Pharmacy technician involvement in community pharmacy medication therapy management.

OBJECTIVES: To assess the impact of technician involvement on the completion of medication therapy management (MTM) services in a community pharmacy setting and to describe pharmacists' and technicians' perceptions of technician involvement in MTM-related tasks and their satisfaction with the technician's role in MTM. DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: In the fall of 2015, pharmacists and selected technicians from 32 grocery store-based community pharmacies were trained to use technicians within MTM services. MAIN OUTCOME MEASURES: Completed MTM claims were evaluated at all pharmacies for 3 months before training and 3 months after training. An electronic survey, developed with the use of competencies taught in the training and relevant published literature, was distributed via e-mail to trained employees 3 months after training. RESULTS: The total number of completed MTM claims at the 32 pharmacy sites was higher during the posttraining time period (2687 claims) versus the pretraining period (1735 claims). Of the 182 trained participants, 112 (61.5%) completed the survey. Overall, perceived technician involvement was lower than expected. However, identifying MTM opportunities was the most commonly reported technician MTM task, with 62.5% of technicians and 47.2% of pharmacists reporting technician involvement. Nearly one-half of technicians (42.5%) and pharmacists (44.0%) agreed or strongly agreed they were satisfied with the technician's role in MTM services, and 40.0% of technicians agreed that they were more satisfied with their work in the pharmacy after involvement in MTM. CONCLUSION: Three months after initial training of technicians in MTM, participation of technicians was lower than expected. However, the technicians involved most often reported identifying MTM opportunities for pharmacists, which may be a focus for future technician trainings. In addition, technician involvement in MTM services may increase satisfaction with many aspects of work for actively involved technicians.

SMN Blood Levels in a Porcine Model of Spinal Muscular Atrophy.

BACKGROUND: Spinal Muscular Atrophy (SMA) is an autosomal recessive motor neuron disease that results in loss of spinal motor neurons, muscular weakness and, in severe cases, respiratory failure and death. SMA is caused by a deletion or mutation of the SMN1 gene and retention of the SMN2 gene that leads to low SMN expression levels.The measurement of SMN mRNA levels in peripheral blood samples has been used in SMA clinical studies as a pharmacodynamic biomarker for response to therapies designed to increase SMN levels. We recently developed a postnatal porcine model of SMA by the viral delivery of a short-hairpin RNA (shRNA) targeting porcine SMN (pSMN). scAAV9-mediated knockdown of pSMN mRNA at postnatal day 5 results in denervation, weakness and motor neuron and ventral root axon loss that begins 3-4 weeks after viral delivery, and this phenotype can be ameliorated by subsequent viral delivery of human SMN (hSMN). OBJECTIVE: To determine if the effect of modulating SMN levels using gene therapy can be measured in blood. METHODS: We measured expression of pSMN mRNA and hSMN mRNA by quantitative droplet digital PCR (ddPCR). RESULTS: We found that the endogenous expression of pSMN mRNA in blood increases in the first month of life. However, there were no significant differences in blood levels of pSMN mRNA after knock-down or of human SMN mRNA after gene therapy. CONCLUSIONS: Our results, obtained in a large animal model of SMA that is similar in size and anatomy to human infants, suggest that measurement of SMN mRNA levels in blood may not be informative in SMA clinical trials involving intrathecal delivery of SMN-modulating therapies.

Impact of a pharmacy student-driven medication delivery service at hospital discharge.

