Burden of treatment for chronic illness: a concept analysis and review of the literature

Context Treatment burden, the burden associated with the treatment and management of chronic illness, has not yet been well articulated. Objective Using Rodgers' (1989, Journal of Advanced Nursing, 14, 330–335) method of concept analysis, this review describes the ways in which treatment burden has been conceptualized to define the concept and to develop a framework for understanding its attributes, antecedents and consequences. Methods Leading databases were searched electronically between the years 2002 and 2011. To ensure the review focused on actual observations of the concept of interest, articles that did not measure treatment burden (either qualitatively or quantitatively) were excluded. An inductive approach was used to identify themes related to the concept of treatment burden. Main results Thirty articles, identified from 1557 abstracts, were included in the review. The attributes of treatment burden include burden as a dynamic process, as a multidimensional concept, and comprising of both subjective and objective elements. Prominent predisposing factors (antecedents) include the person's age and gender, their family circumstances, possible comorbidity, high use of medications, characteristics of treatment and their relationship with their health-care provider. The most dominant consequences are poor health and well-being, non-adherence to treatment, ineffective resource use and burden on significant others. Furthermore, many of these consequences can also become antecedents, reflecting the cyclic and dynamic nature of treatment burden. Conclusion The findings underscore the need for researchers and health-care professionals to engage in collaborative discussions and make cooperative efforts to help alleviate treatment burden and tailor treatment regimens to the realities of people's daily lives

Increased Glycemic Variability Is Independently Associated With Length of Stay and Mortality in Noncritically Ill Hospitalized Patients

OBJECTIVE To investigate the association between glycemic variability (GV) and both length of stay (LOS) and 90-day mortality in noncritically ill hospitalized patients. RESEARCH DESIGN AND METHODS This study retrospectively analyzed 4,262 admissions to the general medicine or surgery services during a 2 year period. Patients with point-of-care glucose monitoring and a minimum of two glucose values per day on average were selected. GV was assessed by SD and coefficient of variation (CV). Data were analyzed with linear and logistic multivariate regression analysis in separate models for SD and CV. Analysis was performed with generalized estimating equations to adjust for correlation between multiple admissions in some individual cases. RESULTS After exclusions, 935 admissions comprised the sample. Results of adjusted analysis indicate that for every 10 mg/dL increase in SD and 10–percentage point increase in CV, LOS increased by 4.4 and 9.7%, respectively. Relative risk of death in 90 days also increased by 8% for every 10-mg/dL increase in SD. These associations were independent of age, race, service of care (medicine or surgery), previous diagnosis of diabetes, HbA1c, BMI, the use of regular insulin as a sole regimen, mean glucose, and hypoglycemia occurrence during the hospitalization. CONCLUSIONS Our results indicate that increased GV during hospitalization is independently associated with longer LOS and increased mortality in noncritically ill patients. Prospective studies with continuous glucose monitoring are necessary to investigate this association thoroughly and to generate therapeutic strategies targeted at decreasing GV. Inpatient hyperglycemia is common, and it has been associated with increased morbidity and mortality in patients with and without diabetes (1–7). In the intensive care unit (ICU) setting, hypoglycemia has also been independently associated with a significant increase in mortality (8–10). Recently, a third metric of glucose control, known as glycemic variability (GV), has been proposed to be additionally implicated in the disease-associated process of dysglycemia (11). GV refers to fluctuations of blood glucose values around the mean and has been posited as a novel marker for poor glycemic control (12,13). In vitro and human studies suggest that high GV leads to greater oxidative stress than does sustained hyperglycemia (14,15). Studies of ICU patients have consistently demonstrated that increased GV is independently associated with higher mortality (16–19). Notably, results from a large multicenter study concluded that GV was a stronger predictor of ICU mortality than was mean glucose concentrations (20). Although there is no consensus as to the best method to determine GV in hospitalized patients, the use of SD of glucose values has been well validated by previous ICU studies (16,20). Coefficient of variation (CV) has also been suggested as a strong independent index for measuring GV because it corrects for mean glucose levels (21,22). Despite substantial scientific evidence from the ICU, no previous studies have investigated the association between GV and clinical outcomes in patients admitted to the general medical and surgical wards. The purpose of this study was therefore to investigate the association between GV and length of stay (LOS) and 90-day mortality in noncritically ill hospitalized patients. We hypothesize that increased GV in this setting is associated with increased LOS and mortality

