Pain Acceptance as a Predictor of Medical Utilization and School Absenteeism in Adolescents With Chronic Pain.

Objective: Identifying factors contributing to high medical utilization and productivity loss is important, given the high cost of pediatric chronic pain. The current study examined chronic pain acceptance as a predictor of medical utilization and school absenteeism in adolescents with chronic pain. Methods: In all, 122 adolescents (aged 12-21 years) with chronic pain and their parents/guardians completed questionnaires assessing medical visits (past 6 months), medication usage, and number of school absences (past month). Homebound school status was also reported. Adolescents completed the Chronic Pain Acceptance Questionnaire and pain intensity ratings, and underwent a diagnostic psychological evaluation. Results: Multivariate generalized linear model analyses indicated lower pain acceptance predicted increased inpatient hospitalizations and higher number of opioid and nonopioid prescription medications, controlling for pain intensity, age, and sex. Pain acceptance was not associated with outpatient consultations or number of nonprescription medications. Exploratory moderation analyses indicated lower pain acceptance significantly predicted increased emergency department visits and inpatient hospitalizations for patients diagnosed with an internalizing psychological disorder. Patients in homebound schooling reported low pain acceptance and for those in school full-time, linear regression indicated lower pain acceptance significantly predicted higher number of school absences. Conclusions: Findings suggest that lower pain acceptance contributes to the use of higher-level medical care (especially for adolescents with internalizing disorders) and increased productivity loss owing to school absences or homebound school status. Clinical implications exist for recommending acceptance-based interventions for pain acceptance promotion and continued development of cost-effective, easily disseminated acceptance-based therapy modules to curb the economic burden of chronic pain.

SALL4 is a key transcription regulator in normal human hematopoiesis.

BACKGROUND: Stem cell factor SALL4 is a zinc finger transcription factor. It plays vital roles in the maintenance of embryonic stem cell properties, functions as an oncogene in leukemia, and has been recently proposed to use for cord blood expansion. The mechanism(s) by which SALL4 functions in normal human hematopoiesis, including identification of its target genes, still need to be explored. STUDY DESIGN AND METHODS: Chromatin immunoprecipitation followed by microarray hybridization (ChIP-chip) was used for mapping SALL4 global gene targets in normal primary CD34+ cells. The results were then correlated with SALL4 functional studies in the CD34+ cells. RESULTS: More than 1000 potential SALL4 downstream target genes have been identified, and validation of binding by ChIP-quantitative polymerase chain reaction was performed for 5% of potential targets. These include genes that are involving in hematopoietic differentiation and self-renewal, such as HOXA9, RUNX1, CD34, and PTEN. Down regulation of SALL4 expression using small-hairpin RNA in these cells led to decreased in vitro myeloid colony-forming abilities and impaired in vivo engraftment. Furthermore, HOXA9 was identified to be a major SALL4 target in normal human hematopoiesis and the loss of either SALL4 or HOXA9 expression in CD34+ cells shared a similar phenotype. CONCLUSION: Taken together, SALL4 is a key regulator in normal human hematopoiesis and the mechanism of its function is at least in part through the HOXA9. Future study will determine whether modulating the SALL4/HOXA9 pathway can be used in cellular therapy such as cord blood expansion and/or myeloid engraftment.

Validation of short-term handling and storage conditions for marrow and peripheral blood stem cell products.

BACKGROUND: Allogeneic hematopoietic stem cell transplants from unrelated donors are routinely used in the treatment of patients with hematologic malignancies. These cellular products are often collected off-site and require transport from the collection site to transplantation centers. However, the effects of transport conditions and media on stem cell graft composition during short-term storage have not been well described. STUDY DESIGN AND METHODS: Five bone marrow (BM), four filgrastim-mobilized peripheral blood stem cell (PBSC), and four nonmobilized peripheral blood mononuclear cell (PBMNC) products were collected from healthy volunteer donors and stored at 4 or 20°C for up to 72 hours in 10% PlasmaLyte A plus anticoagulants such as 10% acid citrate dextran-A (ACD-A) and/or 10 IU/mL heparin. Products were evaluated at 0, 24, 48, and 72 hours for cellular content, viability, and metabolic activities. RESULTS: BM products maintained equivalent cell viability when stored at either 4 or 20°C over 72 hours, but cell viability was better maintained for PBSC products stored at 4°C. The mean viable CD34+ cell recovery for PBSC and BM products stored over 72 hours at 4°C was higher than 75%. Significantly lower CD34+ cell and colony-forming unit recoveries were seen in PBSC products but not BM products stored at room temperature. Faster lactic acid accumulation was observed in PBMNC and PBSC products stored without ACD-A. CONCLUSIONS: Seventy-two-hour storage of BM, PBSC, and PBMNC products at refrigerated temperature maintains optimal cell viability and recovery. Anticoagulation with ACD-A is preferred over heparin to reduce lactic acid accumulation in the product media.