PURPOSE: A pharmacy student-driven discharge service developed for patients to reduce the number of medication errors on after-visit summaries (AVSs) is discussed. METHODS: An audit of AVS documents was conducted before the implementation period (September 3 to October 23, 2013) to identify medication errors. As part of the audit, a pharmacist review of the discharge medication list was completed to determine the number and types of errors that occurred. A student-driven discharge service with AVS review was developed in collaboration with nursing and medical residents. Students reviewed a patient's AVS, delivered the discharge prescriptions to bedside, and conducted medication reconciliation with the patient and family. The AVS audit was conducted after implementation of these services to assess the impact on medication errors. RESULTS: It was observed that 72% (108 of 150) of AVSs contained at least 1 error before discharge and AVS review. During the 2-month postimplementation period (September 3 to October 23, 2014), this decreased to 27% (34 of 127), resulting in a 52% absolute reduction in the number of AVSs with at least 1 medication error (p < 0.0001). The most common error was as-needed medication with no indication, which decreased from 55% in the preimplementation audit to 16% in the postimplementation audit. Prescribing to Nationwide Children's Hospital's outpatient pharmacy increased from 57% in the preimplementation period to 73% in the postimplementation period for the general pediatrics service. CONCLUSION: A pharmacy student-driven discharge and medication delivery service reduced the number of AVSs and increased access to medications for patients.

Healthcare Costs Reduced After Incorporating the Results of the American College of Surgeons Oncology Group Z0011 Trial into Clinical Practice.

The purpose of our study was to quantitate the changes in axillary lymph node dissection (ALND), frozen section (FS), and the impact on costs after the publication of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial. We compared axillary nodal management and cost data in breast cancer patients who met Z0011 criteria and were treated with lumpectomy and sentinel lymph nodes (SLN) biopsy from 2007 to July 2013. Of 800 patients, 67 (13.5%) and 34 (12.5%) patients in the pre- and post-Z0011 era had 1-2 positive SLN. ALND decreased from 78% to 21% (p < 0.001) after publication of Z0011. The mean overall cost of SLN biopsy was $41,059 per patient, while SLN biopsy with completion ALND was $50,999 (p < 0.001). Intraoperative FS use decreased from 95% to 66% (p = 0.015). Omitting the FS decreased mean costs from $4,319 to $2,036. The application of Z0011 resulted in an overall mean cost savings of $571,653 from 2011 to July 2013. ACOSOG Z0011 significantly impacted axillary management resulting in a 20% reduction in the mean overall cost per patient by omitting ALND. In these patients, intraoperative FS analysis had poor sensitivity (56%) and doubled the cost of pathologic examination. Fewer ALND and intraoperative FS were performed after the publication of ACOSOG Z0011. Eliminating FS and ALND in patients who met Z0011 criteria, results in significant cost savings.

Impact of rapid identification of Acinetobacter Baumannii via matrix-assisted laser desorption ionization time-of-flight mass spectrometry combined with antimicrobial stewardship in patients with pneumonia and/or bacteremia.

We evaluated the clinical and economic outcomes of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) with stewardship intervention in patients with Acinetobacter baumannii (AB) pneumonia and/or bacteremia. 66 patients were included in the pre-intervention group and 53 in the intervention group. The combination of AB identification via MALDI-TOF MS and ID PharmD intervention significantly reduced the median time to effective therapy compared to conventional identification without intervention [77.7 (95% CI: 73.1-84.8) to 36.6 (95% CI: 25.9-50.9) hours (P < 0.0001)]. Rapid organism identification along with ID PharmD intervention was also associated with a 19% increase in clinical cure (15% versus 34%, P = 0.016) and a decreased length of stay during antibiotic therapy (13 [8-18] versus 11 [7-15] days, P = 0.021). No difference in 14-day mortality was observed (20% versus 25%, P = 0.526). Median costs during infection were approximately $6500 less in the intervention group ($49,402 [35,307-86,566] versus $42,872 [26,966-74,506]; P = 0.243). AB identification via MALDI-TOF MS combined with stewardship intervention allows for timely, effective antimicrobial therapy and is associated with increased clinical cure.

Pharmacotherapy in Conjunction with a Diet and Exercise Program for the Treatment of Weight Recidivism or Weight Loss Plateau Post-bariatric Surgery: a Retrospective Review.