Investigating the Evidence of the Real-Life Impact of Acute Hyperglycaemia

Poorly controlled diabetes mellitus (DM) is associated with the development of long-term micro- and macro-vascular complications. The predominant focus of anti-diabetic therapy has been on lowering glycosylated haemoglobin levels, with a strong emphasis on fasting plasma glucose (particularly in Type 2 DM). There is considerable evidence indicating that post-meal hyperglycaemic levels are independently associated with higher risks of macro-vascular disease. Although some have identified mechanisms which may account for these observations, interventions which have specifically targeted postprandial glucose rises showed little or no effect in reducing cardiovascular risk. Clinical experience and some recent studies suggest acute hyperglycaemia affects cognition and other indicators of performance, equivalent to impairment seen during hypoglycaemia. In this brief report, we evaluated the published studies and argue that acute hyperglycaemia is worth investigating in relation to the real-life implications. In summary, evidence exists suggesting that acute hyperglycaemia may lead to impaired cognitive performance and productivity, but the relationship between these effects and daily activities remains poorly understood. Further research is required to enhance our understanding of acute hyperglycaemia in daily life. A better appreciation of clinically relevant effects of acute hyperglycaemia will allow us to determine whether it needs to be addressed by specific treatment

The Effect of Wall Inertia on High-Frequency Instabilities of Flow Through an Elastic-Walled Tube

We examine the effect of wall inertia on the onset of high-frequency self-excited oscillations in flow through an elastic-walled tube. The previous asymptotic model of Whittaker et al. (Proc. Roy. Soc. A466, 2010), for a long-wavelength high-frequency instability in a Starling-resistor set-up, neglected inertia in the tube wall. Here, we extend this model by modifying the ‘tube-law’ for the wall mechanics to include inertial effects. The resulting coupled model for the fluid and solid mechanics is solved to find the normal modes of oscillation for the system, together with their frequencies and growth rates. In the system and parameter regime considered, the addition of wall inertia reduces the oscillation frequency of each mode, however its effect on the stability of the system is not as straightforward. Increasing wall inertia lowers the mean flow rate required for the onset of instability, and is therefore destabilising. However, at higher flow rates the instability growth rate is decreased, and so wall inertia is stabilising here. Overall, the addition of wall inertia decreases the sensitivity of the system to the mean axial flow rate. The theoretical results show good qualitative and reasonable quantitative agreement with direct numerical simulations performed using the oomph-lib framework

A meta-analysis of rate ratios for nocturnal confirmed hypoglycaemia with insulin degludec vs. insulin glargine using different definitions for hypoglycaemia

Aims: A prospective meta-analysis of phase 3 trials showed lower rates of nocturnal hypoglycaemia with insulin degludec vs. insulin glargine. We investigated the consistency of the results across different definitions of hypoglycaemia. Methods: This post-hoc, patient-level meta-analysis included six randomized, controlled, 26- or 52-week phase 3a trials in insulin-naïve participants with Type 2 diabetes mellitus (Type 2 diabetesinsulin naïve), participants with Type 2 diabetes mellitus using basal−bolus therapy (Type 2 diabetesBB) and those with Type 1 diabetes mellitus. We used three definitions of hypoglycaemia and different timescales for the nocturnal period. Rates were analysed for the entire core trial period, the ‘maintenance period’ only, and the extension trial set population. Analyses utilized a negative binomial regression model. Results: In Type 2 diabetesinsulin naïve participants, risk of nocturnal hypoglycaemia was significantly lower with insulin degludec vs. insulin glargine for all hypoglycaemia definitions and trial periods. Risk was also lower for the timescale 21.59–05.59, but not 00.01–07.59. For Type 2 diabetesBB, nocturnal hypoglycaemia rates were lower with insulin degludec vs. insulin glargine across all definitions, timescales and trial periods, with one exception. For individuals with Type 1 diabetes mellitus, nocturnal hypoglycaemia risk was significantly lower with insulin degludec during the maintenance period for the original definition (plasma glucose < 3.1 mmol/l, timescale 00.01–05.59) and in the extension trial set population for all hypoglycaemia definitions except for the nocturnal timescale 00.01–07.59. Conclusions: Compared with insulin glargine, insulin degludec is associated with lower rates of nocturnal hypoglycaemia in people with Type 2 diabetes mellitus, and similar or lower rates in Type 1 diabetes mellitus, across different definitions

