Optimizing Patient Education of Oncology Medications: A Patient Perspective.

The medication information needs of patients with cancer have been primarily studied using quantitative methods and little qualitative research on this topic exists. The purpose of this study was to explore patients' perspectives of optimal oncology medication education provided to patients at the Nova Scotia Health Authority (NSHA). Adult (≥ 18 years) outpatients in medical, gynecological and hematology oncology at NSHA were invited to participate in focus groups, which were audio-recorded, transcribed and analyzed thematically. Three focus groups, including 21 outpatients, were conducted. Four major themes were identified: (1) preparing for what lies ahead consisted of: readiness to receive information, anxiety over the unknown, setting expectations and patients supporting one another; (2) bridging the information gaps was made up of gap in provision of patient education, gap in continuity of patient education, and gap in trustworthy information; (3) understanding the education needs of the patients was comprised of sources of information, education timing and setting, prioritizing information needs, and individuality; and (4) experience within the health care system encompassed: interactions with health care professionals, willingness to ask questions, patient satisfaction, and financial implications. This study identified previously unknown patient education needs and also supported ideas reported in the literature. This data will guide the strategies that will be used to optimize the delivery of oncology medication education at our facility and other health care institutions.

Food for thought. Malnutrition risk associated with increased risk of healthcare-associated infection.

BACKGROUND: Infection and malnutrition are interconnected. UK and Irish guidelines recommend the Malnutrition Universal Screening Tool (MUST) for nutritional risk screening. Patients with a MUST score of ≥2 are considered at high risk of malnutrition and referral for nutritional assessment is recommended. AIM: To explore the association between healthcare-associated infection (HCAI) and the MUST score categories of patients. METHODS: This was a cross-sectional study in May 2017 on ten representative wards in our institution. Patient demographics, MUST score, presence of medical devices, HCAI and antimicrobial use were collected. FINDINGS: Of 240 patients, the HCAI prevalence was 10.4% (N = 25) and 26% (N = 63) were at high risk of malnutrition (MUST score ≥2). Patients with HCAI were more likely to have had surgery (odds ratio (OR): 5.5; confidence interval (CI): 2.1-14.3; P < 0.001), a central vascular catheter (OR: 10.0; CI: 3.6-27.2; P < 0.001), or a urinary catheter in situ (OR: 7.5; CI: 2.8-20.0; P < 0.001), and to have a high risk of malnutrition (OR: 4.3; CI: 1.7-11.2; P < 0.001). A higher MUST score remained a significant predictor of a patient having HCAI on multivariate regression analysis (CI: 0.2-0.6; P < 0.001). CONCLUSION: Patients at risk of malnutrition when assessed with the MUST were more likely to have HCAI. However, prospective studies are required to investigate the temporal association between MUST and HCAI and which interventions best address malnutrition risk and HCAI reduction in different settings.

Donor-specific CD8+ Foxp3+ T cells protect skin allografts and facilitate induction of conventional CD4+ Foxp3+ regulatory T cells.

CD4(+) regulatory T cells play a critical role in tolerance induction in transplantation. CD8(+) suppressor T cells have also been shown to control alloimmune responses in preclinical and clinical models. However, the exact nature of the CD8(+) suppressor T cells, their induction and mechanism of function in allogeneic transplantation remain elusive. In this study, we show that functionally suppressive, alloantigen-specific CD8(+) Foxp3(+) T cells can be induced and significantly expanded by stimulating naïve CD8(+) T cells with donor dendritic cells in the presence of IL-2, TGF-ß1 and retinoic acid. These CD8(+) Foxp3(+) T cells express enhanced levels of CTLA-4, CCR4 and CD103, inhibit the up-regulation of costimulatory molecules on dendritic cells, and suppress CD4 and CD8 T cell proliferation and cytokine production in a donor-specific and contact-dependent manner. Importantly, upon adoptive transfer, the induced CD8(+) Foxp3(+) T cells protect full MHC-mismatched skin allografts. In vivo, the CD8(+) Foxp3(+) T cells preferentially traffic to the graft draining lymph node where they induce conventional CD4(+) Foxp3(+) T cells and concurrently suppress effector T cell expansion. We conclude that donor-specific CD8(+) Foxp3(+) suppressor T cells can be induced and exploited as an effective form of cell therapy for graft protection in transplantation.

Rapamycin-conditioned donor dendritic cells differentiate CD4CD25Foxp3 T cells in vitro with TGF-beta1 for islet transplantation.

