Learning to work together - lessons from a reflective analysis of a research project on public involvement.

PLAIN ENGLISH SUMMARY: Patient and public involvement (PPI) in research is very important, and funders and the NHS all expect this to happen. What this means in practice, and how to make it really successful, is therefore an important research question. This article analyses the experience of a research team using PPI, and makes recommendations on strengthening PPI in research. There were different PPI roles in our study - some people were part of the research team: some were on the advisory group; and there were patient groups who gave specific feedback on how to make research work better for their needs. We used minutes, other written documents, and structured individual and group reflections to learn from our own experiences over time. The main findings were:- for researchers and those in a PPI role to work in partnership, project structures must allow flexibility and responsiveness to different people's ideas and needs; a named link person can ensure support; PPI representatives need to feel fully included in the research; make clear what is expected for all roles; and ensure enough time and funding to allow meaningful involvement. Some roles brought more demands but also more rewards than others - highlighting that it is important that people giving up their time to help with research experience gains from doing so. Those contributing to PPI on a regular basis may want to learn new skills, rather than always doing the same things. Researchers and the public need to find ways to develop roles in PPI over time. We also found that, even for a team with expertise in PPI, there was a need both for understanding of different ways to contribute, and an evolving 'normalisation' of new ways of working together over time, which both enriched the process and the outputs. ABSTRACT: Background Patient and public involvement (PPI) is now an expectation of research funders, in the UK, but there is relatively little published literature on what this means in practice - nor is there much evaluative research about implementation and outputs. Policy literature endorses the need to include PPI representation at all stages of planning, performing and research dissemination, and recommends resource allocation to these roles; but details of how to make such inputs effective in practice are less common. While literature on power and participation informs the debate, there are relatively few published case studies of how this can play out through the lived experience of PPI in research; early findings highlight key issues around access to knowledge, resources, and interpersonal respect. This article describes the findings of a case study of PPI within a study about PPI in research. Methods The aim of the study was to look at how the PPI representatives' inputs had developed over time, key challenges and changes, and lessons learned. We used realist evaluation and normalisation process theory to frame and analyse the data, which was drawn from project documentation, minutes of meetings and workshops, field notes and observations made by PPI representatives and researchers; documented feedback after meetings and activities; and the structured feedback from two formal reflective meetings. Results Key findings included the need for named contacts who support, integrate and work with PPI contributors and researchers, to ensure partnership working is encouraged and supported to be as effective as possible. A structure for partnership working enabled this to be enacted systematically across all settings. Some individual tensions were nonetheless identified around different roles, with possible implications for clarifying expectations and deepening understandings of the different types of PPI contribution and of their importance. Even in a team with research expertise in PPI, the data showed that there were different phases and challenges to 'normalising' the PPI input to the project. Mutual commitment and flexibility, embedded through relationships across the team, led to inclusion and collaboration. Conclusion Work on developing relationships and teambuilding are as important for enabling partnership between PPI representatives and researchers as more practical components such as funding and information sharing. Early explicit exploration of the different roles and their contributions may assist effective participation and satisfaction.

Recognition by family members that relatives with neurodegenerative disease are likely to die within a year: a meta-ethnography.

OBJECTIVE: To synthesize evidence of family members recognizing that their relative is likely to die within the year, and identifying the need for palliative care. DESIGN: A meta-ethnography of studies of family members in multiple sclerosis (MS), Parkinson's disease (PD) and motor neuron disease (MND). REVIEW METHODS: Systematic search in electronic databases; thematic synthesis guided by the principles of meta-ethnography, which is a method for thematic synthesis of qualitative studies. RESULTS: Nine articles were included. The results of the synthesis identified two key themes. First, family members are intimately aware of changes in their relative's health and well-being. Sub-themes include family member awareness of different and progressive stages of the disease, noticing deterioration, noticing decline in functional abilities and recognizing that their relative will die. The second key theme is dilemmas of being involved in prognostication. Sub-themes include family member ambivalence toward hearing about prognostication, health professionals not being knowledgeable of the disease and family reluctance to receive palliative care. CONCLUSIONS: Family members monitor and recognize changes in their relative with PD, MND and MS and in themselves. Thus, drawing on the expertise of family members may be a useful tool for prognostication.

