Building capacity in primary care rehabilitation clinical practice guidelines: a South African initiative.

BACKGROUND: The large number of South Africans with disability who cannot access good quality rehabilitation presents a public health and human rights challenge. A cost-effective, efficient approach is required to address this. Implementation of high-quality, contextually relevant clinical practice guidelines (CPGs) could be a solution; however, this requires significant investment in innovative capacity-building. METHODS: A qualitative descriptive national study was conducted to explore the perspectives of South African stakeholders in rehabilitation, regarding CPG capacity-building. Twenty rehabilitation professionals (physiotherapists, occupational therapists, speech language therapists, podiatrists, rehabilitation managers or directors) were interviewed. Transcribed interview data were analysed using a deductive content analysis approach, mapping findings to an international capacity-building framework to produce new knowledge. RESULTS: Capacity-building is required in content, purpose and construction of locally relevant CPGs, as well as personal, workforce and systems capacity. Principles and strategies were derived to underpin implementation of CPGs that are user friendly, context specific, relevant to the needs of end-users, and achievable within available resources. Collaboration, networks and communication are required at national, provincial and regional level, within and between sectors. A central agency for CPG methods, writing, implementation and evaluation is indicated. CONCLUSION: South African rehabilitation can benefit from a multi-level CPG capacity-building focusing on performance, personal, workforce and systems issues.

Standardising evidence strength grading for recommendations from multiple clinical practice guidelines: a South African case study.

BACKGROUND: Significant resources are required to write de novo clinical practice guidelines (CPGs). There are many freely-available CPGs internationally, for many health conditions. Developing countries rarely have the resources for de novo CPGs, and there could be efficiencies in using CPGs developed elsewhere. This paper outlines a novel process developed and tested in a resource-constrained country (South Africa) to synthesise findings from multiple international CPGs on allied health (AH) stroke rehabilitation. METHODS: Methodologists, policy-makers, content experts and consumers collaborated to describe the pathway of an 'average' stroke patient through the South African public healthcare system and pose questions about best-practice stroke rehabilitation along this pathway. A comprehensive search identified international guidance documents published since January 2010. These were scanned for relevance to the South African AH stroke rehabilitation questions and critically appraised for methodological quality. Recommendations were extracted from guidance documents for each question. Strength of the body of evidence (SoBE) gradings underpinning recommendations were standardised, and composite recommendations were developed using qualitative synthesis. An algorithm was developed to guide assignment of overall SoBE gradings to composite recommendations. RESULTS: Sixteen CPGs were identified, and all were included, as they answered different project questions differently. Methodological quality varied and was unrelated to currency. Seven clusters, outlining 20 composite recommendations were proposed (organise for best practice rehabilitation, operationalise strategies for best practice communication throughout the patient journey, admit to an acute hospital, refer to inpatient rehabilitation, action inpatient rehabilitation, discharge from inpatient rehabilitation and longer-term community-based rehabilitation). CONCLUSION: The methodological development process, tested by writing a South African AH stroke rehabilitation guideline from existing evidence sources, took 9 months. The process was efficient, collaborative, effective, rewarding and positive. Using the proposed methods, similar synthesis of existing evidence could be conducted in shorter time periods, in other resource-constrained countries, avoiding the need for expensive and time-consuming de novo CPG development.

South African primary health care allied health clinical practice guidelines: the big picture.