Dendritic cells (DCs) conditioned with the mammalian target of rapamycin (mTOR) inhibitor rapamycin have been previously shown to expand naturally existing regulatory T cells (nTregs). This work addresses whether rapamycin-conditioned donor DCs could effectively induce CD4(+)CD25(+)Foxp3(+) Tregs (iTregs) in cell cultures with alloantigen specificities, and whether such in vitro-differentiated CD4(+)CD25(+)Foxp3(+) iTregs could effectively control acute rejection in allogeneic islet transplantation. We found that donor BALB/c bone marrow-derived DCs (BMDCs) pharmacologically modified by the mTOR inhibitor rapamycin had significantly enhanced ability to induce CD4(+)CD25(+)Foxp3(+) iTregs of recipient origin (C57BL/6 (B6)) in vitro under Treg driving conditions compared to unmodified BMDCs. These in vitro-induced CD4(+)CD25(+)Foxp3(+) iTregs exerted donor-specific suppression in vitro, and prolonged allogeneic islet graft survival in vivo in RAG(-/-) hosts upon coadoptive transfer with T-effector cells. The CD4(+)CD25(+)Foxp3(+) iTregs expanded and preferentially maintained Foxp3 expression in the graft draining lymph nodes. Finally, the CD4(+)CD25(+)Foxp3(+) iTregs were further able to induce endogenous naïve T cells to convert to CD4(+)CD25(+)Foxp3(+) T cells. We conclude that rapamycin-conditioned donor BMDCs can be exploited for efficient in vitro differentiation of donor antigen-specific CD4(+)CD25(+)Foxp3(+) iTregs. Such in vitro-generated donor-specific CD4(+)CD25(+)Foxp3(+) iTregs are able to effectively control allogeneic islet graft rejection.

Kramers' law for a bistable system with time-delayed noise.

We demonstrate that the classical Kramers' escape problem can be extended to describe a bistable system under the influence of noise consisting of the superposition of a white Gaussian noise with the same noise delayed by time tau . The distribution of times between two consecutive switches decays piecewise exponentially, and the switching rates for 0

Distribution of residence times in bistable noisy systems with time-delayed feedback.

We analyze theoretically and experimentally the residence time distribution of bistable systems in the presence of noise and time-delayed feedback. We explain various nonexponential features of the residence time distribution using a two-state model and obtain a quantitative agreement with an experiment based on a Schmitt trigger. The limitations of the two-state model are also analyzed theoretically and experimentally using a semiconductor laser with optoelectronic feedback.

Experimental investigation of a bistable system in the presence of noise and delay.

We experimentally analyze the behavior of a non-Markovian bistable system with noise, using a vertical cavity surface emitting laser with time-delayed optoelectronic feedback. The effects of the delayed feedback are observed in the probability distribution of the residence times of the two orthogonal polarization states, and in the polarization-resolved power spectrum. They agree well with recent theoretical predictions based on a two-state model with transition rates depending on an earlier state of the system. We also observe experimentally and explain theoretically that the residence time probability distribution deviates from exponential decay for residence times close to (and smaller than) the delay time.

Experimental observation of traveling waves in the transverse section of a laser.

The selection of a transverse traveling wave by an inhomogeneous pump profile has been experimentally observed in a class B laser structure. The laser structure consisted of a wide-aperture edge-emitting laser diode operating in pulsed mode to avoid thermal guiding effects. The injection current's profile was modified from the usual top-hat configuration to a Lorentzian-like profile by the inclusion of a 10-mum p-type expitaxial spreading layer. Spatial dependance of the far field on the near field was observed. The same behavior is also demonstrated numerically by use of Maxwell-Bloch equations for semiconductor lasers.

The human amnion is a site of MHC class Ib expression: evidence for the expression of HLA-E and HLA-G.

The expression of HLA class I Ag by term human amnion epithelial cells was investigated. In immunostaining and FACS analysis, mAb to monomorphic class I Ag reacted extensively with amnion cells, whereas polymorphic mAb reactivity was more limited and variable. Further studies were conducted on amnion cell preparations containing negligible contaminants. Northern analysis with use of locus-specific probes demonstrated that amnion expresses two class Ib genes, HLA-E and HLA-G. Radio-immunoprecipitation with use of monomorphic mAb identified two fully glycosylated cell surface class I H chains of 44 and 41 kDa; polymorphic mAbs failed to immunoprecipitate the 41-kDa product, although 44-kDa products, typical of class Ia Ag, were identified in some preparations. Class I H chains were isolated from amnion by affinity chromatography. Microsequencing revealed that the first nine residues of the N-terminus of the 41-kDa product aligned perfectly only with HLA-E. Overall, amnion at term appears to express class Ib Ag with limited class Ia Ag. HLA-G is therefore expressed in two extrafetal epithelia: amnion and trophoblast. Identification of the class Ib protein HLA-E in amnion epithelium may have implications for preterm labor that can be associated with infection of the placental membranes.