Zoonoses action plan Salmonella monitoring programme: an investigation of the sampling protocol.

The Zoonoses Action Plan (ZAP) Salmonella Programme was established by the British Pig Executive to monitor Salmonella prevalence in quality-assured British pigs at slaughter by testing a sample of pigs with a meat juice enzyme-linked immunosorbent assay for antibodies against group B and C(1) Salmonella. Farms were assigned a ZAP level (1 to 3) depending on the monitored prevalence, and ZAP 2 or 3 farms were required to act to reduce the prevalence. The ultimate goal was to reduce the risk of human salmonellosis attributable to British pork. A mathematical model has been developed to describe the ZAP sampling protocol. Results show that the probability of assigning a farm the correct ZAP level was high, except for farms that had a seroprevalence close to the cutoff points between different ZAP levels. Sensitivity analyses identified that the probability of assigning a farm to the correct ZAP level was dependent on the sensitivity and specificity of the test, the number of batches taken to slaughter each quarter, and the number of samples taken per batch. The variability of the predicted seroprevalence was reduced as the number of batches or samples increased and, away from the cutoff points, the probability of being assigned the correct ZAP level increased as the number of batches or samples increased. In summary, the model described here provided invaluable insight into the ZAP sampling protocol. Further work is required to understand the impact of the program for Salmonella infection in British pig farms and therefore on human health.

Preparation and evaluation of microspheres prepared from novel polyester-ibuprofen conjugates blended with non-conjugated ibuprofen.

A novel polyester, poly(glycerol-adipate-co-omega-pentadecalactone) (PGA-co-PL), was conjugated with a model drug, ibuprofen, through the free hydroxyl groups of the former and the free carboxyl group of the latter at various levels of substitution. The conjugated material was processed into microspheres by both emulsion solvent evaporation and spray-drying methods. Samples of conjugated material were also blended with non-conjugated drug and the microspheres produced were evaluated by various methods. Morphologically, the microspheres produced were satisfactory. However, there was some initial burst drug release from all samples, probably due to the presence of non-conjugated drug. Subsequent drug release was very slow due to the relative stability of the covalent bonding of the drug-polyester conjugate. Stability tests showed that storage at high relative humidity resulted in increased burst release.

A national facilitation project to improve primary palliative care: impact of the Gold Standards Framework on process and self-ratings of quality.

BACKGROUND: Improving quality of end-of-life care is a key driver of UK policy. The Gold Standards Framework (GSF) for Palliative Care aims to strengthen primary palliative care through facilitating implementation of systematic clinical and organisational processes. OBJECTIVES: To describe the general practices that participated in the GSF programme in 2003-5 and the changes in process and perception of quality that occurred in the year following entry into the programme, and to identify factors associated with the extent of change. METHODS: Participating practices completed a questionnaire at baseline and another approximately 12 months later. Data were derived from categorical questions about the implementation of 35 organisational and clinical processes, and self-rated assessments of quality, associated with palliative care provision. PARTICIPANTS: 1305 practices (total registered population almost 10 million). Follow-up questionnaire completed by 955 (73.2%) practices (after mean (SD) 12.8 (2.8) months; median 13 months). FINDINGS: Mean increase in total number of processes implemented (maximum = 35) was 9.6 (95% CI 9.0 to 10.2; p<0.001; baseline: 15.7 (SD 6.4), follow-up: 25.2 (SD 5.2)). Extent of change was largest for practices with low baseline scores. Aspects of process related to coordination and communication showed the greatest change. All dimensions of quality improved following GSF implementation; change was highest for the "quality of palliative care for cancer patients" and "confidence in assessing, recording and addressing the physical and psychosocial areas of patient care". CONCLUSION: Implementation of the GSF seems to have resulted in substantial improvements in process and quality of palliative care. Further research is required of the extent to which this has enhanced care (physical, practical and psychological outcomes) for patients and carers.