BACKGROUND: Bariatric surgery is an effective therapeutic option for management of obesity. However, weight recidivism (WR) and weight loss plateau (WLP) are common problems. We present our experience with the use of two pharmacotherapies in conjunction with our standard diet and exercise program in those patients who experienced WR or WLP. METHODS: From June 2010 to April 2014, bariatric surgery patients who experienced WR or WLP after undergoing Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB), and who were treated with phentermine (Ph) or phentermine-topiramate (PhT), were reviewed retrospectively. Generalized estimating equations were used to compare patient weights through 90 days between initial surgery type and medication type. Patient weights, medication side effect, and co-morbidities were collected during the first 90 days of therapy. RESULTS: Fifty-two patients received Ph while 13 patients received PhT. Overall, patients in both groups lost weight. Among those whose weights were recorded at 90 days, patients on Ph lost 6.35 kg (12.8% excess weight loss (EWL); 95% confidence interval (CI) 4.25, 8.44) and those prescribed PhT lost 3.81 kg (12.9% EWL; CI 1.08, 6.54). Adjusting for baseline weight, time since surgery, and visit through 90 days, patients treated with Ph weighed significantly less than those on PhT throughout the course of this study (1.35 kg lighter; 95% CI 0.17, 2.53; p = 0.025). There were no serious side effects reported. CONCLUSIONS: Phentermine and phentermine-topirimate in addition to diet and exercise appear to be viable options for weight loss in post-RYGB and LAGB patients who experience WR or WLP.

Prevalence of antipsychotic prescriptions among patients with anxiety disorders treated in inpatient and outpatient psychiatric settings.

BACKGROUND: An increasing number of prescribers are using antipsychotics for treatment of anxiety disorders, despite lack of FDA-approved indications and mixed efficacy results from clinical trials. The objective of this study was to examine the prevalence of antipsychotics prescription in psychiatric inpatients and outpatients with anxiety disorders. METHODS: This is a retrospective study of de-identified data from patients with a DSMIV-TR anxiety disorder diagnosis in an academic psychiatric setting in 2013. The final cohort of patients, after exclusion of bipolar/psychotic comorbidity, includes 1699 patients. Logistic regression models were used to explore associations between antipsychotic prescription and patient characteristics. RESULTS: Among non-psychotic/non-bipolar patients with anxiety disorder, 53.6% of inpatients and 16.6% of outpatients received antipsychotic medication. Rates varied with the disorder. Outpatients with post-traumatic stress disorder (OR: 2.24, 95% CI: 1.66-3.01) and obsessive compulsive disorder (OR: 2.80, 95% CI: 1.86-4.19) received antipsychotic prescriptions more often than those without these diagnoses. Comorbidity with depression was common while comorbidity with borderline personality disorder was rare; both increased odds of receiving prescription of antipsychotics (OR: 1.57, 95% CI: 1.16-2.12 for depression; OR: 2.63, 95% CI 1.42-4.88 for borderline personality disorder, respectively). Additionally, age was significantly associated with increased odds of being on an antipsychotic. Quetiapine and aripripazole were the most prescribed antipsychotics and very few patients received rescue medication for extrapyramidal symptoms. LIMITATIONS: Lack of specific indications for the psychotropic prescriptions. CONCLUSIONS: A substantial percentage of patients with anxiety disorders are prescribed antipsychotics, especially among inpatients. This practice may reflect the severity of the anxiety disorder or the high prevalence of comorbidity. Based on frequency of rescue medication prescription, treatment seemed well tolerated for extra-pyramidal neurological side-effects.

Magnetic resonance imaging fluid-attenuated inversion recovery sequence signal reduction after endoscopic endonasal transcribiform total resection of olfactory groove meningiomas.

