Conscientiousness and Medication Adherence: A Meta-analysis

Background

Approximately a quarter to a half of all people fail to take their medication regimen as prescribed (i.e. non-adherence). Conscientiousness, from the five-factor model of personality, has been positively linked to adherence to medications in several recent studies.

Purpose

This study aimed to systematically estimate the strength and variability of this association across multiple published articles and to identify moderators of this relationship.

Method

A literature search identified 16 studies (N?=?3,476) that met the study eligibility criteria. Estimates of effect sizes (r) obtained in these studies were meta-analysed.

Results

Overall, a higher level of conscientiousness was associated with better medication adherence (r?=?0.15; 95 % CI, 0.09, 0.21). Associations were significantly stronger in younger samples (r?=?0.26, 95 % CI, 0.17, 0.34; k?=?7).

Conclusion

The small association between conscientiousness and medication adherence may have clinical significance in contexts where small differences in adherence result in clinically important effects.     

Planning and managing a complex multisite study in the age of technology

A 2‐year long, multisite research study that evaluated cardiopulmonary resuscitation skill decay among nursing students was conducted at 10 schools of nursing across the United States. The study was conducted in two phases and required carefully timed sessions for skill performance. Multisite studies in nursing education need to be carefully planned. Time delays should be anticipated with processes and Institutional Review Board protocols across sites. All team members were trained and consistently supported during the entire study. While challenges and obstacles were identified, innovative solutions were implemented that assisted the research team to successfully complete the study. The use of new and existing technology allowed the team to surmount many of the challenges encountered in this study. The purpose of this article is to describe the logistics, processes, challenges, and lessons learned related to conducting a complex multisite study.     

Encounters with difference: Mental health nurses and Indigenous Australian users of mental health services

This article presents findings from the multi‐sited ethnography of mental health nursing practice as it relates to the care of Indigenous users of public mental health services in Australia. It provides an analysis of mental health nurses beliefs and ideas about Aboriginal and Torres Strait Islander people encountered over the course of this research. The Indigenous service user was positioned as Other to the non‐Indigenous mental health nurse, and to non‐Indigenous service users. Cultural difference and the legacy of colonization, including its impact on the health of Aboriginal and Torres Strait Islander peoples, contributed to these beliefs of alterity. Despite emphasizing the differences with Aboriginal and Torres Strait Islander people in mental health services, nurses did not clearly relate this to Indigenous ways of understanding ill health. While cultural differences were recognized, what they meant for the nurses or their nursing practice was interpreted in different ways. In these circumstances, approaches towards care for Aboriginal and Torres Strait Islander people varied between nurses.     

Cholesteryl esters stabilize human CD1c conformations for recognition by self-reactive T cells

