The measurement of patients' expectations for health care: a review and psychometric testing of a measure of patients' expectations.

BACKGROUND: There is recognition of the importance of measuring patients' experiences, expectations and satisfaction. OBJECTIVES: To assess the literature on the concept and measurement of patients' expectations for health care, and to develop and test a measure of patients' expectations, using adult patients in community, general practice and hospital outpatient departments in Greater London, Norwich and Essex, UK. DATA SOURCES: Major electronic databases including the British Nursing Index, EMBASE, MEDLINE, PsycINFO and the Applied Social Sciences Index and Abstracts were searched between 2000 and 2009. REVIEW METHODS: Narrative review, semi-structured exploratory study and surveys of GP patients and hospital outpatients immediately before and after their surgery/clinic visit to measure their pre-visit expectations for their health care and their post-visit experiences (expectations met and satisfaction with visit) (site specific). RESULTS: A total of 20,439 titles and 266 abstracts were identified, of which 211 were included in the review. Most research designs were weak, with small or selected samples, and a theoretical frame of reference was rarely stated. The origin of questions about expectations was often absent, questions were frequently untested and those with reported reliability or validity data had generally mixed results. In the survey data the expectations measures met acceptability criteria for reliability; all exceeded the threshold of α = 0.70, in each mode of administration and sample type. Items and subscales also correlated at least moderately with those variables that they were expected to be associated with, supporting their validity. The item means within subscales were generally similar between samples and all-item-total correlations exceeded the acceptability threshold. Descriptive findings revealed that most patients ideally expected cleanliness, information about where to go, convenient and punctual appointments and helpful reception staff, the doctor to be knowledgeable, clear and easy to understand, to be involved in treatment decisions and to experience a reduction in symptoms/problems. Expectations least likely to be met included being seen on time and choice of hospital/doctor (items requested by the ethics committee). Other items that had low met expectations included helpfulness of reception staff, doctor being respectful and treating with dignity (hospital sample), doctor knowledgeable (hospital), being given reassurance, receiving advice about health/condition, information about cause and management of condition and information about benefits/side effects of treatment, being given an opportunity to discuss problems, and the three items on outcome expectancies. Previous consultations/experiences of health services and health-care staff/professionals most commonly influenced expectations. Overall, pre-visit realistic expectations were lower than patients' ideals or hopes. Most post-visit experiences indicated some unmet expectations (e.g. cause and management of health/condition, benefits/side effects of treatments) and some expectations that were exceeded. Generally, GP patients reported higher pre-visit expectations and post-visit met expectations. Correlations between subscale domains were strongest between the structure and process of health care, doctor-patient communication style and doctor's approach to giving information, all common indicators of the quality of health care, supporting the validity of the measures. The post-visit experiences subscale significantly predicted single-item summary ratings of overall met expectations and satisfaction. GP rather than hospital patients were also independently predictive of expectations met. Other predictors were having no/little anxiety/depression, older age (satisfaction) and fewer effects of health on quality of life (met expectations). LIMITATIONS: The surveys in clinics were based on convenience, not random sampling methods. CONCLUSIONS: These findings have implications for establishing the quality of health services and informing their improvement. Awareness of the patient's met and unmet expectations should enable staff to understand the patient's perspective and improve communication. This study examined the perspective of the patient only; it is not possible to examine the extent to which any expectations might have been unrealistically too high or too low. This is a challenge for future research. FUNDING: The National Institute for Health Research Health Technology Assessment programme and the National Co-ordinating Centre for Research Methodology (NCCRM).

Young people's experiences of managing asthma and diabetes at school.

PURPOSE: To examine the experiences and concerns of young people and their parents regarding the management of medication for asthma or diabetes whilst at school. METHODS: Face-to-face semi-structured interviews were conducted with 69 young people aged 8-15 years (43 with asthma and 26 with diabetes) and their parents (138 interviews in total) in their own homes. Respondents were recruited through randomly selected general practice surgeries in contrasting areas in South East England. Interviews were audio-recorded, transcribed verbatim and analysed using established qualitative analytical procedures. RESULTS: Young people with asthma and diabetes discussed difficulties regarding access to and use of their medicines at school which may jeopardise optimal condition management. School medicines policies could be a further hindrance. Young people endeavour to find ways to accommodate their medication and condition related needs whilst at school, in an attempt to limit the impact of their condition upon school activities such as sport, school trips and relationships with peers. Parents expressed concern regarding the awareness and levels of support available to their sons/daughters, in particular if a crisis should develop. DISCUSSION: In order to ensure optimal care, there is a need for the development of protocols tailored to the needs of young people with different conditions. These should preferably be devised in partnership between the young person, their parents and the school to ensure that the flexibility and support required for optimal management are offered.

