Since the global financial crisis, UK NHS spending has reduced considerably. Respiratory care is a large cost driver for Betsi Cadwaladr University Health Board, the largest health board in Wales. Under the remit of ‘prudent healthcare’ championed by the Welsh Health Minister, a Programme Budgeting Marginal Analysis (PBMA) of the North Wales respiratory care pathway was conducted.A PBMA panel of directors of medicines management, therapies finance, planning, public health and healthcare professionals used electronic voting to establish criteria for decision-making and vote on candidate interventions in which to disinvest and invest.A sum of £86.9 million was spent on respiratory care in 2012–13. Following extensive discussion of 13 proposed candidate interventions facilitated by a chairperson, 4 candidates received recommendations to disinvest, 7 to invest and 2 to maintain current activity. Marginal analysis prioritized mucolytics and high antibiotic prescribing as areas for disinvestment, and medicines waste management and pulmonary rehabilitation for investment.This exercise demonstrates the potential for health boards to use evidence-based approaches to reach potentially controversial disinvestment and investment decisions. Initial progress has begun with communication from the Medical Director in relation to the disinvestment in mucolytics prescribing and possible redirection of funding options being explored. At this time of culture shift in the NHS in Wales, the Health Minister for Wales, Professor Mark Drakeford, has called 2014 the ‘Year of prudent healthcare’. He has described prudent healthcare as: ‘healthcare that fits the needs and circumstances of patients and actively avoids wasteful care that is not to the patients benefit’.4 It is evitable that ministers face difficult decisions regarding healthcare spending and resources. As part of ‘prudent healthcare’ in Wales, this paper describes Programme Budgeting and Marginal Analysis (PBMA) as an approach to make resource allocation decisions that impact the respiratory care pathway in Betsi Cadwaladr University Health Board (BCUHB), the largest health board in Wales.Since the global financial crisis, NHS spending in the UK has been cut per year by 0.4% on average, leading to a decrease in NHS spending of 7.3% as a percentage of gross domestic product.5 PBMA has eight stages: choose a set of meaningful programmes; identify current activity and expenditure in those programmes; think of improvements; weigh up incremental costs and incremental benefits and prioritize a list; consult widely; decide on changes; effect the changes and evaluate progress.5PBMA is a framework that helps decision-makers to reallocate resources so that benefits are maximized.et al.6 PBMA has been used previously as an approach to make resource reallocation decisions in healthcare settings.10 Bolaji11 using PBMA in Lincolnshire UK to assess chronic obstructive pulmonary disease (COPD) and asthma pathways identified disinvestment opportunities, including medicines management and inappropriate access to oxygen therapy. The process also identified investment areas including, tobacco control, non-invasive ventilation and a new pulmonary rehabilitation programme with a focus on patient education. Below, we describe applying PBMA to the respiratory care pathway at BCUHB.The role of PBMA as a framework for rational disinvestment has been championed by Donaldson A PBMA operational group composed of a chairperson, BCUHB finance staff, BCUHB and Public Health Wales staff with an interest in respiratory care and health economists with previous experience conducting PBMA exercises. This operational group oversaw the running of the PBMA exercise as a whole, gathering evidence on proposed candidates, arranging meetings and inviting staff to establish the PBMA panel.12 However, we developed new methods during this exercise; these methods are described in more detail below.Members of the operational group had previous experience undertaking PBMA exercises.The PBMA panel are responsible for making the investment and disinvestment recommendations. For this particular PBMA exercise, we took advice from the Executive Director of Public Health of BCUHB and a project team of BCUHB staff who had undertaken previous work examining the pathway as to whom to invite to the PBMA panel. A PBMA panel was established with representation invited from clinicians (primary and secondary care), nursing staff (primary and secondary care), budget holding healthcare managers , finance, service users and business support. The panel were invited to take part in the PBMA exercise via e-mail and as their participation was voluntary they were informed they could withdraw their participation from the process at any time. As the exercise was instigated from BCHUB with sponsorship from the Executive Director of Public Health, ethic approval was not required.The panel met on three occasions between February and June 2014. Meetings were held in accessible locations to minimize travel as much as possible. Video conferencing was also provided at all meetings. These meetings outlined the process, the panel's roles and responsibilities, established and discussed criteria for decision-making and provided an opportunity to discuss and vote on candidate interventions in which to disinvest and invest. A description of what happened during each meeting is described in Fig. BCUHB finance staff were asked to provide detail of the 2012–13 spend on respiratory care in BCUHB. Finance staff were also asked to describe this spend in terms of the split between primary and secondary care and spend per head.12 the panel members were encouraged to submit candidates based on their views or experiences via a pro forma sheet . This pro forma detailed the types of information required for each candidate and provided an example to ensure the submitted candidates had the same degree of information for ease of comparability and the respondents understood the type and level of information required. As clinicians were involved in the process, we were concerned some would view the pro forma as a time-consuming task; therefore, we decided to improve engagement further by using a third and final approach. An online Survey Monkey questionnaire was created, which divided the pro forma into separate questions. The link to this survey was distributed to all invited panel members who were also asked to forward it onto anyone else who wished to contribute. We asked for wider distribution to increase our chances of developing a broad range of candidates for resource reallocation as part of this consultation exercise.Candidate interventions for resource reallocation were generated by asking for opinions from staff and managers about what they felt worked or did not work in the pathway based on their knowledge and experiences. Candidate interventions were developed through three approaches. First, by initial work conducted by the respiratory project team at BCUHB who critically appraised the pathway, looking to evidence, guidance and other healthcare systems for ways to improve the pathway. Second, based on previous experience,Supplementary data, Additional File 2 for an example of the evidence booklet presented to panel members). The evidence booklet contained a description of the proposed candidate; the life course stage the candidate related to; the current spend on this candidate (if the candidate was a service or programme currently conducted by BCUHB), its evidence; potential risks; likely impacts  and additional notes for example, relevant reports or points to consider. The booklet was sent to all panel members 2 weeks prior to the final meeting.For each candidate, a rapid review of national guidance included guidance from NICE, British Thoracic Society, IMPRESS and the Cochrane Library of Systematic Reviews. Local guidelines for BCUHB were also used as an evidence source. Where there was limited or no guidance available, a search using key terms for each candidate was conducted using the OVID health database. BCUHB finance staff who were part of the PBMA operational group were also asked to provide information on the potential cost-savings from proposed candidate interventions, where possible, to allow the panel to consider the concept of opportunity cost when appraising the candidate interventions. Opportunity cost is the value of benefits foregone by not using resources in their next best alternative use. All evidence was summarized in an evidence booklet .12During the first PBMA session, the 16 panel members who were in attendance were presented with the following criteria: evidence of cost-effectiveness; evidence of clinical effectiveness; evidence of impact for reducing inequalities in health; patient views and local experts  opinions and views. These criteria were developed by the operational group based on previous PBMA exercises.n = 5), cost-effectiveness (n = 8) and impact on reducing health inequalities (n = 3) were the most important. The panel were asked whether they wished to suggest any further criteria. The panel suggested one other criterion of effecting changes that were relatively simple and easy to implement so they could be done quickly.Results from an electronic voting exercise demonstrated the panel felt that evidence of clinical effectiveness , 13 proposed candidate interventions were generated for discussion by the panel. Each candidate was an individual proposal for resource reallocation, ranging from specific interventions (e.g. pulmonary rehabilitation), to cross agency partnership and working .Based upon the three approaches of candidate generation , a list of 13 candidate interventions was generated. During the final PBMA session, the panel discussed each of the 13 candidate interventions in turn, and voted upon whether to maintain current activity or to seek alternatives by investing or disinvesting in the candidate intervention. At this final session, the panel unfortunately did not have representation from primary care clinicians or patients. However, the panel had representation from medical consultants, nursing staff, pharmacy, public health, informatics support, managers including chiefs of staff and executives. A summary of the discussion and results from the electronic voting by the 13 panel members is presented in Table The panel were asked to rank in order their top priority to their lowest priority for candidates they stated they wished to invest in. The exercise was then repeated for the candidates the panel stated they wished to disinvest in. During the task, the panel prioritized mucolytics and high-cost antibiotic prescribing as areas for disinvestment, and medicine waste management and pulmonary rehabilitation for investment. The results of the disinvestment ranking exercises are presented in Fig. This study demonstrates the PBMA framework can be used at a local health board level to make resource reallocation decisions. It also demonstrates the need to adapt techniques to find an appropriate way for panel members to fully engage with the process, in this case using online platforms to connect with clinicians whose time is extremely limited. The recommendations made by the panel were forwarded to the Medical Director of BCUHB as part of discussions of how to improve the respiratory care pathway. Initial progress has already begun, with communication from the Medical Director in