Synthesis and evaluation of novel polyester-ibuprofen conjugates for modified drug release.

Ibuprofen was conjugated at different levels to a novel polyester, poly(glycerol-adipate-co-omega-pentadecalactone) (PGA-co-PL), via an ester linkage to form a prodrug. The conjugates were characterized by differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), infrared (IR), gel permeation chromatography (GPC), ultraviolet (UV), and high-performance liquid chromatography (HPLC). The conjugates had a molecular weight between 18 and 24 kDa, and there was a suppression of the free hydroxyl groups within the conjugated polymer. DSC scans showed a lowering of the melting point (T(m)) when compared with the polyester alone and a difference in the number and area of T(m) peaks. Drug release studies showed an initial burst release (13-18%) followed thereafter by very slow release (maximum 35% after 18 days). Continuous work may produce ester-linked conjugates that are sufficiently labile to allow for complete release of ibuprofen over the time period studied.

Provision for advanced pain management techniques in adult palliative care: a national survey of anaesthetic pain specialists.

INTRODUCTION: It is estimated that 8% of cancer patients could benefit from advanced pain management techniques; some 12,000 patients per year in the UK. In 2002, Linklater et al. surveyed palliative medicine consultants to assess their access and attitude to such techniques, finding under-utilization with a lack of formal arrangements for referral. We report a survey of pain specialist anaesthetists on the same topic. METHOD: Postal questionnaire survey of lead anaesthetists in UK pain clinics. RESULTS: 106 responses were received from 170 questionnaires sent (62%). Referral rates from palliative medicine to pain clinics were low; only 31% of respondents received more than 12 per year. Joint consulting arrangements were rare, but were associated with more referrals. Only 25% of anaesthetists' job plans had time allocated for palliative medicine referrals, but where present this correlated positively with referrals received (P <0.002). Total interventions were estimated at less than 1000 per year. DISCUSSION: There is evidence of under-referral of patients for advanced pain management procedures with a lack of integrated services.

Evaluation of ibuprofen-loaded microspheres prepared from novel copolyesters.

The utility of two novel linear random copolyesters to encapsulate and control the release of ibuprofen, via microspheres, was investigated. Various manufacturing parameters, including temperature, disperse phase volume and polymer:ibuprofen ratios were altered during the microsphere production. The effects of these changes on the morphological characteristics of the microspheres, yield, drug loading, encapsulation efficiency and drug release rates were examined. The diameter of the microspheres ranged from 36 to 89 microm and showed both smooth and ridged surfaces. Microsphere diameter was probably determined by the internal phase volume, while surface morphology was controlled by manufacturing temperature. Greater encapsulation efficiency was obtained by increasing the polymer:ibuprofen ratio and by reducing the internal phase volume. For all batches there was an initial burst drug release into phosphate buffer (pH 7.4) over the first 2-4h, which was followed by a much slower release rate over the remaining time period. Drug release rates during both these phases were dependent upon the amount and nature of the polymer in the microspheres, noting that the more hydrophilic polymer provided faster release rates. Ibuprofen solubility appeared to play a dominant role in controlling release, although both encapsulation efficiency and microsphere morphology were also contributing factors.

Compressed xanthan and karaya gum matrices: hydration, erosion and drug release mechanisms.

Directly compressed matrices were produced containing either xanthan gum or karaya gum as a release-controlling agent. These swellable hydrophilic natural gums were used to control the release of varying proportions of two model drugs, caffeine and diclofenac sodium, which have different solubilities in aqueous medium. Gum erosion, hydration and drug release studies were carried out using a dissolution apparatus (basket method) at two agitation speeds. Xanthan gum displayed a high degree of swelling due to water uptake and a small degree of erosion due to polymer relaxation. Neither agitation speed nor drug solubility had any significant effect on water uptake, but matrices with the lower proportion of gum produced a lesser degree of hydration. In contrast, karaya gum displayed a much lower hydration capacity and a higher rate of erosion, both markedly affected by agitation speed. Drug release from xanthan and karaya gum matrices depended on agitation speed, solubility and proportion of drug. Both xanthan and karaya gums produced near zero order drug release with the erosion mechanism playing a dominant role, especially in karaya gum matrices.

Development and evaluation of a multiple-unit oral sustained release dosage form for S(+)-ibuprofen: preparation and release kinetics.

Mini-matrix tablets containing S(+)-ibuprofen have been prepared by the wet granulation method. The hydrophilic matrix was formed with either xanthan gum, karaya gum or hydroxymethylcellulose (HPMC) together with a choice of additives from lactose, Encompress(R), Avicel(R) PH101, talc and Lubritab(R). Multiple unit dosage forms (MUDFs) were subsequently obtained by encapsulating the mini-matrix tablets into hard gelatin capsules. Preparation, in vitro release profiles and release kinetics are presented.

Solvent influence on spray-dried biodegradable microspheres.

Microspheres of fixed poly(D,L-lactic acid) (PDLLA) composition--Resomer R104:R202H (30:70)--containing 20% w/w rifampicin have been spray-dried from a range of acetonic, halogenated, and solvent mixtures thereof under constant process conditions to examine the influence of solvent selection on microsphere characteristics. Solubility of the polymer composite in the studied solvents determined the kinetics of polymer deposition during drying. Viscosity studies provided an indirect index of solvent power in ascending order: acetone (ACT) < dichloromethane (DCM) < chloroform (CFM) < halothane (HAL). Accordingly, poorer acetonic solvents produced a more open, porous matrix of increased mean diameter, whereas DCM, CFM and HAL generated more coherent matrices of greater density and elevated glass transition temperature, which significantly retarded drug release. Yield generally increased in parallel with solvent strength and microsphere density consistent with the proposed generalized particle formation mechanism. Residual solvent also increased with particle density, both parameters being interrelated and dictated by the inherent affinity of the polymer composite for individual solvents. In turn, the position of glass transition temperature (Tg) and the quantity of associated polymer stress-relaxation were a direct function of amount and persistence of organic residue. The magnitude of these changes determined the relative rates and extents of microsphere ageing, as measured by drug release studies. In general, rate of drug release increased with Tg, after corrections were made for specific surface area (r2 = 0.963). Overall, solvent choice for spray-drying has a remarkable influence on microsphere characteristics and, accordingly, technological as well as toxicological considerations should be paid during selection of same.

Modulation of rifampicin release from spray-dried microspheres using combinations of poly-(DL-lactide).

Microspheres containing 20% w/w rifampicin (RIF) with smooth morphology have been readily prepared from combinations of low, R104 (Mw, 2000) and moderate, R202H (Mw, 9000), molecular weight poly(D,L-lactide) (PDLLA) as a means to modulate drug release from either polymer when used alone. These have been characterized with respect to their drug loading, granulometry, in vitro drug release and thermal behaviour. Particle size distributions were Gaussian, whereby mean microsphere diameter was found to increase from 2.11 to 2.98 microns as the proportion of more viscous R202H increased, whilst > 95% of particles were < 10 microns, irrespective of the polymer blend used. Use of a reduced inlet temperature for spray-drying gave uncharacteristically high production yields in the range of 55.8-80.7% for the process. Encapsulation efficiencies were quantitative with the weight proportion of drug co-dissolved (p < 0.05), yielding microspheres of high and predictable RIF loading. In vitro drug release revealed a dramatic shift in release profile between 40 and 60% R104. Closer examination in this range showed the predicted pattern of increased release rate as the fraction of more hydrophilic R104 increased. However, disproportionate differences were evident between 44 and 48% R104. From the apparent temperature dependent drug release, the criticality of matrix composition was attributed to the coincidence of matrix softening with the dissolution medium temperature and consequent hydration, which, at a finite composition, resulted in a controlled auto-hydration mechanism. Dramatic dependence of release rate with dissolution methodology was accountable to the fact that drug release was considerably quicker where microspheres remained suspended and individualized with the USP paddle method as opposed to aggregated with the shaking bath methodology. In conclusion, the utility of blending racemic PDLLA to modulate drug release and the convenience of spray-drying as a technique to produce microspheres of predictable character have been demonstrated. The temperature-dependent release exhibited may have application in the site-specific delivery of drugs where local increased biochemical activity promotes drug release in response to an increased pharmacological need.