The Lutheran blood group glycoprotein, another member of the immunoglobulin superfamily, is widely expressed in human tissues and is developmentally regulated in human liver.

Glycoproteins expressing the Lutheran blood group antigens were isolated from human erythrocyte membranes and from human fetal liver. Amino acid sequence analyses allowed the design of redundant oligonucleotides that were used to generate a 459-bp, sequence-specific probe by PCR. A cDNA clone of 2400 bp was isolated from a human placental lambda gt 11 library and sequenced, and the deduced amino acid sequence was studied. The predicted mature protein is a type I membrane protein of 597 amino acids with five potential N-glycosylation sites. There are five disulfide-bonded, extracellular, immunoglobulin superfamily domains (two variable-region set and three constant-region set), a single hydrophobic, membrane-spanning domain, and a cytoplasmic domain of 59 residues. The overall structure is similar to that of the human tumor marker MUC 18 and the chicken neural adhesion molecule SC1. The extracellular domains and cytoplasmic domain contain consensus motifs for the binding of integrin and Src homology 3 domains, respectively, suggesting possible receptor and signal-transduction function. Immunostaining of human tissues demonstrated a wide distribution and provided evidence that the glycoprotein is under developmental control in liver and may also be regulated during differentiation in other tissues.

Complement regulatory proteins in early human fetal life: CD59, membrane co-factor protein (MCP) and decay-accelerating factor (DAF) are differentially expressed in the developing liver.

The human fetus appears to be capable of protecting itself from maternal complement (C) from an early stage in development by expressing the C regulatory proteins decay-accelerating factor (DAF), membrane co-factor protein (MCP) and CD59 on fetally derived trophoblast at the feto-maternal interface. In this study we have examined the ontogeny of these proteins within the fetus itself and have focused on the liver which represents a major site of haemopoiesis during development. Immunostaining revealed that DAF, MCP and CD59 are all expressed from at least 6 weeks of gestation in the liver but that these proteins display distinct distribution patterns. CD59 was broadly distributed both within the epithelial and haemopoietic compartments, but expression of C3 convertase regulators was more restricted. DAF expression was limited to isolated cells within haemopoietic nests and the epithelium was DAF-negative. Although MCP expression on haemopoietic cells was also limited, by contrast with DAF the developing hepatic epithelium was strongly MCP-positive. Typical CD59 and MCP components were observed in fetal liver extracts by immunoblotting, although liver MCP components consistently migrated 4000-5000 MW ahead of those observed on placental trophoblast. Differences in the distribution of these proteins were also observed between the fetal and adult liver. In particular, by comparison with fetal hepatic epithelium, there was an apparent loss of MCP expression from adult hepatocytes. Thus, MCP appears to be developmentally regulated in the human liver and is expressed in the absence of DAF on the early hepatic epithelium. Overall, this study suggests that C regulatory proteins, and in particular CD59 and MCP, are required from the very early stages of gestation within the fetus itself.

Evidence for the expression of non-HLA-A,-B,-C class I genes in the human fetal liver.

HLA class I Ag expression was investigated in the human fetal liver. By immunostaining, mAb to monomorphic class I Ag showed widespread reactivity with both epithelial and hemopoietic cells. By contrast, mAb to polymorphic determinants showed more restricted reactivity that was confined to a proportion of hemopoietic cells: the hepatic epithelium was essentially unreactive. This suggested that the developing liver might express nonclassical HLA class I. Class I Ag were examined in membrane and cytosol fractions of mid-trimester fetal liver. Because of its broad reactivity with HLA-A,-B, mAb Q1/28 was selected to identify classical class I Ag in these studies. Immunoprecipitations were carried out against radiolabeled glycoprotein extracts of fetal liver membranes. W6/32 detected a 40-kDa product characteristic of nonclassical class I proteins, as well as a 43-kDa product, in lysates immunodepleted with Q1/28. By immunoblotting, an anti-H chain antiserum (HC) identified a Q1/28- 40-kDa component and a 43-kDa Q1/28+ component in fetal liver membrane glycoproteins. The fetal liver cytosol fraction was found to contain a 42- to 43-kDa product by W6/32-chromatography. This component partitioned to the aqueous phase upon condensation in TritonX-114 detergent and by immunoblotting was reactive with monomorphic mAb HC10 but not with Q1/28. Total RNA and polymerase chain reaction amplified class I transcripts of fetal liver were probed using oligonucleotides specific for HLA-E, -F, and -G. HLA-F, was readily detected in total RNAs by Northern analysis. HLA-E, HLA-F, and HLA-G were all detected in fetal liver by polymerase chain reaction. Differential expression of these genes may occur between the first and second trimester of liver development. Overall therefore, the human fetal liver expresses multiple class I protein products and contains transcripts for non-classical class I genes; particularly HLA-F.

