At this conference the Director General of the WHO, Halfdan Mahler, succeeded incoalescing the often disparate views and agendas of the representatives of 134 governmentsand crafted a statement which may now be considered prophetic for its time. In thisstatement the delegates unanimously agreed that, "the time has come for all levels of thehealth system to review critically their methods, techniques equipment and drugs, with theaim of only using those technologies that have really proved their worth and can beafforded"16. A decade later Gordon Guyatt8 (1991) coined the phrase "evidence-based medicine" and theadvocates of evidence-based medicine proclaimed a shift to a "new paradigm", in whichhealthcare decisions should be based on the best available evidence obtained through theuse of robust research methods7.A sound knowledge of the effectiveness of healthcare interventions is not only arequirement but an ethical imperative for all clinicians. Appeals for the improvedassessment of effectiveness in healthcare interventions have an extensive history. The mostrecent of these has led to the growth of the evidence-based healthcare movement, generallybelieved to have originated in the late 70’s with the work of White, Cochrane and Illich,the unreservedly recognised giants of clinical epidemiology. The World Health Organisation(WHO) added to the momentum through the timely release of a statement at the Alma-AtaConference14. The inadequacy ofthis definition, by apparently excluding the patient from the decision process, motivatedits subsequent revision by Sackett to highlight the contemporary view of the patient as apartner in the concept and it is now defined as, "the integration of best research evidencewith clinical expertise and patients values"13. The recrafting of this definition appears to have "strengthened" thecontribution of clinicians’ individual skills, conceivably to allay their fears of a"prescriptive" slant to the concept.Sackett and his colleagues define Evidence-based medicine (EBM) as, "the conscientious,explicit and judicious use of current best evidence in making decisions about the care ofindividual patients"2 (1992) whoexamined the accumulated evidence, over the period 1960-1990, on the effectiveness ofanti-arrhythmic and other medications, to reduce the risk of heart attack. They thencompared the "current best evidence" to what interventions the "experts" were recommending.Their study found major discrepancies between the accumulating evidence and the experts’recommendations. In most instances where studies showed treatments to be effective,experts’ recommendations lagged several years behind the evidence. In summary they notedthat some experts "have not yet mentioned effective therapies, while others continue torecommend those that are ineffective or possibly harmful"2.The discrepancies which occur with a reliance on expert knowledge alone have beenhighlighted by Antman, et al.13 claiming to be systematicreviews out of 1,184 articles published in that same time period. However none of thesewere registered with the Cochrane Collaboration, and of the 5 "systematic reviews" nonewere reviews of randomized controlled trials or controlled clinical trials alone.Evidence-based healthcare then seeks to support clinicians in choosing healthcareinterventions through the identification of high quality research evidence as a basis fordecision making. What impact to date has this had on the specialties of oral surgery, oralmedicine, oral pathology, oral radiology and endodontics? Taking one of the leadingjournals that cover these specialties as an example: between January 2001 and July 2005Oral Surgery Oral Medicine Oral Pathology Oral Radiology & Endodontics published 3articles5. Initially it wouldappear that the evidence based medicine movement assumed that the existence of high qualityevidence, summarized in systematic reviews and published in accessible formats would be ofitself sufficient to induce change in practice. However it has been recognized that such"passive" means of dissemination are insufficient to produce significant change inbehaviour4. In 1994 the CochraneEffective Practice and Organisation of Care (EPOC) group was established to identifymethods which could be adopted to improve professional practice and the delivery ofeffective health services11. Of course, in the tradition ofevidence-based medicine, the EPOC group achieves this aim through undertaking systematicreviews of the effectiveness of methods to improve practice. There is a growing recognitionthat these methods should include organizational, financial and regulatory interventions,rather than simply focusing on education.Dental specialty journals are not unusual in this slow adoption of evidence-baseddentistry. Despite a burgeoning interest in the conduct of systematic reviews and theproduction of clinical guidelines, interest and adoption of evidence based healthcare hasgenerally been slow amongst clinicians and educators despite its early connections withmedical education10 (2001) summarise thebarriers to the uptake of evidence-based dentistry by practitioners as: knowledge andattitude of the practitioner; patient factors; practice environment; educationalenvironment; the wider health system, and the social environment. McGlone and colleaguesargue that the culture of a society will determine patients’ expectations of medical anddental encounters, for example many patients attending a doctor or dentist in Westernsociety will have expectations of prescription, either of drug or other treatment leadingto for example the inappropriate prescribing of antibiotics12. Such cultural influences on the adoption of evidence basedhealthcare are likely to vary across countries. The culture of healthcare practice will bein part determined by the learning experiences of healthcare professionals during training.The concepts and methods of evidence-based healthcare should form the foundation of theteaching and learning of healthcare professionals.McGlone, et al.A health system which includes remuneration for treatment will encourage a practitioner toprescribe treatment regardless of effectiveness (particularly if the practitioner is notaware of evidence suggesting the intervention to be ineffective or harmful), and suggeststhat healthcare (and remuneration) should be organized to encourage the adoption of carebased on the best available evidence.4 (1998) were able to identify interventions which haveconsistently been found to be effective in promoting behavioural change in healthcareprofessionals: educational interventions were effective if they included an element ofoutreach with education taking place in the workplace, and if they were interactive (thatis they include discussion or practice of skills); reminders ; interventions which involved combinationsof methods such as reminders, audit and feedback, involvement of professionals in devisingguidelines. Educational materials and didactic educational meetings were consistently foundto have little or no effect on uptake of evidence-based care.Having identified the barriers to the adoption of evidence-based healthcare, what effectivetechniques can be adopted to promote a change in the behaviour of healthcare professionals.From a systematic review of 18 systematic reviews Bero, et al.17. Such an approach will avoid theunnecessary repetition of trials where a clear clinical effect (or lack of effect) has beenestablished. We recommend such a policy to the editorial boards of all dental journals.If evidence-based healthcare is to occupy a central role, as it should, in the decisionmaking process of clinicians then it is not sufficient for research to continue to providethe best evidence and hope that it is taken up by clinicians, active processes ofdissemination should be adopted including the introduction of structural changes (such asmodifications to systems of remuneration) that encourage the practice of evidence basedhealthcare. Perhaps the most appropriate technique for ensuring that evidence baseddentistry is adopted by practitioners is to encourage researchers to conduct and publishsystematic reviews. A recent Lancet editorial states that in future clinical trials willnot be accepted for publication in that journal unless there it is clear from a systematicreview of the literature that indicates the necessity for a new trial


Irinotecan (CPT-11) is a potent chemotherapeutic agent, however, its clinical usage is often limited by the induction of severe gastrointestinal (GI) toxicity, especially late-onset diarrhea. HuangQin Decoction (HQD), commonly used for the treatment of GI ailments, has been proved could significantly ameliorate the intestinal toxicity of CPT-11. To reveal the mechanisms of CPT-11-induced toxicity and the modulation effects of HQD, a previous untargeted metabolomics study was performed and the results indicated that HQD may protect the GI tract by altering the metabolism of bile acids (BAs). Nevertheless, the untargeted assays are often less sensitive and/or efficient. In order to further confirm our previous findings, here in this paper, serum and tissues metabolic profiles of 17 BAs were analyzed using liquid chromatography-tandem mass spectrometry based targeted metabolomics. The results indicated that serum and tissues levels of most BAs were significantly decreased after CPT-11 administration, except some hydrophobic BAs. Co-treatment with HQD could markedly attenuate CPT-11-induced GI toxicity and reverse the alterations of hydrophobic BAs. Despite the fact that the BAs pool size remained unchanged, the balance of BAs had shifted leading to decreased toxicity after HQD treatment. The present study demonstrated for the first time that the precise interaction between HQD, CPT-11-induced intestinal toxicity and BAs’ homeostasis. Irinotecan (CPT-11), a water-soluble derivative of camptothecin, is a highly effective chemotherapeutic agent which has been widely used in clinical practice to treat colon , gastricShang Han Lun of the Han Dynasty, has been established for more than 1800 years for the treatment of abdominal spasms, diarrhea, vomiting, and nausea, the same symptoms commonly observed toxic effects in cancer patients receiving chemotherapy (HuangQin Decoction (HQD), a traditional Chinese formulation from otherapy . Some anotherapy . HoweverScutellaria baicalensis Georgi, Glycyrrhiza uralensis Fisch, Paeonia lactiflora Pall, and Ziziphus jujuba Mill. The chemical components of HQD usually act simultaneously and synergistically on multiple targets in the body based on holistic concepts. Metabolomics, a novel holistic approach to study metabolic changes, is consistent with the spirit of Traditional Chinese Medicine (TCM). Focusing on endogenous metabolites will provide a global insight into the actions of HQD. Previously, an untargeted metabolomics study using gas chromatography-mass spectrometry (GC/MS) and ultra-fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry (UFLC-IT–TOF/MS) in combination was performed. The study demonstrated that HQD is really a kind of effective modulators of CPT-11. Meanwhile, the potential endogenous metabolites changes associated with CPT-11-induced perturbations and