BACKGROUND: Olfactory groove meningiomas grow insidiously and compress adjacent cerebral structures. Achieving complete removal without further damage to frontal lobes can be difficult. Microsurgical removal of large lesions is a challenging procedure and usually involves some brain retraction. The endoscopic endonasal approaches (EEAs) for tumors arising from the anterior fossa have been well described; however, their effect on the adjacent brain tissue has not. Herein, the authors utilized the magnetic resonance imaging fluid attenuated inversion recovery (FLAIR) sequence signal as a marker for edema and gliosis on pre- and post-operative images of olfactory groove meningiomas, thus presenting an objective parameter for brain injury after surgical manipulation. METHODS: Imaging of 18 olfactory groove meningiomas removed through EEAs was reviewed. Tumor and pre/postoperative FLAIR signal volumes were assessed utilizing the DICOM image viewer OsiriX(®). Inclusion criteria were: (1) No previous treatment; (2) EEA gross total removal; (3) no further treatment. RESULTS: There were 14 females and 4 males; the average age was 53.8 years (±8.85 years). Average tumor volume was 24.75 cm(3) (±23.26 cm(3), range 2.8-75.7 cm(3)), average preoperative FLAIR volume 31.17 cm(3) (±39.38 cm(3), range 0-127.5 cm(3)) and average postoperative change volume, 4.16 cm(3) (±6.18 cm(3), range 0-22.2 cm(3)). Average time of postoperative scanning was 6 months (range 0.14-20 months). In all cases (100%) gross total tumor removal was achieved. Nine patients (50%) had no postoperative FLAIR changes. In 2 patients (9%) there was minimal increase of changes postoperatively (2.2 cm(3) and 6 cm(3) respectively); all others demonstrated image improvement. The most common complication was postoperative cerebrospinal fluid leakage (27.8%); 1 patient (5.5%) died due to systemic complications and pulmonary sepsis. CONCLUSIONS: FLAIR signal changes tend to resolve after endonasal tumor resection and do not seem to worsen with this operative technique.

Spinal Muscular Atrophy Biomarker Measurements from Blood Samples in a Clinical Trial of Valproic Acid in Ambulatory Adults.

BACKGROUND: Clinical trials of therapies for spinal muscular atrophy (SMA) that are designed to increase the expression the SMN protein ideally include careful assessment of relevant SMN biomarkers. OBJECTIVE: In the SMA VALIANT trial, a recent double-blind placebo-controlled crossover study of valproic acid (VPA) in ambulatory adult subjects with SMA, we investigated relevant pharmacodynamic biomarkers in blood samples from SMA subjects by direct longitudinal measurement of histone acetylation and SMN mRNA and protein levels in the presence and absence of VPA treatment. METHODS: Thirty-three subjects were randomized to either VPA or placebo for the first 6 months followed by crossover to the opposite arm for an additional 6 months. Outcome measures were compared between the two treatments (VPA and placebo) using a standard crossover analysis. RESULTS: A significant increase in histone H4 acetylation was observed with VPA treatment (p = 0.005). There was insufficient evidence to suggest a treatment effect with either full length or truncated SMN mRNA transcript levels or SMN protein levels. CONCLUSIONS: These measures were consistent with the observed lack of change in the primary clinical outcome measure in the VALIANT trial. These results also highlight the added benefit of molecular and pharmacodynamic biomarker measurements in the interpretation of clinical trial outcomes.

Survival benefit of induction immunosuppression in cystic fibrosis lung transplant recipients.

BACKGROUND: Despite resistant microbes, induction immunosuppression is used in patients with cystic fibrosis (CF) undergoing lung transplantation (LTx). METHODS: To evaluate the effect of induction immunosuppression on survival, the United Network for Organ Sharing (UNOS) was queried restricting analysis to transplant patients 6-55years old from 2001 to 2012, who received induction agents (INDUCED) or did not (NONE). RESULTS: A total of 1721 CF patients who underwent LTx were included in the analysis; of these 791 (46%) were INDUCED. Of the INDUCED patients, 65% received basiliximab, 10% alemtuzumab, and 25% thymoglobulin/anti-lymphocyte globulin/anti-thymocyte globulin. Mean age was 28.0years (SD=9.7) and 28.5 (SD=9.5) for the INDUCED and NONE groups, respectively. The median survival in the INDUCED group was 93.8months (95% CI: 73.8, --) compared to 61.8months (95% CI: 55.8-73.8) for the NONE group (log rank p-value <0.001). CONCLUSIONS: Antibody-based induction immunosuppression had a survival benefit in CF patients undergoing LTx.

