Implementation science is the study of strategies used to integrate evidence-based practices into real-world settings :1, 2006). Central to the identification of replicable, feasible, and effective implementation strategies is the ability to assess the impact of contextual constructs and intervention characteristics that may influence implementation, but several measurement issues make this work quite difficult. For instance, it is unclear which constructs have no measures and which measures have any evidence of psychometric properties like reliability and validity. As part of a larger set of studies to advance implementation science measurement , we will complete systematic reviews of measures that map onto the Consolidated Framework for Implementation Research  and the Implementation Outcomes Framework :65-76, 2011), the protocol for which is described in this manuscript.measure; (3) terms for evidence-based practice; (4) terms for implementation; and (5) terms for mental health. Two trained research specialists will independently review all titles and abstracts followed by full-text review for inclusion. The research specialists will then conduct measure-forward searches using the “cited by” function to identify all published empirical studies using each measure. The measure and associated publications will be compiled in a packet for data extraction. Data relevant to our Psychometric and Pragmatic Evidence Rating Scale (PAPERS) will be independently extracted and then rated using a worst score counts methodology reflecting “poor” to “excellent” evidence.Our primary databases will be PubMed and Embase. Our search strings will be comprised of five levels: (1) the outcome or construct term; (2) terms for We will build a centralized, accessible, searchable repository through which researchers, practitioners, and other stakeholders can identify psychometrically and pragmatically strong measures of implementation contexts, processes, and outcomes. By facilitating the employment of psychometrically and pragmatically strong measures identified through this systematic review, the repository would enhance the cumulativeness, reproducibility, and applicability of research findings in the rapidly growing field of implementation science.The online version of this article (10.1186/s13643-018-0728-3) contains supplementary material, which is available to authorized users. Implementation science—the study of strategies used to integrate evidence-based practices into real-world settings —is a rapOne specific issue is the synonymy, homonymy, and instability of constructs . In thisOver the past decade, seven systematic reviews of contextual factors have been conducted in the field of implementation science.The Society for Implementation Research and CollaborationThis manuscript provides a detailed account of the systematic review protocol used to advance the aim: identify CFIR and IOF-linked measures that demonstrate both psychometric and pragmatic evidence. Although development of the pragmatic construct and its associated rating criteria is currently underway , 21, we Over 60 theories, frameworks, and models for dissemination and implementation now exist . Includisustainability) and synonymous or relevant terms ; (2) terms for measure ; (3) terms for evidence-based practice ; (4) terms for implementation ; and (5) terms for mental health . Search parameters will also be set to identify those written in English, published in peer-reviewed journals, and published from 1985 onwards. We chose to limit our search to articles published after 1985 because implementation science literature did not begin to take shape until the late 1980s.To identify CFIR- and IOF-related measures, we will access two widely used bibliographic databases: (1) PubMed will allow for automatic inclusion of synonyms and Medical Subject Headings, and (2) Embase will maximize our ability to capture international content, spanning biomedical journals from 90 countries . We willThe following inclusion/exclusion criteria will be applied to both the title and abstract review and full-text review; see Table readiness for implementation while item content might represent constructs such as implementation climate, available resources, or leadership engagement. In order to account for these additional content areas, we will utilize an established item-analysis approach employed in a recent measure-focused systematic review [intervention characteristics, characteristics of individuals, inner setting, outer setting, or process.The final set of articles within each construct will be carefully evaluated for the existence of one or more CFIR- or IOF-related measures. We acknowledge the possibility that measures might have items or subscales that map onto several constructs, therefore we will catalog each measure in a construct assignment phase. We will utilize a two-pronged approach to construct assignment. First, we will record the author’s decision regarding which construct it purportedly measures regardless of whether a definition is provided. However, we observed in our pilot work that authors’ measure descriptions (or labels) often fail to capture the range of item content . That isc review . SpecifiOnce measures are assigned to their respective constructs and domains, we will complete measure-forward literature searches in PubMed and Embase bibliographic databases utilizing the “cited by” function. We will start by searching for the article that describes the measure’s development or the