Complement regulatory proteins at the feto-maternal interface during human placental development: distribution of CD59 by comparison with membrane cofactor protein (CD46) and decay accelerating factor (CD55).

The complement (C) regulatory proteins decay-accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46), which control C3 convertases, together with CD59, an inhibitor of the membrane attack complex (MAC), were found to be present in the developing human placenta from at least 6 weeks of gestation until term. Immunostaining revealed differences in the distribution of these proteins on the fetally derived trophoblast epithelium, especially in early placentae which contain trophoblast populations of diverse proliferative potential and differentiation status. Expression of all three proteins occurred on the terminally differentiated syncytiotrophoblast epithelium covering chorionic villi and which is in direct contact with maternal blood. CD59 was also expressed on the underlying villous cytotrophoblast cells and on their extra-villous derivatives. These two populations showed differential expression of the C3 convertase regulators. Villous cytotrophoblast cells expressed MCP but were largely devoid of DAF. Proliferation of this population to generate extra-villous cytotrophoblast cell columns was associated with both an increase in DAF expression and a decrease in MCP expression. Throughout placental development, expression of DAF appeared to be lower than that of MCP and CD59 as assessed by solid-phase binding assays on isolated trophoblast membranes. Early placentae were also found to contain both DAF+ and DAF- chorionic villi. Conversely, expression of CD59 appeared comparatively high and transcripts for CD59 were found to be much more abundant than those for DAF in purified trophoblast cells. C regulatory proteins appear to play an important role throughout gestation in protecting the fetally derived human conceptus from maternal C. The differential expression patterns of the proteins on trophoblast may reflect differences in requirement for specific functional activities at different locations within the placenta.

Developmental dimensions of DSM-III diagnoses in adolescent psychiatric patients.

In a study of the relationship between ego development and DSM-III diagnoses among 140 psychiatrically hospitalized adolescents, it was found that severity of psychiatric diagnosis decreased with increased ego development. Discussion focuses on the need to introduce innovative and empirically valid developmental perspectives into the process of diagnosing children and adolescents who require mental health services.

Adaptation in adolescence: the influence of time and severe psychiatric disorder.

This study reports the development of adaptive processes in two groups of adolescents assessed initially and 2 years later with clinical research interviews. Students from a public high school (N = 44) and inpatients on an adolescent psychiatric ward (N = 51) formed the two subject groups. The psychiatrically hospitalized group had significantly improved scores after a 2-year interval on four of six adaptive process Summary Scales: Task Orientation, Relatedness, Self Knowledge, and Inner Synthetic Functions. However, these higher scores did not reach the levels of the high school group at either point of assessment. The scores in the high school group remained stable over time except for an increase in the area of Self Knowledge. The value of this interview-derived assessment, in comparison to other forms of measurement, is discussed, and consideration is given to factors which contribute to the differences between groups.

Preferential expression of the complement regulatory protein decay accelerating factor at the fetomaternal interface during human pregnancy.

The expression of decay accelerating factor (DAF) was investigated in human fetal and extra-fetal tissues using a panel of mAb directed against different epitopes on the DAF molecule. By immunostaining, extensive reactivity was observed on the placental trophoblast epithelium and this was confined exclusively to sites of direct contact with maternal blood and tissues at the fetomaternal interface. Within the fetus, by contrast, very little staining was observed especially on hemopoietic cell populations in the developing liver. The antibodies identified a component of 70,000 m.w., comigrating on SDS-PAGE with red cell DAF, on isolated trophoblast membranes and an apparently quantitative increase in the expression of DAF was observed during placental development. Northern analysis using a DAF cDNA clone revealed 1.5-, 1.6-, and 2.2-kb mRNA transcripts typical of DAF in mRNA prepared from whole term placentae and from purified trophoblast cells. DAF appears to be preferentially expressed at the fetomaternal interface during development and may function specifically to inhibit amplification convertases formed at this site either directly or indirectly as a result of maternal complement activation. This molecule may play an important role in protecting the semiallogeneic human conceptus from maternal C-mediated attack.