Effect of pulmonary hypertension on survival in patients with idiopathic pulmonary fibrosis after lung transplantation: an analysis of the United Network of Organ Sharing registry.

BACKGROUND: Pulmonary hypertension (PH) is a comorbidity associated with idiopathic pulmonary fibrosis (IPF). There is limited research regarding the effect on survival after lung transplantation (LTx). METHODS: To assess the effect of PH on survival in patients with IPF who received LTx, the United Network for Organ Sharing was queried for eligible patients with recorded mean (PAmean) and systolic (PAsystolic) pulmonary artery pressure. The analysis was restricted to the post-lung allocation scoring system starting May 1, 2005, to provide a cohort receiving present-day therapies and management. The last update of the data set was July 6, 2012, so a cutoff date of July 6, 2011, was chosen to allow for the possibility of at least 1 year of follow-up. Thresholds of ≥25 and ≥35 mm Hg were chosen for PAmean and PAsystolic, respectively, as indicators of PH. RESULTS: Of 23,951 LTxs in the UNOS data set, 2,542 met inclusion criteria, 1,234 (49%) with PAmean ≥ 25 mm Hg and 1,680 (66%) with PAsystolic ≥ 35 mm Hg. PAmean and PAsystolic were highly correlated, with an estimated correlation coefficient ρ = 0.93 (p < 0.001). Patients with PH (PAmean ≥ 25 mm Hg or PAsystolic ≥ 35 mm Hg) tended to have higher ischemic times, lung allocation score values, forced vital capacity percentage predicted at LTx, and supplemental oxygen requirement at rest values. In addition, a larger proportion of patients with PH was African American, male, had diabetes, and received bilateral LTx compared with single LTx. Comparing PAmean < 25 vs ≥ 25 mm Hg and PAsystolic < 35 vs ≥ 35 mm Hg, median survival in months was 60.4 (95% confidence interval [CI], 55.2-80.4) vs 61.4 (95% CI, 56.9-66.9; log-rank p = 0.876) and 57.6 (95% CI, 50.9-68.0) vs 64.3 (95% CI, 57.5-71.3; log-rank p = 0. 247), respectively. Hazard ratios for both definitions of PH from univariable and multivariable Cox proportional hazard models were close to 1 and none were statistically significant. CONCLUSIONS: On the basis of our models and despite PH being prevalent, there is no strong evidence suggesting that PH significantly alters the risk of death in IPF patients after LTx.

Impact of induction immunosuppression on survival in heart transplant recipients: a contemporary analysis of agents.