HQD treatment were screened out -based targeted metabolomics.S. baicalensis Georgi (Hebei Province), G. uralensis Fisch (Inner Mongolia of China), P. lactiflora Pall (Anhui Province), and Z. jujuba Mill (Henan Province) were authenticated by Dr. Ehu Liu .Cholic acid (CA), glycocholic acid (GCA), taurocholic acid (TCA), chenodeoxycholic acid (CDCA), glycochenodeoxycholic acid (GCDCA), taurochenodeoxycholic acid (TCDCA), ursodeoxycholic acid (UDCA), glycoursodeoxycholic acid (GUDCA), tauroursodeoxycholic acid (TUDCA), deoxycholic acid (DCA), glycodeoxycholic acid (GDCA), taurodeoxycholic acid (TDCA), taurolithocholic acid (TLCA), and cortisone acetate were purchased from Sigma-Aldrich . α-Muricholic acid (α-MCA) and tauromuricholic acid (TMCA) were purchased from Steraloids Inc . All other reagents and solvents were of high performance liquid chromatography (HPLC) grade. Deionized water was purified using a Milli-Q system . TM, Pfizer Inc., USA) directions and the published papers, to duplicate the clinical formulation: 20 mg/mL CPT-11, 45 mg/mL sorbitol , and 0.9 mg/mL lactic acid  dissolved in deionized water and subsequently heated to 70–90°C until the solution turned to clear. The pH was adjusted to 3.5 using 1 M NaOH. The resulting solution was sterile-filtered and stored protected from light until the moment of administration  was obtained as irinotecan hydrochloride. It was prepared, according to manufacturer’s  initially weighing 200 ± 20 g were used in present study. Animals were housed in a routine laboratory conditions with a temperature-controlled (25°C) environment and a 12 h dark/light cycle throughout the acclimatization and experimental periods. The experimental protocols were in accordance to the Guide for the Care and Use of Laboratory Animals and approved by the Animal Ethics Committee of China Pharmaceutical University (License Number: SYXK 2012-0035). After 1 week adaptation, rats were randomly divided into three groups either received vehicle alone, CPT-11 alone, or CPT-11 and HQD. The toxicity model was constructed by treatment of animals with CPT-11 at 150 mg/kg by intravenous injection (i.v.) once a day for two consecutive days . AnimalsFigure 1.Diarrhea observed immediately (occur within 2 h) after the dosing of CPT-11 and approximately 48 h after the final administration were considered to be acute diarrhea and late-onset diarrhea, respectively. Serum and tissues  were collected on day 5, the most severe day of late-onset diarrhea. After coagulation (1 h) and centrifugation , serum samples were aliquoted and then stored at -80°C until needed for preparation and analysis. Some tissue samples were used for histological examination and others were used for quantitative analysis. The scheme of the whole experiment is shown in Tissue sections  were dissected on the most severe day of late-onset diarrhea (day 5), fixed in 10% neutral formalin and stained with hematoxylin–eosin. The routine histopathology assessment was performed in a blinded manner.m/z. Nitrogen was used as sheath (40 arb) and auxiliary (25 arb) gas. Argon was used as the collision gas (1.0 mTorr). BAs with no reference (β-MCA and ω-MCA) were semi-quantified by using calibration curve of homologous standards (α-MCA). The main parameters for MS/MS detection of BAs as well as the internal standard cortisone acetate are summarized in Table 1.Metabolomic profiling of different classes of BAs in biological samples was assayed by a LC-MS/MS-validated method. Serum samples were thawed at room temperature. A total of 200 μL methanol and 10 μL cortisone acetate  were added to 50 μL serum and the mixture was vortexed for 5 min. After centrifuged twice at 16,000 rpm (4°C) for 10 min, the supernatant was used for LC-MS/MS analysis. Approximately 100–150 mg tissue samples, including liver and intestines, were homogenized in 10 volumes of methanol. After 10 min of centrifugation , 50 μL supernatant was spiked with 10 μL IS and 150 μL methanol, vortexed, centrifuged, and then used for further analysis. The separation was finally carried out on a ZORBAX Eclipse XDB-C18  (Agilent Technologies). The mobile phase consisted of (A) acetonitrile and (B) 0.1% formic acid. The gradient elution started with 25% A for 20 min, linearly increased to 60% B in 65 min and brought back to 25% A in 5 min followed by 10 min of re-equilibration. The mass spectrometry (MS) analysis was performed in a triple quadruple TSQ Quantum mass spectrometer via electrospray ionization (ESI) interface . The parameters were as follows: ESI (-), spray voltage, 3.8 kV; capillary temperature, 380°C; scan width for multiple-reaction monitoring (MRM), 0.1 The method used in this study was developed in terms of linearity, accuracy, precision, extraction recovery, matrix effects, and stability following the compliance criteria described by Food and Drug Administration (FDA) guidance for Bioanalytical Method Validation. Charcoal-treated serum and tissues homogenates were served as biological matrices for the preparation of standards and quality control (QC) samples. Calibration curves were constructed by plotting the peak–area ratio of each BA to IS versus the concentrations of the BA in each corresponding matrix. Intraday and interday accuracy and precision were determined using 3QC concentrations distributed throughout the calibration range for each analyte. Extraction recoveries only took into account the efficiency of the extraction procedure. Matrix effects were determined by adding the analytes to each blank matrix after extraction and compared with the same amount of analytes in pure solvents. The freeze–thaw, short-term, long-term, and post-preparative stability of the BAs were also investigated in current method.U-test . Differences were considered the results with P-values <0.05.All the results are present as mean ± standard deviation (SD). The multivariate data analysis, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were conducted by SIMCA-P . Statistical evaluations were performed using non-parametric Mann–Whitney A fully validated method is appropriate for all the determinations. The accuracy ranges from 86.85 to 111.81% in all tested samples. Precision, measured as coefficient of variation (CV), was below 14.37 and 13.30% for intraday and interday for all BAs, respectively. In terms of linearity, the regression coefficients for all the calibration curves of BAs were higher than 0.99. Extraction recoveries at all QC concentrations were >83.42% in serum, >71.79% in liver, and >78.46% in intestine. No significant matrix effects for BAs were observed. In addition, stability studies indicated that BAs were stable in serum and tissues for at least 8 h at room temperature, at least three freeze–thaw cycles, in the -80°C for 2 weeks, and also in the reconstitution solution at 16°C for 12 h.Figure 2). Histological sections verified that the CPT-11-induced toxicity model was successfully produced in present study and co-treatment with HQD effectively ameliorated the intestinal damages induced by CPT-11.As anticipated, marked intestinal pathological changes were observed in rats received CPT-11 alone, including epithelial degeneration, villus shortening, gland atrophy, inflammatory cellular infiltration, and submucosal edema. The histologic lesions were extremely severe in ileum, followed by cecum, and minimal in jejunum and colon. Conversely, liver histology appeared normal. These intestinal damages were significantly alleviated in rats co-treated with HQD (Table 2).Rats repeated dosing CPT-11 (150 mg/kg/day i.v.) for two consecutive days appeared serious anorexia and rapid decrease in body weight, reached 85.57 ± 2.20% of initial body weight by day 5. However, rats co-administered with HQD significantly attenuated body weight loss (91.49 ± 2.54% by day 5) and had a higher food intake level as compared with rats only received CPT-11. In addition, severe acute (occurred within 2 h after CPT-11 injection on days 1–2) and late-onset  diarrhea were observed in rats treated with CPT-11 alone. Rats co-administered with HQD significantly improved the late-onset diarrhea induced by CPT-11, but failed to prevent the acute diarrhea on days 1 and 2. As expected, rats received the vehicle alone did not show any significant signs of toxicity. None of the rats died during the experiment . The quantitative results showed that HQD mainly regulated the hydrophobic BAs . Hydrophobicity is an important determinant of the biological activity exhibited by BAs .BAs, the end products of cholesterol metabolism, are major components of bile. They are synthesized exclusively in the liver and further delivered to the intestinal tract, where they are metabolized by the gut microbiota into the secondary BAs. In addition to digesting and absorbing of lipids, BAs are also important signaling molecules that are involved in regulation of various metabolic processes via activation of some specific nuclear receptors and G protein-coupled receptor . Researc+ T cells  ligands   remained unchanged, it was of interest to note that multiple unconjugated and conjugated hydrophobic BAs were significantly decreased in serum and tissues of rats upon HQD treatment. Besides, the global BAs metabolic profiles in HQD group was more similar to normal control group. Although the mechanisms behind why HQD could regulate the BAs metabolism homeostasis were not solved in this paper, it has been reported that the bioactive constituents of HQD can directly interfere with the normal metabolism of BAs. For example, some natural flavonoids like baicalein and chrysin in  ligands , 2013. Gor (FXR) . Both PXor (FXR) . Liquirior (FXR) . P. lactchanisms . What’s chanisms . Since tchanisms . Thus, wIn the present study, LC-MS/MS based targeted metabolomics revealed for the first time that the effects of CPT-11-induced intestinal toxicity and HQD’s ability on rat enterohepatic BAs. Compared with total or selected individual BAs level, a whole profile of BAs subspecies may more sensitively reflect the information about intestinal malfunction. Tissues and serum levels of most BAs were significantly decreased after CPT-11 administration, except some hydrophobic BAs. Co-treatment with HQD could markedly attenuate CPT-11-induced GI toxicity and reverse the alterations of BAs. Despite that there was no change in total BAs levels compared with model group, the balance of BAs had shifted leading to decreased toxicity after HQD treatment. Although the mechanisms behind why specific BA was elevate or decreased in diarrhea rats and why HQD could improve the BAs metabolism homeostasis were not solved in this paper, the value of further research was emphasized.XW carried out most of the studies, performed statistical analysis, and wrote the manuscript. DC and XD participated in the animal experiments. JW and WZ provided professional advices. ZZ and FX designed the study and revised the manuscript. All authors have read and approved the final version.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. The reviewer JW and handling Editor declared their shared affiliation, and the handling Editor states that the process nevertheless met the standards of a fair and objective review.


