Primary Reason For Change Research Articles

Guideline implementation, drug sequencing, and quality of care in heart failure: design and rationale of TITRATE-HF.

Current heart failure (HF) guidelines recommend to prescribe four drug classes in patients with HF with reduced ejection fraction (HFrEF). A clear challenge exists to adequately implement guideline-directed medical therapy (GDMT) regarding the sequencing of drugs and timely reaching target dose. It is largely unknown how the paradigm shift from a serial and sequential approach for drug therapy to early parallel application of the four drug classes will be executed in daily clinical practice, as well as the reason clinicians may not adhere to new guidelines. We present the design and rationale for the real-world TITRATE-HF study, which aims to assess sequencing strategies for GDMT initiation, dose titration patterns (order and speed), intolerance for GDMT, barriers for implementation, and long-term outcomes in patients with de novo, chronic, and worsening HF. A total of 4000 patients with HFrEF, HF with mildly reduced ejection fraction, and HF with improved ejection fraction will be enrolled in >40 Dutch centres with a follow-up of at least 3years. Data collection will include demographics, physical examination and vital parameters, electrocardiogram, laboratory measurements, echocardiogram, medication, and quality of life. Detailed information on titration steps will be collected for the four GDMT drug classes. Information will include date, primary reason for change, and potential intolerances. The primary clinical endpoints are HF-related hospitalizations, HF-related urgent visits with a need for intravenous diuretics, all-cause mortality, and cardiovascular mortality. TITRATE-HF is a real-world multicentre longitudinal registry that will provide unique information on contemporary GDMT implementation, sequencing strategies (order and speed), and prognosis in de novo, worsening, and chronic HF patients.

Thapsigargin-resistant thiacalix[4]arene C-1087-sensitive component of the contractile activity in rat myometrium reflects the functioning of plasma membrane calcium pump

Background. According to existing knowledge, thiacalix[4]arene С-1087 is highly capable of inhibiting Са2+-pump (Са2+, Mg2+-АТРase) of the plasma membrane; at the same time it inhibits the functioning of Са2+-pump of the sarcoplasmic reticulum of uterine smooth muscles to some degree. The aim of this research was to study the effects of С-1087 on the concentration of Ca2+ ions and contractile activity of the rat myometrium cells using an inhibitor of Са2+-pump of the sarcoplasmic reticulum – thapsigargin. Materials and Methods. The experiments were conducted using outbred white non-pregnant rats. The contractile activity in the preparations of longitudinal SM of uterine horns with preserved endothelium was registered in the isometric mode. To determine the changes in [Ca2+]i level, myocytes were treated with probes Hoechst 33342 (to test the nucleus of the cell) and fluo-4 AM (to test the change in Са2+-concentration in the cell). Results. The tenzometric studies with the subsequent mechanokinetic analysis demonstrated that under the action of thapsigargin (0.5 µM), thiacalix[4]arene C-1087 (10 µM) caused considerable changes in the kinetics of the spontaneous contractile activity processes in the myometrium of rats, including the decrease in the maximal contraction velocity and the increase in the maximal relaxation velocity. By means of confocal microscopy with Ca2+-sensitive fluorescent probe fluo-4, it was demonstrated that the application of thiacalix[4]arene С-1087 to immobilized myocytes of the uterus against the background of thapsigargin caused a transient spike of Са2+-signal with the subsequent turn of the intracellular concentration of Ca ions to the stable increased level. The effects of С-1087 under the action of thapsigargin regarding the relaxation phase in the spontaneous myometrium contractions were removed after the preliminary blocking of nitric oxide synthases L-NAME (100 µM). Under the action of L-NAME, thiacalix[4]arene С-1087 (10 µM) caused complete inhibition of the relaxation process in the contraction of myometrium preparations, induced by high-potassium solution (80 mM). Conclusions. The primary reason for changes in the contractile activity and Ca2+-signal in uterine myocytes under the effect of thiacalix[4]arene С-1087 is its ability to inhibit Са2+-pump of the plasma membrane; further С-1087-induced changes in the smooth muscle tissues may be caused by the increased level of Са2+ concentration in myocytes. The obtained results demonstrate thiacalix[4]arene С-1087 is a promising compound for the elaboration of pharmacological preparations for modulating the contractile activity in smooth muscles, including myometrium.

Evaluation of the impact of the addition of a heart failure prescribing pharmacist to consultant-led heart failure ward round at a tertiary hospital

ObjectivePharmacists attending general medical post-admission ward rounds is established good practice. However, there is a lack of evidence on the impact of specialist heart failure (HF) prescribing pharmacists on consultant...

