The generation of consensus guidelines for carrying out process evaluations in rehabilitation research.

BACKGROUND: Although in recent years there has been a strong increase in published research on theories (e.g. realist evaluation, normalization process theory) driving and guiding process evaluations of complex interventions, there is limited guidance to help rehabilitation researchers design and carry out process evaluations. This can lead to the risk of process evaluations being unsystematic. This paper reports on the development of new consensus guidelines that address the specific challenges of conducting process evaluations alongside clinical trials of rehabilitation interventions. METHODS: A formal consensus process was carried out based on a modified nominal group technique, which comprised two phases. Phase I was informed by the findings of a systematic review, and included a nominal group meeting with an expert panel of participants to rate and discuss the proposed statements. Phase II was an in depth semi-structured telephone interviews with expert panel participants in order to further discuss the structure and contents of the revised guidelines. Frequency of rating responses to each statement was calculated and thematic analysis was carried out on all qualitative data. RESULTS: The guidelines for carrying out process evaluations within complex intervention rehabilitation research were produced by combining findings from Phase I and Phase II. The consensus guidelines include recommendations that are grouped in seven sections. These sections are theoretical work, design and methods, context, recruitment and retention, intervention staff, delivery of the intervention and results. These sections represent different aspects or stages of the evaluation process. CONCLUSION: The consensus guidelines here presented can play a role at assisting rehabilitation researchers at the time of designing and conducting process evaluations alongside trials of complex interventions. The guidelines break new ground in terms of concepts and theory and works towards a consensus in regards to how rehabilitation researchers should go about carrying out process evaluations and how this evaluation should be linked into the proposed trials. These guidelines may be used, adapted and tested by rehabilitation researchers depending on the research stage or study design (e.g. feasibility trial, pilot trial, etc.).

Improving skills and care standards in the support workforce for older people: a realist synthesis of workforce development interventions.

OBJECTIVES: This evidence review was conducted to understand how and why workforce development interventions can improve the skills and care standards of support workers in older people's services. DESIGN: Following recognised realist synthesis principles, the review was completed by (1) development of an initial programme theory; (2) retrieval, review and synthesis of evidence relating to interventions designed to develop the support workforce; (3) 'testing out' the synthesis findings to refine the programme theories, and establish their practical relevance/potential for implementation through stakeholder interviews; and (4) forming actionable recommendations. PARTICIPANTS: Stakeholders who represented services, commissioners and older people were involved in workshops in an advisory capacity, and 10 participants were interviewed during the theory refinement process. RESULTS: Eight context-mechanism-outcome (CMO) configurations were identified which cumulatively comprise a new programme theory about 'what works' to support workforce development in older people's services. The CMOs indicate that the design and delivery of workforce development includes how to make it real to the work of those delivering support to older people; the individual support worker's personal starting points and expectations of the role; how to tap into support workers' motivations; the use of incentivisation; joining things up around workforce development; getting the right mix of people engaged in the design and delivery of workforce development programmes/interventions; taking a planned approach to workforce development, and the ways in which components of interventions reinforce one another, increasing the potential for impacts to embed and spread across organisations. CONCLUSIONS: It is important to take a tailored approach to the design and delivery of workforce development that is mindful of the needs of older people, support workers, health and social care services and the employing organisations within which workforce development operates. Workforce development interventions need to balance the technical, professional and emotional aspects of care. TRIAL REGISTRATION NUMBER: CRD42013006283.

Evaluating a systematic voiding programme for patients with urinary incontinence after stroke in secondary care using soft systems analysis and Normalisation Process Theory: findings from the ICONS case study phase.