INTRODUCTION: The impact of induction immunosuppression on long-term survival in heart transplant recipients is unclear. Over the past three decades, practices have varied as induction agents have changed and experiences grew. We sought to evaluate the effect of contemporary induction immunosuppression agents in heart transplant recipients with the primary endpoint of survival, utilizing national registry data. METHODS: We queried the United Network for Organ Sharing (UNOS) data registry for all heart transplants from 1987 to 2012. We restricted our analysis to adult (≥18 yr) recipients performed from 2001-2011 (to allow for the potential for a minimum of 12 months post-transplant follow-up) who received either: no antibody based induction (NONE) or the contemporary agents (INDUCED) of either: basiliximab/daclizumab (IL-2Rab), alemtuzumab, or ATG/ALG/thymoglobulin. Kaplan-Meier estimates of the survival function as well as Cox proportional hazards models were utilized. RESULTS: Of the 17 857 heart transplants that met the inclusion criteria, there were 4635 (26%) reported deaths during the follow-up period. There were 8216 (46%) patients who were INDUCED. Of the INDUCED agents, 55% were IL-2Rab, 4% alemtuzumab, and 40% ALG/ATG/thymoglobulin. Donor and recipient characteristics were evaluated. Overall, being INDUCED did not significantly affect survival in univariable (p = 0.522) and multivariable (p = 0.130) Cox models as well as a propensity score adjusted model (p = 0.733). Among those induced, ATG/ALG/thymoglobulin appeared to have superior survival as compared with IL-2Rab (log-rank p = 0.007, univariable hazard ratio [HR] = 0.886; 95% CI: 0.811-0.968; p = 0.522). However, in a multivariable Cox model that adjusted for recipient age, VAD, BMI, steroid use, CMV match, and ischemic time, the hazard ratio for ALG/ATG/thymoglobulin vs. IL-2Rab was no longer statistically significant (HR = 0.948; 95% CI: 0.850-1.058; p = 0.341). CONCLUSION: In a contemporary analysis of heart transplant recipients, an overall analysis of induction agents does not appear to impact survival, as compared to no induction immunosuppression. While ALG/ATG/thymoglobulin appeared to have a beneficial effect on survival compared to IL-2Rab in the univariable model, this difference was no longer statistically significant once we adjusted for clinically relevant covariates.

To induce or not to induce: a 21st century evaluation of lung transplant immunosuppression's effect on survival.

INTRODUCTION: The impact of induction immunosuppression on long-term survival in lung transplant recipients remains unclear. We sought to evaluate the effect of contemporary induction immunosuppression agents in lung transplant recipients' survival, utilizing national registry data. METHODS: We queried the United Network for Organ Sharing registry from 2001 to 2012 for adult, deceased donor lung transplants who received no antibody-based induction (NONE) or the contemporary agents of basiliximab, alemtuzumab, thymoglobulin, antilymphocyte globulin, or antithymocyte globulin (INDUCED). Kaplan-Meier estimates of the survival and Cox proportional hazards models assessed differences in overall survival between the INDUCED and NONE groups; logistic regression models assessed differences in survival and rejection (TR1Y). RESULTS: There were 23 951 lung transplants performed with 12 858 meeting the inclusion criteria; 5713 (44%) were INDUCED. Of INDUCED agents, 62% were basiliximab and 14% alemtuzumab. Being INDUCED significantly increased overall survival (p < 0.0001). Median INDUCED survival was 71.3 months (confidence interval [CI]: 65.7-75.5) as compared with 63.2 months (CI: 60.1-65.9). Of INDUCED, both basiliximab and alemtuzumab had higher median survival times at 75.1 months (CI: 68.6-81.3) and 75.5 months (CI: 63.5-∞), respectively. There was less TR1Y in INDUCED patients (37%), as compared to NONE (42%; p < 0.0001). CONCLUSION: In a contemporary analysis of lung transplant recipients, induction immunosuppression has a significantly positive effect on survival.

Impact of pulmonary hypertension on survival in patients with cystic fibrosis undergoing lung transplantation: an analysis of the UNOS registry.