The impact of accreditation agencies and other powerful stakeholders on the performance measurement in Polish universities

PurposeThe purpose of this paper is to extend the understanding of how internal organisational processes change in response to external demands, by investigating the changes undertaken by two Polish business schools (b-schools) in anticipation of and in response to the demands of accreditation agencies (AAs) and other powerful stakeholders. Specifically, it examines the internal research-related performance measurement (PM) system and changes in the use of performance information (PI).Design/methodology/approachThe case study method is adopted, using data from publicly available documents and interviews with the faculty and management at the two schools. The data are interpreted and analysed using the neo-institutional theory.FindingsPowerful stakeholders are the primary reason for changes in PM systems and the manner in which PI is used. Specifically, AAs reflect an additional layer in the PM system, allowing for a downward cascading PI effect. This also leads to a wider use of PI across different organisational levels.Research limitations/implicationsThis study focusses on two case studies in a region still undergoing transition. Thus, this analysis could be reinforced through additional cases, different data collection methods and cross-country and between-country comparative analyses.Originality/valueThe changes in PM systems and particularly the use of PI are discussed in the context of Polish higher education (HE) and, more broadly, the entire Central and Eastern Europe (CEE) region. Moreover, the consideration of two b-school cases facilitates a comparative analysis of the differences in PM systems and the use of PI in the context of stakeholders’ PI needs.

The Impact of Accreditation Agencies and Other Powerful Stakeholders on the Performance Measurement in Polish Universities

Purpose: This study aims to extend our understanding of how internal organizational processes change in response to external demands, by investigating the changes undertaken by two Polish business schools (b-schools) in anticipation of and in response to the demands of accreditation agencies and other powerful stakeholders. Specifically, it examines the internal research-related performance measurement (PM) system and changes in the use of performance information (PI). Design/Methodology: The case study method is adopted, using data from publicly available documents and interviews with the faculty and management at the two schools. The data are interpreted and analyzed using neo-institutional theory. Findings: Powerful stakeholders are the primary reason for changes in PM systems and the manner in which PI are used. Specifically, accreditation agencies reflect an additional layer in the PM system, allowing a downward cascading PI effect. This also leads to a wider use of PI across different organizational levels. Research Limitations: This study focuses on two case studies in a region still undergoing transition. Thus, this analysis could be reinforced through additional cases, different data collection methods, and cross-country and between-country comparative analyses. Originality/Value: The changes in PM systems and particularly the use of PI are discussed in the context of Polish higher education and, more broadly, the entire Central and Eastern Europe (CEE) region. Moreover, the consideration of two b-school cases facilitates a comparative analysis of the differences in PM systems and the use of PI in the context of stakeholders’ PI needs.

Simplification of the zinc-sulfur-iodine thermochemical cycle for the production of H2 and CO

Abstract In this paper, three simplification plans for the zinc-sulfur-iodine thermochemical cycle are designed, namely the open-loop system, the five-step cycle, and the electrochemical cycle. Parameters for each simplified cycle are presented. Thermal efficiency is regarded as the evaluation criterion of the whole system, and thermal balance for each cycle is investigated. Results show that the variation of thermal load for the whole system is the primary reason for changes in thermal efficiency. Thermal efficiency of the open-loop system is improved to 57% under proper operating conditions, and concentrated H2SO4 with a mass fraction of 92.5 wt% is output. As for the electrochemical cycle, its thermal efficiency almost keeps the same with the original one, since study on its critical factor, the electrochemical Bunsen reaction, is not enough. What's more, chemical processes of the five-step and electrochemical cycle are simplified drastically by comparing to the original one.

Abstract 17182: Patterns of Discontinuation for Non-vitamin K Oral Anticoagulants in Atrial Fibrillation: Results From the ORBIT-AF II Registry

