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Background: Patients with diabetic kidney disease (DKD) often struggle with blood pressure control. In team-based models of care, pharmacists and primary care providers (PCPs) play important roles in supporting patients' blood pressure management.Objective: To describe whether PCPs' acceptance of pharmacists' recommendations impacts systolic blood pressure (SBP) at 36 months.Design: An observational analysis of a subset of participants randomized to the intervention arm of the Simultaneous risk factor control using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study.Participants: STOP-DKD participants for whom (1) the pharmacist made at least one recommendation to the PCP; (2) there were available data regarding the PCP's corresponding action; and (3) there were SBP measurements at baseline and 36 months.Intervention: Participants received monthly telephone calls with a pharmacist addressing health behaviors and medication management. Pharmacists made medication-related recommendations to PCPs.Main Measures: We fit an unadjusted generalized linear mixed model to assess the association between the number of pharmacists' recommendations for DKD and blood pressure management and PCPs' acceptance of such recommendations. We used a linear regression model to evaluate the association between PCP acceptance and SBP at 36 months, adjusted for baseline SBP.Key Results: Pharmacists made 176 treatment recommendations (among 59 participants), of which 107 (61%) were accepted by PCPs. SBP significantly declined by an average of 10.5 mmHg (p < 0.01) among 47 of 59 participants who had valid measurements at baseline and 36 months. There was a significant association between the number of pharmacist recommendations and the odds of PCP acceptance (OR 1.19; 95%CI 1.00, 1.42; p < 0.05), but no association between the number of accepted recommendations and SBP.Conclusions: Pharmacists provided actionable medication-related recommendations. We identified a significant decline in SBP at 36 months, but this reduction was not associated with recommendation acceptance.Trial Registration: NCT01829256. [ABSTRACT FROM AUTHOR]

Peripheral intravenous cannula (PIVC) insertion is one of the most common invasive procedures performed in neonates and is frequently associated with adverse events. There are no studies in the neonatal population looking at the possibility of reducing the risk of PIVC-related complications by elective replacement of PIVC. A randomised, non-blinded, control trial was conducted in a tertiary level neonatal unit in Melbourne, Australia, to examine rates of extravasation in neonates with elective replacement of PIVC as compared to standard practice. Neonates born at 32 weeks of gestation or more were randomly assigned to have their PIVC replaced electively (every 72-96 h) or when clinically indicated in a 1:1 allocation ratio after parental consent. Primary outcome studied was rate of extravasation. Secondary outcomes included rates of phlebitis, leakage or spontaneous dislodgement of PIVC. One hundred thirteen infants were enrolled. Extravasation was noted in 33 (60%) of standard practice group vs. 28 (48.3%) of elective replacement (RR 0.80, CI 0.57-1.13, p = 0.21) infants. Time to first extravasation was similar between the groups (hazard ratio 0.69, CI 0.42-1.15). Extravasation events per 1000 IV hours were also similar between groups. Similar results were seen by both intention to treat and per protocol analyses. There was an increase in leaking rates (HR1.98, CI 1.03-3.81, p = 0.04) in the elective group, while phlebitis and spontaneous dislodgement rates were similar to standard group.Conclusion: Elective replacement of PIVC in neonates is not associated with reduction in extravasation rates.Trial registration: This trial has been registered with the Australian and New Zealand Clinical Trials Register. Identifier: ACTRN12615000827538. What is Known: • The reported incidence of extravasation injury is as high as 70% in the neonatal and paediatric population and has an association with cannula dwell time. • Adult studies have done to look at the possibility of reducing intravenous cannula-related complications with routine replacement of the cannulas but no similar studies have been done in the neonatal population. What is New: • Routine replacement of intravenous cannula in neonates between 72 and 96 h of use does not reduce the rate of extravasation injuries. • There might be some added complications associated with such a practice. [ABSTRACT FROM AUTHOR]