first article detailing the measure’s empirical use , as not all articles have an associated formal measure development study. Once locating the measure’s source article, we will engage the “cited by” search feature to yield a preliminary list of articles to be reviewed. Measures with published names  will alThe Psychometric and Pragmatic Evidence Rating Scale (PAPERS) criteria are based on our previous measurement work . The oriInternal consistency indicates whether several items that purport to measure the same construct actually produce similar scores in the same test . Convergpoor anchor for measures that have been tested and demonstrate poor performance on a particular psychometric property. This will allow for more nuanced reporting of the existing evidence. For example, in an assessment of a measure’s predictive validity, a null or even negative association may result in a poor rating. Moving forward, we will also subject each measure subscale to the full set of criteria given that our pilot work revealed many researchers have used only a single subscale of a given measure. Finally, revisions were made in an effort to capture additional statistical analyses and reporting norms in the field to obtain a broader understanding of the state of the literature. In consultation with statisticians and psychometricians, we have integrated other fit indices or metrics into the revised criteria. A final version of the psychometric evidence rating scale can be found in Additional file Evidence of the aforementioned properties will be extracted from each measure packet to inform criterion-specific and overall scores (process described below in the “data extraction” section). Although the previous version of our rating scale contained a 5-point anchor system ranging from 0 (no evidence) to 4 (excellent evidence), we adopted a − 1 or Two trained research specialists will independently extract data on psychometrically relevant information within each measure packet. Specifically, we will locate all information pertaining to the nine psychometric properties found in the PAPERS criteria described above. To do this, research specialists will be trained by the principal investigator in measure development, psychometric properties, and the specific PAPERS criteria. Research specialists will read articles generated by the study team e.g., , 7, 19),, 19,7, 1Once data are extracted from the packets, they will be analyzed per the nine psychometric evidence rating scale criteria. Each packet will be reviewed by two trained research specialists, who will work independently to complete the rating phase. As noted above, the rating scale for each criterion is “poor” (− 1), “none” (0), “minimal/emerging” (1), “adequate” 2), “good” (3), or “excellent” (4), with the specifics of the rating scale for each criterion located in Additional file , “good” To describe the overall availability and quality of psychometric evidence of the measures, simple statistics  will be calculated. A total score is given to each measure by calculating the sum of the nine psychometric evidence rating scale criteria. Bar charts will display head-to-head comparisons of the nine criteria for all the measures within the various constructs of interest. Each bar chart will provide a visual comparison of overall-measure quality between measures, evaluated through the length of the bar. Additionally, the shading of the bar charts will provide a visual comparison within-criterion to assess the evidence of each criterion for the measures. For an example of the bar chart layout, please Additional file This manuscript offers a detailed description of a systematic review protocol for identifying and rating quantitative measures of implementation-relevant constructs and outcomes. The strengths of this approach include its broad coverage of constructs and expansive set of rating criteria. Despite these strengths, there are two key limitations. First, our criteria favor classical test theory-informed measure development and testing. Item response theory offers a more contemporary, alternative approach to measure development that would be of benefit to implementation science, but it is not one our rating system is capable of accommodating. Second, our scope was necessarily constrained to reflect the priorities of our funding agency . Thus, although the CFIR and implementation outcomes have widespread relevance across health (and into other settings), our review will only yield measures (and associated evidence from use) in the behavioral health space. Complementary efforts to expand this work into the broader physical health space are ongoing .Upon completion of the systematic review, anticipated in October 2018, we will build a centralized, accessible, searchable repository through which researchers, practitioners, and other stakeholders can identify psychometrically and pragmatically strong measures of implementation contexts, processes, and outcomes. The repository’s graphical interface will display measures’ psychometric and pragmatic ratings and facilitate head-to-head comparisons of measures of the same construct, where multiple measures exist. With information available on an expanded set of psychometric criteria, repository users can select measures with the highest ratings overall or the highest rating on a specific criterion , depending on their needs. The creation of a centralized, accessible, searchable repository of psychometrically and pragmatically rated measures of core constructs in two of