Background: Oral anticoagulation (OAC) is effective at preventing stroke in patients with atrial fibrillation (AF), yet warfarin is often poorly tolerated. Non-vitamin K oral anticoagulants (NOACs) are as or more effective as warfarin, yet their tolerance and persistence in clinical practice is not known. Methods: We assessed patterns of persistent OAC use among 2,345 AF patients starting on therapy in the ORBIT-AF II registry (71% starting on a NOAC, and 29% on warfarin). Results: By 6 months, 364 (22%) patients started on a NOAC had discontinued or changed initial therapy versus 143 (21%) started on warfarin initially (p=0.5). Among warfarin users, patients who switched or discontinued therapy were of similar age (median ages 72 and 74 vs. 74 for stable users, p=0.7) and CHA2DS2-VASc scores (mean 98 and 3.66 vs. 3.84, p=0.4). Among NOAC users, those who discontinued treatment were younger (median age 68 vs. 73 for those who switched and 72 for stable users; p=0.0004), and lower CHA2DS2-VASc scores (3.02 vs. 3.58 and 3.47, respectively; p=0.0008). The median time to change or discontinuation was more rapid in those started on a NOAC vs warfarin (97 days vs. 122 days, p=0.003). Among those on warfarin at baseline, 7.6% (n=52) were switched to a NOAC within 6 months, whereas transitions from NOAC to warfarin was 2.5% (n=42).Transitions among NOACs occurred in 9.8%, 3.2%, and 5.5% of patients on baseline dabigatran, rivaroxaban, and apixaban, respectively. Physician preference was the most common reason for both OAC and warfarin changes (Table). Drug cost was the primary reason for change of therapy in 15% of NOAC users (vs. 0 for warfarin). Conclusions: At 6-month follow-up, one in five newly started on OAC had discontinued or changed. These rates of change were similar among warfarin and NOAC treated patients. Cost concerns drove discontinuation in a modest number of patients, however, cost concerns were more prevalent in NOAC-treated patients.

Sleep Changes in Multiple Sclerosis: from the Individual’s Perspective

Sleep Changes in Multiple Sclerosis: from the Individual’s Perspective Sleep difficulties are common in multiple sclerosis (MS), with prevalence rates ranging from 36% to 62%. Sleep problems have been shown to have a grave impact on individuals in the general population and to contribute to reports of fatigue and reduced quality of life in MS. However, despite these high rates and overall impact, sleep problems in MS frequently go unrecognized. The present investigation sought to examine sleep changes among a sample of 97 individuals with MS and to gain a better appreciation as to what individuals with MS report as contributing to their change in sleep. Approximately 58% of participants complained of changes in their sleep. Among these 56 participants, bladder incontinence, muscle stiffness and leg spasms were most often endorsed as a contributor, with rates ranging from 57% to 63%. When asked about the primary attribution of their sleep change, the majority of individuals (43%) described problems with bladder incontinence. Following this, 17% and 15% reported worry and problems with leg spasms as the primary contributors, respectively. Furthermore, those who rated worry as their primary reason for change in their sleep also endorsed greater symptomatology of depression and anxiety. These findings suggest that sleep difficulties in MS may be a result of many physical and/or psychological symptoms. Proper identification of the etiology of sleep changes in MS is warranted in order to treat these problems and hopefully ameliorate individuals’ difficulty with sleep and fatigue.

Rates and Reasons for Early Change of First HAART in HIV-1-Infected Patients in 7 Sites throughout the Caribbean and Latin America

BackgroundHAART rollout in Latin America and the Caribbean has increased from approximately 210,000 in 2003 to 390,000 patients in 2007, covering 62% (51%–70%) of eligible patients, with considerable variation among countries. No multi-cohort study has examined rates of and reasons for change of initial HAART in this region.MethodologyAntiretroviral-naïve patients > = 18 years who started HAART between 1996 and 2007 and had at least one follow-up visit from sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Time from HAART initiation to change (stopping or switching any antiretrovirals) was estimated using Kaplan-Meier techniques. Cox proportional hazards modeled the associations between change and demographics, initial regimen, baseline CD4 count, and clinical stage.Principal FindingsOf 5026 HIV-infected patients, 35% were female, median age at HAART initiation was 37 years (interquartile range [IQR], 31–44), and median CD4 count was 105 cells/uL (IQR, 38–200). Estimated probabilities of changing within 3 months and one year of HAART initiation were 16% (95% confidence interval (CI) 15–17%) and 28% (95% CI 27–29%), respectively. Efavirenz-based regimens and no clinical AIDS at HAART initiation were associated with lower risk of change (hazard ratio (HR) = 1.7 (95% CI 1.1–2.6) and 2.1 (95% CI 1.7–2.5) comparing neverapine-based regimens and other regimens to efavirenz, respectively; HR = 1.3 (95% CI 1.1–1.5) for clinical AIDS at HAART initiation). The primary reason for change among HAART initiators were adverse events (14%), death (5.7%) and failure (1.3%) with specific toxicities varying among sites. After change, most patients remained in first line regimens.ConclusionsAdverse events were the leading cause for changing initial HAART. Predictors for change due to any reason were AIDS at baseline and the use of a non-efavirenz containing regimen. Differences between participant sites were observed and require further investigation.

