Identification of case complexity and increased health care utilization in patients with rheumatoid arthritis.

OBJECTIVES: To document biopsychosocial profiles of patients with rheumatoid arthritis (RA) by means of the INTERMED and to correlate the results with conventional methods of disease assessment and health care utilization. METHODS: Patients with RA (n = 75) were evaluated with the INTERMED, an instrument for assessing case complexity and care needs. Based on their INTERMED scores, patients were compared with regard to severity of illness, functional status, and health care utilization. RESULTS: In cluster analysis, a 2-cluster solution emerged, with about half of the patients characterized as complex. Complex patients scoring especially high in the psychosocial domain of the INTERMED were disabled significantly more often and took more psychotropic drugs. Although the 2 patient groups did not differ in severity of illness and functional status, complex patients rated their illness as more severe on subjective measures and on most items of the Medical Outcomes Study Short Form 36. Complex patients showed increased health care utilization despite a similar biologic profile. CONCLUSIONS: The INTERMED identified complex patients with increased health care utilization, provided meaningful and comprehensive patient information, and proved to be easy to implement and advantageous compared with conventional methods of disease assessment. Intervention studies will have to demonstrate whether management strategies based on INTERMED profiles can improve treatment response and outcome of complex patients.

Prevention du diabète de type 2: état des connaissances [Prevention of type 2 diabetes: where do we stand?]

It is anticipated that one out of 3 children born in the year 2000 in the United States may develop diabetes. In Switzerland, a population based study in the city of Lausanne (CoLaus) has shown that about 30% of the participants have abnormal glucose homeostasis, and that the prevalence of obesity in the younger age groups has doubled since 1992. In this review, we describe clinical and biological factors associated with an increased risk to develop diabetes and summarize the most important intervention studies that have shown a beneficial effect in the prevention of diabetes. While life style modifications should be recommended for everybody, the place of pharmacological interventions (oral hypoglycemic agents, blood pressure and cholesterol lowering agents) is more controversial.

Building Evidence for Dementia Prevention

As was the case in 2010 when the National Institutes of Health issued a consensus statement on the prevention of Alzheimer’s and other dementias, there remains a lack of firm evidence for dementia prevention. Because of the difficulties in studying this phenomenon, no modifiable risk factors for dementia have been definitively established, and no pharmaceutical or nutritional supplements been proven to prevent Alzheimer’s disease or cognitive decline. However, longitudinal observational studies have identified several factors associated with dementia. A recent review article summarizes the current epidemiological evidence about Alzheimer’s and other dementias, and presents three ongoing large scale randomized control trials (RCTs) that focus on preventing dementia. The review argues that there is substantial evidence for many factors that, in combination, might reduce the risk of, or delay the onset of, dementia. Although no specific cure for dementia exists, and no specific pathway between risk factor and disease onset has been identified, several cardiovascular, stress, toxicity, and psychosocial variables have been repeatedly associated with dementia. Protective factors, such as high education, physical exercise, and not smoking cigarettes, have been identified as well. Intervention studies that account for these multiple factors may well identify strategies for preventing or delaying dementia. However, the protective effects and risk factors suggested by observational data have yet to be assessed in RCT research. The role of such factors in reducing or increasing the risk for dementia needs to be more specifically defined. Three ongoing RCT studies in Europe show promise in this area, as they target multiple risk and protective factors by promoting healthy lifestyle changes and medical treatment of vascular diseases. These are: FINGER, a Finnish trial involving 1,200 older adults at risk for dementia. This intervention features nutritional guidance, physical activity, cognitive and social engagement, and medical management of risk factors. Participants were involved in previous, intensive observational studies of vascular health and health behavior, so FINGER will provide a level of relevant information about its research subjects that is normally impossible for clinical RCTs to attain;MAPT, a multicenter study of 1,680 frail older adults in France. This study will compare the efficacy of omega-3 dietary supplementation with a multidomain training intervention that involves physical and cognitive training. The study will include follow-up assessments after five years;PreDIVA, a Dutch study of 3,534 community dwelling participants between 70 and 78 years old, recruited from primary care clinics. This study will compare standard medical care with a multicomponent vascular health intervention. The study will last for six years and measure both dementia and disability outcomes. These studies are an important step in dementia research, using earlier observational studies as the basis for rigorously assessed interventions. Although a cure for dementia has not been identified, this new research may identify preventive strategies against dementia. �� Source: Mangialasche F, Kivipelto M, et al. (2012). Dementia prevention: current epidemiological evidence and future perspective. Alzheimer’s Research and Therapy 4:6.

