Quality of care in the oncology outpatient setting from patients' perspective: a systematic review of questionnaires' content and psychometric performance.

BACKGROUND: Cancer care is increasingly provided in the outpatient setting, requiring specific monitoring of care quality. The patients' perspective is an important indicator of care quality and needs to be assessed with well designed, psychometrically sound questionnaires. We performed a systematic literature review of currently available patient satisfaction measures for use in cancer outpatient care settings. METHODS: We carried out MEDLINE/PubMed, PsycINFO, CINAHL, and Scopus searches of papers published over the past 15 years that describe cancer patient satisfaction questionnaires for use in the outpatient setting. We used the adapted COSMIN checklist to assess the quality of the questionnaires' measurement properties. RESULTS: A total of 6677 citations were identified and 76 relevant articles were read, of which 55 were found either not to be relevant or to provide insufficient psychometric information. The remaining 21 studies pertained to 14 patient satisfaction questionnaires. Continuity and transition, accessibility, and involvement of family/friends were less frequently addressed despite their relevance in outpatient oncology. Almost half of the psychometric studies did not provide information on item level missing data. Most internal consistency estimates (Cronbach's α) were satisfactory. Few studies reported test-retest assessment (n = 5), used confirmatory factor analysis (n = 2), or assessed fit to a graded response item response theory model (n = 3). Only three questionnaires were cross-culturally validated. CONCLUSION: Important aspects of care may be missed by current patient satisfaction questionnaires for use in the cancer outpatient setting. Additional evidence is needed of their psychometric performance, especially for cross-cultural comparative assessments.

Assessment of needs, health-related quality of life, and satisfaction with care in breast cancer patients to better target supportive care.

BACKGROUND: This study assessed whether breast cancer (BC) patients express similar levels of needs for equivalent severity of symptoms, functioning difficulties, or degrees of satisfaction with care aspects. BC patients who did (or not) report needs in spite of similar difficulties were identified among their sociodemographic or clinical characteristics. PATIENTS AND METHODS: Three hundred and eighty-four (73% response rate) BC patients recruited in ambulatory or surgery hospital services completed the European Organisation for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ)-C30 quality of life [health-related quality of life (HRQOL)], the EORTC IN-PATSAT32 (in-patient) or OUT-PATSAT35 (out-patient) satisfaction with care, and the supportive care needs survey short form 34-item (SCNS-SF34) measures. RESULTS: HRQOL or satisfaction with care scale scores explained 41%, 45%, 40% and 22% of variance in, respectively, psychological, physical/daily living needs, information/health system, and care/support needs (P < 0.001). BC patients' education level, having children, hospital service attendance, and anxiety/depression levels significantly predicted differences in psychological needs relative to corresponding difficulties (adjusted R² = 0.11). Medical history and anxiety/depression levels significantly predicted differences in information/health system needs relative to degrees of satisfaction with doctors, nurses, or radiotherapy technicians and general satisfaction (adjusted R² = 0.12). Unmet needs were most prevalent in the psychological domains across hospital services. CONCLUSIONS: Assessment of needs, HRQOL, and satisfaction with care highlights the subgroups of BC patients requiring better supportive care targeting.

Short-term psychological impact of the BRCA1/2 test result in women with breast cancer according to their perceived probability of genetic predisposition to cancer.

BACKGROUND: The effect of BRCA1/2 gene test result on anxiety, depression, cancer-related thought intrusion or avoidance and perceived control over cancer risk was assessed in breast cancer (BC) patients, according to their perceived probability of genetic predisposition to cancer. METHODS: Two hundred and forty-three (89% response rate) women with BC completed questionnaires after an initial genetic counselling visit (T1), of which 180 (66%) completed questionnaires again after receiving the BRCA1/2 results (T2). The discrepancy between women's perceived probability of cancer genetic predisposition at T1 and the geneticist's computed estimates was assessed. RESULTS: In all, 74% of women received a negative uninformative (NU), 11% a positive BRCA1/2 and 15% an unclassified variant (UV) result. On hierarchical regression analysis, in women with a positive BRCA1/2 result (vs NU or UV), a lower perceived probability of cancer genetic predisposition than objective estimates at T1 predicted lower levels of anxiety at T2 (ß=-0.28; P<0.01), whereas in women receiving a UV result (vs NU or positive BRCA1/2), a lower perceived probability of cancer genetic predisposition than objective estimates at T1 predicted higher levels of anxiety (ß=0.20; P<0.01), depression (ß=0.19; P<0.05) and intrusion (ß=0.18; P<0.05) at T2. CONCLUSION: The type of BRCA1/2 test result differently affects distress according to women's perceived probability of genetic predisposition before testing.