The Pain of Invisibility: A Perspective on the Treatment of Pediatric Chronic Pain.

Although chronic pain can be debilitating and severely impacting, it can also be an affliction many take on privately. For many chronic pain patients and their families, the toll of symptom invisibility is often a prominent concern. The article expounds upon the theme of "symptom invisibility" and the need for and practice of developing a validating provider-family relationship in the treatment of children and adolescents with chronic pain. Suggestions for therapeutic pathways to building adaptive validation are provided.

It hurts to move (on): A family's experience with chronic pain, grief, and healing.

This article describes a family that had to deal with grief from losing a family member. They sought help for 13-yr-old Katie's prolonged pain following a sprain. The family's unresolved grief over their second child's passing continued to emerge, peeping through the small talk, the wry smiles, the daily efforts to move and do, despite physical pain. As the demands of Katie's rehabilitation stripped away reserves of politeness and energy, the family's emotional pain became more fully uncovered.The author describes the 6-week course of physical and occupational therapies, pain medicine management, and individual and family behavioral health support. In this period of family crisis, the author was their partner, coach, advocate, and confidante. (PsycINFO Database Record

Traumatic Stress and Pediatric Pain: Towards a Neurobiological Stress-Health Perspective.

This theoretical review aims to present the limited findings on traumatic stress and pain in children and adolescents, highlight recent discoveries regarding neurobiological processes, and suggest an alternative stress-health perspective in the future study and conceptualization of pediatric pain and traumatic stress based on results. Current literature highlights a positive correlation between pain and trauma symptoms in youth and suggests a complex relationship that may have mutually maintaining dynamics and intertwined physiological processes. Developmentally sensitive, longitudinal, process-oriented designs assessing neurobiological alterations and stress responses should be utilized in the examination of the trauma-pain relationship. Such investigations may provide a more unified explanation of the relationship between chronic pain and traumatic stress.

Screening for the risk for bleeding or thrombosis.

BACKGROUND: Numerous tests are available to assess patient risk for bleeding or thrombosis. Appropriate use of these tests must involve consideration of the clinical setting, disease prevalence, performance characteristics of the tests, cost, and consequences of false-positive and false-negative results. PURPOSE: To summarize information about coagulation testing in three common clinical settings: nonsurgical hospitalized patients, surgical patients, and patients having a first venous thromboembolic event. DATA SOURCES: All English-language studies identified in searches of MEDLINE (1966 to April 2002) and reference lists of key articles. STUDY SELECTION: All published studies of blood coagulation testing as routine diagnostic tests or in the preoperative care of patients reporting postoperative bleeding complications, and all published studies of patients with the factor V Leiden mutation reporting venous thromboembolic outcomes. DATA EXTRACTION: 5 observational studies of routine coagulation testing in nonsurgical hospitalized patients and 12 observational studies of preoperative coagulation testing, from which both sensitivity and specificity could be calculated. DATA SYNTHESIS: Test performance characteristics for the partial thromboplastin time in predicting postoperative hemorrhage were pooled by type of surgery. Likelihood ratios for positive and negative results were calculated for each group; 95% confidence intervals were calculated. Patients with prolonged partial thromboplastin times did not have a statistically significantly increased risk for postoperative complications. CONCLUSION: For nonsurgical and surgical patients without synthetic liver dysfunction or a history of oral anticoagulant use, routine testing has no benefit in assessment of bleeding risk. Routine testing after a first episode of venous thromboembolism is not recommended for most patients.

Preclinical regulatory validation of a 3-stage amniotic mesenchymal stem cell manufacturing protocol.

PURPOSE: Because of the 4 to 6-month interval between a diagnostic amniocentesis and birth, clinical application of amniotic mesenchymal stem cell (AMSC)-based therapies demands a 3-stage cell manufacturing process, including isolation/primary expansion, cryopreservation, and thawing/secondary expansion. We sought to determine the feasibility and cell yield of such a staged cell manufacturing process, within regulatory guidelines. METHODS: Human AMSCs isolated from diagnostic amniocentesis samples (n = 11) were processed under Food and Drug Administration-accredited good manufacturing practice. Expanded cells were characterized by flow cytometry and cryopreserved for 3 to 5 months. Cell release criteria included more than 90% CD29+, CD73+, and CD44+; less than 5% CD34+ and CD45+; negative mycoplasma quantitative polymerase chain reaction (QPCR) and endotoxin assay; and at least 70% viability. RESULTS: Isolation and ample expansion of AMSCs was achieved in 54.5% (6/11) of the samples. Early processing and at least a 2-mL sample were necessary for reliable cell manufacturing. Cell yield before cryopreservation was 223.2 +/- 65.4 x 10(6) cells (44.6-fold expansion), plus a 14.7 x 10(6)-cell backup, after 36.3 +/- 7.8 days. Cell viability postthaw was 88%. Expanded cells maintained a multipotent mesenchymal progenitor profile. CONCLUSIONS: Human amniotic mesenchymal stem cells can be manufactured in large numbers from diagnostic amniocentesis, by an accredited staged processing, under definite procurement guidelines. These data further support the viability of clinical trials of amniotic mesenchymal stem cell-based therapies.

Tissue engineering from human mesenchymal amniocytes: a prelude to clinical trials.

PURPOSE: The surgical treatment of congenital anomalies using tissues engineered from amniotic fluid-derived mesenchymal cells has been validated experimentally. As a prerequisite for testing the clinical feasibility of this therapeutic concept, this study was aimed to expand human mesenchymal amniocytes in the absence of animal products. METHODS: Human mesenchymal cells were isolated from amniotic fluid samples (n = 12) obtained at 20 to 37 weeks' gestation. Their phenotypic profiles and cell proliferation rates were compared during expansion under 2 different media, containing either fetal bovine serum or allogeneic human AB serum. Statistical analyses were by the 2-sided Wilcoxon signed rank test and linear regression (P < .05). RESULTS: Mesenchymal cells could be isolated and expanded at any gestational age. There was a greater than 9-fold logarithmic expansion of mesenchymal cells, with no significant differences in the overall proliferation rates based on serum type (P = .94), or gestational age (P = .14). At any passage, cells expanded for up to 50 days remained positive for markers consistent with a multipotent mesenchymal progenitor lineage, regardless of the medium used. CONCLUSIONS: Human mesenchymal amniocytes retain their progenitor phenotype and can be dependably expanded ex vivo in the absence of animal serum. Clinical trials of amniotic fluid-based tissue engineering are feasible within preferred regulatory guidelines.

Investigations into the role of anti-HLA class II antibodies in TRALI.

BACKGROUND: TRALI is thought to be triggered by recipient-specific anti-HLA class I or antibodies against neutrophils in donor plasma. Recently, anti-HLA class II have also been implicated. The prevalence of anti-HLA class II was investigated in normal volunteer platelet donors and in two nonfatal TRALI cases utilizing a flow-based assay. Potential target antigens also were investigated. STUDY DESIGN AND METHODS: Commercial flow cytometry-based assays (FlowPRA, One Lambda, Inc.) for anti-HLA class I and II were compared with standard lymphocytotoxicity tests. Subsequently, 151 volunteer platelet donors and two clinical cases of TRALI were screened with FlowPRA. Immunohistochemical studies were performed on lung tissue from a surgical case, an autopsy case, and a fatal TRALI case. RESULTS: The FlowPRA assays showed moderate concordance for anti-HLA class I (kappa = 0.448) and good concordance for class II antibodies (kappa = 0.801), when compared to standard lymphocytotoxicity assays. Ten and 9 percent of female platelet donors were positive for anti-HLA class I and class II, respectively. Two nonfatal cases of TRALI showed both anti-HLA class I and anti-HLA class II. Immunohistochemical analysis of a TRALI case revealed granulocyte aggregation in alveolar capillaries with activated vascular endothelial cells. HLA class II antigen expression was not present on vascular endothelium or intravascular WBCs; however, strong expression was seen on alveolar macrophages. CONCLUSION: FlowPRA assays often detect anti-HLA class I not detected by conventional lymphocytotoxicity assays. These assays reveal anti-HLA class II in normal female donor plasma and in sera implicated in TRALI. Immunohistochemical studies failed to reveal endothelial or intravascular-WBC HLA class II antigen expression in lung tissue derived from TRALI cases or controls, but demonstrated HLA class II expression on pulmonary macrophages.