relation to the disinvestment in mucolytics prescribing and redirection of funding options being explored, for example investment in pulmonary rehabilitation. Through informal discussion the panel stated they viewed, this PBMA exercise as a transparent, evidence-based decision-making tool for BCUHB. BCUHB saw the exercise presented here as a demonstration exercise, allowing the health board to explore the impact, usefulness and commitment regarding staff time and input required to employ a PBMA approach. Following the recommendations of the respiratory care pathway PBMA, BCUHB is considering the use for the PBMA framework across the health board.10 and has been applied to a national health improvement budget, containing multiple activities.12 This PBMA exercise, mirrored certain findings from Bolaji,11 recommending medicine waste management and pulmonary rehabilitation as areas for investment.The PBMA framework has been shown to work across a range of healthcare settings12 this exercise required different skills and engagement techniques, with particular emphasis on communication. We would argue that undertaking this type of exercise in a rural area is perhaps more difficult than in an urban area. This is mainly attributed to geographical spread and inconvenience of travelling to face-to-face meetings. We found adapting the pro forma into a Survey Monkey questionnaire the most fruitful approach to generate candidates for resource reallocation, in particular with gaining opinions from clinicians and nurses.This paper demonstrates how the PBMA framework can be applied successfully by a local health board at a micro-level to appraise a specific care pathway, in a challenging rural setting, with co-operation from a range of staff. Though members of the operational group had undertaken PBMA previously,For others wishing to apply PBMA in their local setting, the authors based on their experience offer the following advice, first ensure high-level sponsorship for the exercise (e.g. from directors or managers). This will help stakeholders and potential panel members engage with the exercise in the first place and may improve momentum in the form of retaining membership throughout the exercise, compared with an unsponsored exercise. Second, be flexible in how you initially engage with your panel, use all forms of communication to facilitate discussion and gather opinions. Third, endeavour to gain membership in the PBMA operational group from finance staff. Finance staff are particularly important in quantifying what changes to resource allocation could mean to the setting  in terms of potential cost-savings or investment required in order to effect changes. This information is vital in order to help panel members consider the concept of opportunity cost when appraising the candidates. Resource reallocation decisions will often be made against the backdrop of constrained or shrinking budgets; therefore, panel members need to understand that placing resources into one service, could mean taking resources away from another. Fourth, present evidence gathered on each of the candidates, pathway or components of a service in a consistent and accessible way. Evidence should be presented consistently, if you have used set categories to relay information for one candidate, pathway or component, then these categories should be repeated and populated for all candidates, pathways or components. If evidence is unavailable for one of the set categories, be transparent and explicitly state the evidence is not available. Finally, endeavour to gain opinions and recommendations to invest or disinvest through anonymized communication such as anonymous electronic voting handsets. This will reduce the risk of bandwagon voting. It will also allow panel members to express their own opinion without being influenced by others, especially if a panel member's line manager is also a member of the same PBMA panel.Clinical engagement was an issue throughout the process due to senior clinical commitments. We tried a number of strategies to reduce this limitation by alternating the location of the sessions to give equal representation to each of the three sites within the health board, provided video-conferencing facilities at every meeting and developed an online survey for invited panel members to propose ideas for resource re-allocation. Despite the best efforts of the operational group, there was no representation from primary care staff or patients at the final PBMA session when the panel were discussing and voting on the 13 proposed candidate interventions. Patient representation was an issue throughout the process and despite the best efforts of the operational group by contacting multiple patient representation groups and liaisons, we were unable to find a patient to be a panel member. The lack of primary care and patient input during discussion is a limitation of the process and could provide lessons for other health boards that plan on conducting similar PBMA exercises.The use of PBMA has significance in times of austerity when frameworks are needed to manage spending and provide a way forward. PBMA uses evidence and incorporates engagement with staff and service users on whom the recommendations from the process will ultimately effect. Against a backdrop of constrained and shrinking healthcare budgets, PBMA offers an evidence-based, transparent framework to make healthcare resource reallocation decisions. This process can be applied at a micro-level to explore a particular pathway and/or in a local setting as demonstrated by the exercise described. PBMA can also be applied at a macro-level exploring an entire service or national budget encompassing multiple activities.A.J. chaired the PBMA sessions, facilitating the discussion, introducing the topics to be discussed and keeping the sessions to time. G.B., K.T. and F.J. provided clinical evidence for the proposed candidates presented to the panel and were present at the sessions to answer any specific questions related to the clinical evidence. V.V. and B.P. provided the budget information of respiratory care and financial evidence for the proposed candidate used in the PBMA exercise. V.V. and B.P. were also present at all sessions to answer any questions about the programme budget. J.M.C. and R.T.E. provided health economics expertise, and economic evidence for the evidence booklet. J.M.C. and R.T.E. provided procedural guidance on how to conduct a PBMA exercise based on their previous experiences applying the PBMA framework. J.M.C. also developed and conducted the electronic vote. G.B. and J.M.C. created the evidence pro forma and adapted the pro forma into an online questionnaire. All authors have contributed to and approved the final version of the manuscript for publication.PUBMED online.Supplementary Material is available at A.J., F.J., V.V. and B.P. are employed by Betsi Cadwaladr University Health Board, though received no specific funding to conduct this PBMA exercise. G.B. and K.T. are employed by Public Health Wales, though received no specific funding to conduct this PBMA exercise. J.C. and R.T.E. are employed by Bangor University and are also consultant health economists for Public Health Wales, though received no additional funding for providing expertise to this PBMA exercise.


Musculoskeletal pain, the most common cause of disability globally, is most frequently managed in primary care. People with musculoskeletal pain in different body regions share similar characteristics, prognosis, and may respond to similar treatments. This overview aims to summarise current best evidence on currently available treatment options for the five most common musculoskeletal pain presentations  in primary care.A systematic search was conducted. Initial searches identified clinical guidelines, clinical pathways and systematic reviews. Additional searches found recently published trials and those addressing gaps in the evidence base. Data on study populations, interventions, and outcomes of intervention on pain and function were extracted. Quality of systematic reviews was assessed using AMSTAR, and strength of evidence rated using a modified GRADE approach.Moderate to strong evidence suggests that exercise therapy and psychosocial interventions are effective for relieving pain and improving function for musculoskeletal pain. NSAIDs and opioids reduce pain in the short-term, but the effect size is modest and the potential for adverse effects need careful consideration. Corticosteroid injections were found to be beneficial for short-term pain relief among patients with knee and shoulder pain. However, current evidence remains equivocal on optimal dose, intensity and frequency, or mode of application for most treatment options.This review presents a comprehensive summary and critical assessment of current evidence for the treatment of pain presentations in primary care. The evidence synthesis of interventions for common musculoskeletal pain presentations shows moderate-strong evidence for exercise therapy and psychosocial interventions, with short-term benefits only from pharmacological treatments. Future research into optimal dose and application of the most promising treatments is needed. Pain as a result of musculoskeletal problems of the back, neck, shoulder, knee and multi-site pain is an increasing cause of diminished quality of life, and increased demands on healthcare –3. PrognMusculoskeletal pain is managed by a plethora of treatment options, most delivered in primary care by first contact clinicians such as general practitioners, physiotherapists, chiropractors and osteopaths. These include non-pharmacological treatments , complementary therapies (e.g. acupuncture), and pharmacological interventions , corticosteroid injections). For those with refractory symptoms, surgical interventions  may be considered. However, for the overarching aim of reducing pain and improving function, recommendations are equivocal in respect to the effectiveness of various treatment options that are used across a range of common musculoskeletal pain presentations. For example, evidence for the effectiveness of corticosteroid injections for relief of shoulder or knee pain is inconsistent , 7. SimiEvidence from trials and systematic reviews indicate that most treatments for musculoskeletal pain provide small to moderate short-term benefits, with a lack of evidence for long-term effectiveness . Also, tPrevious reviews and guidelines that describe the effectiveness of treatments for musculoskeletal pain specifically focus on single regional pain sites, such as shoulder pain , 14, kneThe aim of this study was to critically appraise current best evidence regarding the effectiveness of treatments to reduce pain and /or improve function for people with the five most common musculoskeletal pain presentations in primary care . The spidentify effective treatment options for the five most common musculoskeletal pain presentations andhighlight gaps in evidence and priorities for policy or future research.The review also identified, where available, evidence regarding patient subgroups most likely to respond to different treatment options.http://hsl.mcmaster.libguides.com/ebm). Therefore, using national clinical guidelines, policy documents, care pathways such as Map of Medicine (MoM), and clinical evidence summaries as a starting point, the search for evidence for this overview