Cluster of differentiation 1c (CD1c)-dependent self-reactive T cells are abundant in human blood, but self-antigens presented by CD1c to the T-cell receptors of these cells are poorly understood. Here we present a crystal structure of CD1c determined at 2.4 Å revealing an extended ligand binding potential of the antigen groove and a substantially different conformation compared with known CD1c structures. Computational simulations exploring different occupancy states of the groove reenacted these different CD1c conformations and suggested cholesteryl esters (CE) and acylated steryl glycosides (ASG) as new ligand classes for CD1c. Confirming this, we show that binding of CE and ASG to CD1c enables the binding of human CD1c self-reactive T-cell receptors. Hence, human CD1c adopts different conformations dependent on ligand occupancy of its groove, with CE and ASG stabilizing CD1c conformations that provide a footprint for binding of CD1c self-reactive T-cell receptors.Cluster of differentiation 1 (CD1) proteins are a family of MHC class I-like glycoproteins that present lipid antigens to T cells. CD1 restricted T cells are abundant in humans and play important roles in host defense and immune regulation. Human CD1 proteins comprise five CD1 isoforms, CD1a, CD1b, CD1c, CD1d, and CD1e, which exhibit different intracellular trafficking behaviors and ligand binding preferences (1). Structurally, the main differences between these CD1 isoforms lie in the architecture of their lipophilic ligand binding grooves. Whereas all CD1 isoforms share a highly conserved A′ channel (or pocket) for binding C18–C26 acyl chains, specialization is provided by further connecting channels (2–7). In CD1a, the A′ channel is “fused” to a wide and shallow F′ channel, enabling binding of lipopeptides such as mycobacterial didehydroxymycobactin (DDM) (8). CD1b features a unique T′ tunnel that connects A′ and F′, thereby forming a “superchannel” for accommodating very long acyl chains (e.g., mycobacterial mycolates) (2, 4). CD1d, the only isoform also conserved in rodents, exhibits a two-branched ligand binding groove with two linear channels A′ and F′ connected near the main portal into the groove, known as the F′ portal. A similar two-branched arrangement of A′ and F′ is seen in CD1e, the only CD1 isoform not expressed on the cell surface. Compared with CD1d, CD1a, and CD1b, the portal into the groove in CD1e is widely exposed, consistent with its known role in lipid transfer processes inside lysosomes (6).CD1c presents foreign- (9, 10) as well as self-lipid antigens to T cells (11). Two recent crystal structures of human CD1c revealed a two-branched design similar to that of CD1d and CD1e, with two channels A′ and F′ connecting near the groove portal. In these structures, a mycobacterial phosphomycoketide (PM) or mannosyl-β1-phosphomycoketide (MPM) occupied the A′ channel, whereas an undefined short ligand was present in the F′ channel (7, 12). The spatial arrangement of these ligands in the CD1c groove was very similar to and virtually overlapping in 3D comparisons with that of alpha-galactosylceramide (αGC) in human CD1d (Fig. S1 A and B). Because CD1c and CD1d are known to traffic to the same intracellular compartments for antigen sampling (13), these CD1c-PM and CD1c-MPM structures did not readily explain how CD1c and CD1d could functionally differentiate. Furthermore, the F′ channel in both CD1c-PM and CD1c-MPM was widely open to solvent, which was strikingly different from known structures of CD1a, CD1b, and CD1d and reminiscent of CD1e (7, 12). Based on these facts we hypothesized that human CD1c might undergo substantial conformational transformations in the F′ channel region upon binding of more optimal ligands, with relevance for T-cell receptor binding.Open in a separate windowFig. S1.Published CD1d-αGC and CD1c-MPM structures show a similar arrangement of their bound ligands in both the A′ and F′ channel. (A) Comparison of the configurations of bound ligands in CD1d-αGC (PDB ID code 1ZT4), CD1c-MPM (PDB ID code 3OV6), and CD1c-SL (PDB ID code 5C9J). (B) Ligands bound to CD1d (PDB ID code 1ZT4) (αGC; shown in yellow) and CD1c (PDB ID code 3OV6) (MPM; shown in blue, and spacer lipid shown in cyan) are superimposed and shown in two different orientations.     

Differential coupling of CC chemokine receptors to multiple heterotrimeric G proteins in human interleukin-2-activated natural killer cells

Using two different approaches, we have investigated the types of G proteins coupled to CC chemokine receptors. First, permeabilization of interleukin-2-activated natural killer (IANK) cells with streptolysin-O and introduction of anti-G protein antibodies inside these cells resulted in the following. (1) Anti-G(s), anti-G(o), and anti-G(z) inhibited the migration of IANK cells in response to macrophage- inflammatory protein-1 alpha (MIP-1 alpha), monocyte chemoattractant protein-1 (MCP-1), or regulated on activation normal T cell expressed and secreted (RANTES). (2) Anti-Gi inhibited their migration in response to MCP-1 or RANTES but not in response to MIP-1 alpha. Second, incubation of IANK cell membranes with anti-G protein antibodies before incubating with (gamma-35S) GTP or (gamma-32P) GTP, resulted in the following. (1) Anti-G(s), anti-G(o), or anti-G(z) inhibited GTP binding and GTPase activity in the presence of MIP-1 alpha, or RANTES. (2) Anti- G(i) inhibited GTP binding and GTPase activity in the presence of MCP-1 or RANTES but not in the presence of MIP-1 alpha. The inhibitory effect of anti-G protein antibodies was reversed upon incubating these antibodies with their respective synthetic peptides before addition to IANK cell membranes. These results suggest that MCP-1 and RANTES receptors are promiscuously coupled to multiple G proteins in IANK cell membranes and that this coupling is different from MIP-1 alpha receptors, which seem to be coupled to G(s), G(o), and G(z) but not to G(i).     

Percutaneous transluminal coronary angioplasty of a right coronary artery arising from the left main coronary artery

Angioplasty of anomalous coronary arteries presents unique technical challenges. Correct guiding catheter selection is important to ensure adequate access to the anomalous vessel and to provide support to cross the lesion. A case of successful PTCA of a lesion in an anomalous right coronary artery arising from the left main coronary artery is presented. © 1993 Wiiey-Liss, Inc.     