BACKGROUND: Urinary incontinence (UI) affects between 40 and 60% of people in hospital after stroke, but is often poorly managed in stroke units. OBJECTIVES: To inform an exploratory trial by three methods: identifying the organisational context for embedding the SVP; exploring health professionals' views around embedding the SVP and measuring presence/absence of UI and frequency of UI episodes at baseline and six weeks post-stroke. DESIGN: A mixed methods single case study included analysis of organisational context using interviews with clinical leaders analysed with soft systems methodology, a process evaluation using interviews with staff delivering the intervention and analysed with Normalisation Process Theory, and outcome evaluation using data from patients receiving the SVP and analysed using descriptive statistics. SETTING: An 18 bed acute stroke unit in a large Foundation Trust (a 'not for profit' privately controlled entity not accountable to the UK Department of Health) serving a population of 370,000. PARTICIPANTS: Health professionals and clinical leaders with a role in either delivering the SVP or linking with it in any capacity were recruited following informed consent. Patients were recruited meeting the following inclusion criteria: aged 18 or over with a diagnosis of stroke; urinary incontinence (UI) as defined by the International Continence Society; conscious; medically stable as judged by the clinical team and with incontinence classified as stress, urge, mixed or 'functional'. All patients admitted to the unit during the intervention period were screened for eligibility; informed consent to collect baseline and outcome data was sought from all eligible patients. RESULTS: Organisational context: 18 health professionals took part in four group interviews. Findings suggest an environment not conducive to therapeutic continence management and a focus on containment of UI. Embedding the SVP into practice: 21 nursing staff took part in six group interviews. Initial confusion gave way to embedding of processes facilitated by new routines and procedures. Patient outcome: 43 patients were recruited; 28 of these commenced the SVP. Of these, 6/28 (21%) were continent at six weeks post-stroke or discharge. CONCLUSION: It was possible to embed the SVP into practice despite an organisational context not conducive to therapeutic continence care. Recommendations are made for introducing the SVP in a trial context.

Mental health crisis and respite services: service user and carer aspirations.

There is emerging evidence that crisis resolution services can provide alternatives to hospital admission, reducing demand on inpatient beds. Following a public consultation exercise in Lancashire (England), a team of nurses undertook a study, using interactive research methodology, to gain an understanding of how users and carers define a crisis and what range of crisis services, resources and interventions service users and carers thought would help avoid unnecessary hospital admission. Data collection comprised postal questionnaires and 24 group meetings with service users and carers, which were held during 2006. Data were analysed, and seven themes were identified: (1) definitions of a crisis; (2) access to services; (3) interventions; (4) range of services required (before, during and after crisis); (5) place of treatment; (6) recovery and rehabilitation; and (7) community support. We conclude that expressed preferences of service users and carers for pre-emptive services that are delivered flexibly will present a challenge for service commissioners and providers, particularly where stringent access criteria are used. Home-based pre-emptive services that reduce the need for unnecessary hospital treatment may avoid progression to social exclusion of service users.

Identification of selective inhibitors of cyclin dependent kinase 4.

A new structural type of kinase inhibitor, containing a benzocarbazole nucleus, has been identified. Members of the series are selective for inhibition of the cyclin dependent kinase family of enzymes. Although the cdks are highly homologous, representatives of the series showed intra-cdk selectivities, especially for cdk4. SAR studies elucidated the important features of the molecules for inhibition.

Quinazolines as cyclin dependent kinase inhibitors.

Quinazolines have been identified as inhibitors of CDK4/D1 and CDK2/E. Aspects of the SAR were investigated using solution-phase, parallel synthesis. An X-ray crystal structure was obtained of quinazoline 51 bound in CDK2 and key interactions within the ATP binding pocket are defined.

Re-thinking stroke rehabilitation: the Corbin and Strauss chronic illness trajectory framework.