followed a pyramidal tract through a hierarchy of available evidence. Sources of evidence for the overview included: Clinical Knowledge Summaries, Map of Medicine, TRIP Database , the Cochrane Library , MEDLINE and EMBASE , reference lists of included systematic reviews and guidelines, research stakeholders and experts in the field of musculoskeletal research. Evidence sources were initially accessed in January 2014 and regularly checked for new updates at eight week intervals through to March 2015 whilst the review was ongoing. A Cochrane library search update was conducted in February and August 2016 in order to identify newly published Cochrane reviews.Integrated information from higher levels of evidence has been suggested as an “ideal source of evidence for clinical decision-making” by the Evidence Based Practice group (All Cochrane reviews matching the inclusion criteria were included in the synthesis. Relevant non-Cochrane systematic reviews were added where there were no (up-to-date) Cochrane reviews summarising the effectiveness of a particular treatment. Additional searches of the bibliographic databases, MEDLINE and EMBASE  were carried out to identify and retrieve (1) relevant systematic reviews, and (2) more recently published relevant RCTs that had not yet been summarised in reviews or guidelines or where evidence gaps clearly existed. For the bibliographic database searches, retrieved search results were limited to published articles from 2000 until December 2014 initially, and then updated in August 2016. The search strategy and search terms for these additional searches are profiled in supplementary Relevant publications  were obtained and assessed against predefined eligibility criteria according to the study protocol by two reviewers.Study populations: Reviews/studies of adults (18 years and over) presenting with at least one of the five most common musculoskeletal pain presentations: back, neck, shoulder, knee and multi-site pain .Type of treatments: Reviews/studies of currently available treatments , aids and devices, and other treatments ) for musculoskeletal pain patients consulting in primary care were considered. Referral options for psychosocial interventions  and surgery were also included. Comparison groups could include usual care, no intervention or other active interventions.Outcomes: Reviews/studies had to report outcomes of pain , and/or functional disability. These were considered primary outcomes for this review. Secondary outcomes such as psychological well-being / depression, catastrophising, quality of life (QOL), work related outcomes , and cost of treatment were highlighted, but were not required for inclusion in the review.Narrative reviews, letters, editorials, commentaries, and meeting abstracts were excluded, as were biomechanical, laboratory studies, animal studies as well as previous RCTs that were already summarised in included reviews, cohort, case-control, and cross-sectional studies.Reviews/studies published in other languages than English.Reviews/studies of musculoskeletal pain populations with suspected serious pathologies , inflammatory arthritis, crystal disease, spondyloarthropathy, polymyalgia rheumatica, whiplash injuries, pregnancy-related pain problems, and vulnerable patients .In order to weigh the conclusion of reviews within our evidence summaries, the methodological quality of non-Cochrane systematic reviews was assessed using the 11-item ‘assessment of multiple systematic reviews’ (AMSTAR) checklist . The guiData were extracted by one reviewer using a data collection form and independently checked for consistency and completeness by a second reviewer. Clarifications were sought where needed and disagreements between reviewers resolved by discussion. Data were extracted on the effectiveness of non-pharmacological, pharmacological and surgical treatments for each musculoskeletal pain presentation separately, and where available, guidance or conclusions regarding patient subgroups mostly likely to respond to specific treatments. More specifically, data were extracted regarding:population characteristics ,primary and secondary outcome measures (as stated above),estimates of treatment effect ,estimates of treatment effect for patient subgroups (where available),treatment setting (e.g. primary care), andsources of evidence.Treatments were assessed for short-term (up to 3 months) and long-term (greater than 6 months) effectiveness based on the primary outcomes of pain and function.http://www.gradeworkinggroup.org/). Summary evidence from all included reviews and guidelines were graded, taking into account the:Summaries of the overall evidence for the effectiveness of treatment options and strength of recommendations for each pain site were assessed based on (a modified) GRADE rating : expert opinion or consensus in guidelines was rated as very weak evidence, while RCTs, systematic reviews and evidence-based guidelines were graded as higher level of evidenceQuality of systematic reviews Magnitude of effect where a standardised mean difference (SMD) of 0.2 was considered small, 0.5 as medium, and 0.8 as large according to Cohen , and forLevel of precision The consistency of results across systematic reviews or RCTs.For each treatment option, evidence was graded as:“Very weak evidence”—based solely on expert opinion or consensus in guidelines only or in the absence of systematic review evidence“Limited evidence”—in the presence of little evidence from systematic reviews/evidence-based guidelines AND when there were small, inconsistent, or non-significant treatment effect sizes“Moderate evidence”–in the presence of little evidence from systematic reviews/evidence-based guidelines (as in 2) but showing a medium to large treatment effect OR in the presence of strong evidence from high quality systematic reviews, but with small or inconsistent treatment effect sizes“Strong evidence”—in the presence of strong evidence from high quality systematic reviews and evidence-based clinical guidelines AND medium or large effect sizes.Each summary of evidence / analysis was graded using the adapted GRADE criteria as described above and a narrative synthesis was subsequently presented, indicating the strength of the evidence as very weak, limited, moderate, or strong.A narrative synthesis approach was undertaken. Given expected heterogeneity of sources of evidence, treatment settings, and the wide remit of this review , the evidence was summarised at a high level (using systematic reviews and guidelines where available), and therefore no new meta-analyses were conducted. However, pooled estimates of treatment effectiveness from systematic reviews, as well as comments on the consistency and magnitude of treatment effects were extracted and reported. Additional information from policy documents and guidelines on treatment recommendations and priorities, including the type of evidence from which it was generated  was also noted. The gathered evidence was included in summary tables  Tables tA total of 3,588 unique citations (including Cochrane reviews) were retrieved from the electronic bibliographic databases. On assessing titles, abstracts and full texts against the inclusion criteria, 71 Cochrane systematic reviews met the selection criteria and were included. Non-Cochrane systematic reviews (n = 75) were only included where a gap not already covered by Cochrane reviews was identified, or if they represented new research that had not yet been considered within updated guidelines and care pathways. The remaining papers were excluded because they were not a systematic review (n = 798), focused on an area already covered by one of the included Cochrane systematic reviews (n = 234), were duplicate publications or did not fit the inclusion criteria (n = 2131). A summary of the review process outlining the selection of evidence is presented in As Cochrane reviews followed a generic protocol specifying methods and review protocols go through a comprehensive peer review process prior to publication, the methodological quality of most Cochrane reviews included in this evidence synthesis was satisfactory . CochranOur searches identified reviews, guidelines and care pathways that covered a large range of treatment options for each musculoskeletal pain presentation. Based on specific review questions, authors of each review used particular criteria for identifying relevant trials in terms of setting, participants and interventions, resulting in variation across reviews in terms of the musculoskeletal condition, type and number of trials included, interventions, and reported outcomes of the reviews. A detailed description of the settings, populations, treatments and outcomes is provided in Effectiveness of available treatments for musculoskeletal pain was highlighted in the following order: self-management advice and education, exercise therapy, manual therapy, pharmacological interventions, aids and devices, other treatments , psychosocial interventions and surgery. A summary of the findings is presented in Evidence base: Evidence was extracted from two clinical guidelines, one clinical pathway and eight reviews about the effectiveness of self-management advice and education. As assessed by AMSTAR, the methodological quality of systematic reviews was moderate or high but the primary studies within those reviews were generally low or moderate in quality. Given mostly in the form of oral and / or written information, advice and education was directed at improving patients' understanding of their musculoskeletal pain, and self-management techniques, addressing patients’ concerns about serious causes and outcomes, supporting return to function, and minimising dependence on healthcare providers , 29–38.Magnitude of effects: Self-management advice and education was typically provided to either individuals or patient groups, as part of an intervention programme and were not tested in isolation against a control treatment . TherefoStrength of evidence: The evidence for self-management advice and education supporting expert opinion in clinical guidelines and consensus meetings as well as systematic reviews showed small effects on pain and function. Pooled results from meta-analyses tended to have wide confidence intervals although recommendations for the use of advice and education were consistent. Overall strength of evidence was graded as limited.Bottom line: Despite the limited evidence-base, there were strong recommendations for the use of self-management advice and education as a first line treatment option for musculoskeletal pain.Evidence base: Synthesized evidence for the effectiveness of exercise on musculoskeletal pain included 10 Cochrane reviews , 39–46, Magnitude of effects: Exercise therapy was determined to be beneficial for pain, function and quality of life in all five pain presentations –60, 63. There appears to be little empirical evidence in favour of any particular exercise type, programme or mode of delivery, either as structured individual or group treatment for musculoskeletal pain , 72, 73,Strength of evidence: On the basis of medium to large summary effects sizes from high quality reviews, and clinical guidelines, the strength of evidence for the effectiveness of exercise therapy for pain, function, and quality of life for patients with musculoskeletal pain, was graded as strong.Bottom line: Current evidence shows significant positive