Injuries in children aged 0 to 14 years and inequalities

Injury mortality and morbidity among children aged 0-14 varies substantially depending on the child's age, gender, socio-economic group, cultural and/or ethnic group, and where they live. This report describes and seeks to understand these variations and explains why each factor is associated with injury risk. It then highlights how a range of intervention studies have attempted to address these inequalities.

Assessing medication adherence: options to consider.

Background Adherence to chronic therapy is a key determinant of patient health outcomes in chronic disease. However, only about 50 % of patients adhere to chronic therapy. One of the challenges in promoting adherence is having an accurate understanding of adherence rates and the factors that contribute to non-adherence. There are many measures available to assess patient medication adherence. Aim of the review This review aims to present the commonly used indirect methods available for measuring medication adherence in routine healthcare and research studies. Method A literature review on medication adherence measures in patient populations with chronic conditions taking chronic medications was conducted through Medline (2003-2013). A complementary manual search of references cited in the retrieved studies was performed in order to identify any additional studies. Results Of the 238 initial Medline search results, 57 full texts were retrieved. Forty-seven articles were included as a result of the manual search. Adherence measures identified were: self-report (reported in 50 publications), electronic measures (33), pharmacy refills and claims data (26) and pill counts (25). Patient self-report, electronic measures, pharmacy refill and claims data were the most commonly used measures of adherence in research, routine practice, epidemiological and intervention studies. These methods, and their strengths and limitations have been described in this paper. Conclusion A multitude of indirect measures of adherence exist in the literature, however, there is no "gold" standard for measuring adherence to medications. Triangulation of methods increases the validity and reliability of the adherence data collected. To strengthen the adherence data collected and allow for comparison of data, future research and practice interventions should use an internationally accepted, operational standardized definition of medication adherence and clearly describe the medication adherence methods used.

Dysfunctional psychological responses among Intensive Care Unit nurses: a systematic review of the literature

AbstractOBJECTIVETo systematically review evidence on dysfunctional psychological responses of Intensive Care Units nurses (ICUNs), with focus on anxiety and depressive symptoms and related factors.METHODA literature search was performed in CINAHL, PubMed and Scopus databases, from 1999 to present, along with a critical appraisal and synthesis of all relevant data. The following key words, separately and in combination, were used: "mental status" "depressive symptoms" "anxiety" "ICU nurses" "PTSD" "burnout" "compassion fatigue" "psychological distress".RESULTSThirteen quantitative studies in English and Greek were included. The results suggested increased psychological burden in ICUNs compared to other nursing specialties, as well as to the general population.CONCLUSIONSStudies investigating psychological responses of ICUNs are limited, internationally. Future longitudinal and intervention studies will contribute to a better understanding of the phenomenon.

Prophylactic use of bevacizumab to avoid anterior segment neovascularization following proton therapy for uveal melanoma.

