A Pharmacist-Driven Education and Intervention Program that Improves Outcomes for Hypertensive Patients.

Purpose: Uncontrolled hypertension is serious and may lead to severe cardiovascular events and death. To better educate and empower patients to meet their blood pressure (BP) management goals, a large, integrated academic healthcare system implemented the Blood Pressure Goals Achievement Program (BPGAP), a longitudinal intervention embedding community pharmacists within healthcare teams. This study evaluated BPGAP on its ability to promote patient BP management goals. Methods: A pre-/post-intervention analysis was conducted whereby BP measurements were evaluated longitudinally within acuity groups determined by k-means clustering. Generalized linear mixed models evaluated trends in BP by time period, and proportions of patients meeting BP management goals (<140/90 mmHg) were assessed in relation to BPGAP enrollment date. Results: There were 5,125 patients who were clustered into Uncontrolled, Borderline, and Controlled blood pressure groups; 2,108 patients had BP measurements across 4 time periods before and after BPGAP enrollment. Groups differed by patient age, sex, and other demographics (p<0.0001). Patients in the Uncontrolled and Borderline BP clusters demonstrated significant BP decreases after BPGAP enrollment, continuing at least to 1-year post-intervention; Controlled cluster patients maintained BPs throughout the study period. The proportion of patients with controlled BPs increased from 56% immediately pre-BPGAP to 74% in the 3- to 6-months following enrollment. Conclusion: BPGAP is effective at helping patients achieve their BP management goals. Pharmacists may play a key role in hypertension control through measuring BPs and including updates and recommendations in the electronic health record, educating patients, and engaging in communication with healthcare teams.

Nebulized ketamine for managing acute pain in the pediatric emergency department: A case series.

Administration of sub-dissociative doses of ketamine is used via intranasal (IN) and intravenous routes in the pediatric emergency department for managing acute pain. Due to difficulties in both obtaining intravenous access and compliance with IN medications in children, administration of ketamine via breath-actuated nebulizer can serve as a valuable modality for timely analgesia in children where dosing titration is patient controlled. We describe five pediatric patients who received ketamine via breath-actuated nebulizer at 0.75 mg/kg, 1 mg/kg, and 1.5 mg/kg, with all patients experiencing a decrease in pain score. This case series introduces ketamine inhalation as a modality for managing pain in children.

Implications of immune-mediated metastatic growth on metastatic dormancy, blow-up, early detection, and treatment.

Metastatic seeding of distant organs can occur in the very early stages of primary tumor development. Once seeded, these micrometastases may enter a dormant phase that can last decades. Curiously, the surgical removal of the primary tumor can stimulate the accelerated growth of distant metastases, a phenomenon known as metastatic blow-up. Recent clinical evidence has shown that the immune response can have strong tumor promoting effects. In this work, we investigate if the pro-tumor effects of the immune response can have a significant contribution to metastatic dormancy and metastatic blow-up. We develop an ordinary differential equation model of the immune-mediated theory of metastasis. We include both anti- and pro-tumor immune effects, in addition to the experimentally observed phenomenon of tumor-induced immune cell phenotypic plasticity. Using geometric singular perturbation analysis, we derive a rather simple model that captures the main processes and, at the same time, can be fully analyzed. Literature-derived parameter estimates are obtained, and model robustness is demonstrated through a time dependent sensitivity analysis. We determine conditions under which the parameterized model can successfully explain both metastatic dormancy and blow-up. The results confirm the significant active role of the immune system in the metastatic process. Numerical simulations suggest a novel measure to predict the occurrence of future metastatic blow-up in addition to new potential avenues for treatment of clinically undetectable micrometastases.

A stochastic model for cancer metastasis: branching stochastic process with settlement.

We introduce a new stochastic model for metastatic growth, which takes the form of a branching stochastic process with settlement. The moving particles are interpreted as clusters of cancer cells, while stationary particles correspond to micro-tumours and metastases. The analysis of expected particle location, their locational variance, the furthest particle distribution and the extinction probability leads to a common type of differential equation, namely, a non-local integro-differential equation with distributed delay. We prove global existence and uniqueness results for this type of equation. The solutions' asymptotic behaviour for long time is characterized by an explicit index, a metastatic reproduction number $R_0$: metastases spread for $R_{0}>1$ and become extinct for $R_{0}<1$. Using metastatic data from mouse experiments, we show the suitability of our framework to model metastatic cancer.

A mathematical model for the immune-mediated theory of metastasis.

Accumulating experimental and clinical evidence suggest that the immune response to cancer is not exclusively anti-tumor. Indeed, the pro-tumor roles of the immune system  -  as suppliers of growth and pro-angiogenic factors or defenses against cytotoxic immune attacks, for example  -  have been long appreciated, but relatively few theoretical works have considered their effects. Inspired by the recently proposed "immune-mediated" theory of metastasis, we develop a mathematical model for tumor-immune interactions at two anatomically distant sites, which includes both anti- and pro-tumor immune effects, and the experimentally observed tumor-induced phenotypic plasticity of immune cells (tumor "education" of the immune cells). Upon confrontation of our model to experimental data, we use it to evaluate the implications of the immune-mediated theory of metastasis. We find that tumor education of immune cells may explain the relatively poor performance of immunotherapies, and that many metastatic phenomena, including metastatic blow-up, dormancy, and metastasis to sites of injury, can be explained by the immune-mediated theory of metastasis. Our results suggest that further work is warranted to fully elucidate the pro-tumor effects of the immune system in metastatic cancer.