Purpose: Ammonia is used as a stimulant in strength based sports to increase arousal and offset fatigue however little is known about its physiological and performance effects. The purpose of this study was twofold (1) establish the physiological response to acute ammonia inhalation (2) determine whether the timing of the physiological response corresponds with a performance enhancement, if any.Methods: Fifteen healthy males completed two trials. Trial one investigated the beat-to-beat middle cerebral artery blood flow velocity (MCAv), heart rate (HR) and mean arterial pressure (MAP) response to ammonia inhalation. During trial two, participants performed a maximal single mid-thigh pull (MTP) at various time points following ammonia inhalation in a randomised order: MTPs were conducted immediately, 15, 30 and 60 s following ammonia inhalation. A MTP with no ammonia inhalation served as the control. During this trial maximal MTP force, rate of force development (RFD) and electromyography (EMG) activity were recorded.Results: MCAvmean increased and peaked on average by 6 cm s(-1) (P < 0.001), 9.4 ± 5.5 s following ammonia inhalation. Similarly, HR was increased by 6 ± 11 beats per minute 15 s following ammonia inhalation (P < 0.001). MAP remained unchanged following inhalation (P = 0.51). The use and timing of ammonia inhalation had no effect on maximal force, RFD or EMG (all P > 0.2) compared to control.Conclusions: MCAv was elevated despite no increase in MAP occurring; this is indicative of a cerebrovascular vasodilation. Despite the marked cerebrovascular and cardiovascular response to ammonia inhalation no ergogenic effect was observed during the MTP, irrespective of the timing of administration. [ABSTRACT FROM AUTHOR]

Patient- (e.g., health literacy), provider- (e.g., clinical inertia), and system-level (e.g., under-empowered care teams) barriers have contributed to suboptimal cardiovascular disease (CVD) risk management among US Veterans.[1] Among Veterans using the Veterans Health Administration (VHA), more than 80% have at least two CVD risk factors,[2] with approximately 34% and 49% having a diagnosis of hypertension and dyslipidemia, respectively.[3] Innovative care delivery models that use patient-generated health data, integrate non-physician providers into the primary care team, and facilitate patient-provider interaction have the potential to control CVD risk factors at the individual- and population-level.[4], [5] Therefore, the objective of the Team-supported, Electronic health record (EHR)-leveraged, Active Management (TEAM) pilot study was to assess the feasibility of a multi-component CVD risk management intervention among Veterans in rural North Carolina. As the primary care infrastructure is increasingly stretched thin, this two-pronged approach may be a sustainable solution to address uncontrolled CVD risk factors for it promotes patients' awareness and management of their CVD risk and enables a single member of the primary care team to oversee a large patient panel. First, personalized CVD risk letters have the potential to educate a large population of at-risk patients and thus increase patient self-management and participation in healthcare decision-making. [Extracted from the article]

The article offers information on improving care coordination for Veterans Within Veterans' Health Administration (VA) and healthcare system. It mentions coordinating care is essential for improving patients' clinical outcomes, enhancing patients' experiences of care, increasing provider satisfaction, and decreasing costs; and also mentions in the patient-centered medical home (PCMH) model, primary care is the locus for coordinating care.

Patients may fail to successfully undergo a switch in therapy associated with a formulary change. The aim of this study was to measure health care costs and outcomes among patients who failed a formulary change in proton pump inhibitors in a VA medical center. Patients who failed a switch from omeprazole to lansoprazole (N = 51) were matched with patients who were successfully switched (N = 51). Health care utilization data was gathered from VA electronic databases and medical records for six months before and after the switch and, for failure patients, during the lansoprazole trial period. Statistical comparisons between failure and success patients were performed on changes in health care costs between these time periods. Health outcome data for the lansoprazole trial period and subsequent omeprazole reinstatement period were obtained through a telephone questionnaire of failure patients. Changes in total health care utilization costs did not differ significantly between failure and success groups for any of the time periods. Failure patients had significantly poorer health outcomes during their lansoprazole trial periods with significantly greater severity of heartburn and severity and frequency of acid regurgitation (P < 0.001). In conclusion, the formulary change had a negative impact upon health outcomes among failure patients but did not significantly affect their health care utilization costs. Identification of failure patients early in their lansoprazole trial periods could improved their health outcomes and satisfaction with medical care. [ABSTRACT FROM AUTHOR]