PURPOSE: To investigate whether the prophylactic use of bevacizumab reduces the rate of rubeosis after proton therapy for uveal melanoma and improves the possibility to treat ischemic, reapplicated retina with laser photocoagulation. DESIGN: Comparative retrospective case series. METHODS: Uveal melanoma patients with ischemic retinal detachment and treated with proton therapy were included in this institutional study. Twenty-four eyes received prophylactic intravitreal bevacizumab injections and were compared with a control group of 44 eyes without bevacizumab treatment. Bevacizumab injections were performed at the time of tantalum clip insertion and were repeated every 2 months during 6 months, and every 3 months thereafter. Ultra-widefield angiography allowed determination of the extent of retinal ischemia, which was treated with laser photocoagulation after retinal reapplication. Main outcome measures were the time to rubeosis, the time to retinal reattachment, and the time to laser photocoagulation of ischemic retina. RESULTS: Baseline characteristics were balanced between the groups, except for thicker tumors and larger retinal detachments in the bevacizumab group, potentially to the disadvantage of the study group. Nevertheless, bevacizumab prophylaxis significantly reduced the rate of iris rubeosis from 36% to 4% (log-rank test P = .02) and tended to shorten the time to retinal reapplication until laser photocoagulation of the nonperfusion areas could be performed. CONCLUSIONS: Prophylactic intravitreal bevacizumab in patients treated with proton therapy for uveal melanoma with ischemic retinal detachment prevented anterior segment neovascularization, until laser photocoagulation to the reapplied retina could be performed.

Monitoring drug therapy.

Drug development has improved over recent decades, with refinements in analytical techniques, population pharmacokinetic-pharmacodynamic (PK-PD) modelling and simulation, and new biomarkers of efficacy and tolerability. Yet this progress has not yielded improvements in individualization of treatment and monitoring, owing to various obstacles: monitoring is complex and demanding, many monitoring procedures have been instituted without critical assessment of the underlying evidence and rationale, controlled clinical trials are sparse, monitoring procedures are poorly validated and both drug manufacturers and regulatory authorities take insufficient account of the importance of monitoring. Drug concentration and effect data should be increasingly collected, analyzed, aggregated and disseminated in forms suitable for prescribers, along with efficient monitoring tools and evidence-based recommendations regarding their best use. PK-PD observations should be collected for both novel and established critical drugs and applied to observational data, in order to establish whether monitoring would be suitable. Methods for aggregating PK-PD data in systematic reviews should be devised. Observational and intervention studies to evaluate monitoring procedures are needed. Miniaturized monitoring tests for delivery at the point of care should be developed and harnessed to closed-loop regulated drug delivery systems. Intelligent devices would enable unprecedented precision in the application of critical treatments, i.e. those with life-saving efficacy, narrow therapeutic margins and high interpatient variability. Pharmaceutical companies, regulatory agencies and academic clinical pharmacologists share the responsibility of leading such developments, in order to ensure that patients obtain the greatest benefit and suffer the least harm from their medicines.

Misconceptions about fructose-containing sugars and their role in the obesity epidemic.

A causal role of fructose intake in the aetiology of the global obesity epidemic has been proposed in recent years. This proposition, however, rests on controversial interpretations of two distinct lines of research. On one hand, in mechanistic intervention studies, detrimental metabolic effects have been observed after excessive isolated fructose intakes in animals and human subjects. On the other hand, food disappearance data indicate that fructose consumption from added sugars has increased over the past decades and paralleled the increase in obesity. Both lines of research are presently insufficient to demonstrate a causal role of fructose in metabolic diseases, however. Most mechanistic intervention studies were performed on subjects fed large amounts of pure fructose, while fructose is ordinarily ingested together with glucose. The use of food disappearance data does not accurately reflect food consumption, and hence cannot be used as evidence of a causal link between fructose intake and obesity. Based on a thorough review of the literature, we demonstrate that fructose, as commonly consumed in mixed carbohydrate sources, does not exert specific metabolic effects that can account for an increase in body weight. Consequently, public health recommendations and policies aiming at reducing fructose consumption only, without additional diet and lifestyle targets, would be disputable and impractical. Although the available evidence indicates that the consumption of sugar-sweetened beverages is associated with body-weight gain, and it may be that fructose is among the main constituents of these beverages, energy overconsumption is much more important to consider in terms of the obesity epidemic.