A pilot study evaluating the use of ABCD2 score in pre-hospital assessment of patients with suspected transient ischaemic attack: experience and lessons learned

Background: Suspected transient ischaemic attack (TIA) is a common presentation to emergency medical services (EMS) in the United Kingdom (UK). Several EMS systems have adopted the ABCD2 score to aid pre-hospital risk stratification and decision-making on patient disposition, such as direct referral to an Emergency Department or specialist TIA clinic. However, the ABCD2 score, developed for hospital use, has not been validated for use in the pre-hospital context of EMS care. Methods: We conducted a pilot study to assess eligibility criteria, recruitment rates, protocol compliance, consent and follow-up procedures to inform the development of a definitive study to validate the ABCD2 tool in pre-hospital evaluation of patients with suspected TIA. Results: From 1st May–1st September 2013, nine patients with an EMS suspected diagnosis of TIA had the TIA diagnosis later confirmed by a specialist from five participating sites. This recruitment rate is comparable to stroke trials in the EMS setting. Bureaucratic obstacles and duplication of approval processes across participating sites took 13 months to resolve before recruitment commenced. Due to the initial difficulty in recruitment, a substantial amendment was approved to modify inclusion criteria, allowing patients with atrial fibrillation and/or taking anticoagulant therapy to participate in the study. Conclusions: It is possible to identify, recruit and follow up patients with suspected TIA in the EMS setting. Training large numbers of EMS staff is required as exposure to TIA patients is infrequent. Significant insight was gained into the complexity of NHS research governance mechanisms in the UK. This knowledge will facilitate the planning of a future adequately powered study to validate the ABCD2 tool in a pre-hospital setting

Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

BACKGROUND: Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel(®)) to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. METHODS: Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC) viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. RESULTS: Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye). In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected) compared to saline (12 of 12 infected) and a control gel (5 of 7 infected). CONCLUSION: These results suggest that physiologic or microbicide-induced acid immobilization and killing of infected white blood cells may be effective in preventing sexual transmission of cell-associated HIV

Benefits of combination of insulin degludec and liraglutide are independent of baseline glycated haemoglobin level and duration of type 2 diabetes

AIM: To evaluate, using post hoc analyses, whether the novel combination of a basal insulin, insulin degludec, and a glucagon-like peptide-1 receptor agonist, liraglutide (IDegLira), was consistently effective in patients with type 2 diabetes (T2D), regardless of the stage of T2D progression. METHODS: Using data from the DUAL I extension [insulin-naïve patients uncontrolled on oral antidiabetic drugs (OADs), n = 1660, 52 weeks] and DUAL II (patients uncontrolled on basal insulin plus OADs, n = 398, 26 weeks) randomized trials, the efficacy of IDegLira was investigated with regard to measures of disease progression stage including baseline glycated haemoglobin (HbA1c), disease duration and previous insulin dose. RESULTS: Across four categories of baseline HbA1c (≤7.5-9.0%), HbA1c reductions were significantly greater with IDegLira (1.1-2.5%) compared with IDeg or liraglutide alone in DUAL I. In DUAL II, HbA1c reductions were significantly greater with IDegLira (0.9-2.5%) than with IDeg in all but the lowest HbA1c category. In DUAL I, insulin dose and hypoglycaemia rate were lower across all baseline HbA1c categories for IDegLira versus IDeg, while hypoglycaemia was higher with IDegLira than liraglutide, irrespective of baseline HbA1c. In DUAL II, insulin dose and hypoglycaemia rate were similar with IDegLira and IDeg (maximum dose limited to 50 U) independent of baseline HbA1c. The reduction in HbA1c with IDegLira was independent of disease duration and previous insulin dose but varied depending on pre-trial OAD treatment. CONCLUSIONS: IDegLira effectively lowered HbA1c across a range of measures, implying suitability for patients with either early or advanced T2D