BACKGROUND: Good quality clinical practice guidelines (CPGs) are a vehicle to implementing evidence into allied health (AH) care. This paper reports on the current 'state of play' of CPGs in a lower-to-middle-income country (South Africa), where primary healthcare (PHC) AH activities face significant challenges in terms of ensuring quality service delivery in the face of huge PHC need. METHODS: A qualitative study was conducted, using semi-structured interviews with purposively-sampled individuals involved in AH PHC CPGs in South Africa. They included national and state government policy-makers, academics and educators, service managers, clinicians, representatives of professional associations, technical writers, and members of informal professional networks. The interview data was transcribed and de-identified, and analysed descriptively by hand-coding. The COREQ statement guided study conduct and reporting. A framework to guide research in other countries into perspectives of AH PHC CPG activities was established. RESULTS: Of the 32 invited, 29 people participated: of these 25 were interviewed and four provided meeting notes. Most participants had multiple professional roles, being engaged concurrently in clinical practice, academia, professional associations and / or government. Key themes comprised Players (sub-themes of sampling frame, participants, advice, role players and collaboration); Guidance (sub-themes of nomenclature, drivers, purpose, evidence sources) and Role of AH in PHC (sub-themes of discipline groupings, disability and rehabilitation, AH recognition). CONCLUSION: There was consistently-expressed desire for quality guidance to support better quality AH PHC activities around the country. However no international CPGs were used, and there were no South African CPGs specific to local PHC AH practice. The guidance gap was filled by non-evidence-based documents produced often without training, to deal with specific clinical situations. This led to frustration, duplication and fragmentation of effort, confusing nomenclature, and an urgent need for standardised and agreed guidance. We provided a standardised framework to capture perspectives on CPGs activities in other AH PHC settings.

Building capacity for development and implementation of clinical practice guidelines.

Robust, reliable and transparent methodologies are necessary to ensure that clinical practice guidelines (CPGs) meet international criteria. In South Africa (SA) and other low- and middle-income countries, upskilling and training of individuals in the processes of CPG development is needed. Since de novo CPG development is time-consuming and expensive, new emerging CPG-development approaches (adopting, contextualising, adapting and updating existing good-quality CPGs) are potentially more appropriate for our context. These emerging CPG-development methods are either not included or sparsely covered in existing training opportunities. The SA Guidelines Excellence (SAGE) team has responded innovatively to the need for CPG training in SA. We have revised an existing SA course and developed an online, open-access CPG-development toolkit. This Guideline Toolkit is a comprehensive guideline resource designed to assist individuals who are interested in knowing how to develop CPGs. Findings from the SAGE project can now be implemented with this innovative CPG training programme. This level of CPG capacity development has the potential to influence CPG knowledge, development, practices and uptake by clinicians, managers, academics and policy-makers around the country.

Barriers and enablers for the development and implementation of allied health clinical practice guidelines in South African primary healthcare settings: a qualitative study.

BACKGROUND: The South African allied health (AH) primary healthcare (PHC) workforce is challenged with the complex rehabilitation needs of escalating patient numbers. The application of evidence-based care using clinical practice guidelines (CPGs) is one way to make efficient and effective use of resources. Although CPGs are common for AH in high-income countries, there is limited understanding of how to do this in low- to middle-income countries. This paper describes barriers and enablers for AH CPG uptake in South African PHC. METHODS: Semi-structured individual interviews were undertaken with 25 South African AH managers, policymakers, clinicians and academics to explore perspectives on CPGs. Interviews were conducted by researcher dyads, one being familiar with South African AH PHC practice and the other with CPG expertise. Rigour and transparency of data collection was ensured. Interview transcripts were analysed by structuring content into codes, categories and themes. Exemplar quotations were extracted to support themes. RESULTS: CPGs were generally perceived to be relevant to assist AH providers to address the challenges of consistently providing evidence-based care in South African PHC settings. CPGs were considered to be tools for managing clinical, social and economic complexities of AH PHC practice, particularly if CPG recommendations were contextusalised. CPG uptake was one way to deal with increasing pressures to make efficient use of scarce financial resources, and to demonstrate professional legitimacy. Themes comprised organisational infrastructures and capacities for CPG uptake, interactions between AH actors and interaction with broader political structures, the nature of AH evidence in CPGs, and effectively implementing CPGs into practice. CONCLUSION: CPGs contextualised to local circumstances offer South African PHC AH services with an efficient vehicle for putting evidence into practice. There are challenges to doing this, related to local barriers such as geography, AH training, workforce availability, scarce resources, an escalating number of patients requiring complex rehabilitation, and local knowledge. Concerted attempts to implement locally relevant CPGs for AH primary care in South Africa are required to improve widespread commitment to evidence-based care, as well as to plan efficient and effective service delivery models.

South African Guidelines Excellence (SAGE): Adopt, adapt, or contextualise?

Clinical practice guideline (CPG) activities must be planned carefully for efficient use of available resources and evidence-based implementation. De novo development of CPGs may sometimes 'recreate the wheel' and delay implementation. Three innovative alternatives to de novo CPG development (adopt, contextualise or adapt) are outlined, which have greater potential than de novo development to best use the limited available resources, personnel and time in settings such as South Africa.

Enalaprilat attenuates ischemic rises in intracellular sodium in the isolated rat heart via the bradykinin receptor.

PURPOSE: Angiotensin-converting enzyme (ACE) inhibitors have been shown to have beneficial effects on ischemic myocardium. We examined whether the ACE inhibitor, enalaprilat (EN), improves intracellular sodium homeostasis during myocardial ischemia and the relationship of this effect to bradykinin. METHODS: EN (3.2 nM) was administered to isolated rat hearts that were subjected to ischemia and reperfusion. Intracellular sodium and pH were monitored using magnetic resonance spectroscopy (MRS). The specific bradykinin B2 receptor antagonist, HOE 140 (10 nM), was administered with EN in some hearts to determine the effect of bradykinin blockade on EN-mediated effects. RESULTS: EN blunted the rise in ischemic intracellular sodium, measured using MRS. With reperfusion, EN-treated hearts recovered 80% of their preischemic ventricular function, compared with negligible recover, in controls. These beneficial effects of EN were blocked when the bradykinin receptor antagonist, HOE 140, was coadministered with EN. HOE 140 also blocked EN-mediated attenuation of ischemic intracellular acidosis. CONCLUSIONS: These results suggest that EN exerts beneficial effects on ischemic intracellular sodium and pH homeostasis via the bradykinin receptor. These effects of EN may provide a mechanism for the beneficial actions of this agent during ischemia.

Evaluation of multiple-quantum-filtered 23Na NMR in monitoring intracellular Na content in the isolated perfused rat heart in the absence of a chemical-shift reagent.

The feasibility of employing triple-quantum-filtered (TQF) or double-quantum-filtered (DQF) 23Na NMR spectra to monitor intracellular Na (Nain) content in isolated rat hearts perfused in the absence of a chemical-shift reagent (SR) was investigated. This necessitated characterization of the following: first, the pool of Nain represented by the intracellular TQF (TQFin) spectrum; second, the maximum extent to which altered transverse relaxation times affect TQFin spectral amplitudes; and finally, the situations for which the SR-free method can reliably be applied. The rates of increase in peak amplitudes of both intracellular TQF spectra, adjusted for changes in both fast (T2f) and slow (T2s) transverse relaxation times, and intracellular single-quantum (SQin) spectra were identical during no-flow ischemia, indicating that TQFin and SQin spectra represent the same Nain population. Addition of an Na/K ATPase inhibitor, ouabain (>/=500 microM), and no-flow ischemia induced similar rates of increase of Nain content. However, the Nain level for which the T2 values started to increase was lower for ischemic (<140% of preischemic values) than for ouabain-exposed (>165%) hearts, which is consistent with the known earlier onset of intracellular swelling in ischemic hearts. Exposure of hearts to hyperosmotic perfusate (200 mM sucrose) increased [Nain], due to a decreased cell volume and an unchanged Nain content, but caused a decrease in T2 values, a trend opposite to that observed with exposure of hearts to ouabain or ischemia. T2 values therefore consistently correlated only with cell volume, not with Nain content or concentration, indicating an important role for intracellular macromolecule concentration in modulating transverse relaxation behavior. The combined effect of ischemia-induced increases in T2 values and their inhomogeneous broadened forms was an approximately 6% overestimation of Nain content from amplitudes of SR-aided TQFin spectra, indicating negligible effect of transverse relaxation-dependent alterations on TQFin spectral amplitudes. Thus, Nain content may be reliably determined from SR-free TQF spectra when the contribution from extracellular Na does not appreciably vary, such as during constant pressure perfusion. Following complete reduction in perfusion pressure, both SR-free TQF and DQF spectra respond to increases in Nain content. However, SR-free DQF NMR provides an estimate of Nain content much closer to that provided by the SR-aided method, due to the appreciable decrease of the extracellular DQF signal resulting from destructive interference between second- and third-rank tensors.