Up to 70% of lung cancer survivors are affected by chronic obstructive pulmonary disease (COPD), a common, debilitating, comorbid disease. Lung cancer and COPD are both characterized by symptoms such as breathlessness, fatigue, and psychological distress. These distressing chronic symptoms are exacerbated by stress and detract from an individual’s quality of life.The aim of this study was to identify and evaluate evidence-based, commercially available apps for promoting mindfulness-based strategies among adults with a COPD or lung cancer history .For this review, an interdisciplinary research team used 19 keyword combinations in the search engines of Google and iOS app stores in May 2017. Evaluations were conducted on the apps’ (1) content, (2) usability heuristics, (3) grade-level readability, and (4) cultural sensitivity.The search resulted in 768 apps (508 in iOS and 260 in Google stores). A total of 9 apps met the inclusion criteria and received further evaluation. Only 1 app had below an eighth-grade reading level; the ninth one did not have enough text to calculate a readability score. None of the 9 apps met the cultural sensitivity evaluation criteria.This systematic review identified critical design flaws that may affect the ease of using the apps in this study. Few mobile apps promote mindfulness-based strategies among adults with chronic lung disease , but those that exist, overall, do not meet the latest scientific evidence. Recommendations include more stringent regulation of health-related apps, use of evidence-based frameworks and participatory design processes, following evidence-based usability practices, use of culturally sensitive language and images, and ensuring that content is written in plain language. Prevalence of Lung Cancer and Chronic Obstructive Pulmonary DiseaseLung cancer is the second most commonly diagnosed cancer in the United States, accounting for 13.2% of new cases in 2017 -6. In paMindfulness-Based Stress Reduction for Chronic Lung DiseaseThe 5-year survival rates have steadily improved over the past decade for chronic lung disease; however, these rates are highly dependent on the stage of disease at the time of diagnosis -12. EffoWith the growing ubiquity of mobile technologies, survivors are increasingly using the Internet as a resource for health information . AccordiBesides Coulon et al’s  review oA total of 19 keyword combinations were created using COPD or Lung Cancer, followed by MSBR, meditation, breathing, diaphragmatic, stress management, progressive muscle relaxation, or yoga. Each combination was searched in Google and iOS app stores in May 2017 using compatible mobile devices see .. Drawing on the work of Coulon and colleagues .-23.21-23Readability was evaluated using the approach employed by Smith and colleagues . ReadabiTo our knowledge, there are no validated measures for evaluating the cultural sensitivity of commercially available apps. Therefore, we adapted the Cultural Sensitivity Checklist (CSC) developed by Friedman and Hoffman-Goetz  to evaluDomain 1: evidence of scienceApp contains terminology (or other form of) evidence, research, science, and/or studyApp contains scientific reference for the app strategyApp contains evidence that it was developed by an established institution that conducts researchDomain 2: scientific strategy and engagementApp contains a skill-building, behavior-change component as evidenced by skill-related instructionsApp provides available opportunities for continued engagementDomain 3: evidence-based stress management strategies and structuresStrategiesDiaphragmatic breathing refers to slow, paced breathing in through the nose and out through the mouth by contracting the diaphragm or distending the abdomen; monitoring muscle tension while tensing and releasing muscles sequentially throughout the bodyMeditation, mindfulness refers to intentional focus on thoughts and sensations experienced in the present moment, without judging them positively or negativelyCognitive restructuring refers to the identification, evaluation, monitoring, and altering specific thoughts that may be distorted, unhelpful, or maladaptiveActive coping, behavioral activation refers to goal setting and engagement in activities that may improve mood and a sense of wellness, with the purpose of preventing or decreasing avoidant and isolative behaviors that can occur in times of duressSeeking social support refers to engaging with trusted others who may provide emotional or functional supports Problem solving refers to an attempt to remove a stressor, or to reduce its magnitude, frequency, or duration, by describing the problem, brainstorming solutions, selecting and testing a solution, and refining the solutionVisualization, imagery refers to the use of the 5 senses to imagine a specific stimulus  in great detail, to achieve a state of relaxation, pleasure, or comfortStructuresAssessment: App provides an opportunity to complete a measure of perceived stressSelf-monitoring: App provides ongoing opportunities to rate perceived stress and/or behavioral indicators of evidence-based stress managementPsychoeducation: App provides educational information on the benefits of evidence-based stress management strategies and/or mechanisms of actionDomain 4: transparent app presentationAuthoritative: App should state the qualifications of the app authors or developers; states degrees and/or specific training should be presentComplementary: App should state that the app content should support, not replace, medical care and provider-patient relationshipsConfidentiality or privacy: App should state the privacy and confidentiality securities for personal data submitted to the site by the userReferences: App should state the source(s) of published informationJustification: App should state the content of published information that supports claims relating to benefits and performanceContact details: App should provide information for contacting developers or app managersFinancial disclosure: App should identify funding source, company, or publisherAdvertising policy: App should distinguish advertising and paid-service content from editorial contentOf the 9 evaluated apps, 7 contained no indication that they were supported by science. Of the 2 remaining apps, 1 somewhat met 1 criterion because it included external links to national organizations, though it did not specify whether its content was based on the linked guidelines. The final app almost met the criteria for this domain. It was developed by a company known for conducting research, though it contained no scientific references.Of the 9 apps, 5 fully met this domain’s criteria. Of the remaining 4 apps, 2 only partially met domain 2 criteria—specifically, the criterion for continued engagement . However, this app failed to provide instruction on how to use its skill-building content. The 2 remaining apps did not meet any of this domain’s criteria.Of the 9 apps, 3 contained at least one evidence-based stress management strategy and at least one structure. Of the remaining 6 apps, 3 did not have at least one strategy and structure. Of the other 3 apps, 1 did not contain any evidence-based strategies, but somewhat included 2 potential, evidence-based structures through a breathing measure. Given that no empirical evidence was provided, we were unable to establish that these structures were evidence-based. The 2 remaining apps partially contained 2 strategies. One of the apps recommended seeking social support but did not provide tools or resources to do so; the other app contained breathing exercises, but we were unable to establish if these were consistent with diaphragmatic breathing. Of the 2 remaining apps, 1 did not contain any evidence-based structures and 1 app somewhat seemed to contain all 3 structures. Again, however, we were unable to establish that these structures were evidence-based. Among the apps that had at least one evidence-based stress management strategy, the most common strategies were meditation and mindfulness, diaphragmatic breathing, and seeking social support. The most common evidence-based structures were self-monitoring and assessment.Of the 9 apps, 2 did not meet any of this domain’s 8 criteria, and none met all criteria. Some of the apps were predominantly educational and did not collect user data; thus, we did not expect these apps to meet the confidentiality and privacy criteria. Only 1 app met 5 criteria, but it, along with all the other apps, failed to meet the references and advertising policy criteria. However, the latter unlikely applied to this app given that it contained no advertisements. The most commonly met criteria were presentation of contact details and indication that app content intended to complement rather than replace professional medical care.Usability varied across the apps . Of the Visibility was problematic in 8 of the 9 apps. In particular, some apps had a complex navigation structure, including a lack of headers and feedback, leading to feeling lost in the app. Moreover, 4 apps utilized a small font size, problematic for many cancer survivors over the age of 50 years.A mismatch between the system and the real world was another usability issue, problematic in 7 apps. Examples included the use of technical jargon, a disorganized menu, and use of advanced yoga terms not obvious in meaning to novice users.A third usability heuristic was error prevention. Of the 9 apps, 8 contained issues related to disorganized content or functions, or buttons too close together. Furthermore, some apps that required health information , or self-report of medication practices, did not allow users to edit information they had entered or made it very difficult to enter information (due to font size or entry fields).All 9 apps contained issues related to recognition rather than recall. Instructions were often hard to find . Some apps had so much functionality that they were overwhelming to first-time users. This led to difficulty in navigation, how to use specific functionality , and even how to figure out the app’s purpose. There were 2 apps that did offer a tutorial for first-time users, and this feature mitigated some of these recognition or recall issues.Finally, 8 of the 9 apps contained help and documentation issues. Similar to recognition issues, many of these problems stemmed from a lack of, or difficult-to-find, instructions. Furthermore, developer contact information was often unavailable, making it difficult to request help or report an issue.Of the 9 apps evaluated, none met any of the CSC criteria. One of the apps was predominantly intended for tracking symptoms and thus contained minimal text, making it difficult to evaluate cultural sensitivity .Of the 9 apps evaluated, 3 focused on providing support for individuals with asthma , 2 aimed to support individuals with COPD , 2 provided general relaxation and breathing training , and 2 contained videos and exercises to support individuals with lung cancer .Though all 9 apps were marketed as breathing management and stress reduction, only 3 met the criteria for having both an evidence-based stress management strategy and an evidence-based stress management structure , and neither referenced peer-reviewed literature or other scientific evidence. In addition, most apps either met or partially met the criteria for