Metastatic colorectal cancer (mCRC) patterns of care: Implications for clinical trial design

4079 Background: New approaches have expanded options for patients (pts) with mCRC. To characterize current practice paradigms that might bear on clinical trial design, we analyzed decision-making and treatment patterns in pts treated at a Comprehensive Cancer Center since the introduction of cetuximab (CET), and bevacizumab (BV). Methods: A retrospective review of all pts diagnosed with mCRC between 3/1/04 and 8/28/06 treated at Fox Chase Cancer Center. Results: 160 pts were treated, with 157 pts receiving at least one therapy regimen by 10 attending oncologists. There were 350 changes in therapy with 246 (70%) including continuation of at least one prior drug (92 BV, 111 fluoropyrimidines, 43 other). The most common reasons for treatment change were toxicity (33%), progressive disease (PD) (29%), treatment breaks (15%), and metastasectomy (11%) ( Table ). PD was a more common cause for treatment discontinuation in later phases of treatment (18% initial regimen vs. 36% subsequent regimens, p=0.0002). 24% of pts treated with oxaliplatin (OX) discontinued due to neuropathy. Hypersensitivity caused discontinuation in 5% of pts with OX and 7% of pts with CET. Resection of metastases was undertaken in 38% of pts. 43% of these pts received neoadjuvant therapy, and 56% received adjuvant therapy. 30% of pts have died, 29% remain on active treatment, 28% are on a treatment break, 3% are on hospice, and 11% are lost to follow-up. Conclusions: PD is no longer the primary reason for change of therapy in pts with mCRC. Metastasectomy is common and OX neuropathy is often treatment-limiting. These findings have important implications for endpoint selection and design of clinical trials in mCRC. Future clinical trials in mCRC must recognize treatment complexities and capture key components of decision-making that may result in prolonged survival. Furthermore, treatment breaks represent a potential window for the evaluation of new drugs. [Table: see text] No significant financial relationships to disclose.

Effect of preparation conditions on the thermal stability of an epoxy-functional inorganic–organic hybrid material system with phenyl side group

A hybrid material system consisting of (3-glycidyloxypropyl)trimethoxysilane and dimethyldimethoxysilane as matrix materials and diphenyldimethoxysilane (DPDMS) as both a matrix material and a potential thermal stabiliser by the sol–gel method. A detailed thermogravimetric analysis study of the influence of processing parameters, including DPDMS content, UV irradiation and sol ageing, on the thermal stability of the resultant thin films was presented. FT-IR spectroscopy was used to monitor the changes in the relative amount of epoxy rings in the system during processing. It was demonstrated that the crosslinking of epoxy groups in the structure is the primary reason for changes in the thermal stability of the system. It was also shown that the thermal stability, in terms of 10% mass loss, of the material system could be improved up to 280 °C, by adjusting the preparation conditions, compatible with several subsequent high temperature optoelectronic integration processes.

Obesity in children and young people: a crisis in public health.

Ten per cent of the world’s school-aged children are estimated to be carrying excess body fat (Fig. 1), with an increased risk for developing chronic disease. Of these overweight children, a quarter are obese, with a significant likelihood of some having multiple risk factors for type 2 diabetes, heart disease and a variety of other co-morbidities before or during early adulthood. The prevalence of overweight is dramatically higher in economically developed regions, but is rising significantly in most parts of the world. In many countries the problem of childhood obesity is worsening at a dramatic rate. Surveys during the 1990s show that in Brazil and the USA, an additional 0.5% of the entire child population became overweight each year. In Canada, Australia and parts of Europe the rates were higher, with an additional 1% of all children becoming overweight each year. The burden upon the health services cannot yet be estimated. Although childhood obesity brings a number of additional problems in its train – hyperinsulinaemia, poor glucose tolerance and a raised risk of type 2 diabetes, hypertension, sleep apnoea, social exclusion and depression – the greatest health problems will be seen in the next generation of adults as the present childhood obesity epidemic passes through to adulthood. Greatly increased rates of heart disease, diabetes, certain cancers, gall bladder disease, osteoarthritis, endocrine disorders and other obesityrelated conditions will be found in young adult populations, and their need for medical treatment may last for their remaining life-times. The costs to the health services, the losses to society and the burdens carried by the individuals involved will be great. The present report has been written to focus attention on the issue and to urge policy-makers to consider taking action before it is too late. Specifically, the report: