Chapter 6: Conclusion and recommendations
6.1 Overview of key findings
Prior to our study, no study had been conducted to determine a robust estimate of the global prevalence of PLP. Therefore, we aimed to address the gap in the literature by conducting a systematic-review and meta-analysis including 37 studies (39 data sets) with a total of 12738 participants from various global regions. The pooling of all studies using the random-effects model revealed a prevalence estimate of 64% [95%CI: 60.0 – 68.1]. This high prevalence estimate, in conjunction with the narrow confidence interval suggests that six out of 10 people with amputations globally are experiencing PLP.
We were also interested in determining if the prevalence of PLP differs significantly amongst people with amputations living in developed countries versus those living in developing countries. The subgroup analyses stratified by the developmental status of the countries in which the studies were conducted revealed an estimated pooled prevalence of 67% [95% CI: 62.0 –71.6] in developed countries and 54% [95% CI: 44.8–63.1] in developing countries, with a significantly lower prevalence rate in developing countries [U = 57, p = 0.03]. While the aim of this research was not to determine the reasons for such a significant difference, we hypothesised that the lower prevalence estimates in developing countries may be attributed to, among other reasons, a low number of studies
conducted in developing countries. This was mostly notable when we could not find any study determining the prevalence of PLP in an African population.
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Our exploratory analysis of the risk factors for PLP revealed several risk factors that were consistently positively associated with PLP. These risk factors included having a lower limb amputation, residual limb pain, non-painful phantom sensations, persistent pre-amputation pain, proximal site of amputation, and diabetic cause of amputation were grouped into pre-operative, peri-operative, and post-operative domains. From amongst these important risk factors, persistent pre-amputation pain and residual limb pain play a crucial role in the initiation and maintenance of pain, respectively. Further, these predictors for PLP are modifiable and could be used as targets for treatment in the prevention or management of PLP.
In consideration of the paucity of research investigating the prevalence of and risk factors for PLP in African populations, we conducted a cross-sectional study aiming to determine the PLP prevalence and risk factors for PLP in people who have undergone limb amputations at GSH. The study included 106 participants [male (n=66); female (n=40)] with lower limb amputations and a median [IQR] age of 59 [53 – 67]. Data were analysed using 129 amputation cases because 23 participants had double amputations. The overall prevalence of PLP during the week preceding data collection was 51% [95%
CI: 41.8 – 59.7]. This prevalence estimate is in keeping with the results of the meta-analysis of PLP prevalence studies conducted in developing countries (Chapter 2). Likewise, pre-amputation pain was identified as a predictor for PLP, thus confirming its significant role in the onset of PLP in people with amputations. The high burden of PLP raises the need for strengthening strategies for creating awareness on PLP and associated complications, and for developing guidelines for effective patient- centred management.
The current NICE guidelines for the management of PLP may not be appropriate because
pharmacological treatments included in these guidelines are no more effective than placebo. In fact, there is level 1 evidence that recommended pharmacological treatments are ineffective: memantine (30mg/day for 4 days), gabapentin (2.4g/day for 6 weeks) and amitriptyline (10 - 125mg/day for 6 weeks) showed no benefit over placebo (23). The weak evidence for pharmacological treatments
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and the inability to conduct meta-analyses for non-pharmacological interventions (due to use of varying treatment protocols and study methodologies) meant that consensus on the best
management of PLP had to be generated using an alternative approach. Therefore, we conducted a Delphi study aiming to reach expert consensus and make recommendations on effective treatments for PLP in people with limb amputations. Twenty experts who completed the study were
anaesthesiologists (n=3), physiatrists (n=3), psychologists (n=2), neurologists (n=2), physiotherapists (n=8), nurse (n=1) and occupational therapist (n=1). Fifteen of these, described themselves as clinician-researchers, three described themselves as full-time researchers and two described themselves as full-time clinicians. Consensus was reached on seven treatments [non-
pharmacological (n=6); pharmacological (n=1)] that were considered effective for managing PLP, and on two treatments [citalopram (60%) and PRFS of the dorsal root ganglion (70%)] that were
considered ineffective because of a lack of scientific evidence supporting their efficacy in people with PLP. Graded Motor Imagery, mirror therapy and amitriptyline were endorsed by most experts because of the available supporting scientific evidence and their reported efficacy in clinical practice.
Cognitive Behavioural Therapy, virtual reality training and use of a functional prosthesis were endorsed by most experts because of their reported efficacy in clinical practice, even though there is essentially no scientific evidence supporting the use of these treatments for PLP. The findings of this study indicate the important role for non-pharmacological interventions in the effective
management of PLP. In addition, they raise a need for research to develop evidence for treatments that were endorsed for their efficacy in clinical practice. Further, the various treatments endorsed in this study indicate the importance of managing PLP using an interdisciplinary approach addressing the biopsychosocial determinants of pain.
The current treatment guidelines for the management of people with LLAs were formulated with the contribution of health care professionals only, who may not always prioritise the elements of care that are important to the patient at a specific time-point.
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The growing evidence indicates that patients may not receive the treatment they need or want as a result of not being involved in clinical decision-making. To address a mismatch in patient-healthcare provider care priorities, we conducted a final study with the aim of generating patient consensus on care priorities for people with LLAs during the first year and treatment priorities after the first year.
In addition, we aimed to gather rationales for endorsing each of the proposed care priorities. In this study, we included 20 participants [Male (n=16); Female (n=4)] with a median [IQR] age of 65.5 [50 – 71]. All the participants had lower limb amputations and had undergone amputation a median of 16 [11.5 – 31] months at the time of recruitment. The indications for amputations were complications due to uncontrolled diabetes, peripheral vascular diseases, infection, and trauma. According to our knowledge, this is the first study on patient-generated care priorities for people with LLAs. In this study, consensus was reached on 24 short-term care priorities (first year) [biomedical (n=8);
psychological (n=8); practical (n=8)] and 12 long-term care priorities [biomedical (n=2); psychological (n=4); practical (n=6)]. The analysis of qualitative data on the rationales for endorsing the care priorities generated three themes: (1) preparedness, (2) mental health, and psychological and spiritual well-being, and (3) participating in life, with respect and dignity like everyone else. The consensus among the participants was that pre-amputation they wanted education support to help them manage their expectations and prepare for life after amputation. In the early stage after amputation, they wanted help with dealing with the psychological trauma of having lost a limb. In the long-term, however, the participants prioritised the need for living a functional and normal life, with respect and dignity like everyone else.
The four related studies enhance our understanding of the burden of PLP, expert recommendations on the best management of PLP, and patient-generated short- and long-term care priorities for people with LLAs.
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