being interactive or engaging, and over half of these incorporated a skill-building component. For example, in addition to offering breathing exercises and general lung education, Lung+ Pioneering Healthcare featured a multistage, interactive saxophone player breathing game that challenged players to blow rhythmically into their mobile microphones to the tune of jazz music.Transparency was variable across the apps with Lung+ Pioneering Healthcare meeting the most criteria (5 of 8). The average grade-level readability in our review was 10th grade, which is 2 grades above the acceptable level . Many ofThis review focused on evaluating apps for the most common, evidence-based stress management techniques . Therefore, less-common evidence-based stress management strategies may be used but were excluded in our review.Compared with Coulon and colleagues’ findings , the appRegarding transparency, our review produced results consistent with those of Coulon and colleagues , but criFinally, our review included a comprehensive heuristic evaluation to determine usability, which was more in-depth than the review by Coulon and colleagues . TherefoOn the basis of our evaluation, we make 5 key recommendations for improving the quality of commercially available apps aimed at adults with a COPD or lung cancer history.Institute more stringent regulation of apps for health. Apps that make therapeutic claims or present health-related information should be required to cite scientific evidence to substantiate their claims or information. These apps should also contain prominent disclaimers about the outcomes a user should expect, particularly when claims are made about benefiting users’ health. Currently, no federal regulatory standards govern the production of commercially available, health-related apps  [ucation) . The Fooucation) . Languagucation) . Beyond ucation) . For a mUse evidence-based frameworks and participatory design processes for app design. Although both Apple and Google provide guidance for app development largely based on industry standards, the apps evaluated were highly variable in the extent to which they executed these guidelines. Usability standards should be updated for mobile devices because most current guidelines were built with desktop layouts in mind. More specifically, Yáñez Gómez and colleagues [lleagues  recalibrlleagues  heuristilleagues . ConformIn addition to normal user testing, which is part of a traditional app development cycle, Owens  has recoUse culturally sensitive language and images in health-related apps. Although lung cancer mortality is more common among African Americans [mericans  and thismericans , no appsmericans ,42. Genemericans ,44. Howemericans ,28. To emericans . These tEnsure that apps are written in plain language. One objective of the US Department of Health and Human Services’ Healthy People 2020 initiative is to improve health literacy [literacy . Health literacy ,47. Indiliteracy . There aliteracy . One strliteracy . The Plaliteracy . One priliteracy . Althougliteracy . Readabiliteracy . Many scliteracy , but it Follow evidence. Our target user group consisted of lung-cancer survivors, typically aged 50 years and older. Apps designed for this population need to use larger font (for better visibility), employ nontechnical language , have features that mitigate the ability to introduce errors when entering information , accommodate users’ working memory limitations , and provide ample help if or when users encounter problems (help and documentation). These recommendations mirror evidence-based design recommendations for older users [er users . FollowiFew mobile apps exist for promoting mindfulness-based strategies among adults with a chronic lung disease. Among those available, few meet the criteria for the 4 content evaluation domains . Although the usability of apps reviewed varied greatly, most had design flaws that may compromise their helpfulness to populations with low technology usage or self-efficacy or limited experience with apps. In addition, the app content was not culturally sensitive or written for audiences with lower reading levels. To enhance the accessibility of evidence-based, commercially available apps for promoting mindfulness-based strategies among adults with a chronic lung disease, we outlined 5 key recommendations. Future research should assess the feasibility and efficacy of implementing these recommended processes within an app development lifecycle. Additionally, future app reviews should also include an assessment of apps for potentially harmful strategies.


A shift in the culture and practice of health and development research is required to maximise the real-world use of evidence by non-academic or non-research-oriented audiences. Many frameworks have been developed to guide and measure the research utilisation process, yet none have been widely applied. Some frameworks are simplified to an unrealistic linear representation while others are rendered overly complex and unusable in an attempt to capture all aspects of the research utilisation process. Additionally, many research utilisation frameworks have focused on the policy development process or within a clinical setting, with less application of the translation process at the programme level. In response to this gap – and drawing from over a decade of experience implementing research utilisation strategies – we developed a simple, four-phase framework to guide global health and development efforts that seek to apply evidence to policies and programmes. We present a detailed description of each phase in our framework, with examples of its relevance and application illustrated through our own case study experiences in global health. We believe the utility of this framework extends beyond the health sector and is relevant for maximising use of evidence to achieve the Sustainable Development Goals. In 2004, WHO published the World Report on Knowledge for Better Health , emphasiIn response to the know–do gap, publications on the conceptualisation of research utilisation (RU) – a term that is often used interchangeably with knowledge translation, research uptake or evidence-informed policy – have increased, and included identification of barriers and facilitators to use as well as strategies to improve research uptake , 3, 5, 8Additionally, published RU frameworks have focused largely on the policy development process or within a clinical setting, with less application of the translation process at the programme level , 16–19. In response to the need for a RU framework driven by both policy and programme needs, inclusive of specific RU strategies and applicable to LMICs, we developed a simple, four-phase framework that builds on the current RU literature and reflects over a decade of experience implementing RU strategies to improve global health policy and practice.Figure We present a description of each phase in our framework and provide examples of its relevance and application within global health research, policy and programming. Although we focus on our experiences in global health, we believe the utility of this framework extends beyond the health sector and is relevant for concerted action to achieve the Sustainable Development Goals.The three categories of key actors represented in the framework are evidence producers, knowledge brokers and end users of evidence. These key actors have differing roles and commitments throughout each of the phases. Individual evidence producers and knowledge brokers are typically from academic institutions and research or policy institutes such as think tanks, or are employed within research units of governmental or non-governmental organisations. Organisations and institutions may also be considered evidence producers and knowledge brokers, in addition to individuals. Evidence producers, as the name suggests, are those who lead the design and execution of research or data collection activities. Knowledge brokers are considered intermediaries to help communicate evidence and facilitate evidence use between producers and end users . End useThe capacity of individuals or institutions to perform these three key roles within a country may differ. For instance, the capacity of local evidence producers to supply high-quality research and data may be limited in some countries as compared to others; this is often the case in LMICs, though many donors have been directing resources for years toward building local research capacity , 22. Addto gain consensus about areas where increased research effort including collaboration, coordination, and investment will have wide benefits to society” [The foundation phase emphasises the engagement of various stakeholders to understand the most pressing knowledge needs and to set research priorities. Stakeholders who are involved in research priority-setting may include policy-makers, civil society representatives, researchers, donors, health providers, private sector representatives, advocates, implementing partner organisations and individual citizens. The primary aim of research priority-setting is “society” . The fouResearch priority-setting is particularly important in contexts with limited financial and human resources as it is essential to maximise the impact of research investments . HoweverPriority-setting at the country level should be country-led and feed into national strategies and implementation plans. Specific activities related to research priority-setting can include open fora, town hall meetings, conferences, targeted consultations or workshops. These activities allow different stakeholder groups to interact and identify synergies for achieving shared goals and objectives, within or across sectors.The research phase consists of study conceptualisation and implementation, including protocol development, data collection, and data analysis and interpretation. While researchers are the main actors during implementation and analysis within our framework, all key actors – evidence producers, knowledge brokers and end users – take part in study conceptualisation to ensure its relevance, which maximises eventual uptake of the findings. FHI 360 developed a RU planning tool, most often applied by the RU expert playing the knowledge broker role, as a guide to consider determinants of eventual uptake and to make decisions regarding research design, stakeholder engagement and communication strategies, and dissemination approaches. For instance, a key recommendation for intervention studies or pilot feasibility projects is to design the intervention as part of the existing system, rather than rolling out a highly complex and managed model, in order to increase the likelihood that it can be scaled up . AnotherEngagement of stakeholders throughout the research phase, not only during conceptualisation but also during the development of a research utilisation plan, data analysis and interpretation, and results synthesis, supports greater participation during dissemination and uptake of recommendations . Stakeho2At the end of the research phase, the framework notes a critical decision point – the decision to translate. The decision to translate is the active decision to develop and disseminate knowledge products based on research findings to drive thoughtful discussion and widespread use of the evidenced-based