Faculty Bibliography

BACKGROUND:Advanced tumors of the thoracic spine are difficult to treat and can lead to complex pain syndromes. Following conventional oncologic treatments, pharmacologic therapy may be insufficient to manage pain. Minimally invasive interventional procedures offer alternatives to treat malignant thoracic spinal pain. METHODS:Thirteen patients with metastatic disease and poorly controlled thoracic axial and/or radicular pain were identified via a retrospective chart review. Patients were either treated with radiation, surgery, chemotherapy, or a combination of these. Then, the patients were organized into groups based on their diagnoses, anatomical disease locations, symptoms, prior treatments, and interventional pain procedures offered. RESULTS:All cases of intercostal nerve, costotransverse junction, erector spinae plane, and paravertebral blocks resulted in pain relief without any reported complications. A patient who received a thoracic epidural injection had a complete resolution of pain when combined with radiation therapy two weeks after the injection. One patient who underwent repeat thoracic epidurals eventually had an intrathecal pump placement resulting in reduced opioid usage. Finally, one patient who received a thoracic medial branch block with a relief of thoracic axial pain reported greater pain relief with a medial branch nerve cryoablation. CONCLUSION/CONCLUSIONS:We propose a treatment algorithm to manage patients with thoracic spinal tumor-related pain. Interventional thoracic axial procedures may be safe and efficacious pain treatments for cancer patients. This article is protected by copyright. All rights reserved.

Objective/UNASSIGNED:Although healthcare-associated (HA) viral respiratory infections (VRIs) are common in pediatrics, no benchmark for comparison exists. We aimed to determine, compare, and assess determinants of unit-specific HA-VRI incidence rates in 2 children's hospitals. Methods/UNASSIGNED:This study was a retrospective comparison of prospective cohorts. The Montreal Children's Hospital and the Cohen Children's Medical Center of New York perform prospective surveillance for HA-VRI using standardized definitions that require the presence of symptoms compatible with VRI and virus detection. Cases detected between April 1, 2010, and March 31, 2013, were identified using surveillance databases. Annual incidence rates were calculated, and a generalized estimating equation model was used to assess determinants of HA-VRI rates. Results/UNASSIGNED:The overall HA-VRI rate during the 3-year study period was significantly higher at Montreal Children's Hospital than that at Cohen Children's Medical Center of New York (1.91 vs 0.80 per 1000 patient-days, respectively; P < .0001). Overall, the HA-VRI incidence rate was lowest in the neonatal intensive care unit. Rates in the pediatric intensive care, oncology, and medical/surgical units were similar. The most common etiology of HA-VRI at both institutions was rhinovirus (49% of cases), followed by parainfluenza virus and respiratory syncytial virus. Hospitals with less than 50% single rooms had HA-VRI rates 1.33 (95% confidence interval, 1.29-1.37) times higher than hospitals with more than 50% single rooms for a given unit type. Conclusions/UNASSIGNED:HA-VRI rates were substantial but different among 2 children's hospitals. Future studies should examine the effect of HA-VRI and evaluate best practices for preventing such infections.

OBJECTIVE:To identify and compare volumetric measures used by healthcare providers in communicating dosing instructions for pediatric liquid prescriptions to parents/caregivers. STUDY DESIGN/METHODS:Dosing instructions were retrospectively reviewed for the 10 most frequently prescribed liquid medications dispensed from 4 community pharmacies for patients aged ≤ 12 years during a 3-month period. Volumetric measures on original prescriptions (ie, milliliters, teaspoons) were compared with those utilized by the pharmacist on the pharmacy label dispensed to the parent/caregiver. RESULTS:Of 649 prescriptions and corresponding pharmacy labels evaluated, 68% of prescriptions and 62% of pharmacy labels communicated dosing in milliliters, 24% of prescriptions and 29% of pharmacy labels communicated dosing in teaspoonfuls, 7% of prescriptions and 0% of pharmacy labels communicated dosing in other measures (ie, milligrams, cubic centimeters, "dose"), and 25% of dispensed pharmacy labels did not reflect units as written in the prescription. CONCLUSION/CONCLUSIONS:Volumetric measures utilized by healthcare professionals in dosing instructions for prescription pediatric oral liquid medications are not consistent. Healthcare professionals and parents/caregivers should be educated on safe dosing practices for liquid pediatric medications. Generalizability to the larger pediatric population may vary depending on pharmacy chain, location, and medications evaluated.

BACKGROUND: There is paucity of information on the pattern of bacterial colonization of a new neonatal intensive care unit. OBJECTIVE: To study the pattern of bacterial colonization on the environmental surfaces in a new neonatal intensive care unit (NICU) and correlate it with infections in the infants. METHODS: Environmental cultures from the faucets and computer keyboards in the NICU were obtained prospectively every 2 weeks for 1 year. Positive blood, cerebrospinal fluid, and respiratory cultures from the infants in the NICU were also obtained. RESULTS: A total of 175 swab cultures was collected, which were sterile for initial 6-week period. Subsequently, 31 cultures grew microbes: 26 (83.8%) from the faucets and 5 (16.2%) from the computers keyboard (P < .001). Of the 48 positive blood cultures in NICU patients, 6 (12.5%) matched the organism growing from the surveillance sites, but the correlation was not significant (P = .076). None of the 31 positive respiratory cultures and 1 positive cerebrospinal fluid culture correlated to the organisms grown from the NICU environment. CONCLUSION: The environment was colonized after an initial period of sterile cultures in a new NICU. Once colonized, they can persist, increasing the risk of developing resistance to antibiotics. They did not correlate with the positive cultures from the infants admitted to the NICU during the study period.

We studied a sample of parolees and health service providers in the state of California in 2005-2006 to examine the relative physical closeness to health providers (and the potential demand of these providers) of parolees based on their demographic and prior offending characteristics. Although African-American and Latino parolees have more health providers nearby, these providers have considerably more potential demand. The health providers near long-term prisoners and sex offenders have more potential demand. The results suggest inequity in access to services, as minority parolees and those with greater needs may live near more impacted providers. The results also suggest some differences in access based on rural, suburban, or urban location.

OBJECTIVE:A lack of skilled health professionals, and net migration from developing to more developed countries, are widely recognised as barriers to the delivery of effective health care. However, few studies have investigated this issue from the perspective of pharmacists, although they are increasingly viewed as a potentially valuable and underexploited health care resource. The objectives of this study were to examine the professional aspirations and perceived opportunities of final year pharmacy students in a developing country; and consider what developments may encourage them to remain in, and contribute to, health care in their home country. METHOD/METHODS:Final year pharmacy students from the Faculty of Pharmacy, KNUST, Kumasi, Ghana, were randomly selected and invited to participate in in-depth interviews. These were audio-recorded (with permission of respondents) and transcribed verbatim to enable a qualitative analysis. MAIN OUTCOME MEASURE/METHODS:professional aspirations, and perceived opportunities and barriers to their achievement in Ghana and abroad. Results Participants viewed themselves, and wished to be viewed by others, as health professionals. They described a commitment to applying their clinical knowledge and to education beyond their first degree. However, they identified significant barriers to the achievement of professional aspirations in Ghana, which would diminish their opportunities to contribute to health care. Whilst most students expressed the expectation or desire to travel at some point, usually early, in their career, they all demonstrated a commitment to their country and stated a wish to return. CONCLUSION/CONCLUSIONS:Overall the study highlighted prospective pharmacists in Ghana as ambitious, committed potential health professionals. The study indicates that a lack of attention by policy makers and professional bodies to ways of exploiting the contribution of pharmacists to public health, may represent a lost potential human resource for health in developing countries.

High mobility group box 1 (HMGB1) is a chromatin protein that acts as an immunomodulatory cytokine upon active release from myeloid cells. HMGB1 is also an alarmin, an endogenous molecule released by dying cells that acts to initiate tissue repair. We have previously reported that osteoclasts and osteoblasts release HMGB1 and release by the latter is regulated by parathyroid hormone (PTH), an agent of bone remodeling. A recent study suggests that HMGB1 acts as a chemotactic agent to osteoclasts and osteoblasts during endochondral ossification. To explore the potential impact of HMGB1 in the bone microenvironment and its mechanism of release by osseous cells, we characterized the effects of recombinant protein (rHMGB1) on multiple murine bone cell preparations that together exhibit the various cell phenotypes present in bone. We also inquired whether apoptotic bone cells release HMGB1. rHMGB1 enhanced the RANKL/OPG steady state mRNA ratio and dramatically augmented the release of tumor necrosis factor-alpha (TNFalpha) and interleukin-6 (IL6) in osteoblastogenic bone marrow stromal cell (BMSC) cultures but not in the calvarial-derived MC3T3-E1 cells. Interestingly, rHMGB1 promoted GSK-3beta phosphorylation in MC3T3-E1 cells but not in BMSCs. Apoptotic bone cells released HMGB1, including MLO-Y4 osteocyte-like cells. MLO-Y4 release of HMGB1 was coincident with caspase-3 cleavage. Furthermore, the anti-apoptotic action of PTH on MC3T3-E1 cells correlated with the observed decrease in HMGB1 release. Our data suggest that apoptotic bone cells release HMGB1, that within the marrow HMGB1 is a bone resorption signal, and that intramembraneous and endochondral osteoblasts exhibit differential responses to this cytokine