Occipital mass in antenatal sonography.

Biophysical profile (BPP) with ultrasound performed for a 32-year-old G5P3013 admitted at 31 weeks gestation with preterm, premature rupture of membranes (PPROM) noted an extracalvarial mass concerning for an encephalocele. Fetal MRI demonstrated edema over the occiput with no definable lesion visualized. Preterm labor requiring Cesarean delivery resulted in a live male neonate at 33 weeks gestation. An occipital mass was observed on neonatal physical exam. Postnatal ultrasound and MRI were consistent with cephalohematoma. This was surprising given the lack of vaginal delivery. We hypothesize that the occiput was positioned against the maternal ischial tuberosity and developed chronic trauma secondary to normal fetal movement over time, resulting in a cephalohematoma. Postnatal imaging confirmed this diagnosis as the mass gradually decreased and ultimately resolved. Although other etiologies are possible, this case emphasizes the need to consider cephalohematoma in the differential of CNS masses during pregnancy without abdominal trauma and/or vaginal delivery.

Impact of Comprehensive Medication Management on Hospital Readmission Rates.

In 2012, the Fairview Health System implemented a formal care transitions process that included referrals to outpatient services provided by medication therapy management (MTM) pharmacists, among other clinical services. This analysis evaluates the impact of the MTM-provided comprehensive medication management (CMM) service on readmission rates. Retrospective electronic medical record (EMR) data were used to identify hospital admissions between December 1, 2012, and July 31, 2015. Thirty- and 60-day readmission rates were calculated in both a CMM and comparator cohort. Readmission rates also were stratified by readmission risk category. A total of 43,711 patients, contributing 57,673 hospitalizations, were included in the analysis. Of those, 1291 hospitalizations had a CMM visit within 30 days of discharge (median 6 days) and were considered the CMM cohort. Patients who received a CMM visit had a significantly lower rate of 30-day readmissions (8.6% vs. 12.8%, P < 0.001). The 60-day readmission rate remained lower among CMM patients but did not reach statistical significance (15.6% vs. 17.6%; P = 0.0528). When patients in each cohort were stratified by readmission risk category, the CMM cohort had a statistically significant lower rate of 30-day readmission in the highest risk groups (Average: 7.1% vs. 9.5%, P = 0.025; Elevated: 9.9% vs. 21.4%, P < 0.001; High: 18.3% vs. 35.9%, P < 0.001; Extreme: 36.4% vs. 77.7%, P = 0.006). CMM performed by an MTM pharmacist reduces the rate of readmission at 30 days post discharge and may have the largest impact among patients at highest risk of readmission.

Mathematical Modeling of the Role of Survivin on Dedifferentiation and Radioresistance in Cancer.

We use a mathematical model to investigate cancer resistance to radiation, based on dedifferentiation of non-stem cancer cells into cancer stem cells. Experimental studies by Iwasa 2008, using human non-small cell lung cancer (NSCLC) cell lines in mice, have implicated the inhibitor of apoptosis protein survivin in cancer resistance to radiation. A marked increase in radio-sensitivity was observed, after inhibiting survivin expression with a specific survivin inhibitor YM155 (sepantronium bromide). It was suggested that these observations are due to survivin-dependent dedifferentiation of non-stem cancer cells into cancer stem cells. Here, we confirm this hypothesis with a mathematical model, which we fit to Iwasa's data on NSCLC in mice. We investigate the timing of combination therapies of YM155 administration and radiation. We find an interesting dichotomy. Sometimes it is best to hit a cancer with a large radiation dose right at the beginning of the YM155 treatment, while in other cases, it appears advantageous to wait a few days until most cancer cells are sensitized and then radiate. The optimal strategy depends on the nature of the cancer and the dose of radiation administered.

Can oxygen tension contribute to an abnormal placental cytokine milieu?

OBJECTIVE The aim of this study was to determine whether culturing human placental explants under different oxygen tensions will alter expression of pro- and anti-inflammatory mediators. METHODS Placental explant cultures from second-trimester, elective, terminations-of-pregnancy were incubated under 21, 5, or 1% O(2) concentrations for 24 hr in the presence or absence of IL-10. Cytokine concentrations in the conditioned medium were quantified by immunoassay. RESULTS Culture of placental explants under 21, 5, or 1% O(2) concentrations produced hyperoxic (143 ± 1.6 mmHg), normoxic (37 ± 1.6 mmHg), and hypoxic (18.2 ± 1.6 mmHg) pO(2) levels for the maternal-fetal interface in the medium. Oxygen tension had profound effects on basal placental cytokine levels as well as on IL-10-stimulated cytokine production. IL-1ß and TNF-α, but not IFN-γ production, was reduced by 21% O(2) . Moreover, 21% O(2) levels increased the anti-inflammatory cytokines IL-10 and IL-13 while 1% O(2) tended to decrease the production of these cytokines. CONCLUSIONS Five percent- O(2) incubation more accurately represents in vivo pO(2) conditions at the maternal-fetal interface. Routine culture of placental explants in room air produces a superphysiologic oxygen tension that tended to increase the production of anti-inflammatory and decrease the production of pro-inflammatory cytokines. In addition, low pO(2) may reduce responsiveness of the placenta to the anti-inflammatory actions of IL-10.