programme, practice or policy . IdeallyThe translation phase actualises the first decision to start turning evidence into actionable products for wide dissemination and use. Through its three sub-phases and a decision point, knowledge products are created, dissemination and advocacy activities are conducted to promote wide adoption of the evidence, and uptake of evidence-based practices or research results is actively supported. This phase is the longest in the framework, signifying that it often takes time to achieve uptake and transition to true institutionalisation.According to the framework, evidence producers and knowledge brokers work together to develop knowledge products that effectively synthesise evidence and facilitate its application to programmes and policies. Knowledge products may include evidence briefs, technical guidelines, programme and intervention guidance, and job aids. Studies with decision-makers have shown that key messages, or take-home messages, that are solution-oriented and in short form, such as evidence briefs, are more effective than a research report . TargeteA dissemination strategy for spreading research results or evidence-based practices to target audiences through the most effective channels , 35, whiThe decision to adopt the evidence-based programme, practice or policy is the second critical decision point along the framework and is made by end users, including communities, programme managers, implementing organisations or policy-makers . End useOnce end users have decided to adopt a piece of evidence into policy and/or programmes, it must be applied in real-life scenarios. To do so, evidence-producers and knowledge brokers may provide technical assistance to end-users to conduct study tours to see application of the evidence at scale, revise or update policies or norms, develop monitoring and improvement plans, and/or build technical capacity for implementation. Adoption and replication of an effective intervention or practice often requires the proper policies and guidelines that are relevant to the local context to be in place, testing and refining of the core programme elements, and training practitioners to implement appropriately, with ongoing assistance and capacity-building , 37, 38.It is important to note that a given RU effort may jump between or move concurrently through the subcomponents of the Translation phase, or between and through the Translation and Institutionalisation phases, as happened in our case study of community-based family planning (CBFP) in Zambia described below.Institutionalisation of evidence-based programmes, practices and policies is the main outcome of the evidence translation process. The institutionalisation phase is where evidence use is established as an organisational norm and proven interventions are maintained, funded and scaled-up . SustainIdentifying sustainable human resources and financing mechanisms are the biggest challenges in the institutionalisation of promising and innovative solutions in low-income countries. While low-income countries take on over 50% of the global disease burden, they account for less than 2% of global public health spending . EffortsHerein, we will describe a RU framework experience from a demonstration project of a CBFP programme in which depot-medroxyprogesterone acetate (DMPA) was added to the family planning (FP) methods already being provided by community-based distributors (CBD) in Zambia . In ZambThere were several key actors involved in the CBFP demonstration project in Zambia. End users were comprised of the Government of Zambia MOH officials, health workers and associations of health professionals, and non-governmental organisations implementing community health programmes in the country. Evidence producers were researchers at FHI 360, who led the research and supported implementation of the programme by Childfund Zambia. ChildFund staff were both evidence producers, as they were deeply involved in study design and data interpretation, and end users since, as they were able to incorporate findings into future programme implementation. Knowledge brokers included RU experts within FHI 360 who partnered with researchers and worked closely with implementers and end users throughout and after the study. The building, re-building and strengthening of relationships among key actors was instrumental in the institutionalisation of the programme, particularly as unforeseen changes in the government structures and policy-level stakeholders occurred during the process.strengthen family planning and contraceptive choice programmes, with a special focus on rural districts” [The 2006–2010 National Health Strategic Plan of Zambia identified “stricts”  as a keystricts” , 45. In With approval from the Government of Zambia, FHI 360 and ChildFund convened an initial stakeholder meeting to discuss the design of the pilot study to add injectable contraception to ChildFund’s CBFP programme. Government officials and national stakeholders requested measures of programme impact to be included, in addition to local confirmation of the safety, feasibility and acceptability of CBD agent provision of injectable contraception. From November 2009 to February 2011, a RU expert, acting as knowledge broker, supported the study during this phase, managing stakeholder engagement, contributing to study design, tracking cost information and documenting implementation details using the intervention tracking tool. Preliminary findings were presented to a small group of stakeholders in May 2011. At this meeting, a ‘decision to translate’ effectively occurred when the FP Technical Working Group made several recommendations to the MOH based on the preliminary findings. These included to continue provision of DMPA by CBD agents in pilot districts, develop a phased national scale-up plan, and revise policy to permit CBD agents to administer DMPA. During this time, a high level well-respected champion was brought on board to present at the meeting and help implement recommendations, greatly facilitating the transition to the translation phase.In this case study, activities overlapped between the Translation and Institutionalisation phases, with considerable movement between the two Fig. . FollowiInitial expansion within the pilot study districts and one new district began in January 2012 and required technical assistance to the MOH and the newly formed Ministry of Community Development, Maternal and Child Health to advance the policy change dialogue and foster high-level ownership of the Road Map. By July 2012, the government pledged to increase contraceptive prevalence through various strategies, including reducing barriers to task sharing and doubling budget allocations for FP, an important step toward institutionalisation. In September 2012, a delegation of Zambian stakeholders participated in a study tour to observe Rwanda’s robust CBFP programme and to engage with stakeholders around important policy-level and operational issues. Despite ongoing stakeholder engagement and advocacy during this period, DMPA services stalled by June 2013 due to the lack of policy change and funds. However, high-level endorsements, including from the First Lady of Zambia, helped spur subsequent actions, including a rapid assessment of the performance of CBD distribution of DMPA and development of a National CBD of Injectables Strategy. Additional technical assistance was provided in the development of the guidelines, training curriculum and programme implementation tools based on learning from the pilot project. On January 22, 2016, the Zambia MOH gave official authorisation to scale-up the use of CBDs in the provision of injectable contraceptives. With funding, tools and guidance in place, and technical capacity within implementing organisations, this decision reflects a substantive move into the institutionalisation phase.is simple enough for use by many different audiences, including end users of evidence;captures the fluid and dynamic RU process through its circular representation and explicit acknowledgement of feedback loops;is relevant for application in LMICs, having drawn from our organisational expertise working in these contexts;builds upon other evidence-based RU frameworks;highlights the important roles of, and interplay between, three categories of key actors, namely evidence producers, knowledge brokers and end users of evidence, all of whom must interact and collaborate for the success of RU efforts;focuses attention on the required inputs, including time and activities within the important translation phase;can be complimented by a suite of RU tools that we have developed.Ensuring that evidence is understood and meaningfully applied to programmes and polices requires intentional and systematic efforts. This simple, pragmatic framework provides a roadmap for the variety of inputs that are needed to undertake research with the end in mind, ensuring that key actors are engaged at various time points for the production and use of relevant evidence in programmes and policies. We have provided concrete examples of how RU activities within the framework phases were applied, drawing from a real-world case study of CBD of FP services in Zambia, just one of many experiences from over a decade of implementing global health research and programmes that helped to shape the development of this framework. In so doing, we aimed to add value over existing RU frameworks. Specifically, we posit that this framework:Like any framework, this one has its limitations. As we have already noted, it is impossible to develop a framework that will fit every practitioner’s needs, particularly for such a dynamic and complicated process as RU. We opted to keep this framework simple and, in so doing, may not have represented all of the complex systems in which global health and development programmes must work. Nonetheless, it draws upon and reflects a thorough examination of the complex dynamics involved in achieving research utilisation. There may be additional expenses for implementing RU strategies and applying the framework, such as use of knowledge brokers, which are unavailable in non-grant funded situations. Furthermore, many external factors that may dictate the success or failure of research and evidence uptake, such as capacity or political climate, are not visually captured.Like any process, it is important to evaluate whether the RU efforts actually result in increased uptake. Our framework emphasises building on evidence-based interventions, dynamic feedback and iterative processes; however, there is no visual evaluation component in the framework. While there is an increased recognition in the knowledge translation world of the need for evaluation of RU efforts, evaluation of these types of interventions is complex and assessing the impact of research uptake has often been limited to bibliometric methods , small sApplication of this framework offers the potential to improve policy and programmes by increasing the likelihood that research results will be relevant, well-documented, easily communicated and understood, scalable, and built upon existing systems. We hope that global health and development stakeholders will apply it, document its use, assess its utility and improve upon it. It is not enough to just invest in research.