Case complexity and clinical outcome in diabetes mellitus. A prospective study using the INTERMED.

The aim of this study was to assess a population of patients with diabetes mellitus by means of the INTERMED, a classification system for case complexity integrating biological, psychosocial and health care related aspects of disease. The main hypothesis was that the INTERMED would identify distinct clusters of patients with different degrees of case complexity and different clinical outcomes. Patients (n=61) referred to a tertiary reference care centre were evaluated with the INTERMED and followed 9 months for HbA1c values and 6 months for health care utilisation. Cluster analysis revealed two clusters: cluster 1 (62%) consisting of complex patients with high INTERMED scores and cluster 2 (38%) consisting of less complex patients with lower INTERMED. Cluster 1 patients showed significantly higher HbA1c values and a tendency for increased health care utilisation. Total INTERMED scores were significantly related to HbA1c and explained 21% of its variance. In conclusion, different clusters of patients with different degrees of case complexity were identified by the INTERMED, allowing the detection of highly complex patients at risk for poor diabetes control. The INTERMED therefore provides an objective basis for clinical and scientific progress in diabetes mellitus. Ongoing intervention studies will have to confirm these preliminary data and to evaluate if management strategies based on the INTERMED profiles will improve outcomes.

Hemodynamic effects of sodium bicarbonate in critically ill neonates.

OBJECTIVE: To analyze the cardiovascular effects of sodium bicarbonate in neonates with metabolic acidosis. DESIGN: Prospective, open, non-randomized, before-after intervention study with hemodynamic measurements performed before and 1, 5, 10, 20, and 30 min after bicarbonate administration. SETTING: Neonatal intensive care unit, tertiary care center. PATIENTS: Sequential sample of 16 paralysed and mechanically ventilated newborn infants with a metabolic acidosis (pH < 7.25 in premature and < 7.30 in term infants, base deficit > -8). INTERVENTION: An 8.4% sodium bicarbonate solution diluted 1:1 with water (final osmolality of 1000 mOsm/l) was administered in two equal portions at a rate of 0.5 mmol/min. The dose in mmol was calculated using the formula "base deficit x body weight (kg) x 1/3 x 1/2". MEASUREMENTS AND RESULTS: Sodium bicarbonate induced a significant but transient rise in pulsed Doppler cardiac output (CO) (+27.7%), aortic blood flow velocity (+15.3%), systolic blood pressure (BP) (+9.3%), (+14.6%), transcutaneous carbon dioxide pressure (PtcCO2) (+11.8%), and transcutaneous oxygen pressure (PtcO2) (+8%). In spite of the PaCO2 elevation, pH significantly improved (from a mean of 7.24 to 7.30), and the base deficit decreased (-39.3%). Calculated systemic vascular resistance (SVR) (-10.7%) and diastolic BP (-11.7%) decreased significantly, while PaO2 and heart rate (HR) did not change. Central venous pressure (CVP) (+6.5%) increased only slightly. By 30 min after bicarbonate administration all hemodynamic parameters, with the exception of the diastolic BP, had returned to baseline. CONCLUSION: Sodium bicarbonate in neonates with metabolic acidosis induces an increase in contractility and a reduction in afterload.

Stepwise evaluation of syncope: a prospective population-based controlled study.

BACKGROUND: Evaluation of syncope remains often unstructured. The aim of the study was to assess the effectiveness of a standardized protocol designed to improve the diagnosis of syncope. METHODS: Consecutive patients with syncope presenting to the emergency departments of two primary and tertiary care hospitals over a period of 18 months underwent a two-phase evaluation including: 1) noninvasive assessment (phase I); and 2) specialized tests (phase II), if syncope remained unexplained after phase I. During phase II, the evaluation strategy was alternately left to physicians in charge of patients (control), or guided by a standardized protocol relying on cardiac status and frequency of events (intervention). The primary outcomes were the diagnostic yield of each phase, and the impact of the intervention (phase II) measured by multivariable analysis. RESULTS: Among 1725 patients with syncope, 1579 (92%) entered phase I which permitted to establish a diagnosis in 1061 (67%) of them, including mainly reflex causes and orthostatic hypotension. Five-hundred-eighteen patients (33%) were considered as having unexplained syncope and 363 (70%) entered phase II. A cause for syncope was found in 67 (38%) of 174 patients during intervention periods, compared to 18 (9%) of 189 during control (p<0.001). Compared to control periods, intervention permitted diagnosing more cardiac (8%, vs 3%, p=0.04) and reflex syncope (25% vs 6%, p<0.001), and increased the odds of identifying a cause for syncope by a factor of 4.5 (95% CI: 2.6-8.7, p<0.001). Overall, adding the diagnostic yield obtained during phase I and phase II (intervention periods) permitted establishing the cause of syncope in 76% of patients. CONCLUSION: Application of a standardized diagnostic protocol in patients with syncope improved the likelihood of identifying a cause for this symptom. Future trials should assess the efficacy of diagnosis-specific therapy.

Cardiovascular Risk Prediction with Ultrasound

This paper addresses primary care physicians, cardiologists, internists, angiologists and doctors desirous of improving vascular risk prediction in primary care. Many cardiovascular risk factors act aggressively on the arterial wall and result in atherosclerosis and atherothrombosis. Cardiovascular prognosis derived from ultrasound imaging is, however, excellent in subjects without formation of intimal thickening or atheromas. Since ultrasound visualises the arterial wall directly, the information derived from the arterial wall may add independent incremental information to the knowledge of risk derived from global risk assessment. This paper provides an overview on plaque imaging for vascular risk prediction in two parts: Part 1: Carotid IMT is frequently used as a surrogate marker for outcome in intervention studies addressing rather large cohorts of subjects. Carotid IMT as a risk prediction tool for the prevention of acute myocardial infarction and stroke has been extensively studied in many patients since 1987, and has yielded incremental hazard ratios for these cardiovascular events independently of established cardiovascular risk factors. However, carotid IMT measurements are not used uniformly and therefore still lack widely accepted standardisation. Hence, at an individual, practicebased level, carotid IMT is not recommended as a risk assessment tool. The total plaque area of the carotid arteries (TPA) is a measure of the global plaque burden within both carotid arteries. It was recently shown in a large Norwegian cohort involving over 6000 subjects that TPA is a very good predictor for future myocardial infarction in women with an area under the curve (AUC) using a receiver operating curves (ROC) value of 0.73 (in men: 0.63). Further, the AUC for risk prediction is high both for vascular death in a vascular prevention clinic group (AUC 0.77) and fatal or nonfatal myocardial infarction in a true primary care group (AUC 0.79). Since TPA has acceptable reproducibility, allows calculation of posttest risk and is easily obtained at low cost, this risk assessment tool may come in for more widespread use in the future and also serve as a tool for atherosclerosis tracking and guidance for intensity of preventive therapy. However, more studies with TPA are needed. Part 2: Carotid and femoral plaque formation as detected by ultrasound offers a global view of the extent of atherosclerosis. Several prospective cohort studies have shown that cardiovascular risk prediction is greater for plaques than for carotid IMT. The number of arterial beds affected by significant atheromas may simply be added numerically to derive additional information on the risk of vascular events. A new atherosclerosis burden score (ABS) simply calculates the sum of carotid and femoral plaques encountered during ultrasound scanning. ABS correlates well and independently with the presence of coronary atherosclerosis and stenosis as measured by invasive coronary angiogram. However, the prognostic power of ABS as an independent marker of risk still needs to be elucidated in prospective studies. In summary, the large number of ways to measure atherosclerosis and related changes in human arteries by ultrasound indicates that this technology is not yet sufficiently perfected and needs more standardisation and workup on clearly defined outcome studies before it can be recommended as a practice-based additional risk modifier.