Can patients' preferences for involvement in decision-making regarding the use of medicines be predicted?

OBJECTIVE: The current study aimed to develop a model of patients' preferences for involvement in decision-making concerning the use of medicines for chronic conditions in the UK and test it in a large representative sample of patients with one of two clinical conditions. METHODS: Following a structured literature review, an instrument was developed which measured the variables that had been identified as predictors of patients' preferences for involvement in decision making in previous research. Five hundred and sixteen patients with rheumatoid arthritis or type 2 diabetes were recruited from outpatient and primary care clinics and asked to complete the instrument. RESULTS: Multivariate analysis revealed that age, social class and clinical condition were associated with preferences for involvement in decision-making concerning the use of medicines for chronic illness but gender, ethnic group, concerns about medicines, beliefs about necessity of medicines, health status, quality of life and time since diagnosis were not. In total, the fitted model explained only 14% of the variance. CONCLUSION: This study has demonstrated that current research does not provide a basis for predicting patients' preferences for involvement in decision-making. PRACTICE IMPLICATIONS: Building concordant relationships may depend on practitioners developing strategies to establish individuals' preferences for involvement in decision-making as part of the ongoing prescriber-patient relationship.

An anchored linkage map for sugar beet based on AFLP, SNP and RAPD markers and QTL mapping of a new source of resistance to Beet necrotic yellow vein virus.

Rhizomania, caused by Beet necrotic yellow vein virus (BNYVV), is an important sugar-beet disease worldwide and can result in severe losses of root yield and sugar content. We have identified a major QTL for BNYVV resistance from a new source in a segregating population of 158 individuals. The QTL explained an estimated 78% of the observed phenotypic variation and the gene conferring the partial resistance is referred to as Rz4. AFLP was used in combination with bulked segregant analysis (BSA) to develop markers linked to the resistance phenotype. AFLP marker analysis was extended to produce a linkage map that was resolved into nine linkage groups. These were anchored to the nine sugar-beet chromosomes using previously published SNP markers. This represents the first anchored sugar-beet linkage map to be published with non-anonymous markers. The final linkage map comprised 233 markers covering 497.2 cM, with an average interval between markers of 2.1 cM. The Rz4 QTL and an Rz1 RAPD marker were mapped to chromosome III, the known location of the previously identified BNYVV resistance genes Rz1, Rz2 and Rz3. The availability to breeders of new resistance sources such as Rz4 increases the potential for breeding durable disease resistance.

Identification of a cytoskeleton-bound form of phospholemman with unique C-terminal immunoreactivity.

Phospholemman (PLM) is a 72-amino acid transmembrane protein thought to function in Na,K-ATPase regulation or assembly, similar to other members of the FXYD family of proteins. Unique to PLM among these regulatory proteins are sites for C-terminal phosphorylation by PKA and PKC, although a role for phosphorylation in PLM function remains unclear. To study PLM phosphorylation, we used PLM phosphopeptides to generate antibodies to specifically detect phosphorylated PLM. Peptide affinity chromatography isolated two populations of antibodies: one reacting with standard PLM, a collection of closely-spaced 15-kDa protein bands by SDS-PAGE. About 20% of PLM antibodies reacted specifically with a single distinct form of PLM. Levels of this second immunological form (PLM-b) were increased with overexpression of PLM cDNA, and also reacted with a monoclonal antibody against the PLM N-terminus. In complete contrast to standard PLM, however, PLM-b was quantitatively insoluble in nonionic detergents and was released from tight binding by colchicine. Antibodies to PLM-b were present in two different antisera raised to the phosphorylated C-terminal peptide (residues 57-70), but not in antiserum raised to the non-phosphorylated C-terminal peptide. Despite an apparent relationship between PLM-b and phosphorylated PLM, PLM-b levels were not affected by treatment of heart cells with isoproterenol. PLM-b appears to represent a cytoskeleton-attached detergent-insoluble form of PLM with distinctive C-terminal immunoreactivity that might have implications for PLM structure and function.

Choosing not to immunize: are parents making informed decisions?