effects in favour of exercise on pain, function, quality of life and work related outcomes in the short and long-term for all the musculoskeletal pain presentations (compared to no exercise or other control) but the evidence regarding optimal content or delivery of exercise in each case is inconclusive.Evidence base: Six Cochrane reviews , 74–77, Magnitude of effects: Pooled estimates for the effectiveness of manual therapy for musculoskeletal pain were generally statistically significant, but variable in terms of size of the treatment effect For back pain, evidence suggests that manual therapy alone or in combination with other treatments may offer some benefit for pain and function , 85, 88.Strength of evidence: Despite several high quality reviews examining the effects of manual therapy on pain and function for neck, shoulder and back pain, current evidence generally shows small summary effect sizes or concludes no clinical effectiveness of manual therapy compared to sham or other active treatments. Overall strength of evidence was graded as limited.Bottom line: Current evidence regarding manual therapy is beset by heterogeneity across clinical trials. Due to paucity of high quality evidence, it is uncertain if the efficacy of manual therapy might be different for different patient subgroups or influenced by the type and experience of professional delivering the therapy. On the whole, available evidence suggests that manual therapy may offer some beneficial effect on pain and function but it may not be superior to other non-pharmacological treatments (e.g. exercise) for patients with acute or chronic musculoskeletal pain.Evidence base: Thirty systematic reviews of pharmacological interventions for musculoskeletal pain examined the effectiveness of analgesics (opioids and non-opioids) in the short and long-term as well as in acute and chronic pain presentations. Comparisons were against placebo , 95, othMagnitude of effects: Compared to placebo, acetaminophen (paracetamol) was not more effective  for relieving knee and back pain , 103. NSStrength of evidence: With consistent medium summary effect sizes reported across moderate to high quality systematic reviews and clinical guidelines, there is moderate evidence that pharmacological therapies are beneficial for the short-term relief of musculoskeletal pain. Overall strength of evidence was graded as moderate.Bottom line: NSAIDs, Cox-2 selective inhibitors and opioids reduce pain in the short-term, but the effect size is modest and the potential for adverse effects such as gastrointestinal bleeding and opioids-induced hyperalgesia need careful consideration.Evidence base: The evidence base for the effectiveness of injections for musculoskeletal pain involved the synthesis of three clinical guidelines , 113 andMagnitude of effects: A care pathway document , one guiFurthermore, the available evidence did not suggest injections are effective for the management of neck pain , 121–124Generally, in the long-term, injections may be no more effective than non-pharmacological interventions such as exercise , 125. EvStrength of evidence: Supported by high quality reviews, and clinical guidelines, medium to strong effect sizes across the various sources of evidence, injections offer clinically significant benefits for relieving moderate to severe shoulder and knee pain but in the short-term (up to 3 months) only. Overall, the strength of evidence was graded as strong.Bottom line: The evidence indicates that injections offer short-term pain relief for shoulder and knee pain but effectiveness for back and neck pain is uncertain. Across the musculoskeletal pain presentations for which pharmacological injections may be given for pain relief, current evidence is equivocal on the optimal procedure (e.g. guided vs. unguided), frequency, dose and active component of the injections (though corticosteroid injections are more often reported in literature).Evidence base: The evidence for the effectiveness of aids and devices for pain and function included five guidelines , 129, onMagnitude of effects: Either as stand-alone treatment or mostly in combination with other treatments, aids and devices for musculoskeletal pain have generally shown small effects , reports of high clinical and methodological heterogeneity within the trials contributing to reviews preclude statistical pooling of effect estimates. There was also no evidence regarding specific patient subgroups which might benefit most from these treatments.For acupuncture, available evidence from a good quality individual patient data meta-analysis suggests that acupuncture may be effective for short-term relief of back pain and knee pain with medium summary effect sizes  and ) respectively compared with usual care or no acupuncture . HoweverTENS was no more effective for reducing pain than placebo in chronic back pain , 161, neStrength of evidence: There was little empirical evidence for the effectiveness of other treatments including ultrasound, TENS, laser, and superficial ice / hot packs. Presented summary effect sizes and estimates were often small, inconsistent, and non-significant. Although medium short-term effects were found for the effects of acupuncture on back and knee pain, overall strength of evidence was graded as limited.Bottom line: The evidence for the clinical effectiveness of most of these other treatment options was not substantiated by strong evidence. Either as stand alone or in combination with other treatments, the often small effect sizes as a result of these treatments for improving musculoskeletal pain and function was mostly not clinically significant.Evidence base: Evidence base for the effectiveness of psychosocial interventions  included one guideline  and an oMagnitude of effects: Reviews of psychosocial treatments for the management of musculoskeletal pain included a wide range of approaches that aimed to achieve increased self-management, behavioural and/or cognitive changes alongside biomedical management of pain Strength of evidence: Except for shoulder and knee pain, where the strength of evidence was limited, current evidence for the beneficial effects of psychosocial interventions for neck, back and multi-site pain is supported by moderate to high quality reviews, medium effect sizes with precise confidence intervals and this is consistent across sources of evidence. Overall, the strength of evidence was graded as moderate.Bottom line: Available evidence suggests beneficial effects of psychosocial interventions, particularly for patients identified as having a poor prognosis prior to treatment. Also, outcome of psychosocial treatment appears to be influenced by other factors such as patient prognosis, the healthcare professional providing treatment, the settings for treatment delivery and the components of treatment.Evidence base: Evidence for the effectiveness of surgery for the musculoskeletal pain presentations (excluding multi-site pain) was synthesised from one guideline and a care pathway document , 47, ninMagnitude of effects: Most guidelines specify that surgical treatments are indicated in a small proportion of patients (as low as 8%) for neck, shoulder, back and knee pain presentations , 47, 181Strength of evidence: Though reviews were mostly high in methodological quality, summary effect sizes were small. Overall strength of evidence of long-term effectiveness of surgery is limited except where directly indicated by specific serious pathology such as end-stage degenerative knee joint disease, persistent pain and functional limitation which are refractory to conservative treatments.Bottom line: The effectiveness of surgery as a first line treatment option is not established in current literature. The current evidence base is limited in terms of quantity, especially comparing surgical versus conservative interventions but there is moderate evidence from guidelines, Cochrane reviews and other systematic reviews to support short-term efficacy of surgical interventions for pain and function for specific neck, shoulder, knee and back pain presentations. Available evidence also suggests that surgery is not superior to conservative treatment options in the long-term.This review has systematically identified, synthesised and graded a large body of evidence on the effectiveness of treatment for musculoskeletal pain presentations. For most pain presentations, non-pharmacological treatments especially exercise therapy as well as psychosocial interventions, produced medium to large effects on pain and function, with corticosteroid injections potentially offering short-term benefit in those with knee and shoulder pain. NSAIDs and opioids (where appropriate) also offer short-term benefit for musculoskeletal pain, but the potential for adverse effects need careful consideration.The effectiveness of exercise therapy, psychosocial interventions and corticosteroid injections was consistently supported by empirical evidence of mostly medium effect sizes provided by meta-analyses of RCTs, by guidelines, and expert opinion for musculoskeletal pain. With regard to intensity, and modes of applications of most treatments, the amount of clinical contact, the type of provider, setting, and delivery modes/techniques for effective treatment varied widely and, as yet, there is limited evidence to support choices regarding optimal delivery of these treatments. Therefore, further research to investigate the optimal dose and application of these treatment options is needed.In this review, there was little information within the evidence base in relation to patient subgroups most likely to respond to different treatment options. Where available, for each treatment option, evidence regarding patient characteristics such as baseline pain severity and function, duration of pain, and previous pain episodes have been documented It is worth noting that in many of the reviews, guidelines and trials contributing to this evidence-base, individual treatments were rarely used in isolation. Therefore, the evidence for the isolated effectiveness of treatments in some reviews was difficult to assess. For instance, self-management advice and education was typically provided as part of intervention package rather than tested in isolation against a control treatment. Consequently, there was little empirical evidence about its effectiveness despite consistent support of the beneficial effects (by expert opinion and consensus in guidelines). This could impact the quality and level of evidence for the beneficial effects of otherwise promising treatments.As expected, given the breadth of this review there was wide heterogeneity in study populations, outcomes, and statistical methods for estimating summary effect measures in the included systematic reviews. Interpreting findings within this overview was also complicated by variability in both the intervention and control conditions  examined within the reviews, making it difficult to summarise evidence regarding the magnitude of treatment effects. Furthermore, in this overview, the treatments provided in individual studies could not be described in detail; settings, exact content, intensity or dose of interventions may have varied; many interventions may have required specialist staff  and the training and skills of providers are likely to have varied over time and locations. Control conditions were frequently not described in reviews and