Evaluation of triple-quantum-filtered 23Na NMR in monitoring of Intracellular Na content in the perfused rat heart: comparison of intra- and extracellular transverse relaxation and spectral amplitudes.

Multiple-quantum filtered (MQF) NMR offers the possibility of monitoring intracellular (IC) Na content in the absence of shift reagents (SR), provided that (i) the contribution from IC Na to the MQF spectrum is substantial and responds to a change in IC Na content, and (ii) the amplitude of the extracellular (EC) MQF component remains constant during a change in IC Na content. The validity and basis for these conditions were examined in isolated perfused rat hearts using SR-aided and SR-free triple-quantum filtered (TQF) 23NaNMR. Despite a myocardial Na content that was only approximately 1/70 that of EC Na. IC Na contributed to over 25% of the total TQF spectrum acquired in the absence of SR. Transverse relaxation times (T2) were approximately twice as long for EC compared to IC Na, despite SR-induced relaxation of T2 for the former pool. However, the efficiency of generation of the TQF signal was similar for IC and EC Na, indicating that a much greater percentage of IC relative to EC Na exhibits TQ coherence. During constant perfusion with ouabain (0.2 mM for 25 min) or with a hypoxic and aglycemic solution (50 min), the amplitude of the IC TQF spectrum increased by approximately 330% and -280%, respectively. In contrast, the amplitude of the EC TQF spectra remained essentially constant for both interventions. The amplitude for IC Na increased approximately 250% relative to baseline during no-flow ischemia (60 min), whereas the amplitude of the EC TQF spectra decreased by approximately 33% before stabilizing. In SR-free experiments, the TQF spectral amplitude increased approximately 2-fold during the constant perfusion interventions, but did not change significantly during no-flow ischemia. These data suggest that the change in the TQF spectral amplitude during constant perfusion interventions is from IC Na, and that TQF techniques in the absence of SR may be useful in monitoring IC Na during these interventions. The fall in the amplitude of the EC TQF spectral amplitude during no-flow ischemia complicates the use of TQF techniques without SR during this intervention.

NMR measurements of in vivo myocardial glycogen metabolism.

Using 13C and 1H NMR we measured the rate of glycogen synthesis (0.23 +/- 0.10 mumol/min gram wet weight tissue (gww) in rat heart in vivo during an intravenous infusion of D-[1-13C]glucose and insulin. Glycogen was observed within 10 min of starting and increased linearly throughout a 50-min infusion. This compared closely with the average activity of glycogen synthase I (0.22 +/- 0.03 mumol/min gww) measured at physiologic concentrations of UDP-glucose (92 microM) and glucose-6-phosphate (110 microM). When unlabeled glycogen replaced D-[1-13C]glucose in the infusate after 50 min the D-[1-13C]glycogen signal remained stable for another 60 min, indicating that no turnover of the newly synthesized glycogen had occurred. Despite this phosphorylase a activity in heart extracts from rats given a 1 h glucose and insulin infusion (3.8 +/- 2.4 mumol/min gww) greatly exceeded the total synthase activity and if active in vivo should promote glycogenolysis. We conclude that during glucose and insulin infusion in the rat: (a) the absolute rate of myocardial glycogen synthesis can be measured in vivo by NMR; (b) glycogen synthase I can account for the observed rates of heart glycogen synthesis; (c) there is no futile cycling of glucose in and out of heart glycogen; and (d) the activity of phosphorylase a measured in tissue extracts is not reflected in vivo. These studies raise the question whether significant regulation of phosphorylase a activity in vivo is mediated by factors in addition to its phosphorylation state.