There is however, no international consensus on how high quality CPGs should ‘look’; or on whether high quality CPGs from one country can be viably implemented elsewhere. Writing de novo CPGs is generally resource-intensive and expensive, making this challenging in resource-poor environments. This paper proposes an alternative, efficient method of producing high quality CPGs in such circumstances, using existing CPGs layered by local knowledge, contexts and products.Agreed international development standards underpin high quality We undertook a mixed methods case study in South African (SA) primary healthcare (PHC), building on findings from four independent studies. These comprised an overview of international CPG activities; a rapid literature review on international CPG development practices; critical appraisal of 16 purposively-sampled SA PHC CPGs; and additional interrogation of these CPGs regarding how, why and for whom, they had been produced, and how they ‘looked’.Despite a common aim to improve SA PHC healthcare practices, the included CPGs had different, unclear and inconsistent production processes, terminology and evidence presentation styles. None aligned with international quality standards. However many included innovative succinct guidance for end-users . We developed a three-tiered model, a checklist and a glossary of common terms, for more efficient future production of better quality, contextually-relevant, locally-implementable SA PHC CPGs. Tier 1 involves transparent synthesis of existing high quality CPG recommendations; Tier 2 reflects local expertise to layer Tier 1 evidence with local contexts; and Tier 3 comprises tailored locally-relevant end-user guidance.Our model could be relevant for any resource-poor environment. It should reduce effort and costs in finding and synthesising available research evidence, whilst efficiently focusing scant resources on contextually-relevant evidence-based guidance, and implementation. This reflects growing sophistication in clinical epidemiology, technical writing and application of new technologies to evidence synthesis. Changing CPG definitions over this time period highlight this evolution. The Institute of Medicine (IOM) described CPGs in 1990 as ‘Over the past 35 years, internationally-respected CPG development groups have been established, such as (but not limited to) National Institute for Health and Care Excellence (NICE)  and the However, the explosion of CPG activity internationally has led to lack of standardisation about how CPGs are written and the evidence presented. Comparing two or more CPGs on the same topic, even from respected international CPG developers, immediately highlights differences –8. Whilsde novo (new) CPG writing. This research focused on South African (SA) primary healthcare (PHC). Resources for SA CPG writing and evidence implementation have been constrained for three decades, despite the escalating and currently-unmet need for best-evidenced, standardised guidance to redress the increasing prevalence of communicable and non-communicable diseases [In this paper, we describe steps we took to develop a theoretical model aimed at efficiently improving the quality and uptake of contextually-relevant CPGs. Our research grew from a commitment to improve CPG quality, relevance and uptake in environments with limited resources for diseases –17. It iPHC became a SA government priority in the 1994 National Health Plan , 19. PHCEthics approval was provided by the South African Medical Research Council (HREC EC002-2/3014).To produce a simple theoretical model to underpin the efficient production of contextually-relevant good quality CPGs for resource-constrained environments.To identify and address gaps between international CPG standards, and the way evidence was presented in SA PHC CPGs, whilst recognising and addressing local contexts, implementation barriers and end-user needs –19.We conducted a mixed methods case study , 23 whicIn Study 1 (conducted October 2014- January 2015), we deconstructed the ‘mysteries’ of international CPG activities and nomenclature to establish a comprehensive current ‘state of play’ . Study 1st, 1990 to December 31st, 2014, to include publications since the IOM CPG definition was proposed [In Study 2 (conducted December 2014- March 2015), we undertook a systematic rapid review of English language literature reporting on methods of CPG development . The seaproposed , 29.In Study 3 (February 2015- April 2015), we used the AGREE II instrument  to assess the methodological quality of 16 purposively-sampled SA PHC CPGs . AGREE IFor Study 4, we extracted and collated further details from the Study 3 CPGs , regardiFor Studies 3 and 4, the AGREE II methodological quality scores were calculated as:median and interquartile ranges (IQR) for the six quality domains across the 16 CPGs; andoverall quality scores for each CPG. This calculation was undertaken by adjusting the AGREE II domain scoring rubric to include all 23 AGREE II items. Whilst this is not the usual AGREE II scoring approach , it provThe findings from Studies 3 and 4 were compared with international CPG terminology and production methods (Studies 1 and 2), to identify gaps, possible reasons for them, and solutions to improve SA PHC CPG quality.Our summary of the current ‘state of play’ of international CPG activity highlighted not only variability in CPG writing processes and terminology, but also fragmentation in how information was reported . This hi8. question generation; 9. considering importance of outcomes and interventions, values, preferences and utilities; 10. deciding what evidence to include and searching for evidence; 11. summarising evidence and considering additional information; 12. judging quality, strength of certainty of a body of evidence; 13. developing recommendations and determining their strength; 14. wording of recommendations and considerations about implementation, feasibility and equity; 15. reporting and peer-review; 16. dissemination and implementation; 17. evaluation and use; 18. updating [The rapid literature review identified 1501 potentially-relevant records . After screening for relevance, 83 potentially-relevant records were considered in full text. These included one recent comprehensive systematic literature review (102 references) , and 82 Whilst the SA PHC guidance documents were labelled ‘CPGs’, they had variable and generally low scores in the AGREE II methodological quality domains , and nonThere was no standard approach to how the evidence underpinning the SA PHC CPG recommendations had been identified, collated, evaluated or presented, and there was no evidence of utility for end-users in PHC settings. We first considered the content and quality of the five SA PHC CPGs developed by professional associations, and published in two peer-reviewed professional association journals  (2016–2017 impact factor 1.71) and Journal of Endocrinology, Metabolism and Diabetes of SA (JEMDSA) (no current impact factor listed)). The CPGs dealt with conditions of acute asthma in children (SAMJ), acute asthma in adults (SAMJ), COPD (SAMJ), hypertension (SAMJ) and Type 2 diabetes (JEMDSA) See . CompareWe then considered the 11 CPGs which were developed and published by the SA National Department of Health (NDoH), and compared these with international CPG practices. These CPGs provided either condition-specific guidance  or overall guidance for multiple conditions . There was variable information provided on the type and location of the evidence underpinning these CPGs, and no NDoH CPG outlined an evidence searching or appraisal process. Only two CPGs provided the names of experts involved in the writing. Guidance was presented as text, pictures, flow charts and/or decision-making prompts.To address our purpose of improving efficient production of quality, locally-relevant CPGs in SA, we then developed a theoretical three-tiered model from the case study findings, to bridge the quality gaps between the SA PHC CPGs, and international CPG standards .Tier 1 represents current, best-quality CPG recommendations, identified by systematic international searches for relevant CPGs that meet international quality construction standards –14. TierTier 2 describes evidence input from local experts, to put Tier 1 recommendations into context . This step potentially makes Tier 1 ‘what to do’ recommendations relevant to local evidence implementation, end-user needs, indigenous healthcare cultures, costs, feasibility, implementation barriers and patient engagement. Tier 2 draws on people with intimate knowledge of local health systems, contexts and challenges, as well as barriers and solutions to evidence implementation.Tier 3 describes end-user guidance documents (evidence products to support ‘how to do it’). These operationalise the findings of Tiers 1 and 2, and are written specifically to assist end-users to implement evidence. Based on our case study findings, we propose a standard nomenclature for Tier 3 documents.Evidence-based Summary Recommendations. This term could be used where recommendations and explanatory text have been transparently extracted from good quality CPGs, layered with local contexts, and presented as resource material to support best-evidence diagnosis and management of specific conditions in specific environments. These documents may also provide prompts for healthcare providers such as pictures and text descriptions, summary recommendations for practice, checklists and/ or resource material. The SA professional associations’ CPGs are best classified as evidence-based summary recommendations (see as an example the SA Hypertension Society CPG [iety CPG ).Patient Management Tools (PMTs). This describes patient management or decision-support tools designed for situations where frontline healthcare professionals have to make explicit, efficient and effective choices regarding diagnosis, immediate treatment and longer-term management. PMTs could variably include pictures and simple explanatory text, algorithms , symptom lists, management checklists, treatment choices and referral pathways. Many NDoH CPGs were presented as PMTs. An example of a PMT is PC 101 [s PC 101 .Protocols. Protocols provide step-by-step guidance on ‘how to do’ specific healthcare tasks . Standard operating procedures may also be called protocols. Protocols may be embedded in Evidence-based Summary Recommendations and PMTs. We propose that a guidance document could be called a ‘protocol’ when there is only one correct way to complete a task, and this can be outlined by a step-by-step diagram or a series of text prompts.To the best of our knowledge, this paper presents the first theoretical model designed to assist a resource-poor country to efficiently improve the quality of its CPGs.The term ‘CPG’ is internationally recognised as referring to documents that meet international quality construction elements  and scorde novo CPGs (Tier 1) should be questioned in resource-constrained environments. The requisite rigorous evidence-searching required to establish Tier 1 is usually expensive and time-consuming [We propose that investing effort in producing country- or organisation-specific onsuming , 9, 21. onsuming –8, 12–14We further contend that the acknowledged CPG focus in resource-constrained environments should be on local implementation, and not evidence-construction. Thus by carefully layering already available Tier 1 recommendations with expert input and local contexts, barriers to evidence implementation could be efficiently identified and addressed (Tiers 2 and 3) , 21, 34.Based on our case study findings, Tier 3 documents should be viewed as evidence products, as they are designed for specific purposes and end-users, aim to improve and standardise local healthcare practices, and be auditable. Many SA PHC CPGs provided innovative Tier 3 documents which succinctly presented evidence summaries for specific end-user needs, thus providing step-by-step information on ‘how to locally apply’ Tier 1 ‘what to do’ recommendations. They provided a range of ways of fitting evidence to local contexts, cultures, practices and settings, and they presented recommendations in ways that were simple, easy-to-read and navigate. We believed that the SA PHC CPG Tier 3 products reflected the highest scoring AGREE II domains of clarity of presentation, and scope and purpose , 30, as In order to facilitate standard classification of, and terminology in, clinical guidance documents, and to maintain standard reporting practices that meet international requirements for CPG credibility, we developed a checklist to assist CPG writers in resource-constrained environments to identify in which category their guidance document belongs, as well as the requirements for each category . We alsoThis research demonstrated that the quality of SA PHC CPGs could be readily improved by using available high quality CPGs, referencing them appropriately, and focusing scant resources on local implementation. We believe that our three-tiered theoretical model (including proposed Tier 3 nomenclature), checklist and glossary of terms presents a novel resource to underpin efficient high-quality CPG writing activities in resource-constrained environments, and where there is an urgent need for best-evidence implementation to improve local healthcare processes and outcomes. We have confidence that these resources have relevance worldwide, particularly in situations where limited resources could be better spent on putting available evidence into effective practice, and not on ‘recreating’ an already existing evidence-base.S1 Appendix(DOCX)Click here for additional data file.S2 Appendix(DOCX)Click here for additional data file.S3 Appendix(DOCX)Click here for additional data file.