the most widely used conceptual frameworks in the field of implementation science is expected to curtail the proliferation of “home-grown” or one-use measures with dubious or unknown reliability, validity, and practicality. Moreover, by facilitating the employment of psychometrically and pragmatically strong measures identified through this systematic review, the repository would enhance the cumulativeness, reproducibility, and applicability of research findings in the rapidly growing field of implementation science.Additional file 1:PRISMA-P 2015 Checklist: checklist adapted for use with systematic review protocol submissions to BioMed Central journals. (DOCX 36 kb)Additional file 2:Psychometric evidence rating scale: presents nine criteria by which data is extracted and rated. (DOCX 30 kb)Additional file 3:Psychometric head-to-head comparison: example bar chart layout provided to demonstrate overall availability and quality of psychometric evidence of available measure. (DOCX 31 kb)


Herein, we describe the consensus guideline methodology, summarize the evidence-based recommendations we provided to the World Health Organization (WHO) for their consideration in the development of global guidance and present a narrative review of the diagnosis of male infertility as related to the eight prioritized (problem or population (P), intervention (I), comparison (C) and outcome(s) (O) (PICO)) questions. Additionally, we discuss the challenges and research gaps identified during the synthesis of this evidence.The aim of this paper is to present an evidence-based approach for the diagnosis of male infertility as related to the eight prioritized PICO questions.Collating the evidence to support providing recommendations involved a collaborative process as developed by WHO, namely: identification of priority questions and critical outcomes; retrieval of up-to-date evidence and existing guidelines; assessment and synthesis of the evidence; and the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation the quality of the supporting evidence was then graded and assessed for consideration during a WHO consensus.Evidence was synthesized and recommendations were drafted to address the diagnosis of male infertility specifically encompassing the following: What is the prevalence of male infertility and what proportion of infertility is attributable to the male? Is it necessary for all infertile men to undergo a thorough evaluation? What is the clinical (ART/non ART) value of traditional semen parameters? What key male lifestyle factors impact on fertility ? Do supplementary oral antioxidants or herbal therapies significantly influence fertility outcomes for infertile men? What are the evidence-based criteria for genetic screening of infertile men? How does a history of neoplasia and related treatments in the male impact on (his and his partner's) reproductive health and fertility options? And lastly, what is the impact of varicocele on male fertility and does correction of varicocele improve semen parameters and/or fertility?This evidence synthesis analysis has been conducted in a manner to be considered for global applicability for the diagnosis of male infertility. In 2012, the World Health Organization (WHO) held a meeting of experts to scope the field of fertility care in order to develop comprehensive guidelines on infertility. Six Evidence Synthesis Groups (ESG) were established. One group was the WHO ESG on Male Infertility: Diagnosis. Following the initial meeting, key PICO (problem or population (P), intervention (I), comparison (C) and outcome(s) (O)) questions were developed and agreed upon. This included working through the WHO GDG (Guideline Development Group) Committee, as well as through web-based surveys, and through outreach to developing country scholars taking an on-line Geneva Foundation for Medical Education and Research- American Society for Reproductive Medicine- (GFMER-ASRM) WHO evidence-based infertility course. For each PICO question, a systematic analysis of the literature was performed according to the ‘WHO handbook for guideline development’ . A preli- What is the prevalence of male infertility and what proportion of infertility in the couple is attributable to the male?- Is it necessary for all infertile men to undergo a thorough evaluation?- What is the clinical (ART/non ART) value of traditional semen parameters?- What key male lifestyle factors impact on fertility ?- Do supplementary oral antioxidants or herbal therapies significantly influence fertility outcomes for infertile men?- What are the evidence-based criteria for genetic screening of infertile men?- How does a history of neoplasia and related treatments in the male impact on (his and his partner's) reproductive health and fertility options?