BACKGROUND: Pulmonary hypertension (PH) is a comorbidity reported in patients with cystic fibrosis (CF) with research limited to single-center studies. METHODS: To assess the impact of PH in patients with CF who received a lung transplant (LTx), the United Network for Organ Sharing was queried from 1987 to 2012, restricting analysis to transplant patients 6-55 years old between 1/1/2005 and 7/6/2011. RESULTS: Of 23,951 lung transplants, 1177 met inclusion criteria with 831 having mean pulmonary artery pressure (mPAP) data available. For the entire cohort, mean age was 30.3 (SD=9.2, range 12-55), and mean mPAP was 26.5 (SD = 7.8, range 5-66) mmHg. A total of 470 (57%) had PH defined as mPAP ≥ 25 mmHg. Comparing PH to non-PH groups, mean forced expiratory volume in one second (FEV1) was 24.4 (SD = 13.8) vs. 26 (SD=13.9) % of predicted, mean supplemental oxygen requirement at rest was 4.5 (SD = 4.1) vs. 3.7 (SD = 3.0) liters per minute, and mean lung allocation score was 49 (SD = 16) vs. 43 (SD = 12), respectively. For the PH group, median survival was 84.4 months compared to 67.1 months for the non-PH group (log-rank p-value = 0.326). The adjusted hazard ratio for PH vs. non-PH was 0.862 (95% CI: 0.653-1.138; p = 0.293), thus indicating no statistically significant effect of PH on survival. CONCLUSIONS: A high prevalence of PH was found in CF patients prior to LTx. Based on our models despite PH being prevalent, there is no strong evidence suggesting that it significantly alters the risk of death in CF patients after LTx.

A contemporary analysis of induction immunosuppression in pediatric lung transplant recipients.

There is an increasing trend in the use of induction immunosuppression in children undergoing lung transplantation (LTx). To evaluate the effect of this practice on survival, the United Network for Organ Sharing (UNOS) was queried from 1987 to 2012, restricting analysis to transplant patients 6-17 years old from 2001 to 2012, who received no induction (NONE) or induction (INDUCED) with the contemporary agents of basiliximab, alemtuzumab, thymoglobulin, antilymphocyte globulin (ALG), or antithymocyte globulin (ATG). Of 23 951 lung transplants, 330 met inclusion criteria with 177 (54%) being INDUCED. Of the INDUCED agents, 121 (68%) were basiliximab, 3 (2%) alemtuzumab, and 53 (30%) ALG/ATG/thymoglobulin. The mean patient age was 13.6 (SD = 3.2) and 14 (SD = 3.0) years for the INDUCED and NONE groups, respectively. The median survival in the INDUCED group was 77.4 months (95% CI: 46.1, 125.6) compared with 50.8 months (95% CI: 42.9, 61.3) for the NONE (log-rank P-value = 0.3601). The most common cause of death was due to allograft failure or pulmonary complications with only one patient dying from post-transplant lymphoproliferative disorder. The estimated hazard ratio for INDUCED versus NONE was 0.859 (95% CI: 0.620, 1.191; P = 0.3618); there were no significant confounders or effect modifiers among the demographic and clinical variables. In conclusion, antibody-based induction immunosuppression with contemporary agents had a trend toward a protective, but not statistically significant, effect in 6- to 17-year-old patients.

DNA demethylating agents synergize with oncolytic HSV1 against malignant gliomas.

PURPOSE: Oncolytic viruses (OV) based on herpes simplex virus type 1 (HSV1) are being used in clinical trials for a variety of cancers. The OV, rQNestin34.5, uses a nestin promoter/enhancer to selectively drive robust viral replication in malignant glioma cells. We have discovered that this promoter becomes extensively methylated in infected glioma cells, reducing OV efficacy. EXPERIMENTAL DESIGN: We used demethylating drugs [5-azacytidine (5-Aza)], decitabine, or valproic acid (VPA) in both in vitro and in vivo malignant glioma models to determine if they improved the efficacy of rQNestin34.5 therapy. RESULTS: The use of demethylating agents, such as 5-Aza, improved OV replication and tumor cell lysis in vitro and, in fact, synergized pharmacologically on Chou-Talalay analysis. In vivo, the combination of the demethylating agents, 5-Aza or decitabine, with rQNestin34.5 significantly prolonged the survivorship of athymic mice harboring intracranial human glioma xenografts over single agent alone. CONCLUSION: These results, thus, provide further justification for the exploration of demethylating agents when combined with the OV, rQNestin34.5, in preclinical therapeutics and, possibly, clinical trials for malignant glioma.