The burden of traumatic and elective hip surgery is set to grow. With an increasing number of techniques and implants against the background of an aging population, the emphasis on evidence-based treatment has never been greater. The purpose of this study was to assess changes in the levels of evidence in the hip literature over a decade.Hip International, Journal of Arthroplasty, Journal of Bone and Joint Surgery and The Bone and Joint Journal were analysed. Articles were ranked by a five-point level of evidence scale and by type of study, according to guidelines from the Centre for Evidence-based Medicine.Articles pertaining to hip surgery from the years 2000 and 2010 in κ = 0.956, P < 0.01) and for levels of evidence . Between 2000 and 2010, the overall percentage of high-level evidence (levels I and II) studies more than doubled . The most frequent study type was therapeutic; the USA and UK were the largest producers of published work in these journals, with contributions from other countries increasing markedly over the decade.531 articles were analysed from 48 countries. The kappa value for the inter-observer reliability showed excellent agreement between the reviewers for study type (P < 0.001). We recommend that all orthopaedic journals consider implementing compulsory declaration by authors of the level of evidence to help enhance quality of evidence.There has been a significant increase in high levels of evidence in hip surgery over a decade (Level 2: economic and decision analysis. More than 1.7 million hip replacements were performed across the globe in 2013; this figure is expected to increase to 2.5 million by 2020 [The assembly of an experienced Orthopaedic Data Evaluation Panel (ODEP), whose role is to examine the evidence either supporting or refuting the use of certain implants and to apply a grading system depending on their performance, only supports the notion that high-quality evidence is having an ever greater influence on the usage of orthopaedic implants and is only set to increase in the future .The basic principle of evidence-based medicine (EBM) is that we should treat where there is evidence of benefit and not treat where there is evidence of no benefit (or harm) . Higher Journal of Bone and Joint Surgery (JBJS) introduced a section devoted to the promotion and dissemination of high-quality evidence in the year 2000 with randomised controlled trials (level I) forming the main contribution [JBJS is the same used by the authors in this study and is in accordance with the CEBM system.The Oxford Centre for Evidence-based Medicine (CEBM) classifies research into four main types: therapeutic, prognostic, diagnostic and economic. These are further sub-classified into five levels: I (high) to V (low) . The Jouribution . The metJBJS also notably introduced declarations of levels of evidence for research articles at the time of publication in January 2003; this practice is on the rise and looks set to continue. Furthermore, studies have shown that the grading system introduced by the CEBM can be reliably applied and that clinical investigators should pursue studies with a higher level of evidence whenever feasible [The feasible , 9.While recently published studies have shown some improvements in the quality of published orthopaedic research, the consensus decision is that the overall level of evidence remains low . ConsideThe aim of the current study was to investigate the trends of levels of evidence in hip surgery in the year 2000 and again 10 years later in 2010. The study aimed to analyse changes in the quantity of published evidence, the quality and type of this evidence (as per the CEBM), geographical variations in the origin of published studies and the inter-observer agreement of the classification of the level of evidence among the reviewers.Articles published in hip surgery journals in two specific years, 2000 and 2010, were analysed. The study intervals were from January 1, 2000 to December 31, 2000 and from January 1, 2010 to December 31, 2010.Hip International, affiliated to the European Hip Society; the Journal of Arthroplasty, affiliated to the American Association of Hip and Knee surgery; the Journal of Bone and Joint Surgery (JBJS), affiliated to the American Academy of Orthopaedic Surgeons (AAOS); and TheBone and Joint Journal (BJJ), affiliated to the British Orthopaedic Association (BOA). In 2013 the Journal of Bone and Joint Surgery  was renamed the BJJ. In this paper we shall refer to it as the BJJ despite the fact that it refers to the journal titled the JBJS-Br in both time periods captured.We included four well recognised journals that were affiliated to orthopaedic and hip societies. The journals had to be in the English language, and must have published in print and online for the entire period of study. We included Two independent reviewers (AC and AA) analysed the journals and graded them in line with the system described by the CEBM. Each article type was allocated into therapeutic, prognostic, diagnostic and economic, and level of evidence was assigned on a scale of I–V, with I being considered the strongest level and V the weakest level. Any disagreements were discussed with the senior author (AG) and the methodology described by Spindler et al. was used to reassess such papers before a final decision with regard to the article level or type was made . In thisThe methods section is carefully analysed to identify a study type  and a study design . From an EBM point of view, it is important to ask whether control groups were included, whether data was prospectively or retrospectively collected or, in the case or a diagnostic study, was the gold standard investigation used? The authors’ attempts to remove bias from their study is also noted: this can be achieved by the use of independent examiners, for example. The size and composition of the patient population is noted and importantly the length of follow-up as well as rates of patients being lost to follow-up. The statistical analysis is important, particularly as some statistical tests are appropriate for answering particular questions while others are not.The reviewers verified their own levels of evidence against the journal’s level where a level of evidence had been provided by the journal. Case reports with more than three subjects were treated as a case series rather than a case report, thereby upgrading the article from level V to level IV evidence.Published work that was excluded from the study included all animal, cadaveric and basic science studies as well as editorials, surveys, letters to the editor, technical tips and expert opinions.Inter-observer agreement was measured using the kappa statistic. Kappa values were assessed using the criteria described by Fleis .P value <0.05 was considered statistically significant.Fisher’s exact test was used to compare the proportions of the study types and levels of evidence by year of publication, and to compare the proportions of the study types and levels of evidence by journal. Fisher’s exact test was also used to examine the proportions of the study types and levels of evidence by year of publication within the five different journals. All statistical analysis was performed using Stata/IC version 12.1 . A 550 publications were reviewed. 19 papers were excluded as per our criteria, leaving 531 included studies.κ = 0.956, P < 0.01) and showed good agreement for levels of evidence .The kappa values for the inter-observer reliability of study type were excellent (Therapeutic studies constituted the majority of study type (85.7 %) with economic study types in the minority 1.3 %). Level IV evidence was the most frequent (48.6 %) with level I studies the least frequent (9 %) (Table .3 %. LevP < 0.01) (Table P < 0.001).From 2000 to 2010 there were statistically significant rises in the number of therapeutic studies, level I and level II studies  followed by the JBJS (29 %), whereas the BJJ had the least with 23 % high-level evidence publications  to 348 (in 2010). The USA and UK were the major contributors in both 2000 (60 %) and 2010 (48 %); however, contributions from outside these countries increased from 40 % in 2000 to 52 % in 2010  to be 31 %, which compares favourably to other orthopaedic sub-specialties such as foot and ankle, where just 10 % of papers were considered high-level , paediatIt is reassuring that scientific quality of hip-related literature seems to be improving over the last decade. This improvement coincides with an increase in the influence that high-quality evidence is having on the uptake of certain implants and techniques. In the UK this has been overseen by an experienced ODEP made up of senior surgeons and healthcare managers . This haJBJS introduced an author declaration of level of evidence in 2003 [The  in 2003 , which a in 2003 , 17.Epidemiology- and non-epidemiology-trained reviewers can apply the levels-of-evidence guide to published studies with acceptable inter-observer agreement ; this isThe vast majority of papers originated from the USA and UK in both 2000 and 2010, although there was an increasing contribution from the rest of the world. This increase in rest-of-world papers might reflect globalisation and an increased tendency to publish in English-language international journals, or in contrast might reflect an editorial policy that is attempting to be more inclusive.Limitations of this study include detection bias, as the reviewers were not blinded to the journal source. However, the method for inter-observer agreement of level of evidence has been established previously . We acknJBJS and Journal of Arthroplasty) showing significant levels of improvement in high-level evidence. We recommend that all orthopaedic journals consider implementing compulsory declaration of the level of evidence by authors at the time of submission to help enhance quality of evidence in our prestigious journals.We have demonstrated a trend towards higher level of evidence in hip surgery over a decade, with two journals (the


Intelligent machine health monitoring and fault diagnosis are becoming increasingly important for modern manufacturing industries. Current fault diagnosis approaches mostly depend on expert-designed features for building prediction models. In this paper, we proposed IDSCNN, a novel bearing fault diagnosis algorithm based on ensemble deep convolutional neural networks and an improved Dempster–Shafer theory based evidence fusion. The convolutional neural networks take the root mean square (RMS) maps from the FFT (Fast Fourier Transformation) features of the vibration signals from two sensors as inputs. The improved D-S evidence theory is implemented via distance matrix from evidences and modified Gini Index. Extensive evaluations of the IDSCNN on the Case Western Reserve Dataset showed that our IDSCNN algorithm can achieve better fault diagnosis performance than existing machine learning methods by fusing complementary or conflicting evidences from different models and sensors and adapting to different load conditions. As one of the core components of rotating machinery, rolling element bearings are used to constrain relative motions to only the desired motion and reduce friction between moving parts. Bearings are always expected to work 24 h per day in actual production. Any failure with the bearings may lead to unexpected consequence of the whole machine. As bearing failures always bring downtime, expensive repair and hidden cost to enterprises, real time monitoring and precise fault diagnosis are critical to avoid catastrophic damages.In the past decades, a variety of methods have been developed in bearing fault diagnosis, such as vibration analysis , acoustiIn addition to the application of diverse signal preprocessing approaches, many artificial intelligence methods have been applied to features extraction and classification, two main steps in bearing fault diagnosis. Time domain statistical analysis, multi-wavelet transformation and fast Fourier transformation are always used for features extraction. Feature selection methods such as principal component analysis (PCA)  and indeRecently, deep learning methods have received amazing