Infection with enterotoxigenic E. coli (ETEC) induces secretory diarrhea by stimulating net secretion of fluid and electrolytes. We tested the hypothesis that ETEC potentiates jejunal ion secretion induced by other agonists and also examined whether the soluble fiber psyllium ameliorates effects of ETEC-induced pathophysiology. Noninfected or ETEC-infected piglets were given oral electrolyte solution twice daily or electrolyte solution supplemented with psyllium for 48 hr. Jejunal tissues were mounted in flux chambers and basal and stimulated ion transport responses, as reflected by short-circuit current (I(SC)) were measured. The severity of ETEC-induced diarrhea was reduced by psyllium. I(SC) responses to carbachol and 5-hydroxytryptamine were greater in tissues from infected piglets compared with noninfected controls or infected piglets given psyllium. These results suggest that psyllium ameliorates ETEC-induced diarrhea and prevents the enhanced secretory responses to calcium-mediated agonists that occur in ETEC-infected piglet jejunum. [ABSTRACT FROM AUTHOR]

This study was conducted to determine whether one could identify viral and bacterial pulmonary infections with confidence. It has been our impression for some time that one could differentiate viral from bacterial pulmonary infections on the basis of roentgenographic findings alone and to test this hypothesis, we conducted this study where the roentgenographic findings first were categorized as being due to viral or bacterial infection and then compared with clinical results. The overall accuracy was just over 90% and our method of analysis is presented. [ABSTRACT FROM AUTHOR]

The CNS is rich in cholesterol, which is essential for neuronal development and survival, synapse maturation, and optimal synaptic activity. Alterations in brain cholesterol homeostasis are linked to neurodegeneration. Studies have demonstrated that Huntington disease (HD), a progressive and fatal neurodegenerative disorder resulting from polyglutamine expansion in the huntingtin protein, is associated with changes in cellular cholesterol metabolism. Emerging evidence from human and animal studies indicates that attenuated brain sterol synthesis and accumulation of cholesterol in neuronal membranes represent two distinct mechanisms occurring in the presence of mutant huntingtin that influence neuronal survival. Increased knowledge of how changes in intraneuronal cholesterol metabolism influence the pathogenesis of HD will provide insights into the potential application of brain cholesterol regulation as a therapeutic strategy for this devastating disease. [ABSTRACT FROM AUTHOR]

Background: In recent years, much progress has been made in the treatment of multiple myeloma. However, a major limitation of existing chemotherapeutic drugs is the eventual emergence of resistance; hence, the development of novel agents with new mechanisms of action is pertinent. Here, we describe the activity and mechanism of action of pyrrolo-1,5-benzoxazepine-15 (PBOX-15), a novel microtubule-targeting agent, in multiple myeloma cells.Methods: The anti-myeloma activity of PBOX-15 was assessed using NCI-H929, KMS11, RPMI8226, and U266 cell lines, and primary myeloma cells. Cell cycle distribution, apoptosis, cytochrome c release, and mitochondrial inner membrane depolarisation were analysed by flow cytometry; gene expression analysis was carried out using TaqMan Low Density Arrays; and expression of caspase-8 and Bcl-2 family of proteins was assessed by western blot analysis.Results: Pyrrolo-1,5-benzoxazepine-15 induced apoptosis in ex vivo myeloma cells and in myeloma cell lines. Death receptor genes were upregulated in both NCI-H929 and U266 cell lines, which displayed the highest and lowest apoptotic responses, respectively, following treatment with PBOX-15. The largest increase was detected for the death receptor 5 (DR5) gene, and cotreatment of both cell lines with tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), the DR5 ligand, potentiated the apoptotic response. In NCI-H929 cells, PBOX-15-induced apoptosis was shown to be caspase-8 dependent, with independent activation of extrinsic and intrinsic apoptotic pathways. A caspase-8-dependent decrease in expression of Bim(EL) preceded downregulation of other Bcl-2 proteins (Bid, Bcl-2, Mcl-1) in PBOX-15-treated NCI-H929 cells.Conclusion: PBOX-15 induces apoptosis and potentiates TRAIL-induced cell death in multiple myeloma cells. Thus, PBOX-15 represents a promising agent, with a distinct mechanism of action, for the treatment of this malignancy. [ABSTRACT FROM AUTHOR]