Clinical features and outcome in childhood T-cell leukemia-lymphoma according to stage of thymocyte differentiation: a Pediatric Oncology Group Study

The immunophenotypes of lymphoblasts from children with newly diagnosed T-cell acute lymphoid leukemia (T-ALL, n = 101) or T-cell non-Hodgkin lymphoma (T-NHL, n = 31) were analyzed to correlate stage of thymocyte differentiation with clinical features and outcome. The 67 boys and 34 girls with T-ALL were 1 month to 18 years old (median, 8 years) with leukocyte counts ranging from 2 to 810 x 10(9)/L (median, 55 x 10(9)/L). Eighteen of these patients were black, and 70 had a mediastinal mass. Twenty-six boys and five girls with a median age of 9 years (range, 1 to 20 years) had T-NHL. Seven of these patients were black, and 24 had a mediastinal mass. The distributions of thymocyte developmental stages (early [CD7+], intermediate [CD1+ and/or CD4+ and/or CD8+], and mature [CD3+]) in cases of T-ALL and T-NHL were significantly different: 34%, 43%, and 23% v 6%, 62%, and 32% (P = .02). A comparison of the patients' clinical features according to the maturational stage of thymocytes failed to disclose significant differences in the majority of characteristics studied. However, patients with mature-stage T-NHL, with or without the addition of subjects with mature-stage T-ALL, were less likely to have a mediastinal mass (P = .02 for both comparisons). Those with intermediate-stage T-cell malignancy (T-ALL and T-NHL combined) were the subgroup most likely to have a mediastinal mass (P = .01). Response to remission induction therapy was significantly worse in the T-ALL subgroup with an early-stage phenotype: a failure rate of 21% v 0% and 6% for the two more differentiated phenotypic subgroups (P = .007). Event-free survival was not affected by thymocyte maturational stage in cases of either T-ALL or T-NHL. Despite evidence of clinical heterogeneity among the maturational stages of T-cell malignancies in children, these developmental subdivisions do not appear to be critical determinants of outcome once remission is achieved. We conclude that such phenotypes need not be included in the stratification plans for clinical trials using common induction treatment.     

Identification of a second transforming gene, rasn, in a human multiple myeloma line with a rearranged c-myc allele

Multiple myeloma is a disease characterized by a long, slowly progressive phase and a final, more aggressive one. Little is known about the mechanism of transformation of myeloma cells, although the clinical characteristics of the disease suggest a multi-step process. Recently, a myeloma cell line, NCI-H929, was isolated from a patient with aggressive preterminal disease and found to have a rearranged myc allele. This myeloma cell line has been further characterized in a focus formation assay to determine whether its unusual growth characteristics were associated with a second activated transforming gene. We now report that the NCI-H929 myeloma cell line has an activated rasn allele in addition to a rearranged myc allele. This is the first identification of an activated transforming gene in a multiple myeloma cell line; furthermore, the characterization of two independently activated oncogenes in this B cell malignancy has implications for both the pathogenesis and evolution of the disease.     

A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands.

The modulation of DNA-protein interactions by methylation of protein-binding sites in DNA and the occurrence in genomic imprinting, X chromosome inactivation, and fragile X syndrome of different methylation patterns in DNA of different chromosomal origin have underlined the need to establish methylation patterns in individual strands of particular genomic sequences. We report a genomic sequencing method that provides positive identification of 5-methylcytosine residues and yields strand-specific sequences of individual molecules in genomic DNA. The method utilizes bisulfite-induced modification of genomic DNA, under conditions whereby cytosine is converted to uracil, but 5-methylcytosine remains nonreactive. The sequence under investigation is then amplified by PCR with two sets of strand-specific primers to yield a pair of fragments, one from each strand, in which all uracil and thymine residues have been amplified as thymine and only 5-methylcytosine residues have been amplified as cytosine. The PCR products can be sequenced directly to provide a strand-specific average sequence for the population of molecules or can be cloned and sequenced to provide methylation maps of single DNA molecules. We tested the method by defining the methylation status within single DNA strands of two closely spaced CpG dinucleotides in the promoter of the human kininogen gene. During the analysis, we encountered in sperm DNA an unusual methylation pattern, which suggests that the high methylation level of single-copy sequences in sperm may be locally modulated by binding of protein factors in germ-line cells.