BACKGROUND: Childhood immunization is an important aspect of childhood preventive health, world wide, with programmes such as the Expanded Programme on Immunization organized by the World Health Organization. Unlike other countries, the immunization programme is not compulsory in the UK, and the decision whether to immunize a child or not is parental. OBJECTIVE: The objective of this study was to explore the decision-making process of parents who have chosen not to have their children immunized. METHODS: This was a qualitative study, using semi-structured interviews with parents either in their own homes or at their places of work. The study was set in an inner city area with a high level of deprivation. The district immunization co-ordinator and health visitors within the area referred parents to the researcher. Parents subsequently were selected using purposive maximum variation sampling. Data were analysed using consistent and systematic review. An initial coding frame that was derived from the first few transcripts was revised and developed through its application to subsequent transcripts. The final stage of analysis involved comparing the data using the revised coding frame for drawing conclusions and verification. RESULTS: Interviews were completed with 13 parents. Parents discussed their perceptions of childhood diseases and immunization, and the risk-benefit analysis that occurred between the two. All parents identified the risk of side effects as a reason for choosing not to immunize. A proposed model of the decision-making process that represented the experiences of the parents in this study is presented. In response to the question of immunization, three actions were described by parents: a routine response, an emotional response and delaying the decision by entering a questioning stage followed by a cyclical process of seeking and evaluating information. Key to this model was a stage of reflection that most parents described irrespective of their initial action in response to the question of immunization. Parents also discussed their responsibilities in terms of the consequences of their decisions. Health professionals were perceived as providing unbalanced information that was an obstacle in decision making. CONCLUSION: The parents included in this study had chosen not to immunize at least one of their children. Most parents felt they had made an informed decision, based on an assessment of the risks and benefits of immunization and an acceptance of responsibility for that decision. Health professionals were not perceived as providers of balanced information. It is therefore important that parents have easy access to accurate information concerning the pros and cons of treatment, and have the opportunity to discuss their concerns with health professionals.

Over-the-counter medicines and the elderly.

Sales of over-the-counter (OTC) medicines are rising, and will continue to rise as more products are reclassified from prescription-only status to OTC medicines (either pharmacy-only or general sales list). Patients and doctors often omit discussion of OTC medicines when giving or taking a medication history. This has serious potential for identifying adverse drug reactions and drug-drug interactions, which are more common in older people. Therefore, medication histories should include documentation of any OTC medicines taken.

Inducible expression of claudin-1-myc but not occludin-VSV-G results in aberrant tight junction strand formation in MDCK cells.

Occludin and 18 distinct members of the claudin family are tetra-span transmembrane proteins that are localized in cell-specific tight junctions (TJs). A previous study showed that expression of chick occludin in Madin-Darby canine kidney (MDCK) cells raised transepithelial electrical resistance (TER) and, paradoxically, increased mannitol flux. In the present study, we employed epitope tagged canine occludin expression, under the control of the tetracycline repressible transactivator, to determine the extent to which the unexpected parallel increase in TER and mannitol flux was related to a structural mismatch between avian and canine occludins, which are only 50% identical. To determine whether the paradoxical changes in permeability was specific to occludin, we assessed the effect of over-expressing epitope tagged murine claudin-1. Our data revealed that over-expression of either of the epitope tagged mammalian tight junction proteins increased TER, mannitol and FITC-dextran flux. We observed a 2- and up to 5.6-fold over-expression of occludin-VSV-G and claudin-1-myc, respectively, with no change in ZO-1, endogenous occludin or claudin-1 expression. Confocal microscopy revealed that occludin-VSV-G, claudin-1-myc and ZO-1 co-localized at the TJ. In addition, claudin-1-myc formed aberrant strands along the lateral cell surface without an underlying ZO-1 scaffold. In fracture labeled replicas these strands consisted of claudin-1-myc with little accompanying occludin. These observations suggest that in epithelial cells claudin-1 can assemble into TJ strands without the participation of either ZO-1 or occludin. The proximity of the myc tag to the COOH-terminal YV sequence of claudin-1 appeared to interfere with its interaction with ZO-1, since over-expression of non-tagged claudin-1 increased TER but had a minimal effect on solute flux and no aberrant strands formed. From our data we conclude that differences in structure between avian and mammalian occludin do not account for the observed paradoxical increase in mannitol flux. Levels of ZO-1 remained unchanged despite substantial increases in induced TJ integral protein expression, suggesting that an imbalance between levels of ZO-1 and occludin or claudin-1 leads to altered regulation of pores through which non-charged solute flux occurs. We suggest that ion and solute flux are differentially regulated at the TJ.

Rapid reduction of MDCK cell cholesterol by methyl-beta-cyclodextrin alters steady state transepithelial electrical resistance.