- What is the impact of varicocele on male fertility and does correction of varicocele improve semen parameters and/or fertility?The following eight topics were pre-determined and identified by WHO, and were later formulated into PICO questions for systematic analysis, as follows:The methodology used to support the provision of the recommendations was outlined by the We qualified the strength of our recommendations (as strong or weak) based upon consideration of the quality of the evidence. These recommendations were then later assessed through the WHO guideline development processes that are based upon other factors including values and preferences of stakeholders, the magnitude of effect, the balance of benefits versus harm, resource used and the feasibility of implementation.Overall, wherever possible, original literature, and data from recently published systematic and Cochrane reviews were used. However, due to the diagnostic nature of the questions, a significant amount of the literature addressing them does not lend itself to high evidence level RCTs. Therefore, in addition, key guidelines and professional committee opinions were examined, in order to assist in developing a broader and more comprehensive evidence base, as well as in the construction of recommendations, and in particular: ASRM—Diagnostic evaluation of the infertile male: a committee opinion (2015) ; AmericaData were presented in summary form and descriptively, in tables or narratively in the evidence reviews for each PICO question. Where appropriate, meta-analyses were conducted. The GRADE framework was applied to the body of evidence for each outcome within each PICO. The WHO then used the worksheets to summarize the volume and quality of the evidence supporting the recommendations as well as to outline the values, preferences and judgements made about the strength of recommendations. The uniqueness of the WHO process was that these balanced worksheets were also to be used to note considerations especially for low- and middle-income countries or settings, and to be able to record the reasons for changes made to the default strength of the recommendations.The principles or best practice guidance need to be consensus-based and are also intended to underscore the importance of respect for reproductive rights and dignity as recipients of care, and the need to maintain high ethical and safety standards in clinical practice. These principles, in addition to the strategies for implementation, monitoring and evaluation, are expected to guide end-users in the process of adapting and implementing any recommendation provided by the WHO to consider for a range of global contexts and settings.The evidence based and detailed analysis, with GRADE tables where possible for each of the prioritized PICO questions, were commissioned by and provided by the first author to the WHO in support of their guideline processes. A WHO assessment of our evidence-based outcomes was then undertaken with many stakeholders who evaluate other factors including values and preferences of stakeholders, the magnitude of effect, and the balance of benefits versus harms, resource use and the feasibility of implementation to better assure global applicability. As required by WHO, following these outcomes, additional independent expert review would be conducted (2016 and early 2017). Once completed, the WHO will be publishing their expert and stakeholder consensus-driven guidelines together with the detailed evidence base  and related products  or associated with the infertility . The rationale for evaluating the male and the extent of that evaluation depends on the goals of the evaluation. Several medical best practice statements  suggest Evaluations of populations of infertile men have identified patients in each of these categories emphasizing the need for evaluation of the male  suggest The question is: Which diagnostic strategy is optimal? A significant number of identified male factors are associated with abnormalities found by semen analysis. However, the aetiology remains to be robustly quantified, especially in light of causes of infertility such as birth defects, acquired forms of infertility, infection, inability to have an erection or ejaculation, various syndromes as well as metabolic and endocrine disorders. Sexual dysfunction may be associated with normal semen parameters but can be identified through a sexual history. Additionally, there are a number of genetic syndromes that predispose or cause male infertility some of which are associated with abnormal semen parameters. An initial evaluation of the male consisting of a reproductive history, a simple PE and semen analysis would potentially identify the majority of these cases, however, these evaluations must also be sensitive to different cultural practices and different regional aetiologies, e.g. HIV, genital tuberculosis (TB) in TB endemic areas, lifestyle, environmental and occupational hazards. Significant medical conditions have been reported in 1.1–6% of men presenting for infertility evaluations and a number of these men have abnormal semen parameters. Importantly, however, there are limited data on the incidence of significant medical conditions that predispose men to infertility. One older data series reported that 0.16% of men had significant medical conditions but normal semen parameters indicating that conditions will be missed by limiting a male assessment to a reproductive history and semen analysis  semen analyses.- A full evaluation by an urologist or other specialist in male reproduction should be carried out if the initial screening evaluation demonstrates an abnormal PE, an abnormal male reproductive or sexual history, or an abnormal semen analysis is found.