Energy deficit and length of hospital stay can be reduced by a two-step quality improvement of nutrition therapy: the intensive care unit dietitian can make the difference.

OBJECTIVE: Critically ill patients are at high risk of malnutrition. Insufficient nutritional support still remains a widespread problem despite guidelines. The aim of this study was to measure the clinical impact of a two-step interdisciplinary quality nutrition program. DESIGN: Prospective interventional study over three periods (A, baseline; B and C, intervention periods). SETTING: Mixed intensive care unit within a university hospital. PATIENTS: Five hundred seventy-two patients (age 59 ± 17 yrs) requiring >72 hrs of intensive care unit treatment. INTERVENTION: Two-step quality program: 1) bottom-up implementation of feeding guideline; and 2) additional presence of an intensive care unit dietitian. The nutrition protocol was based on the European guidelines. MEASUREMENTS AND MAIN RESULTS: Anthropometric data, intensive care unit severity scores, energy delivery, and cumulated energy balance (daily, day 7, and discharge), feeding route (enteral, parenteral, combined, none-oral), length of intensive care unit and hospital stay, and mortality were collected. Altogether 5800 intensive care unit days were analyzed. Patients in period A were healthier with lower Simplified Acute Physiologic Scale and proportion of "rapidly fatal" McCabe scores. Energy delivery and balance increased gradually: impact was particularly marked on cumulated energy deficit on day 7 which improved from -5870 kcal to -3950 kcal (p < .001). Feeding technique changed significantly with progressive increase of days with nutrition therapy (A: 59% days, B: 69%, C: 71%, p < .001), use of enteral nutrition increased from A to B (stable in C), and days on combined and parenteral nutrition increased progressively. Oral energy intakes were low (mean: 385 kcal*day, 6 kcal*kg*day ). Hospital mortality increased with severity of condition in periods B and C. CONCLUSION: A bottom-up protocol improved nutritional support. The presence of the intensive care unit dietitian provided significant additional progression, which were related to early introduction and route of feeding, and which achieved overall better early energy balance.

Systematic review protocol to define classical IgE-associated diseases from birth to adolescence: the MeDALL study

BACKGROUND: Classical disease phenotypes are mainly based on descriptions of symptoms and the hypothesis that a given pattern of symptoms provides a diagnosis. With refined technologies there is growing evidence that disease expression in patients is much more diverse and subtypes need to be defined to allow a better targeted treatment. One of the aims of the Mechanisms of the Development of Allergy Project (MeDALL,FP7) is to re-define the classical phenotypes of IgE-associated allergic diseases from birth to adolescence, by consensus among experts using a systematic review of the literature and identify possible gaps in research for new disease markers. This paper describes the methods to be used for the systematic review of the classical IgE-associated phenotypes applicable in general to other systematic reviews also addressing phenotype definitions based on evidence. METHODS/DESIGN: Eligible papers were identified by PubMed search (complete database through April 2011). This search yielded 12,043 citations. The review includes intervention studies (randomized and clinical controlled trials) and observational studies (cohort studies including birth cohorts, case-control studies) as well as case series. Systematic and non-systematic reviews, guidelines, position papers and editorials are not excluded but dealt with separately. Two independent reviewers in parallel conducted consecutive title and abstract filtering scans. For publications where title and abstract fulfilled the inclusion criteria the full text was assessed. In the final step, two independent reviewers abstracted data using a pre-designed data extraction form with disagreements resolved by discussion among investigators. DISCUSSION: The systematic review protocol described here allows to generate broad,multi-phenotype reviews and consensus phenotype definitions. The in-depth analysis of the existing literature on the classification of IgE-associated allergic diseases through such a systematic review will 1) provide relevant information on the current epidemiologic definitions of allergic diseases, 2) address heterogeneity and interrelationships and 3) identify gaps in knowledge.