trials, and the definition of terms “routine care”, “standard care” or “no intervention” may vary depending on setting and country. In the conduct of this study however, concerted efforts were made to capture and report available contextual information when summarizing evidence regarding treatment effectiveness.Where possible, given the wide remit of this review, a number of steps were taken to ensure methodological rigour. The focus was on publications providing high quality evidence or recommendations, including Cochrane and other high quality reviews, well-developed clinical guidelines that met specific quality assurance criteria, and evidence-based multidisciplinary care plans as outlined in care pathways. For Cochrane reviews, all reviews used protocols that aimed to minimise bias whilst for non-Cochrane reviews, evidence of using systematic methods was a pre-requisite for inclusion in this study. In addition, separate structured and systematic searches of bibliographic databases were conducted to identify additional trials not covered in previous reviews, where gaps concerning the effectiveness of specific treatment options were identified.This review provides evidence summaries regarding the effectiveness of a wide range of treatments for the five most common musculoskeletal pain presentations in primary care, drawing together findings from a large evidence base. To facilitate this rapid evidence summary, the methodology evolved as a rapid application of systematic review methods to synthesising evidence. Efforts were made to capture, appraise and synthesise the best available evidence in a systematic yet rapid fashion. Definitive elements of typical systematic review methods such as a comprehensive and systematic search of best available evidence, pre-specified inclusion and exclusion criteria, quality appraisal and synthesis have all been preserved. Further strengths of this review included independent assessment of eligibility for inclusion and data extraction for contributing reviews, data checks, appraisal of the quality of systematic reviews, and a standardised approach to synthesising evidence.There are several limitations to this review. First, there was no independent assessment of the methodological quality of primary trials that were included in the reviews. As this is an overview of current best available evidence, methodological quality assessment of included primary studies depended largely on the ratings of systematic review authors rather than our own assessment of the details presented in the individual studies. The overview of evidence incorporating reviews of multiple interventions across many musculoskeletal pain conditions therefore may not follow strictly the process generally applied in a single systematic review of one intervention on a single target population. However, much care has been taken to ensure that our approaches to searching for evidence, quality appraisal and grading of available evidence, and synthesis (as highlighted in the methods section) were as rigorous and as transparent as possible.In this overview, evidence on effectiveness of treatment options for musculoskeletal pain has been presented based on pain presentations at different body regions rather than on specific clinical diagnoses given available evidence of similarity of patient characteristics, prognosis and clinical course of musculoskeletal pain presentations irrespective of specific clinical diagnoses , 24. HowAcross health systems globally, there is wide variation in clinical management of musculoskeletal pain patients whereby the most effective treatment options are not consistently used, leading to inefficient care, unnecessary costs and in some cases harm , 192. InIn this review, despite an extensive search for evidence, there was a paucity of evidence on treatment for those with multi-site pain. This musculoskeletal pain presentation, often managed as chronic widespread pain and / or fibromyalgia has been less examined in the literature because effectiveness of most treatment options has traditionally been compared on a pairwise basis and according to individual regional pain presentations. However, regional pains are known to co-exist in individual patients . PatientThe lack of information regarding patient subgroups most likely to respond to specific treatment options, equivocal recommendations on the optimal mode of treatments, as well as the obvious focus of treatment approaches on single pain sites rather than the individual with multi-site musculoskeletal pain are key specific gaps in the current body of knowledge identified in this review.Effective healthcare depends on high quality evidence. Best available evidence shows that patients with musculoskeletal pain problems in primary care can be managed effectively with non-pharmacological treatments such as self-management advice, exercise therapy, and psychosocial interventions. Pharmacological interventions such as corticosteroid injections (for knee and shoulder pain) were shown to be effective treatment options for the short-term relief of musculoskeletal pain and may be used in addition to non-pharmacological treatments. NSAIDs and opioids also offer short-term benefit for musculoskeletal pain, but the potential for adverse effects must be considered. Furthermore, the optimal treatment intensity, methods of application, amount of clinical contact, and type of provider or setting, are unclear for most treatment options.S1 File(DOCX)Click here for additional data file.S2 File(DOC)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S5 Table(DOCX)Click here for additional data file.S6 Table(DOCX)Click here for additional data file.S7 Table(DOCX)Click here for additional data file.


Thirty two cases are described where the presence of a cluster of neuropsychological symptoms and signs, including unreality feelings, headache, nausea, lassitude, ataxia and tremor, appear to be related to the presence of Air Freshener products. The possible significance of this observation is discussed.


Delay in seeking diagnosis of dementia is common in China. Misinformation and poor knowledge about dementia may contribute to it. The study was designed to explore the nationwide dementia literacy among older adults in urban China and to investigate the factors associated with overall dementia literacy.In a cross-sectional study, a convenience sample of 3,439 community-dwelling old adults aged 60 and over was recruited from 34 cities in 20 provinces between June 20 and August 20, 2014. All participants were administered the face-to-face mental health literacy questionnaire, which included the prevalence, symptoms, intention, and options for treatment of dementia. Stepwise multivariate regression analysis was used to explore factors associated with overall dementia literacy.OR = 1.256, 95% CI (1.022–1.543)], having lower per capita annual income , lower education , and suspected depression  were negatively associated with overall dementia literacy.The response rate was 87.4%. The overall dementia literacy was 55.5% (SD = 20.9%) among all respondents. The correct response rate was higher for questions on symptoms (58.7–89.6%), but lower for questions on the prevalence (22.2%) and choosing appropriate professional care personnel (22.2%). Being male [Dementia literacy among community-dwelling older adults in urban China remains very low, in particular about the impact of dementia and appropriate treatment personnel. Community educational programs aiming to close this knowledge gap are encouraged to focus on those in the population at highest risk of low dementia literacy. Dementia is a progressive, neurodegenerative condition that causes deterioration in memory and other cognitive domains that influence a person’s functioning. The most common type of dementia is Alzheimer’s dementia, which makes up 50–70% of cases. Other common types include vascular dementia, dementia with lewy bodies, and frontotemporal dementia . With thDespite the current absence of a cure for dementia, it is important for people to have access to early assessment and timely diagnosis. In China, the level of undiagnosed dementia remains high . PWD andMental health literacy (MHL), first introduced by Jorm et al. in 1997, refers to knowledge and beliefs about mental disorders which aid their recognition, management, or prevention . It consUp to now, studies have reported large variations in dementia literacy even in high-income countries –10. In sIn contrast, dementia literacy appeared to be much lower in low-resource countries, such as Turkey and Brazil , 12. NeaIn China, the general public’s knowledge and understanding of dementia were found to be inconsistent across six studies in five cities: from 14.4% in Shijiazhuang to 78% in Xi’an –18. ThisIn this study, we aimed to estimate the dementia literacy in urban China by using a validated assessment instrument and to explore the potential factors associated with the literacy. We anticipated that our study would ultimately provide insight into the population most in need of educational intervention to raise their awareness of dementia diagnosis and care.A convenience sample of 3,439 community-dwelling older adults was recruited from 34 cities in 20 provinces  between June 20 and August 20, 2014. The trained research assistants in local communities approached the older adults through posters and telephones with the help of the residential committee officers. Those meeting the inclusion criteria were invited for an interview: (1) aged 60 years or above; (2) living in an urban setting; (3) willing to participate in the study; and (4) capable of basic understanding and writing. Those who had other mental disorders, such as schizophrenia or mental retardation, or severe problems of vision, hearing, or speech, were excluded.The study was approved by the Ethics Review Board of Peking University Institute of Mental Health . Written informed consent was obtained from each participant.We used selected questions in the MHL questionnaire for older adults to assess the dementia literacy . The MHLThe clock-drawing test (CDT) was used for screening for cognitive impairment. The CDT is reliable and easy to administer in primary care settings . A 4-poiThe self-reported version of Geriatric Depression Inventory  was used to screen for depressive symptoms as depressive symptoms are a risk factor of dementia . The GDIAll statistical analyses were performed with SPSS version 20.0 . Pearson’s chi-squared test was used to compare overall dementia literacy among different groups, such as age, gender, schooling educational level, marital status, ethnicity, occupation prior to retirement, per capita annual income, status of cognitive ability, and mood.Univariate logistic regression analysis was used to test the association of one variable with the dementia literacy without considering other variables or confounders . The dependent variable was defined as the overall level of dementia literacy (0 = low literacy and 1 = high literacy). As reported in the original research of the MHL questionnaire, 0.6 is the recommended cutoff value to divide the participants into “low literacy” and “high literacy” groups . The indDue to confounding factors, we implemented multivariate logistic regression analysis, starting with a full model  and using the stepwise selection approach, where likelihood ratio backward was performed at each step. Standard of enter and remove from the model was 0.10 and 0.15, respectively.Among 3,439 participants, 3,007 completed the questionnaire, thus the response rate was 87.4%.As shown in Table 2 = 17.592, p = 0.014), occupation prior to retirement , per capita annual income , and mood status . No significant differences were observed between age groups , schooling education , marital status , ethnicity , and cognitive ability  . The overall dementia literacy differed by gender . However, in a multivariate stepwise logistic regression analysis, only being male , having lower per capita annual income , low education  and suspected depression  were retained as significant negative predictors of dementia literacy.As summarized in Table As far as we are aware, our study is the first large-scale survey on dementia literacy among older adults in China’s urban communities. Moreover, we included many important regions, such as Inner Mongolia, Xinjiang, Liaoning, and Guangxi, which were not included in previous studies. Thus, the current study is representative of a relatively broader spectrum of people than previous studies. We observed that, on average, the research participants answered about 55% of the questions correctly. In addition, our study suggested that male, those with lower income, and those with lower education and suspected depression tended to have lower dementia literacy. These important findings not only highlight the need to improve dementia awareness in urban China but also identifies potential groups that health education program should more closely target.In our study, the overall dementia literacy is 55.5%, i.e., the participants only knew half of the knowledge about dementia tested. This level is almost similar to that in Shanghai (54%), 10 years ago which used the same instrument tool with ours . This maAs we expected, the majority of older adults in our study knew symptoms of dementia and expressed intention for treatment. However, the majority (78%) of the respondents underestimated the prevalence of dementia. This could be partly due to their misunderstanding of the nature of dementia. More than half of the respondents believed that “dementia is part of normal aging.” This belief was shared by Latino and African-American older adults as well as dementia caregivers in China , 25–30. In our study, the rate of intention for treatment was high (nearly 70%), while only one-fifth did not choose traditional practitioners for professional help. With regard to aged care and chronic disease treatment, older Chinese are skeptical of the safety of Western medicine and favor traditional medicine in preference to specialist care . We founThe present study demonstrated that women had a better knowledge about dementia compared to men. This observation is consistent with the previous study by Arai et al . In ChinConsists with studies by Lee et al. and von dem Knesebeck et al., education emerged as the most important factor influencing literacy. Lower level of education negatively correlates with dementia literacy. The results of the present study provide empirical evidence that education can be helpful in increasing dementia literacy. Highly educated individuals tend to know more about the symptoms of mental disease than the less educated individuals do , 37.In contrast, the relationship between age and knowledge about dementia remains inconsistent. Some found that older age was associated with less knowledge , 38, 39.We also found that annual income was negatively associated with overall literacy. Low socioeconomic status may restrict access to health education resources, especially in low-resources areas. Consistent with Tan et al., we suggest that special support programs for low-income people are imperative to improve their knowledge about dementia .Few studies have looked into the effect of mental health status on dementia literacy. Our study found that participants with depressive symptoms have relatively low literacy compared with those without depressive symptoms. After adjusting for potential covariates, depression remains an independent factor of overall literacy. When suffering from depression, older adults tend to reduce participation in community activities, become less interested in social engagement, and thus, decrease the opportunities to gain knowledge , 43. SecOur study had certain limitations that may influence our results. Due to bias in the convenience sample, older adults who consented to the interview may be more active in community participation. As homebound and socially isolated older adults were not recruited, the overall dementia literacy might be overestimated. Hence, the results should be interpreted with caution. However, the age and gender composition in our survey were similar to that of the national population according to the sixth National Population Census. Therefore, this survey might have a relatively high representation  . Second,Our study was designed to describe overall dementia literacy among community-living older adults living in urban areas, using a validated instrument. It shows that although older Chinese have some knowledge about symptoms of dementia, they have poor literacy about the impact of the disease and choosing optimal professional care personnel. We also found that the following risk factors were associated with lower dementia literacy: men, lower income, and those with suspected depression. These findings suggest that overall dementia literacy remains low and educational interventions should be prioritized in the community. Therefore, it will be of great significance to advocate for improving dementia literacy in the future national dementia plan, such as awareness raining campaigns.Our study is the first large-scale survey on dementia literacy among community-dwelling older adults in urban China. It reveals the knowledge gaps about dementia: older Chinese know more about symptoms than the impact and care resources. It also identifies the factors influencing dementia literacy: gender, income, education, and mood status. Further educational programs should not only focus on symptoms but also provide dementia care resources, including memory clinics. In addition, specific population groups such as men, lower income, lower education, and family members of people with suspected depression should be targeted for health education activities in the community. This also poses interesting questions of how well-trained doctors are to relate to these groups and how those with a concern about their memories will access an assessment for dementia in a community health center or elsewhere.This study was carried out in accordance with the recommendations of Ethical Review Guideline, the Ethics Review Board of Peking University Institute of Mental Health  with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Ethics Review Board of Peking University Institute of Mental Health .HW and XY formulated the research questions. HZ, MZ, XL, HW, and XY designed the study and supervised the data collection. HZ, SZ, MZ, XW, JW, XL, and HW collected the data. HZ, SL, MZ, XL, NL, and HW carried out the statistical analysis. HZ, SL, XL, NL, and HW wrote the paper. XY provided critical review and comments on the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Experimental biology and ecology show much promise for informing evidence-based decision making. To do so most immediately and effectively, experimentalists need to consider a number of factors when designing, executing and analyzing experiments to ensure that findings will be deemed relevant and reliable by conservation practitioners. Policy development and management decisions should be based upon the best available evidence. In recent years, approaches to evidence synthesis, originating in the medical realm (such as systematic reviews), have been applied to conservation to promote evidence-based conservation and environmental management. Systematic reviews involve a critical appraisal of evidence, but studies that lack the necessary rigour  to justify their conclusions are typically excluded from systematic reviews or down-weighted in terms of their influence. One of the strengths of conservation physiology is the reliance on experimental approaches that help to more clearly establish cause-and-effect relationships. Indeed, experimental biology and ecology have much to offer in terms of building the evidence base that is needed to inform policy and management options related to pressing issues such as enacting endangered species recovery plans or evaluating the effectiveness of conservation interventions. Here, we identify a number of pitfalls that can prevent experimental findings from being relevant to conservation or would lead to their exclusion or down-weighting during critical appraisal in a systematic review. We conclude that conservation physiology is well positioned to support evidence-based conservation, provided that experimental designs are robust and that conservation physiologists understand the nuances associated with informing decision-making processes so that they can be more relevant. Humans have dominated the planet for much of the last century . The finhttp://www.cochranelibrary.com/cochrane-database-of-systematic-reviews/) and led to standardized practices in the evaluation of evidence, the field of conservation and environmental management is undergoing a paradigm shift toward procedures that provide the critical syntheses needed to properly inform policy and management , experiments provide more certainty with respect to effects. In the context of systematic reviews, a well-designed and executed study is an essential component of evidence synthesis because of its ability to control and describe confounders and sources of heterogeneity. That is, ideally one would assemble a series of independent studies and, often using meta-analytical approaches, aggregate studies to seek more general trends across the broader literature base. Of course, not all experiments are of the highest validity (for a variety of reasons). Therefore, another important part of systematic review is a detailed, critical appraisal of the internal validity  and external validity  of each study to determine its utility in the evidence synthesis process.As systematic reviews become more commonplace in conservation science and environmental management, it is worthwhile to reflect on the characteristics of study design that would be considered indicative of quality. Substantial effort has now been expended on a suite of systematic reviews relating to various conservation and environmental topics. Many of these topics involve studies with classical experimental designs, e.g. biomanipulation for the treatment of eutrophication  and ecology  are conducting research related to understanding our natural world in an applied context. Such research is leading to the development of a number of nascent disciplines  by performing experiments under controlled conditions, which allows scientists to separate the effects of a particular variable from other possible effects . This reThe benefits of increasing power to detect causality in experimental research are especially relevant to the critical appraisal process of systematic review. During critical appraisal, the analyst determines the level of confidence that can be placed on a dataset before incorporating it. In the medical field, a hierarchical approach was proposed to classify the value of data for inclusion in a systematic review . SimilarBiological systems interact with one another in ways that are often difficult to predict . ExperimIt has been argued that the best way to approach the study of complex interactions is through the use of a multi-disciplinary approach . By doinOne of the core elements of a systematic review that differs from other forms of evidence synthesis is the emphasis on critical appraisal of study quality. Although one might assume that papers obtained from the primary peer-reviewed literature are of adequate quality, the reality is that contemporary peer review is not perfect . Indeed,There are no specific standards for quality assessment when it comes to systematic reviews in the realm of conservation and environmental management. This may not be surprising given that this is also the case for health and medicine, where the use of systematic reviews has a long history . BilottaReliability is the extent to which the design of a given study minimizes susceptibility to bias. There are four primary considerations.Selection bias stems from the manner in which treatment groups (including control groups) are amassed . A randoPerformance bias affects conservation research when treatment groups receive different standards of care, which can affect the outcome of the treatment itself . In mediMeasurement or detection bias occurs when knowledge of the intervention alters adequate evaluation of the results . This foThe use of appropriate technology can also minimize measurement bias by ensuring that the techniques are chosen to best fit subjects and/or species. Some tools used to measure physiological parameters are highly sensitive and should be assessed to ensure they measure the relevant metrics to answer the question at hand. For example, point-of-care devices enable researchers to assess various blood-based physiological parameters of wild animals in remote locations only with careful validation of device performance  or the pAttrition bias refers to differences in withdrawal rates among groups of a study, leading to incomplete outcome data . This maRelevance is often considered in terms of the external validity of the study ; how traEcological research is often conducted at the organismal or even down to the sub-organismal scale, but managers typically focus on populations. Exceptions, however, would be for endangered species, for which every individual matters. Therefore, scientists must often extrapolate results to scales that are relevant to management . ExperimBiologists and ecologists must examine the structure and dynamics of biology from the molecular level, all the way through to populations. Innovative physiological tools available for field studies mean that research is not restricted to the laboratory . Indeed,Experimental ecology and conservation science can strive to develop solutions that are relevant to the problem and realistic to the end users. Research funding must be directed toward practical solutions that can be acceptable to stakeholders. Co-development of the research agenda among stakeholders  is essential to ensuring that solutions considered in experiments could, in addition to being effective, be scaled (i.e. be mass-produced and or quickly and easily implemented) and well-received. To do so, experiments must consider possible economic ramifications of experimental interventions. For example, Much conservation and environmental management experimental research aims to understand how environmental alterations will affect species that are already at risk or those living in extreme stenothermal conditions (e.g. Antarctic fishes). These animals are typically very difficult to obtain due to protective laws or expensive and time-consuming retrieval methods, necessitating the use of surrogates , presenting results for all tested predictor and response variables, and all subgroups of data, listing assumptions tested to validate the statistical method implemented, and citing statistical software and, in some cases, the specific functions or packages used to produce results improves the understanding of the interpretation and allows systematic reviewers to verify the relevance of results when appraising studies for systematic review.An emerging challenge to repeatable science is in the methodology that is essential to reproducing the results of a study. Methodological details are used by systematic reviewers for critical appraisal and quantitative details  and are needed for meta-analyses . OptimalP < 0.05. Other researchers have argued for a more ‘information theoretic approach’, which differs from traditional frequentist probability statistics (A related issue is statistical power . This maatistics . AnotherPseudoreplication occurs when experimental replicates are not statistically independent . PseudorIn larger-scale experiments, spatial pseudoreplication can be an additional problem . Almost Control is one of the most basic scientific concepts and is one of the great strengths of experimental approaches to conservation. Incorporating a proper control can provide the power necessary to separate correlation from causation in many studies. Control groups for experimentation may be generated using spatially distinct units, e.g. by comparing sites inside and outside protected areas . ControlControl groups for experimentation must be developed with the broader question in mind so that the control and treatment groups in an experiment are established to provide relevant results. Over-control and isolation of too few potential predictor variables limits discovery of the interesting interactions that occur in nature. Systems-based thinking is necessary to establish experiments that can produce relevant, scalable, transferrable results to real world problems in ecology and conservation.As a crisis discipline, conservation science strives to develop evidence that is timely, reliable and relevant to management . With teDeveloping research projects that generate reliable evidence is key but must rely on a solid partnership between scientists, managers and stakeholders. Not only must managers be able to communicate the pressing questions to scientists, they must be able to acknowledge how evidence at various scales can inform policy at the present scale. However, it is generally the responsibility of scientists to consider what scale to work on in a given situation with the available tools. Although the use of experimental biology has permitted great progress in understanding how biological systems interact with one another, we are still far from completely understanding how rapid environmental changes will interact with ecosystem function, population dynamics and individual physiologies (Evidence is increasingly important in managing all aspects of governance, and conservation is becoming one of the leading disciplines in developing protocols and standards for evidence (


Gastrointestinal Stromal Tumours (GISTs) are the most common mesenchymal tumours. Currently, different pharmacological and surgical options are used to treat localised and metastatic GISTs, although this research field is broad and the body of evidence is scattered and expanding. Our objectives are to identify, describe and organise the current available evidence for GIST through an evidence mapping approach.We followed the methodology of Global Evidence Mapping (GEM). We searched Pubmed, EMBASE, The Cochrane Library and Epistemonikos in order to identify systematic reviews (SRs) with or without meta-analyses published between 1990 and March 2016. Two authors assessed eligibility and extracted data. Methodological quality of the included systematic reviews was assessed using AMSTAR. We organised the results according to identified PICO questions and presented the evidence map in tables and a bubble plot.A total of 17 SRs met eligibility criteria. These reviews included 66 individual studies, of which three quarters were either observational or uncontrolled clinical trials. Overall, the quality of the included SRs was moderate or high. In total, we extracted 14 PICO questions from them and the corresponding results mostly favoured the intervention arm.The most common type of study used to evaluate therapeutic interventions in GIST sarcomas has been non-experimental studies. However, the majority of the interventions are reported as beneficial or probably beneficial by the respective authors of SRs. The evidence mapping is a useful and reliable methodology to identify and present the existing evidence about therapeutic interventions.The online version of this article (doi:10.1186/s12874-017-0402-9) contains supplementary material, which is available to authorized users. Sarcomas are rare malignant tumours of mesenchyme origin that occur in connective tissue. They can be split up into dozens of histological categories, which may develop at any age including childhood, can affect any anatomical localisation, and are of varying aggressiveness, even within the same histological subtype . There aClassically, systematic reviews (SRs) summarise the results of available healthcare studies and provide a high amount of evidence on the effectiveness of healthcare interventions . HoweverIn 2007, the Global Mapping Initiative (GEM) was established as a collaboration of clinical research and policy stakeholders to provide an overview of existing research about traumatic brain injury and spinal cord injury . EvidencThe purpose of this evidence mapping project is to identify, describe and organise the current available evidence about therapeutic interventions on sarcomas. This approach aims to determine the clinical questions assessed in the scientific literature and the corresponding quality of the supporting evidence, as well as to give general information about their claimed effectiveness. This information shall facilitate detecting research gaps and help stakeholders in the decision-making process. For the sake of clarification, this publication focuses exclusively on GIST whereas the mapping of evidence on soft tissue sarcomas will be addressed in future publications.We conducted a mapping of evidence based on the methodology proposed by GEM . In consIn order to framework our mapping project, we consulted the 2013 World Health Organization (WHO) classification , and theWe used a broader definition of SR in order to obtain the largest possible number of documents. The systematic reviews that conducted a search in at least two databases were considered eligible. We included the most updated review if more than one version was identified. We excluded narrative reviews and systematic reviews that were focused on prognosis or cost-effectiveness. We also excluded studies on patients with Kaposi Sarcoma and/or Ewing’s tumours because of their unique biological characteristics and management .The selection was done independently by two researchers.We conducted searches in PubMed, EMBASE, The Cochrane Library, and Epistemonikos from 1990 to March 2016; the former was updated in November 2016. The lower date boundary was chosen taking into account that biological mechanisms were discovered in 1998 and opened the use of biological agents as the key therapeutic approach of GIST that completely changed the management of the disease . “HoweveWe combined keywords and medical subject headings (Mesh terms) for all types of sarcoma according to the WHO 2013 