The role of plasma membrane lipids in regulating the passage of ions and other solutes through the paracellular pathway remains controversial. In this study we explore the contribution of cholesterol (CH) in maintaining the barrier function of an epithelial cell line using the CH-solubilizing agent methyl beta-cyclodextrin (MBCD) to stimulate CH efflux. Inclusion of 20 mM MBCD in both apical and basolateral media reduced CH levels by 70-80% with no significant effect on cell viability. Most of that decrease occurred during the first 30 min of incubation. Recovery of CH content to initial values was nearly complete 22 h after removal of MBCD. Within 30 min of adding MBCD to the culture medium, transepithelial electrical resistance (TER) increased, reaching maximum values 30-40% above controls. This early rise in TER occurred when MBCD was added to either side of the monolayer. The later rapid decline in TER was observed only when MBCD bathed the basolateral surface from which, coincidentally, CH efflux was most rapid. Freeze fracture replicas and transmission electron microscopy of monolayers exposed to MBCD for only 30 min revealed no increase in either the average tight junction (TJ) strand number or the dimensions of the lateral intercellular space. There was a statistically significant increase in the number of TJ particles associated with the E fracture face at this time. This raises the interesting possibility that during CH efflux there is a change in the interaction between TJ particles and underlying cytoskeletal elements. There was no change in staining for occludin and ZO-1. After exposing the basolateral surface to MBCD for 2 h, TER fell below control levels. The accompanying increase in mannitol flux suggests strongly that the decrease in TER resulted from an increase in the permeability of the paracellular and not the transcellular pathway. A decrease in immuno-staining for occludin and ZO-1 at TJs, a striking accumulation of actin at tri-cellular areas as well as a decline in the number of parallel strands, as seen in freeze fracture replicas, suggest that changes in cytoskeletal organization during long incubations with MBCD had physically disrupted the TJ network. Data are presented which suggest that the observed changes in paracellular permeability during CH efflux may be related to increased levels of lipid-derived second messengers, some of which may trigger changes in the phosphorylation status of TJ proteins.

Alterations in cell cholesterol content modulate Ca(2+)-induced tight junction assembly by MDCK cells.

Transepithelial electrical resistance (TER), a measure of tight junction (TJ) barrier function, develops more rapidly and reaches higher values after preincubation of MDCK cells for 24 h with 2 microM Lovastatin (lova), an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase. While this effect was attributed to a 30% fall in cholesterol (CH), possible effects of lova on the supply of prenyl group precursors could not be excluded. In the current study, strategies were devised to examine effects on TER of agents that simultaneously lower CH and increase the flux of intermediates through the CH biosynthetic pathway. Zaragozic acid, 20 microM, an inhibitor of squalene synthase known to increase the synthesis of isoprenoids and levels of prenylated proteins, lowered cell CH by 30% after 24 h, while accelerating development of TER in the same manner as lova. TER was also enhanced, despite a 23% increase in the rate of [3H]acetate incorporation into CH, when total CH was reduced by 45% during a 2-h incubation with 2 mM methyl beta-cyclodextrin (MBCD), an agent that stimulates CH efflux from cells. The fact that the rate of TER development was diminished when cell CH content was elevated by incubation with a complex of CH and MBCD is further evidence that this sterol modulates development of the epithelial barrier. Cell associated CH derived from the complex was similar to endogenous CH with respect to its accessibility to cholesterol oxidase. Lova's effect on TER was diminished when 5 micrograms/mL of CH was added to the medium during the last 11 h of incubation with lova.

Effect of nitric oxide synthase inhibition on bleeding time in humans.

Endothelium-derived nitric oxide (NO) is a potent in vitro inhibitor of platelet adhesion and aggregation, but its role in regulating platelet reactivity in vivo and in humans in particular is undefined. Our primary objective was to determine whether the in vivo inhibition of NO production shortens template bleeding time (BT). The hemodynamic and platelet effects of NG-mono-methyl-L-arginine (L-NMMA), an NO synthase inhibitor, were studied in 12 normal volunteers. Forearm template BT was determined before and 15 min after the intravenous (i.v.) infusion of 4.3 mg/kg L-NMMA. L-NMMA infusion increased mean arterial pressure from 88 +/- 4 to 99 +/- 3 mm Hg (p = 0.0001). Plasma NO levels, determined by chemiluminescence, decreased 65 +/- 10% from basal values (p < 0.05), confirming inhibition of endogenous NO production. Intravenous L-NMMA shortened BT from 5.5 +/- 0.9 to 4.0 +/- 0.6 min (p = 0.026), or by 24 +/- 8% (p = 0.008). L-NMMA infusion did not significantly change ex vivo platelet aggregation. To determine whether vasoconstriction affected BT, we investigated forearm blood flow (FBF; determined by venous occlusion plethymography), and template BT in 3 subjects after the local infusion of L-NMMA (2-4 mg/min intraarterially, i.a.). Intraarterial administration of L-NMMA caused a 39 +/- 3% (p = 0.006) reduction in FBF in the infused arm but did not change BT. These data show that systemic inhibition of NO production shortens BT in humans. However, the precise mechanism by which L-NMMA shortens BT is not completely defined.