- Further evaluation of the male partner should also be considered in couples with unexplained infertility and in couples in whom there is a treated female factor and persistent infertility Fig. , Table IIn summary, we strongly recommend based on a moderate quality of evidence that:There are significant areas for future research. For example, what constitutes the most appropriate minimal PE and does this provide significant additional information for male health in general, does performing a PE improve male engagement in diagnosis and treatment, what is the cost-effectiveness of doing a PE on all men attending an infertility clinic instead of doing a PE only after abnormal findings in semen analysis and/or an abnormal reproductive and sexual history, can a globally validated questionnaire/topic list for reproductive and sexual history be used (encompassing low-income settings) to identify individuals at risk for male infertility, and Is the outcome better with earlier diagnosis and is treatment less expensive with earlier diagnosis?Specifically, we posed two clinical questions. This first question was whether the predictive value of semen analysis for reproductive outcome is better using a combination of several parameters compared to a single semen analysis parameter, and the second was whether an evaluation of a single ejaculate versus two ejaculates is sufficient for referral to infertility investigation and treatment.A fundamental challenge in the analysis of the literature is the quality of the laboratory testing which is often performed using sub-optimal methods .The analysis of studies to address this PICO question was limited to those published after 1 January 2000, based on two key assumptions. First, there has been a very slow increase in compliance with WHO recommendations for semen analysis. The fourth edition was published in 1999 and few publications before that bear evidence of significant and clear compliance with the recommended techniques  and 10 studies focussed on single ejaculate parameters as predictors of fertility. Studies identifying a single semen parameter with significant predictive power for fertility are relatively common but the discriminatory power is very often low e.g. expressed as receiver operating characteristic curve/area under the curve (ROC–AUC) close to 0.500 or OR including 1.00 in the 95% CI. In contrast, studies that have investigated multiple parameters, which are more reflective of testicular production/function and maturation, for example With regard to the first question namely, Is the predictive value of semen analysis for reproductive outcome better using a combination of several parameters compared to a single semen analysis parameter? Studies were regarded as eligible if they presented primary data on predictive values [or odds ratios (OR)] concerning multiple or single analysis parameters. Four studies provided data on multiple assessments of parameters , where an ICC close to 1.00 indicates high reliability between a pair of assessments].n = 6482) provided information that could be used to support or reject a recommendation concerning analysis of a single versus two ejaculates  and live birth. Second, a fundamental problem with developing new therapies or diagnostic tests for male infertility is the limited understanding of the formation, maturation and physiological workings of the normal and dysfunctional spermatozoon. There is an urgent requirement to understand these cellular, molecular biochemical and genetic mechanism(s) in order to formulate appropriate diagnostic assays and rational therapy for the male.This is, and is likely to remain, a topical issue. The focus of the analysis was on obesity, smoking and heat exposure.Obesity is a global health problem. It impacts not only cardiovascular diseases but also on many other related health disorders. Obesity may adversely affect male reproduction by endocrinologic, thermal, genetic and sexual mechanisms . As suchn = 31 and 25 for Based on the number of papers able to be included in each meta-analysis paper , but do not follow this up with information about the effect on semen parameters 6/ml, . AdditioNo RCTs were found and almost all of the data were collected retrospectively. Previous studies often suffer from small sample size . Suffice it to say that further work is required to elucidate the effects of heat exposure on male fertility. Ideally, scrotal temperature, semen parameters and a measure of fertility outcomes, such as live births, would have to be measured in prospective cohort studies. Studies must use comparable measures of semen analysis, methods for measuring scrotal temperature and definitions of infertility in order for comparisons to be made. This would allow a systematic review or meta-analysis of the evidence to be carried out.In summary, we strongly recommend, based on a very low quality of evidence, that there is insufficient evidence to conclude that exposure to heat, be it occupational or as a result of clothing or body position, affect semen quality and/or male fertility (Table P = 0.012) and concentration (P = 0.023) after multivariate analysis. Several cross-sectional and case-control studies found differing effects of smoking on semen quality. For example, P = 0.04), whilst Most of the published literature on cigarette (tobacco) smoking and male fertility only looks at the effect of smoking on semen parameters. The quality of the recent evidence linking cigarette smoking to decreased semen quality is moderate, as a systematic review and meta-analysis of 46 cross-sectional studies  smoking on semen quality/male fertility but not all studies report this. However, as smoking has an adverse effect on general health and wellbeing it is recommended that men trying for a pregnancy should abstain from smoking  affecting male infertility is likely to remain a rapidly developing and topical issue. There are a large number of significant areas for future research. Primarily large-scale prospective