classification . We adapWe managed the search results with the reference manager software COVIDENCE . After rGeneral characteristics from systematic reviews: authors, year of publication, type of systematic review , objective, search methods, design and number of included studies, type and number of patients included, and quality of the systematic review.We built a data extraction form to register the main characteristics and quality of included systematic reviews. We tested a pre-defined data extraction form to ensure consistency among reviewers in a pilot study with 20% of eligible SRs. Two authors extracted data . Disagreements were solved by discussion with a third author (AL). We collected data at three levels:b)Clinical questions assessed in the systematic reviews: we converted the main aim reported in the included systematic review and their eligibility criteria into clinical questions framed in a PICO format . The obtained PICOs were classified in five therapeutic scenarios with the help of a clinical expert (AL). We then extracted details about the population characteristics , the intervention and comparator , and outcomes. For descriptive purposes, we also categorised the conclusions reported by the authors of the included studies, into five categories: “inconclusive”, “no effect”, “harmful”, “probably beneficial” and “beneficial” Characteristics of other research questions addressed in the systematic reviews, here named secondary PICOs: we defined secondary research questions as those for which all the elements of the PICO question were provided but the conclusions about the direction of the effect were described marginally in the article. We extracted the same information described above for the main research question.Two researchers  independently assessed the methodological quality of the included reviews with the AMSTAR tool. Disagreements were discussed until consensus was reached. We calculated AMSTAR scores by adding one point for each item rated as “yes” and no point for items rated as “no”, “cannot answer”, or “not applicable”, resulting in overall score ranging from 0 to 11. According to the total score, SRs were grouped in three categories: low quality (0 to 3 points), 4 to 7 points , and 8 to 11 points  .b)ClinicWe adapted every clinical question addressed in each included review into a PICO format, which specifies the types of population (participants), types of interventions (and comparisons), and the types of outcomes of interest . We clasWe obtained 1791 records from the search after removal of duplicates. Following screening of titles and abstracts, 143 articles were obtained in full text for a final decision. A total of 41 reviews fulfilled the inclusion criteria for the final analysis, of which 17 SRs are focused –36 on GIAmong the 17 included SRs, 10 included a meta-analysis. All SRs were published between 2005 and 2015 including studies conducted between 2001 and 2014. Only two SRs reported a detailed search strategy that allowed replication , 30. A tSeven systematic reviews did not include any controlled clinical trials –32, 35, Patients with localised GIST: Five systematic reviews , 31, 35 Patients with localised KIT (CD117)-positive GIST after complete surgical resection: two SRs , 29 whicPatients with unresectable and/or metastatic GIST: five SRs evaluated different comparisons , 34, 36.Patients with unresectable and/or metastatic GIST after failure of imatinib due to resistance or intolerance: four SRs addressing three different comparisons , 28, 33.Patients with unresectable and/or metastatic GIST after failure of imatinib and sunitinib due to resistance or intolerance: three SRs comprising three different comparisons , 22, 33:We extracted 14 PICO questions from related to GIST SRs. The key characteristics of the PICOs are presented in Table Although no standard definition of evidence mapping has emerged , these rFollowing these criteria, this evidence mapping has identified, described and organised the current available evidence for GIST, as part of a broader project aimed to map the existing evidence for the treatment of soft-tissue sarcomas. This mapping was based on 17 published systematic reviews including 66 individual studies conducted between 2001 and 2014. Regardless of the type of evaluated intervention, three quarters of the included studies in the SR were non-experimental . This is a phenomenon with important clinical and ethical implications since experimental studies are the best design to evaluate the efficacy of new therapeutic options. For instance, it is noteworthy that some clinical guidelines or systematic reviews , 37–39 aThe majority of the interventions reported as “beneficial” were palliative, probably due to a high proportion of patients experiencing relapse or a metastatic process. Another interesting finding was that only three studies assessed the quality of life as an outcome and none of them conducted an economic evaluation. Quality of life measures are very important in cancer care because they can provide information about the impact of diseases and their treatment on the well-being of patients, and complements efficacy and safety data . LikewisThe majority of the interventions were reported by authors as “beneficial” or “probably beneficial”. Only in one comparison between biologic agents  were the results controversial. As shown in the bubble plot, Fig.  one SR  concludeOverall, the quality of the SRs according to AMSTAR was moderate to high. However, the following domains have yet to be improved: reporting the excluded studies (only 4 studies out of 17 did it), the conflicts of interest, and the assessment of the likelihood of publication bias (only 12 did it). Similarly, 4 SRs did not report the quality of the included studies nor use it appropriately in formulating conclusions, one of them being (31) the review with more studies, the second one with more included patients, and the most updated evidence about metastatic GIST after failure of imatinib and sunitinib due to resistance or intolerance. Although the evidence mapping does not usually include a quality assessment process , we consThe Global Evidence Mapping Initiative (GEM) approach that we used is a rational, systematic and constantly improved methodology. A recent systematic review  showed tSome authors consider using highly specific search strategies for evidence mapping , 45. HowWe added two uncommon components in evidence mapping. Firstly, we rated the interventions included in the systematic reviews as “beneficial”, “probably beneficial”, “harmful”, “no effect” or “inconclusive” according to the authors’ conclusions, irrespective of the reported outcomes. It is important to highlight that we did not evaluate the quality of the evidence of the studies included in each SR, which makes this approach shorter than the one required by a SR and appropriate for its descriptive purposes although the provided information is less complete. Secondly, we assessed the quality of included systematic reviews with AMSTAR. This approach allows displaying the results on a bubble plot for each SR with respect to the other ones with the same comparison, providing a quick view of the existing evidence and their quality.According to this experience, the most time-consuming phases were classifying the interventions and extracting the secondary PICOs. Although the time spent in an evidence mapping can vary depending on the topic, we recommend elaborating a protocol before starting the project and performing a pilot study as we did.Some limitations were faced in this study. Firstly, our search for SRs was conducted in 2016 but their respective searches were done much earlier, being the most updated search until 2014. Therefore, we cannot guarantee a comprehensive identification of all primary studies about sarcomas that may have been published beyond this date. However, we believe that these limitations would not substantially change the main results of this evidence mapping. Secondly, as it is a characteristic of all evidence mapping methodologies, we did not assess the quality of the evidence supporting the conclusions, which would have required the use of some complementary criteria such as GRADE . In ordeTherefore, the main practical applications of evidence mapping are: to orientate further research projects; to stimulate the design of more focused RCT and other rigorous evaluative studies to fill the detected gaps in knowledge; to provide useful comprehensive information for establishing priorities when funding research in this field; to compare the obtained results with the recommendations from clinical guideline in order to identify and solve potential contradictions between them; to help future authors of SRs, rapid reviews and scoping reviews avoiding redundant efforts and improve efficiency; and, to explore innovative tools and friendly formats to disseminate the results to interested stakeholders.From a practical point of view, this evidence mapping shows a relatively high consistency of effects reported by the different SRs, except for two SRs  Fig. . The quaIn conclusion, the most common type of study to evaluate therapeutic interventions in GIST sarcomas has been non-experimental studies , frequently based on small samples sizes. The quality of the included SR was moderate to high. The evidence mapping is a useful and reliable methodology to identify and present the current available evidence about therapeutic interventions. Therefore, these results can be helpful to facilitate any review process that may be conducted and orientate research priorities.Additional file 1:Search strategies. (DOCX 44 kb)Additional file 2:SRs excluded. (DOCX 18 kb)


Since the 1990s, laparoscopic surgery (LS) has been a true revolution in the field of surgery. LS decreases the lesions inherent in surgical access modalities, reducing operative morbidity and reaching similar or even better results than those related to open surgery (OS) , and wheInterestingly, in parallel with LS and in response to limitations in the understanding and use of published evidence, evidence-based medicine (EBM) began as a movement in the early 1990s and integrates clinical judgment, recommendations from the best available evidence and the patient's values . In geneObservational studies (ObS) are clinical research designs whose goal is the observation and description of events without any intervention in their natural course. ObS represent 80% of the publications in biomedical journals, independent of the database indexing and eventual impact factor of each journal . Most ofProbably, well-conducted RCTs are the best type of study for determining whether there is a causal relationship between intervention and effect . AlthougAlongside high-quality RCTs with a low risk of systematic error (bias), meta-analyses of these provide the highest level of evidence . DiffereRegarding end-ileostomy, only two observational studies , 18 and Based on the current data, PH prevention with mesh in the context of laparoscopic approach is an unresolved issue. Most research is observational with positive findings and conclusions in favor of the use of a prophylactic mesh in terms of safety and efficacy –19. HoweMLC designed the study, reviewed the literature, wrote the paper, and prepared the final draft. JAP reviewed the manuscript and approved the final draft.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.