Fibrin(ogen) is internalized and degraded by activated human monocytoid cells via Mac-1 (CD11b/CD18): a nonplasmin fibrinolytic pathway.

Fibrin(ogen) (FGN) is important for hemostasis and wound healing and is cleared from sites of injury primarily by the plasminogen activator system. However, there is emerging evidence in plasminogen activator-deficient transgenic mice that nonplasmin pathways may be important in fibrin(ogen)olysis, as well. Given the proximity of FGN and monocytes within the occlusive thrombus at sites of vascular injury, we considered the possibility that monocytes may play an ancillary role in the degradation and clearance of fibrin. We found that monocytes possess an alternative fibrinolytic pathway that uses the integrin Mac-1, which directly binds and internalizes FGN, resulting in its lysosomal degradation. At 4 degrees C, FGN binds to U937 monocytoid cells in a specific and saturable manner with a kd of 1.8 mumol/L. Binding requires adenosine diphosphate stimulation and is calcium-dependent. At 37 degrees C, FGN and fibrin monomer (FM) are internalized and degraded at rates of 0.37 +/- 0.13 and 0.55 +/- 0.03 microgram/10(6) cells/h by U937 cells, 1.38 +/- 0.02 and 1.20 +/- 0.30 microgram/10(6) cells/h by THP-1 cells, and 2.10 +/- 0.20 and 2.52 +/- 0.18 micrograms/10(6) cells/h by human peripheral blood mononuclear cells, respectively. The serine protease inhibitors, PPACK and aprotinin, and the specific elastase inhibitor, AAPVCK, do not significantly inhibit degradation. However, degradation is inhibited by chloroquine, suggesting that a lysosomal pathway is involved. Factor X, a competitive ligand with FGN for the Mac-1 receptor, also blocks degradation, as does a monoclonal antibody to the alpha-subunit of Mac-1. Autoradiography of radioiodinated, internalized FGN shows that FGN proteolysis by the pathway produces a unique degradation pattern distinct from that observed with plasmin. In a fibrin clot lysis assay, Mac-1-mediated fibrinolysis contributed significantly to total fibrinolysis. In summary, FGN is internalized and degraded by activated human monocytoid cells via Mac-1 in the absence of plasmin, thereby providing an alternative fibrinolytic pathway. Thus, in addition to the function of cell adhesion, integrins may also act as receptors that mediate the internalization and degradation of bound ligands.

Antiplatelet properties of protein S-nitrosothiols derived from nitric oxide and endothelium-derived relaxing factor.

S-nitrosothiols may serve as carriers in the mechanism of action of endothelium-derived relaxing factor (EDRF) by stabilizing the labile nitric oxide (NO) radical from inactivation by reactive species in the physiological milieu and by delivering NO to the heme activator site of guanylyl cyclase. Low-molecular-weight thiols, such as cysteine and glutathione, form S-nitrosothiol adducts with vasodilatory and antiplatelet properties, and protein thiols can interact in the presence of NO and/or EDRF to form uniquely stable S-nitroso-proteins. We now show that the S-nitroso-proteins, S-nitroso-albumin, S-nitroso-tissue type plasminogen activator, and S-nitroso-cathepsin B, have potent antiplatelet effects with an IC50 of approximately 1.5 microM. In the dog, S-nitroso-albumin inhibits ex vivo platelet aggregation and significantly prolongs the template bleeding time from 2.15 +/- 0.13 (mean +/- SEM) to 9.70 +/- 1.24 minutes. The antiplatelet action of S-nitroso-proteins is associated with the stimulation of guanylyl cyclase and a significant decrease in fibrinogen binding to platelets. S-Nitroso-proteins undergo thiol-nitrosothiol exchange with low-molecular-weight thiols to form low-molecular-weight S-nitroso-thiols, and they also interact directly with the platelet surface, both of which processes facilitate generation of NO. These data suggest that S-nitroso-proteins are potent antiplatelet agents and may be intermediates in the antiplatelet mechanism of EDRF action.