Re-thinking stroke rehabilitation: the Corbin and Strauss chronic illness trajectory framework The dramatic effects of a stroke can have far-reaching implications for patients and carers. Effective recovery involves a considerable array of coping strategies that facilitate and promote engagement in the social world. Their development is a long-term process that requires considerable effort, motivation and enterprise on the part of patients and their families. Traditional approaches to the provision of stroke rehabilitation services, however, appear to be underpinned by frameworks that are short-term in outlook. As a consequence, nursing interventions often focus on the progression of the patient through the care system, rather than on facilitating future recovery. Much of the work of stroke recovery is consequently done by patients and their families at home, with little provision of ongoing professional help and advice. This paper explores the application of the Corbin and Strauss Chronic Illness Trajectory Framework for stroke. In particular, the major concepts of the framework are applied to a vignette derived from a longitudinal study of patients' experiences of recovery. The trajectory framework is shown to be a useful structure that has the potential to enhance the appropriateness of nursing interventions for stroke patients. However, the validity of the framework can only be established through its application and evaluation in clinical practice. The purpose of this paper is to contribute to a debate that encourages consideration of the framework's utility for nurses to enhance the stroke rehabilitation experience.

Living with stroke: a phenomenological study.

Understanding how stroke sufferers experience their stroke and recovery is essential if the development of rehabilitation services is to be effective and appropriate. Previous research in this area has tended to be either cross-sectional or with a limited amount of informant follow-up, and consequently has limited utility. This paper describes a study underpinned by a phenomenological approach, which tracked the experiences of six patients admitted to a rehabilitation unit in the north-west of England. Informants were followed for at least 12 months after stroke, and a total of 73 interviews were undertaken during the study. The data demonstrate that recovery from stroke involved restructuring and adaptation in physical, social and emotional aspects of an individual's life. Two important features of recovery were highlighted. First, whilst aspects of pre-stroke life may be used to describe individual progress, no end-point to recovery was identified as informants described and anticipated life with stroke. Second, informants focused on the social context of recovery where engagement in the social world was emphasized over discrete physical function. Although no common path of recovery was found, it is recommended that stroke services are structured to take account of the long-term needs of stroke patients and their families in their home environment.

A description of the nursing role in stroke rehabilitation.

A theoretical description of the nursing role in stroke rehabilitation remains elusive in the literature. The United Kingdom strategy for health service development will increasingly require nurses from all clinical specialities to collaborate with other health care professionals and stakeholders to evaluate the services they provide. In stroke rehabilitation, an understanding of the contribution that nursing makes is essential, if that collaboration is to be effective. This paper details a study undertaken to describe the nature of the nursing role in stroke rehabilitation, and the factors that shape this role. A reflective enquiry was used to enable the collection of data grounded in the realities of clinical practice. Study participants were qualified nursing staff (n=13) working in a rehabilitation unit in the north-west of England. A total of 35 in-depth reflections were obtained for analysis. Three role categories were identified in the data: the nurse as care giver, facilitator of personal recovery and care manager. Sub-categories of nursing intervention were identified within each category, together with anticipated outcomes and contextual features that shaped the category. The results of the study were verified by a purposive sample of nursing staff from the rehabilitation unit.

An exploration of the stroke co-ordinator role.

Although there is knowledge of the substantial benefits of collaborative approaches to stroke rehabilitation, information on alternative management strategies is sparse. This paper describes an exploratory survey, undertaken in the north-west of England, to highlight features of the stroke co-ordinator role. The role is explored in terms of rehabilitation management and service development. Some strategies to support practitioners in the role, and areas for role development, are suggested.

Polylactosamines are not obligate receptors for invasion of Plasmodium falciparum malaria as shown in HEMPAS variant II-gal- erythrocytes.

A HEMPAS (hereditary erythroblastic multinuclearity with positive acidified serum test) erythrocyte, atypical Variant II (referred to herein as Variant II-gal-), lacking long-chain polylactosamine on both glycoproteins (Band 3 and 4.5) and glycosphingolipids, was characterized by the carbohydrate profile of the erythrocyte membrane according to Fukuda et al. (Blood, 73, 1331-1339, 1989). Two laboratories previously reported that polylactosamine isolated from the erythrocyte protein Band 3 inhibited invasion of red blood cells by Plasmodium falciparum in malarial culture, suggesting a role for this carbohydrate in adhesion of the parasite. Therefore, HEMPAS erythrocyte Variant II-gal- presented a unique opportunity to further examine this premise. Freshly drawn blood samples (normal and HEMPAS Variant II-gal-) were separately incubated with P. falciparum from mannitol-synchronized cultures. The parasite was found to invade HEMPAS Variant II-gal- erythrocytes at a 30% lower rate through two life cycles, as shown by microscopic evaluation of invasion and by [3H]hypoxanthine incorporation into parasite. This observation, along with the published fact that glycophorin-deficient MkMk cells are also infectable, but at a lower rate, indicates that neither sialoglycoproteins nor polylactosamines are an obligate adhesive ligand for P. falciparum, although the possibility remains that either may still contribute to adhesive events during infection.