multi-centre trials encompassing a variety of geographical locations are required to examine the effects of lifestyle  and environmental factors /toxins) on spermatogenesis, semen analysis, male fertility and fertility outcomes, including the health of subsequent offspring.There is a significant body of data to support the concept that oxidative stress plays a key role in sperm dysfunction and male infertility . Two-thirds of the studies showed some improvement in semen parameters and one study reported a positive effect on sperm membrane integrity  reported in well-characterized groups to examine, for example, the effects of dietary supplementation, vitamins and herbal remedies.The determination of whether an infertile male benefits from having a genetic evaluation depends on the aetiology of the reproductive compromise and the severity. A detailed history and comprehensive PE, coupled with adjunctive tests, such as a semen analysis, hormone assays and on occasion testis biopsy, help clarify to which diagnostic category the patient belongs and, as a helpful consequence, assists in determining which genetic studies may be fruitful. For example, if a male has a reproductive history consistent with a known cause of resultant spermatogenic failure, such as chemotherapy, bilateral mumps, orchitis with resultant atrophy or current use of anabolic steroids, and is presently severely oligozoospermic or azoospermic, it can be assumed that these are the proximate reasons for the reduced/absent spermatogenesis and no genetic evaluation needs to be undertaken. The focus of the recommendations was on Karyotype, Y micro deletions and cystic fibrosis (CF) mutation analysis.No Cochrane reviews were identified. The primary evidence was from studies by Karyotype: Men with a sperm count <5 million/ml show a much higher rate of autosomal abnormalities than fertile populations (around 4%) while the highest frequency is found in NOA men (mostly Klinefelter syndrome). Klinefelter syndrome  is the most common of the sex chromosomal aneuploidies. Translocations may be found in a relatively small percentage of men with severe oligozoospermia and azoospermia  or NOA prior to any therapeutic procedure  may occur that partially or completely eliminate the azoospermia factor (AZF)a or the AZFb/c region from the genome, and, consequently, any important ‘spermatogenic necessary’ genes that reside in those intervals. Frequency data compiled by AZFc region in 1/27 men, which varied depending on the Y haplotype. The importance of Y microdeletion testing in the severely oligozoospermic or azoospermic male prior to any therapy (ICSI using ejaculated sperm or TESE) is for prognosis and consideration of PGD. For example, data show that when a complete AZFa, AZFb or AZFb/c microdeletion is present (~1–2% incidence of each in the NOA man) no spermatozoa will be found on TESE. When there is no possibility that sperm will be present, it is unhelpful and hurtful for the male to be operated upon and, in the latter circumstance, for the female partner to have an ovarian stimulation unnecessarily. Men with AZFc microdeletions can produce spermatozoa that are capable of fertilization, embryo development and term pregnancy  or NOA prior to any therapeutic procedure  testing should be performed on all males with severe oligozoospermia (<5 × 10No Cochrane reviews were identified. The primary evidence was from studies by CFTR) gene  The CFTR gene has 27 exons spanning 250 kb of chromosome 7 (7q31) and encodes an mRNA of 6.5 kb and the final protein contains 1480 amino acids. Certain mutations, such as c.1521_1523delCTT (legacy name: F508del), severely impair either quantity or functional quality of the CFTR protein determined by that allele. Other abnormalities, such as the 5 T polymorphism in intron 8 (5 T), only mildly impair quantity or functional quality of the CFTR protein determined by that allele. It is the combination of the two that correlates to the severity of disease expression. If a person is homozygous for c.1521_1523delCTT, for example, s/he will have problematic respiratory and pancreatic disease manifested and diagnosed in childhood. However, if a male has inherited the ‘5 T’ allele and c.1521_1523delCTT on the opposite allele and is therefore a compound heterozygote, pulmonary and pancreatic function may be clinically normal and CBAVD is the only recognizable phenotypic consequence. Bilateral vasal absence, then, is the most sensitive indicator of a biallelic CF gene abnormality as there is differential expressivity and sensitivity to CFTR in different epithelial tissues. In addition, it has been postulated that severity of phenotype may be modified by polymorphisms in unrelated genes such as TGFB1 (transforming growth factor) and EDNRA (endothelin receptor type A)  will also have absence of the vasa and seminal vesicles bilaterally and will, consequently, have a low volume, low pH, and an azoospermic ejaculate. The incidence in males of northern European heritage is 1:2000. An equal frequency of men with low volume, acidic pH, azoospermia will have congenital bilateral absence of the vas deferens (CBAVD) with little respiratory or pancreatic disease, the vast majority of whom will possess mutations/pathogenic abnormalities in both maternal and paternal CF alleles. Whether one presents with respiratory tree (including sinuses) and/or pancreatic disease, simply absence of the vas deferens or somewhere clinically between these phenotypic extremes depends upon exactly which