Validation of the 34-item Supportive Care Needs Survey and 8-item breast module French versions (SCNS-SF34-Fr and SCNS-BR8-Fr) in breast cancer patients.

This study aimed to assess the psychometric robustness of the French version of the Supportive Care Needs Survey and breast cancer (BC) module (SCNS-SF34-Fr and SCNS-BR8-Fr). Breast cancer patients were recruited in two hospitals (in Paris, France and Lausanne, Switzerland) either in ambulatory chemotherapy or radiotherapy, or surgery services. They were invited to complete the SCNS-SF34-Fr and SCNS-BR8-Fr as well as quality of life and patient satisfaction questionnaires. Three hundred and eighty-four (73% response rate) BC patients returned completed questionnaires. A five-factor model was confirmed for the SCNS-SF34-Fr with adequate goodness-of-fit indexes, although some items evidenced content redundancy, and a one-factor was identified for the SCNS-BR8-Fr. Internal consistency and test-retest estimates were satisfactory for most scales. The SCNS-SF34-Fr and SCNS-BR8-Fr scales demonstrated conceptual differences with the quality of life and satisfaction with care scales, highlighting the specific relevance of this assessment. Different levels of needs could be differentiated between groups of BC patients in terms of age and level of education (P < 0.001). The SCNS-SF34-Fr and SCNS-BR8-Fr present adequate psychometric properties despite some redundant items. These questionnaires allow for the crucial endeavour to design appropriate care services according to BC patients' characteristics.

Identification of a nuclear factor that binds to a conserved sequence of the I-A beta gene.

Human and murine class II genes of the MHC show a striking homology 50 to 120 bp upstream of the transcription start site. This area is composed of two conserved sequences (a 13-mer and an 8-mer separated by 19 to 20 bp). Recently, these conserved sequences have been identified as cis-acting transcriptional regulatory elements. We have sought nuclear factors that bind specifically to an upstream fragment (-245 to +75 bp) of the murine I-A beta chain gene that contains the conserved sequences by application of a modified gel electrophoresis DNA binding assay. We report here the identification of a nuclear factor whose binding site overlaps the 8-mer conserved sequence. This factor is present in murine B and T lymphocytes, macrophages, mastocytes, fibroblasts, and human B lymphocytes and macrophages. The binding site was defined by using DNase I and dimethylsulfate protection assays. The putative binding sequence is closely related to the sequence, CCAAT, which is often found associated with the promoter of a gene and is recognized by the transcriptional factors CCAAT-binding transcription factor and nuclear factor I. Oligonucleotides that contain the binding site sequences for nuclear factor I and the alpha-globin CCAAT element, however, do not compete for binding of the nuclear factor to the sequence identified here, suggesting that, in spite of the similarity of the binding sequence, the nuclear factor identified in this report may be different. This nuclear protein may be one of the trans-acting factors that mediate transcription of class II genes.

Purification and characterization of a novel protein from bovine aorta that inhibits coagulation. Inhibition of the phospholipid-dependent factor-Xa-catalyzed prothrombin activation, through a high-affinity binding of the anticoagulant to the phospholipids.

A novel inhibitor of blood coagulation has been isolated from the intima of bovine aorta. The inhibitor, vascular anticoagulant (VAC), has been purified to an active fraction that contains two Coomassie-blue-staining bands (Mr = 34,000 and Mr = 32,000, as judged by sodium dodecyl sulfate/polyacrylamide electrophoresis). Both bands are single-chain proteins, having no glycoprotein features. Furthermore, they do not contain any detectable 4-carboxyglutamic acid residues. Both proteins have an identical isoelectric pH of approximately 4.5. VAC binds in the presence of calcium ions to a bilayer consisting of 20% dioleoylglycerophosphoserine and 80% dioleoylglycerophosphocholine with a Kd = 6 nM. The binding is dependent on the calcium concentration: half-saturation of binding occurs at a calcium concentration of 0.8 mM. The binding is completely reversible with EDTA. Furthermore the phospholipid/VAC ratio at saturation was n = 112 and n = 32 mol/mol for 0.5 mM Ca2+ and 2 mM Ca2+, respectively. Binding does not occur between VAC and pure dioleoylglycerophosphocholine. In a system with purified coagulation factors VAC inhibits the activation of prothrombin by factor Xa and calcium only in the presence of negatively charged phospholipids. VAC decreases the Vmax and increases the Km of the factor-Xa-catalyzed prothrombin activation. Based on these results, we conclude that we have purified from bovine aortic intima an anticoagulant protein, which exerts its activity through a calcium-dependent binding to negatively charged phospholipids, and thus interferes with the assembly of prothrombinase on the phospholipid surface.