There is increasing pressure for neuroscientists to communicate their research and the societal implications of their findings to the public. Communicating science is challenging, and the transformation of communication by digital and interactive media increases the complexity of the challenge. To facilitate dialogue with the public in this new media landscape, we suggest three courses of action for the neuroscience community: a cultural shift that explicitly recognizes and rewards public outreach, the identification and development of neuroscience communication experts, and ongoing empirical research on the public communication of neuroscience. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to identify potential explanatory factors for racial differences in blood pressure (BP) control.Design: The design of the study was a cross-sectional studyPatients/participants: The study included 608 patients with hypertension who were either African American (50%) or white (50%) and who received primary care in Durham, NC.Measurements and Main Results: Baseline data were obtained from the Take Control of Your Blood pressure study and included clinical, demographic, and psychosocial variables potentially related to clinic BP measures. African Americans were more likely than whites to have inadequate baseline clinic BP control as defined as greater than or equal to 140/90 mmHg (49% versus 34%; unadjusted odds ratio [OR] 1.8; 95% confidence interval [CI] 1.3-2.5). Among factors that may explain this disparity, being older, reporting hypertension medication nonadherence, reporting a hypertension diagnosis for more than 5 years, reporting high levels of stress, being worried about hypertension, and reporting an increased number of medication side effects were related to inadequate BP control. In adjusted analyses, African Americans continue to have poor BP control relative to whites; the magnitude of the association was reduced (OR = 1.5; 95% CI 1.0-2.1). Medication nonadherence, worries about hypertension, and older age (>70) continued to be related to poor BP control.Conclusions: In this sample of hypertensive patients, there were a number of factors associated with poor BP control that partially explained the observed racial disparity in hypertension control including age, medication nonadherence, and worry about BP. Medication nonadherence is of particular interest because it is a potentially modifiable factor that might be used to reduce the racial disparity in BP control. [ABSTRACT FROM AUTHOR]

Opening wedge high tibial osteotomy (OWHTO) is a recently described procedure for medial compartment arthritis of the knee in the active, younger population. Despite having a number of advantages over the traditional closing wedge high tibial osteotomy (CWHTO) a potential complication of OWHTO is a high rate of delayed- and non-union. This study reports the occurrence of delayed- and non-union following OWHTO for medial compartment arthritis of the knee. Questionnaires were sent to all current members of the Australian Knee Society (n=45), a special interest group of the Australian Orthopaedic Group. Surgeons were asked primarily to indicate how many OWHTOs they had performed, and how many of these had progressed to union, delayed-union and non-union. All 45 questionnaires were returned, with 21 surgeons (47%) performing OWHTOs. A total of 188 OWHTO cases were reported, of which 182 were complete. Of these complete cases 167 (91.8%) were classed as united, 12 (6.6%) delay-united and 3 (1.6%) non-united. The results of this study demonstrate that the rate of delayed- and non-union following OWHTO for medial compartment arthritis of the knee is relatively low and comparable to that reported for traditional CWHTO. [ABSTRACT FROM AUTHOR]