The expression of matrix metalloproteinase-13 (MMP-13), involved in bone turnover, is elevated in stretched MC3T3-E1 osteoblast-like cells. Strain-mediated forces impact bone remodeling due in large part to the movement of fluid through the canalicular-lacunar network. The resulting fluid shear stress (FSS) over the surface membranes of bone cells initiates bone remodeling. Although the nuclear events mediating putative FSS-induced changes in osteoblast MMP-13 transcription are unknown, previous studies with bone cells suggest an overlap between osteoblast FSS- and PTH-induced signal response pathways. MMP-13 PTH response is regulated by a 110 bp 5' regulatory region, conserved across the mouse, rat, and human genes, that supports the binding of numerous transcription factors including Runx2, c-fos/c-jun, Ets-1, and nuclear matrix protein 4/cas interacting zinc finger protein (Nmp4/CIZ) a nucleocytoplasmic shuttling trans-acting protein that attenuates PTH-driven transcription. Nmp4/CIZ also binds p130(cas), an adaptor protein implicated in mechanotransduction. Here we sought to determine whether Nmp4/CIZ contributes to FSS-induced changes in MMP-13 transcription. FSS (12 dynes/cm(2), 3-5 h) increased MMP-13 promoter-reporter activity approximately two-fold in MC3T3-E1 osteoblast-like cells attended by a comparable increase in mRNA expression. This was accompanied by a decrease in Nmp4/CIZ binding to its cis-element within the PTH response region, the mutation of which abrogated the MMP-13 response to FSS. Interestingly, FSS enhanced Nmp4/CIZ promoter activity and induced p130(cas) nuclear translocation. We conclude that the PTH regulatory region of MMP-13 also contributes to FSS response and that Nmp4/CIZ plays similar but distinct roles in mediating hormone- and FSS-driven induction of MMP-13 in bone cells.

Immune and bone cells are functionally coupled by pro-inflammatory cytokine intercellular signaling networks common to both tissues and their crosstalk may contribute to the etiologies of some immune-associated bone pathologies. For example, the receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin (OPG)/receptor activator of NF-kappaB (RANK) signaling axis plays a critical role in dendritic cell (DC) function as well as bone remodeling. The expression of RANKL by immune cells may contribute to bone loss in periodontitis, arthritis, and multiple myeloma. A recent discovery reveals that DCs release the chromatin protein high mobility group box 1 (HMGB1) as a potent immunomodulatory cytokine mediating the interaction between DCs and T-cells, via HMGB1 binding to the membrane receptor for advanced glycation end products (RAGE). To determine whether osteoblasts or osteoclasts express and/or release HMGB1 into the bone microenvironment, we analyzed tissue, cells, and culture media for the presence of this molecule. Our immunohistochemical and immunocytochemical analyses demonstrate HMGB1 expression in primary osteoblasts and osteoclasts and that both cells express RAGE. HMGB1 is recoverable in the media of primary osteoblast cultures and cultures of isolated osteoclast precursors and osteoclasts. Parathyroid hormone (PTH), a regulator of bone remodeling, attenuates HMGB1 release in cultures of primary osteoblasts and MC3T3-E1 osteoblast-like cells but augments this release in the rat osteosarcoma cell line UMR 106-01, both responses primarily via activation of adenylyl cyclase. PTH-induced HMGB1 discharge by UMR cells exhibits similar release kinetics as reported for activated macrophages. These data confirm the presence of the HMGB1/RAGE signaling axis in bone.

Nmp4/CIZ proteins (nuclear matrix protein 4/cas interacting zinc finger protein) contribute to gene regulation in bone, blood, and testis. In osteoblasts, they govern the magnitude of gene response to osteotropic factors like parathyroid hormone (PTH). Nmp4/CIZ is recurrently involved in acute leukemia and it has been implicated in spermatogenesis. However, these conserved proteins, derived from a single gene, are expressed in numerous tissues indicative of a more generalized housekeeping function in addition to their tissue-specific roles. To address how Nmp4/CIZ expression is governed, we characterized the 5' regulatory region of the mouse Nmp4 gene, located on chromosome 6. Two adjacent promoters P(1) [-2521 nucleotide (nt)/-597 nt] and P(2) (-2521 nt/+1 nt) initiate transcription of alternative first exons (U(1) and U(2)). Both promoters lack TATA and CCAAT boxes but contain initiator sites and CpG islands. Northern analysis revealed expression of both U(1) and U(2) in numerous adult tissues consistent with the constitutive and ubiquitous activity of a housekeeping gene. Sequence analysis identified numerous potential transcription factor-binding sites significant to osteogenesis, hematopoeisis, and gonadal development. The promoters are active in both osteoblast-like cells and in the M12 B-lymphocyte cell line. Low doses of PTH attenuated P(1)/P(2) activity in osteoblast-like cells. The Nmp4/CIZ promoters are autoregulated and deletion analysis identified regions that drive P(1) and P(2) basal activities as well as regions that contain positive and negative regulatory elements affecting transcription. The Nmp4/CIZ promoters comprise a genomic regulatory architecture that supports constitutive expression as well as cell- and tissue-specific regulation.