Recognition of exon-shuffled class II molecules by T helper cells.

Exon shuffled I-A beta genes transfected into the B lymphoma cell line A20-2J were used to localize the epitope recognized by the monoclonal antibody 10.2.16 to the carboxy terminal portion of the beta 1 domain. In addition, several T helper cell hybrids were tested against these novel I-A molecules and the following observations were made: the beta 1 domain of A beta plays a dominant role in the restricted recognition by T helper cells; there appear to be multiple restriction epitopes on the I-A molecule; these epitopes can consist of conformational epitopes created by specific alpha and beta chains or consist of the polymorphic determinants encoded on the beta chain alone, and these novel I-A molecules serve as restriction elements in the antigen-specific recognition by T cells and in one case stimulate an alloreaction in the absence of antigen.

Probing the structure of 16 S ribosomal RNA from Bacillus brevis.

A majority (approximately 89%) of the nucleotide sequence of Bacillus brevis 16 S rRNA has been determined by a combination of RNA sequencing methods. Several experimental approaches have been used to probe its structure, including (a) partial RNase digestion of 30 S ribosomal subunits, followed by two-dimensional native/denatured gel electrophoresis, in which base-paired fragments were directly identified; (b) identification of positions susceptible to cleavage by RNase A and RNase T1 in 30 S subunits; (c) sites of attack by cobra venom RNase on naked 16 S rRNA; and (d) nucleotides susceptible to attack by bisulfite in 16 S rRNA. These data are discussed with respect to a secondary structure model for B. brevis 16 S rRNA derived by comparative sequence analysis.

The adsorption of prothrombin to phospholipid monolayers quantitated by ellipsometry.

We investigated by means of an automated ellipsometer the calcium-dependent binding of prothrombin from a buffer solution to monolayers of dioleoylphosphatidylserine (DOPS) and dioleoylphosphatidylcholine (DOPC) deposited on chromium slides. This technique allows direct measurements of bound and free protein concentrations and is not hampered by calcium-induced aggregation of vesicles. For pure DOPS a dominant class of binding sites exists with a dissociation constant, Kd = (6 +/- 2) X 10(-10) M (mean +/- S.D.) and maximal binding of prothrombin, gamma max = 0.26 +/- 0.03 micrograms/cm2. Incorporation of a small fraction of DOPC in the monolayer causes a large decrease in the binding affinity with a pronounced biphasic behavior of the binding curve. For monolayers consisting of 20% DOPS and 80% DOPC the binding curve becomes monophasic with Kd = (1.6 +/- 0.6) X 10(-7) M and gamma max = 0.22 +/- 0.03 micrograms/cm2. The procoagulant activity of the monolayers was tested by measuring the generation of thrombin after addition of prothrombin and activated coagulation factors X and V. The thrombin-generating capacity of monolayers and single-bilayer vesicles is comparable but is apparently diffusion limited in the monolayer system. The calcium-dependent formation of stacked multilayers according to the Blodgett technique appeared to be strongly influenced by the DOPS/DOPC ratio in the phospholipid monolayer. From these results it is concluded that for pure DOPS monolayers high-affinity prothrombin-phospholipid and phospholipid-phospholipid interactions exist which are radically disturbed when the monolayer contains more than 20-30% of DOPC.

Complete nucleotide sequence of a 23S ribosomal RNA gene from Bacillus stearothermophilus.

A 23S ribosomal (rRNA) gene from Bacillus stearothermophilus has been cloned in pBR322, and its nucleotide sequence determined. The corresponding mature 23S rRNA is predicted to contain 2928 nucleotides. We compare the primary and secondary structures of 23S rRNA from Escherichia coli and B. stearothermophilus, and discuss their potential contributions to thermal stability.

The adsorption of prothrombin to phosphatidylserine multilayers quantitated by ellipsometry.

We investigated by means of an automated ellipsometer the adsorption of prothrombin from a buffer solution by multilayers of 14:0/14:0- and 18:1/18:1-phosphatidylserine (PS) stacked on chromium slides. In this instrument thickness and refractive index of the adsorbed phospholipid and proteins are monitored continuously. Two equations are derived to relate the mass of stacked phospholipids and the mass of protein adsorbed to the thickness and refractive index. These equations are based upon the Lorentz-Lorenz relation among the molar refractivities, refractive indices, and the densities of binary mixtures. Experimental validation of these equations is performed by measuring stacked multilayers of known mass of phosphatidylserine and the adsorption of [125I] albumin and [3H]prothrombin on these multilayers. Using these equations we measured the dissociation constants Kd and the number of binding sites nb of prothrombin. Values of Kd = 0.15 x 10(-8) M and nb = 122 molecules of PS/molecule of prothrombin were observed for di C14:0 PS and values of Kd = 0.45 x 10(-8) M and nb = 54 molecules of PS/molecule of prothrombin for di C18:1 PS. These data compare well to data obtained by other methods available in the literature.