Busulfan is an alkylating agent that is widely used in preparative regimens for bone marrow transplantation (BMT). We developed a high-performance liquid chromatographic (HPLC) assay for the determination of plasma busulfan concentrations in 30 patients who received oral doses of 1 mg/kg. Concentrations were fit by a one-compartment pharmacokinetic model with first-order absorption. The pattern of absorption and elimination varied widely between patients, with peak concentrations ranging from 1.2 to 10.4 mumol/l (mean, 4.25 +/- 2.49). The elimination half-life ranged from 58 to 433 min (harmonic mean, 140 min). The AUC contributed by a single oral dose ranged from 606 to 5,144 mumol-min/l (mean, 2,012 +/- 1,223). Patients were evaluated for the development of veno-occlusive disease (VOD), a treatment complication that occurs in 20% of patients undergoing BMT and causes 10% of transplantation-related deaths. All six patients who developed VOD had an AUC greater than the mean, and five of them had an AUC that was greater than 1 SD above the mean. The occurrence of VOD was highly correlated with an increased AUC (greater than 1 SD above the mean) (X2 = 18; P less than 0.0001). Using multivariate logistic regression, no other statistically significant pharmacokinetic predictor of VOD was found. The tenfold variability in the busulfan AUC and the statistical association of increased AUC with the development of VOD suggest a possible role for therapeutic monitoring in this setting. [ABSTRACT FROM AUTHOR]

The mucopolysaccharidoses (MPS) are a family of lysosomal storage diseases that result from the accumulation of partially catabolized glycosaminoglycans (GAGs) within lysosomes. A characteristic of most affected individuals is radiographic evidence of symmetrical epiphyseal dysplasia, with short stature and degenerative joint disease. Although there is evidence of epiphyseal dysfunction, little is known of the changes that occur at the morphological level. The growth plate of the femoral head was studied by light and electron microscopy in five cats with MPS VI (Maroteaux-Lamy syndrome, arylsulfatase B deficiency) and 12 normal cats. Compared with the normals, the MPS VI cat growth plates exhibited poorly organized proliferative zones, an almost total loss of column formation in the hypertrophic zone, an uneven chondro-osseous junction, a disorganized calcifying cartilage zone, and abnormal or reduced numbers of osteoclasts. By electron microscopy, the cytoplasm of affected cat chondrocytes was filled with membrane-bound vacuoles. Together these findings indicate that the MPS diseases cause major changes in growth plate structure and function. [ABSTRACT FROM AUTHOR]

Background: Obtaining accurate blood pressure (BP) readings is a challenge faced by health professionals. Clinical trials implement strict protocols, whereas clinical practices and studies that assess quality of care utilize a less rigorous protocol for BP measurement.Objective: To examine agreement between real-time clinic-based assessment of BP and the standard mercury assessment of BP.Design: Prospective reliability study.Patients: One hundred patients with an International Classification of Diseases-9th edition code for hypertension were enrolled.Measures: Two BP measurements were obtained with the Hawksley random-zero mercury sphygmomanometer and averaged. The clinic-based BP was extracted from the computerized medical records.Results: Agreement between the mercury and clinic-based systolic blood pressure (SBP) was good, intraclass correlation coefficient (ICC)=0.91 (95% confidence interval (CI): 0.83 to 0.94); the agreement for the mercury and clinic-based diastolic blood pressure (DBP) was satisfactory, ICC=0.77 (95% CI: 0.62 to 0.86). Overall, clinic-based readings overestimated the mercury readings, with a mean overestimation of 8.3 mmHg for SBP and 7.1 mmHg for DBP. Based on the clinic-based measure, 21% of patients were misdiagnosed with uncontrolled hypertension.Conclusions: Health professionals should be aware of this potential difference when utilizing clinic-based BP values for making treatment decisions and/or assessing quality of care. [ABSTRACT FROM AUTHOR]