within each of these levels there are dimensions for consideration (for example, organizational culture, leadership and diverse ways of working) which affect physicians’ attitudes to, and use of, CPOE.

Conclusion

The CIM provides a contextual differences perspective which can be used to facilitate the implementation of clinical information systems. Developing a clinical information system implementation model serves as a framework to guide future implementations to ensure their safe and efficient use and also improve the likelihood of uptake by physicians.     

Clinical Decision Velocity is Increased when Meta-search Filters Enhance an Evidence Retrieval System

Objective

To test whether the use of an evidence retrieval system that uses clinically targeted meta-search filters can enhance the rate at which clinicians make correct decisions, reduce the effort involved in locating evidence, and provide an intuitive match between clinical tasks and search filters.

Design

A laboratory experiment under controlled conditions asked 75 clinicians to answer eight randomly sequenced clinical questions, using one of two randomly assigned search engines. The first search engine Quick Clinical (QC) was equipped with meta-search filters (the combined use of meta-search and search filters) designed to answer typical clinical questions e.g., treatment, diagnosis, and the second ‘library model’ system (LM) offered free access to an identical evidence set with no filter support.

Measurements

Changes in clinical decision making were measured by the proportion of correct post-search answers provided to questions, the time taken to answer questions, and the number of searches and links to documents followed in a search session. The intuitive match between meta-search filters and clinical tasks was measured by the proportion and distribution of filters selected for individual clinical questions.

Results

Clinicians in the two groups performed equally well pre-search. Post search answers improved overall by 21%, with 52.2% of answers correct with QC and 54.7% with LM (χ² = 0.33, df = 1, p > 0.05). Users of QC obtained a significantly greater percentage of their correct answers within the first two minutes of searching compared to LM users (QC 58.2%; LM 32.9%; χ² = 19.203, df = 1, p < 0.001). There was a statistical difference for QC and LM survival curves, which plotted overall time to answer questions, irrespective of answer (Wilcoxon, p = 0.019) and for the average time to provide a correct answer (Wilcoxon, p = 0.006). The QC system users conducted significantly fewer searches per scenario (m = 3.0 SD = 1.15 versus m = 5.5 SD1.97, t = 6.63, df = 72, p = 0.0001). Clinicians using the QC system followed fewer document links than did those who used LM (respectively 3.9 links SD = 1.20 versus 4.7 links SD = 1.79, t = 2.13, df = 72, p = 0.0368). In 6 of the 8 questions, two meta-search filters accounted for 89% or more of clinicians'' first choice, suggesting the choice of filter intuitively matched the clinical decision task at hand.

Conclusions

Meta-search filters result in clinicians arriving at answers more quickly than unconstrained searches across information sources, and appear to increase the rate with which correct decisions are made. In time restricted clinical settings meta-search filters may thus improve overall decision accuracy, as fewer searches that could otherwise lead to a correct answer are abandoned. Meta-search filters appear to be intuitive to use, suggesting that the simplicity of the user model would fit very well into clinical settings.