mutations/abnormalities in the alleles are inherited. There are >1985 recognized mutations in the CF transmembrane conductance regulator , 5T and CBAVD .The distribution of CFTR mutations and abnormalities, and these cases may be secondary to a distinct genetic aetiology that affects mesonephric duct development. The phenotypic end-product may be CBAVD and unilateral renal agenesis, as described by CFTR mutations are identified, renal ultrasonography is indicated.In situations of CF or CBAVD, it is always necessary to screen the female partner for CF gene abnormalities so as to have a proper assessment of the risks of any offspring inheriting one of the two paternal mutations and the maternal mutation and presenting with clinical CF or, at the least, CBAVD if male. In addition, the benefit of testing the male with CBAVD helps provide information for his siblings who have a 75% chance of harbouring at least one (or possibly both) of the mutations inherited by the patient from his parents. Finally, patients may have mild CF symptoms such as ‘sinusitis’ or ‘bronchitis’, not previously recognized to be CF-mutation related and which, with a full understanding of their genetic basis, may be therapeutically managed in a different fashion. Not all CBAVD appear to be caused by/associated with CFTR mutation analysis should be offered to all males with CBAVD or CF  in low-income settings be developed, and what is the genetic basis of unilateral absence of the vas associated with unilateral renal agenesis?In a number of aspects this was a very challenging question to address. Although there were several reviews in the area, for example However, on a general level, there is consistency in the recommendations of the major medical societies in Europe and USA: the European Society for Medical Onclology  in order to formulate appropriate diagnostic assays, develop rational therapy for the male, and understand how external factors, such as the environment, negatively or positively influence these processes. Not surprisingly, this is not unique to our discipline. For example, a new strategy to understanding neurodegeneration with a primary focus on the formation and function of the cell is now strongly advocated as absolutely essential to accelerate progress for understanding neurodegenerative disorders  whatever the nature of the compromising event(s) . Moreover, this analysis needs to assess the effects in various geographical locations. In addition to the research themes which accompany each question, we identified other areas that require addressing. For example, what is the impact of age on male fertility? What are the underlying causes related to the male for IVF–ICSI treatment failure? Which gene (or epigenetic) defects in men can predict ART outcomes? What are the most effective educational initiatives towards improving understanding of male infertility? What are the attitudes of men and women  towards the investigation of male fertility? Certainly, in presenting this analysis, a plethora of research questions has been generated.A consistent theme was the focus on the quality of evidence available to support any recommendations. The criteria used can be presented in two, not mutually exclusive, formats: Traditionally, the quality of evidence is represented by using a range of different levels. However, it is clear that a considerable degree of the research related to the diagnosis of male infertility does not easily fit into these categories. The evidence is sometimes observational and not easily amenable to meta-analysis. With respect to the scientific and clinical evaluation of diagnostic methods i.e. methods that measure characteristics of the individuals, RCT are not usually appropriate. Primarily there is no inclusion of a separate group to be used as a control i.e. a group not obtaining the investigated treatment. In the evaluation of a diagnostic method, the control of the diagnostic method can be obtained with another independent method, or from the final clinical outcome. From this point of view, the highest level of evidence cannot easily be obtained through a RCT.Where data/evidence were available the quality of the evidence was often judged to be sub-optimal. One issue was the robustness of studies and thus general applicability. The robustness of the evidence base in reproductive medicine has been discussed . Robust Male infertility is a global and significant health problem. A consistent theme is the requirement for national and international efforts with large-scale, multi-centre studies encompassing different geographical locations. Considerable regional variations in key indices of male reproductive health have been reported  may be feasible in most settings but unfortunately they may not be in some areas without specialized storage facilities.in vitro spermatogenesis to dissecting the workings of the mature spermatozoon. However, progress in this arena is comparatively slow. The robustness of the data is sometimes wanting, and thus the ability to provide the strongest evidence-based guidelines has proven to be a challenge. We provided recommendations based upon the evidence available. However, when looking to the future there is a need to understand why it has happened that the data are limited and not forthcoming, in order to inform the direction of future initiatives and endeavours that could result in more studies that yield robust evidence from men residing in high-, middle- and low-income country settings.There are significant