Biochemical analysis of a novel H-2 class I-like glycoprotein expressed in five AKR-(Gross virus) derived spontaneous T cell leukemias.

The H-2 class I Ag profiles of five spontaneous AKR (H-2K) Gross virus leukemic cell lines were analyzed. A novel H-2 class I, "alloantigen"-like glycoprotein was immunoprecipitated and isolated from all the tumor cell lines using an H-2Dd-specific mAb 35-5-8. The novel Ag was also recognized in vitro by anti-H-2Dd-specific CTL. In addition, DNA from all the thymomas, but not the DNA from normal adult AKR thymic cells showed a transcribed gene detectable with an H-2Dd-specific oligonucleotide probe. The molecular profile of the novel antigen was further studied by two-dimensional gel electrophoresis and analyzed by a computer based image analyzer system and reverse-phase HPLC tryptic peptide mapping. Its molecular pattern was different from the syngeneic H-2Kk, H-2Dk, and the allogeneic H-2Dd gene products. The two-dimensional gel pattern of the novel H-2 class I molecule had a different overall structure reflected in isoelectric point, number, and distribution of polypeptide spots. The tryptic peptide map analysis showed six peaks exclusively identified with the novel Ag. The calculated degree of homology with the corresponding H-2Dd, H-Dk, and H-Kk peptides was 41, 56, and 51%, respectively. In addition, an unusual cell surface distribution of the novel Ag was observed in most of the leukemic lines. The removal of sialic acid residues by neuraminidase treatment facilitated the detection of the allodeterminants by anti-H-2Dd-specific mAb and CTL. Furthermore, we showed that in one AKR tumor line, 424, there is a close association of the novel Ag with the syngeneic class I molecules. Prior preclearance of the syngeneic class I molecules revealed the presence of the H-2Dd-like allospecificity. The genetic and molecular relationship between the expression of this novel class I-like glycoprotein and the recently sequenced Q5 gene is under current investigation.

Interaction sequences in families of psychiatrically hospitalized and nonpatient adolescents.

A KEY theme running through competing views of family influences upon adolescent development is that of directionality, on two levels: influences within the flow of family interaction; and influences from family processes to individual adolescent development. In this paper our focus is upon the first level, intrafamilial sequences within families. More specifically, we study links between psychiatric impairment in adolescence and developmentally relevant parent-child and parent-parent sequences. This report extends a previous investigation (Hauser et al. 1984), which described our new family coding system and first correlational findings. We now study the flow of interactions within these families. Although there has been much recent empirical research in adolescent psychosocial development (e.g., Redmore and Loevinger 1979; Loevinger 1976; Adams and Fitch 1982; Hauser et al. 1984), one important area has received less attention--the relationship between developmentally relevant family processes and psychiatric disturbance during adolescence.

Psychologic predictors of compliance in children with recent onset of diabetes mellitus.

A group of 57 children with recent onset of insulin-dependent diabetes mellitus was studied over 18 months. Compliance with the prescribed diabetic treatment deteriorated over this period. Adolescents (aged 13 to 15 years) were less compliant than preadolescents (aged 9 to 12 years). Initial patient reports of self-esteem, perceived competence, social functioning, behavioral symptoms, and their adjustment to diabetes predicted subsequent compliance behaviors. The findings highlight the linkage of child personality and adjustment with self-care of diabetes, and suggest that psychosocial assessment soon after diabetes is diagnosed may help identify patients at risk for later compliance problems.

Sex differences within the family: Studies of adolescent and parent family interactions.

Sex differences in verbal family interactions were investigated in a group of 79 adolescents and parents from normal and psychiatric settings. The analyses were designed to study these differences in both generations, parent and adolescent. Parent and adolescent interactions with one another were observed in a semistructured, revealed-differences family discussion. All of the individual speeches were then scored with our Constraining and Enabling Coding System (CECS). Initial predictions involved both adolescent and parent differences. These hypotheses were only partially confirmed. The strongest findings pertained to parent sex differences, as we found strikingly higher levels of cognitive enabling speeches expressed by fathers and significantly more speeches addressed to fathers. We discuss several alternative interpretations of these findings. Perspectives included in our considerations are direction of effect and influences of task/context upon the expression of family sex differences.