Secondary structure model for 23S ribosomal RNA.

A secondary structure model for 23S ribosomal RNA has been constructed on the basis of comparative sequence data, including the complete sequences from E. coli. Bacillus stearothermophilis, human and mouse mitochondria and several partial sequences. The model has been tested extensively with single strand-specific chemical and enzymatic probes. Long range base-paired interactions organize the molecule into six major structural domains containing over 100 individual helices in all. Regions containing the sites of interaction with several ribosomal proteins and 5S RNA have been located. Segments of the 23S RNA structure corresponding to eucaryotic 5.8S and 25 RNA have been identified, and base paired interactions in the model suggest how they are attached to 28S RNA. Functionally important regions, including possible sites of contact with 30S ribosomal subunits, the peptidyl transferase center and locations of intervening sequences in various organisms are discussed. Models for molecular 'switching' of RNA molecules based on coaxial stacking of helices are presented, including a scheme for tRNA-23S RNA interaction.

Secondary structure model for bacterial 16S ribosomal RNA: phylogenetic, enzymatic and chemical evidence.

We have derived a secondary structure model for 16S ribosomal RNA on the basis of comparative sequence analysis, chemical modification studies and nuclease susceptibility data. Nucleotide sequences of the E. coli and B. brevis 16S rRNA chains, and of RNAse T1 oligomer catalogs from 16S rRNAs of over 100 species of eubacteria were used for phylogenetic comparison. Chemical modification of G by glyoxal, A by m-chloroperbenzoic acid and C by bisulfite in naked 16S rRNA, and G by kethoxal in active and inactive 30S ribosomal subunits was taken as an indication of single stranded structure. Further support for the structure was obtained from susceptibility to RNases A and T1. These three approaches are in excellent agreement. The structure contains fifty helical elements organized into four major domains, in which 46 percent of the nucleotides of 16S rRNA are involved in base pairing. Phylogenetic comparison shows that highly conserved sequences are found principally in unpaired regions of the molecule. No knots are created by the structure.

Kinetic aspects of the interaction of blood clotting enzymes. VIII. The relation between clotting time and clotting velocity.

It is shown that in a system where thrombin acts on fibrinogen, the clotting time can be used to assess coagulation velocity because clotting time and clotting velocity are inversely proportional.

Purification and properties of the phenprocoumon-induced decarboxyfactor X from bovine plasma. A comparison to normal factor X.

1. By a procedure involving adsorption to barium sulfate, chromatography on DEAE-Sephadex and QAE-Sephadex and preparative polyacrylamide gel electrophoresis, decarboxyfactor X was purified from plasma of phenprocoumon-treated cows. No contaminants could be detected in the final preparation by polyacrylamide gel electrophoresis and zone-electrophoresis. 2. The molecular weight of decarboxyfactor X, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis is approximately 55 000, which is equal to that of factor X. The protein consists of two polypeptide chains with molecular weights of 44 000 and 17 000. 3. Decarboxyfactor X has antigenic determinants in common with normal factor X. 4. The amino acid composition and aminoterminal amino acids of normal factor X and decarboxyfactor X are identical. 5. Less than one residue of gamma-carboxyglutamate could be detected per mole of decarboxyfactor X. 6. In the absence of Ca2+, normal factor X has a slightly higher electrophoretic mobility than decarboxyfactor X. In the presence of Ca2+ the mobility of factor X decreases considerably while the mobility of decarboxyfactor X remains unaltered.

The role of blood clotting factor V in the conversion of prothrombin and a decarboxy prothrombin into thrombin.

Purified PIVKA-II exhibits some factor II (prothrombin) activity in the one-stage coagulation assay and this factor II activity does not come from residual amounts of factor II but originates from PIVKA-II itself. It is shown that PIVKA-II is converted by a normal prothrombinase complex (factor Va and factor Xa adsorbed onto a phospholipid interface) more readily than by phospholipids and factor Xa alone. This suggests that binding between PIVKA-II and factor Va is an essential feature in the formation of the enzyme . substrate complex and from this we infer that a direct interaction between factor Va and prothrombin plays a rôle in the prothrombinase . prothrombin complex.