success in pattern recognition and machine learning application domains due to their outstanding capability to learn complex and robust representations. Many classification problems have been successfully solved by various deep learning models such as deep belief network , deep BoAlthough the deep learning methods have achieved great success in fault diagnosis, there still exist two potential issues. First, selecting appropriate network structures, parameters, and algorithms is critical to the success of deep learning approaches. Second, the signal data in all current deep learning methods for fault diagnosis are from a single sensor, which may not provide reliable information in terrible working environments. The adaptability and the anti-interference ability of different sensors varies widely so prediction models based on single source of information could lead to misdiagnosis. It is desirable to exploit multi-sensor information source for more reliable fault diagnosis by effective information fusion approach, which is complicated by the fact that different sensor locations and sensor qualities.In this paper, we propose a novel algorithm that integrates deep neural networks with multiple sensor information with an improved Dempster–Shafer (D-S) evidence theory  based daThe rest of this paper is structured as follows. D-S Evidence Theory is a mathematical theory and general framework for reasoning with uncertainty, which allows one to combine multiple  evidences from different sources and arrive at a degree of belief  that takes into account all the available evidence. D-S evidence theory has been shown ,32 to acD-S evidence theory assumes a finite set of elements D-S evidence theory provides a very useful synthesis formula, which can combine evidence from different evidence sources. For k represents the degree of conflicting evidence and the coefficient 1/(1 − k) is called the normalization factor which ensures that the sum of BPAs can be unit.A, B, C, D, E and Θ are the elements of the frame of discernment, which contains all the categories and can be interpreted as the bearing fault types in our problem.The traditional D-S evidence theory presents a good method for evidence fusion. However, some limitations still exist, which can lead to failure on evidence fusion under certain circumstances such as some complex practical environment with probable conflicts of different evidence. Many researches have been done to solve the evidence paradox issue. k = 1, which causes the denominator of Formula (2) to become zero when we apply Formula (3) to the two evidences m1 and m2. Though evidences m1, m3 and m4 support the proposition, the D-S combination rule cannot be used to synthesize the evidences under this circumstance.In the complete conflict paradox, the conflict factor k can be calculated as k can be calculated as k = 0.99 and the BPAs (basic probability assignment) can be obtained as m(A) = 0, m(B) = 0.727, m(C) = 0.273 according to Formulas (2) and (3). Though evidences m1, m2, and m4 support the proposition A, m2 = 0 totally negates this proposition. Under this circumstance, the BPA for proposition A will always be 0 no matter how many and how strong other evidences support A.For 0 trust paradox, the total conflict factor k = 0.9998 and the synthesis results for propositions A, B and C is m(A) = 0, m(B) = 1, and m(C) = 0. Though all evidences support the proposition B with small BPAs, the synthesis result totally believes the proposition B is the right answer and denies other propositions which is contrary to common senses.For 1 trust paradox, the total conflict factor can be calculated as k = 0.9999 and the synthesis results are m(A) = 0, m(B) = 0.3571, m(C) = 0.4286, m(D) = 0, and m(E) = 0.2143. Though evidences m1, m3, m4, and m5 support proposition A with large BPAs, the synthesis results totally deny it due the high conflicts among evidences.For high conflict paradox, the total conflict factor can be calculated as To address these issues, we proposed an improved D-S evidence theory through Euclidean distance matrix and modified Gini index, as stated below.In this section, we will firstly calculate the similarity matrix through a Euclidean distance function. Then, we combine the similarity matrix with a modified Gini index to get the evidence credibility. We use the evidence credibility as weights to modify the original evidence and decrease the conflict evidence.N stands for the number of propositions in the frame of discernment thj BPA value of the thi evidence. Define thi row in BPA matrix Define NoteThus, we can get a distance matrixIn Equation (4), We define the regularized element for the following evidence credibility as below: Credibility factor ses to 0 .The regularized evidence credibility isThe credibility factor thj proposition of thi evidence of the raw evidence and After we get the creditable factor Because It should be noted that we introduce the end elimination mechanism here and set the minimum BPA to zero through the above expression. This will enhance the BPAs of other propositions intuitively and give higher confidence to the survived propositions. In fault diagnosis, we prefer the diagnosis result with higher probability intuitively.The above results are normalized for the comparison in the latter validation within the same range. The decision rule for the improved D-S evidence theory compares the modified BPAs and selects the fault proposition with the maximum BPA evidence as the fusion result.(1)D and its elements Calculate the distances matrix (2)Calculate the evidence credibility (3)m*(A).Calculate the probability of weighted proposition (4)Calculate the final evidence (5)Calculate the maximum In summary, there are five steps in our improved D-S evidence theory for evidence fusion:There are three steps in our IDSCNN diagnosis model: Data preparation, Model Training, and Model testing, as shown in Data acquisition and preprocessing are needed to train our CNN models, which is described as Blocks 1–5 in b for RMS values will be changed according to the size of RMS maps. Each sub band should have the same length except the last one if N/2 cannot be divided without remainder by the RMS map size. For example, if the size of RMS map is 32 × 32, b = 8192/(32 × 32) = 8 and if the size of RMS is 16 × 16, b = 8192/(16 × 16) = 32. For convenience of calculation, we take two kinds of RMS map sizes (16 × 16 × 1 and 32 × 32) as the size of our training data.Feature extraction from raw sensor data is critical in machine monitoring. As shown in  by Wade , who didAs shown in To investigate IDSCNN performance, we conduct three different ways to build the IDSCNN models: (1) we combine all the diagnosis results from CNN models trained with signals from the drive end sensor; (2) we combine all the diagnosis results from CNN models trained with signal from the fan end sensor; and (3) we combine all the results from CNN models trained with signals from both sensors. The results of the combinations will be discussed in section.To facilitate experiment verification and performance comparison with other related research, we evaluate our diagnosis models over the widely used bearing data from the Case Western Reserve University (CWRU) Bearing Data Center ,43. TherThus, we can get ten fault conditions for each load. The most common way for evaluating a deep learning model is using the training data for modeling and testing the performance of the model through the test data. In order to get an objective result, the test data should not appear in the training data; otherwise, the test result will be overly optimistic. Thus, we apply random uniform sampling to the original accelerator dataset. As shown in In this section, we present two sets of experiment results. In experiment set 1, we evaluate how well our improved D-S (IDS) evidence fusion model addresses the paradoxes compared with several existing fusion methods. In experiment set 2, we evaluate the performance of IDSCNN for bearing fault diagnosis and compare its performance with other methods.m1, m3, and m4 in complete conflict paradox; m1, m2, and m4 in 0 trust paradox; m2, m3, and m4 in 1 trust paradox; and m1, m3, m4, and m5 in high conflict paradox are all consistent evidences in the four paradoxes groups, respectively. The remaining propositions belong to conflict evidences. Traditional D-S evidence has been proved to fail in dealing with these four common paradoxes. Here we take four modified D-S evidence fusion algorithms from Yager [To compare the IDS method with existing evidence fusion methods, we take four paradoxes described in om Yager , Sun [45om Yager  and Dengom Yager  for compIn In the following diagnosis experiments, we choose the proposition with the maximum BPA as the fusion result. Thus, for the maximum BPA, the closer to 1 the more confidence it presents intuitively. As shown in As described before, the CRWU bearing datasets are acquired with different loading levels. To check how the loading level affects the vibration signals, we randomly extract one sample for different fault types  and load condition. We then plot the 16 × 16 input data from different Datasets A, B, and C. In First, we conduct experiments to evaluate the performances of our individual CNN models. In actual fault diagnosis scenario, the bearing load changes at all times. It is thus desirable that the fault prediction model can adapt to different loading conditions. To test this load adaptability of our models, we trained the CNN models on different training Datasets A, B and C corresponding to three different load conditions. We then tested their performance on testing Datasets A, B and C under three load conditions. There are nine combinations between training sets and testing sets, as shown in the top part of As described in In We also compared the performance of models trained with driver-end and fan-end signal with 16 × 16 input sizes . The aveFor further analysis, we applied our IDS fusion method to all the 16 CNN models at the drive end, all the 16 CNN models at the fan end, and all 32 CNN models at both ends . In To further validate the robustness of the proposed method, we selected three best IDSCNN models , one for each load condition. We then evaluate their performance on 20 randomly sampled test datasets for each load condition and plot the Boxplot in We compare our best DSCNN  models and the best IDSCNN models with 5 other bearing fault diagnosis models in To figure out how our improved D-S fusion algorithm improves the prediction performance, we compared the confusion matrices of a drive-end CNN model, a fan-end CNN model, and the IDSCNN fusion model, as shown in To validate that the performance difference between DSCNN and IDSCNN is statistically significant, we repeated C→A test for twenty times. The DSCNN models and IDSCNN models were trained respectively with samples from the load condition C (Dataset C) and each test datum is randomly sampled under the load condition A (Dataset A). We calculated five statistical parameters  according to the 20 times results of the DSCNN and IDSCNN models. In This paper presents IDSCNN, an ensemble convolutional neural network model with improved D-S evidence fusion for bearing fault diagnosis. We proposed an improved fusion algorithm based on the traditional D-S evidence theory by rectifying the raw evidence through evidence credibility, which helps to address its paradox evidence issues. Our extensive experiments on the Case Western Reserve University (CWRU) bearing datasets showed that the traditional D-S fusion method fails to combine the evidences/signals from two sensors located at the fan-end and drive-end of the testing rig due to evidence conflicts. On the other hand, our IDSCNN model can deal with four common paradoxical evidences and achieved higher diagnosis accuracy by fusing signal from two sensors when compared with SVM, MLP, DNN, WDCNN, WDCNN (AdaBN) and DSCNN models. Our IDSCNN model has shown good adaptability on the CWRU bearing fault datasets under different load conditions, which makes it suitable for high-performance bearing fault diagnosis under varying load conditions with multi-sensors signals.