A laparoscopic surgical training and accreditation program up and running.

Beginning in March 1997, a training and accreditation program in laparoscopic surgery was established at our hospital according to the training guidelines provided by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) (1, 2). Registrars were accredited upon satisfactory completion of supervised surgery at each training level. Consultants seeking clinical privileges in advanced laparoscopic surgery were asked to submit a formal application. By August 1998, 143 minor laparoscopic procedures had been formally assessed resulting in 8 of 9 registrars successfully completing training to level 2 laparoscopy. Thirty-three of 83 (39.8%) advanced laparoscopic procedures were directly supervised and an experienced laparoscopic surgeon was available, if required, for a further 15 procedures. Two consultants undertook additional supervised training before being granted full accreditation for level 3 laparoscopic procedures. Another 2 consultants have been given provisional accreditation for level 3 procedures. Although challenging, implementation of the RANZCOG guidelines on training and accreditation in laparoscopic surgery is quite possible. Greater efforts should be undertaken to establish these guidelines as the 'gold standard' for hospital accreditation committees.

Evaluation of biodegradable rifampicin-bearing microsphere formulations using a stability-indicating high-performance liquid chromatographic assay.

The validation of a rapid and selective stability-indicating high-performance liquid chromatographic procedure for the determination of rifampicin (RIF) and its decomposition products in aqueous solution is described. Direct injection and column switching HPLC procedures have been compared and, owing to the increased sensitivity and precision, the latter has been applied to the study of RIF stability in the presence of isoascorbic acid at pH 7.4. The time-dependent hydrolytic decomposition of RIF to 3-formyl rifamycin SV (RSV) was found to be biexponential. Log concentration versus time plots of RIF and RSV decomposition were found to be parallel, indicating a pseudo equilibrium decomposition process. This feature allowed corrections for the amounts lost to secondary reactions to be calculated when the assay was applied to the determination of release characteristics of RIF from biodegradable poly-d, l-lactide-co-glycolide microspheres.

Relationship between swelling, erosion and drug release in hydrophillic natural gum mini-matrix formulations.

The swelling, erosion and solvent front penetration properties of mini-matrices containing xanthan (X), locust bean (LB) and karaya (K) gums were examined, analysed and related to the overall in vitro release kinetics of diclofenac sodium, used as a model drug. Mini-matrices were produced with drug:gum ratios of 1:1 as well as formulations of drug and X in combinations of 2:1, 2:3 and 1:2. The rank order of decreasing swelling index (SI) in both axial and radial dimensions was X?K?LB and each gum showed almost Fickian swelling behaviour. The solvent front penetration rates were consistent with the rates of swelling. However, the order of decreasing drug release and erosion rates was LB>X>K and all formulations demonstrated anomalous (non-Fickian) drug release kinetics. Therefore Fickian drug diffusion and polymer erosion were both occurring simultaneously. The dominant mechanism depended on the nature and content of the gum, as well as the stage in the dissolution time period. There was a loss of matrix integrity in formulations containing a high drug:gum ratio.