The ligand binding signatures of the rat AT1A, AT1B and the human AT1 receptors are essentially identical.

The objective of this study was to determine whether the three isoforms of recombinant Ang II receptors (rAT1A, rAT1B and hAT1), stably and individually expressed in CHO cells, could be pharmacologically distinguished by their ligand binding signatures. Competition studies were performed to characterize the inhibition of [125I]Ang II binding to each of the cell membrane preparations by an extensive series of peptide and nonpeptide Ang II analogs. Scatchard plot analyses revealed the following binding characteristics:rAT1A-Kd = 1.27 +/- 0.14 nM; rAT1B- Site 1:Kd = 0.56 +/- 0.11 nM, Site 2: Kd = 126 +/- 23 nM; and hAT1-Site 1:Kd = 1.06 +/- 0.16 nM, Site 2: Kd = 257 +/- 55 nM. The binding of [125I]Ang II in the three preparations was similarly sensitive to inhibition by GTP gamma S. The ligand binding signatures of the three receptor isoforms are essentially the same and are illustrated by the affinity and order of potency of the following ligands: L-158,809 > or = Sar1, Ile8Ang II > saralasin Ang II > or = Ang III > EXP581 > EXP3174 > losartan > or = EXP811 > GR117,289c > EXP6803 > DuP 532 > Ang I >> PD123177. In conclusion, the two rat AT1 receptor isoforms are pharmacologically indistinguishable from each other and from that of the human.

Identification of the thymidine kinase gene of infectious laryngotracheitis virus.

An an initial step in the development of a recombinant poultry infectious laryngotracheitis virus (ILTV) vaccine, we report on the identification, cloning, and sequencing of a thymidine kinase (tk) gene from a virulent U.S. field isolate of ILTV. Degenerate oligonucleotide primers for the consensus nucleotide (ATP) binding site and the nucleoside (thymidine) binding site of other herpesvirus tk genes were used in the polymerase chain reaction (PCR) to amplify a fragment of ILTV DNA. The 344-base-pair (bp) amplified fragment was cloned into plasmid pKSII and used in Southern hybridizations to locate the ILTV tk gene on a 2.4-kb HindIII fragment. Upon cloning and sequencing this fragment, a 1089-bp open reading frame was identified, which is predicted to encode a protein demonstrating 27.9% amino acid homology to the herpes simplex virus type 1 (HSV-1) thymidine kinase protein. Analysis of the sequence revealed one region of difference from that reported for the Thorne strain of ILTV. In addition, the portion of the TK protein corresponding to the nucleotide binding domain is highly conserved among the avian herpesviruses.

Identification of the infectious laryngotracheitis virus glycoprotein gB gene by the polymerase chain reaction.

The infectious laryngotracheitis virus (ILTV) homologue of the herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) gene was identified by PCR amplification of genomic ILTV DNA. A 488-bp amplified DNA fragment was used to identify and clone two adjacent PstI fragments from genomic ILTV DNA. Sequence analysis of the region surrounding the amplified fragment identified a 2619-bp open reading frame that has 39% homology with both the nucleotide and amino-acid sequences of the HSV-1 gB gene. Northern blot analysis using a portion of the open reading frame as a probe identified a 2.7-kb RNA transcript in ILTV-infected chicken embryo liver cells. Analysis of the predicted amino acid sequence of the ILTV protein indicated that it shares structural features with the gB glycoproteins of other herpesviruses.