advances in male reproductive health from developments on It is fundamental to know the prevalence of a disease in order to provide resources, estimate impact, make effective health economic arguments, present rational research questions and manage patients. However, there is a paucity of clinical data on the scale of the reproductive health problems and infertility in men on a global level, across all health economies. The best estimates on infertility from demographic health studies use the heterosexual woman, as she self-reports a problem with becoming pregnant, which further assumes a diagnosis of female infertility , or possibly, an assumption of an infertile relationship; and, coupled with an even larger paucity of male diagnosis and management of infertility in low- and middle-income countries, any male infertility prevalence values based upon demographic health reports or from small private clinics are, at best, greatly extrapolated and highly inaccurate  of the potential transmission to the next generation of damaging insults to the male germ line by epigenetic mechanisms (The lack of data in key areas reflects the overall paucity of high quality long-term national and international funding streams to support reproductive medicine, and male infertility in particular. Whilst this has been discussed previously it remains a fundamental block to further progress and a critical issue , 2016b. 2 in the atmosphere (Fundamentally, it is necessary to make more robust arguments to national and international agencies to help drive the research agenda and subsequently place reproductive medicine, with demonstrated impact on couples and individuals, at the vanguard of the funding landscape. The coupling of EDCs and male reproductive health may provide an example. In this field strong scientific, socio-economic healthcare and political arguments have consistently been marshalled to support research into what has been termed an ‘epidemic’ of male reproductive health problems . This tymosphere . We needmosphere , 2017. SSupplementary DataClick here for additional data file.


Streptococcus (GBS) disease prevention. In this systematic review, we appraised and synthesised the evidence on the adverse events of IAP in the mother and/or her child.Adverse events from intrapartum antibiotic prophylaxis (IAP) are poorly documented yet essential to inform clinical practice for neonatal group B We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane, and Science Citation Index from date of inception until October 16th 2016. Reference lists of included studies and relevant systematic reviews were hand-searched. We included primary studies in English that reported any adverse events from intrapartum antibiotics for any prophylactic purpose compared to controls. The search was not restricted to prophylaxis for GBS but excluded women with symptoms of infection or undergoing caesarean section. Two reviewers assessed the methodological quality of studies, using the Cochrane Risk of Bias tool, and the Risk of Bias Assessment Tool for Nonrandomised Studies. Results were synthesised narratively and displayed in text and tables.From 2364 unique records, 30 studies were included. Despite a wide range of adverse events reported in 17 observational studies and 13 randomised controlled trials (RCTs), the evidence was inconsistent and at high risk of bias. Only one RCT investigated the long-term effects of IAP reporting potentially serious outcomes such as cerebral palsy; however, it had limited applicability and unclear biological plausibility. Seven observational studies showed that IAP for maternal GBS colonisation alters the infant microbiome. However, study populations were not followed through to clinical outcomes, therefore clinical significance is unknown. There was also observational evidence for increased antimicrobial resistance, however studies were at high or unclear risk of bias.The evidence base to determine the frequency of adverse events from intrapartum antibiotic prophylaxis for neonatal GBS disease prevention is limited. As RCTs may not be possible, large, better quality, and longitudinal observational studies across countries with widespread IAP could fill this gap.CRD42016037195.The online version of this article (doi:10.1186/s12884-017-1432-3) contains supplementary material, which is available to authorized users. Streptococcus (GBS), or Streptococcus agalactiae, a gram-positive bacterium, is the leading cause of mortality and morbidity from neonatal sepsis  versus 1 of 5 [20%] p = 0.01) [E. coli (60% versus 22.7% p = 0.21) or any bacteria causing late-onset serious bacterial infections (57% versus 26% p = 0.19), or ampicillin resistance in E. coli (100% versus 54.5% p = 0.14) or any bacteria causing late-onset serious bacterial infections (85% versus 63% p = 0.19) [p = 0.04). Lastly, Jaureguy et al. (2004) did not find a difference in the number of infants colonised with amoxicillin-resistant Enterobacteriaceae  and amoxicillin-resistant E. coli  in the gut of infants whose mothers were or were not treated with IAP [Of the four observational studies, Glasgow et al. (2005) found that in 62 infants whose mothers were treated with various IAP drugs (indication not stated), 24 39%) had ampicillin-resistant organisms, compared to 13/120 (11%) infants whose mothers were not treated (OR = 5.7 95% CI 2.3-14.3) . The aut = 0.01) . It was  = 0.19) . The aut% had ampKenyon et al. (2008) was the only RCT that reported on the long-term adverse events of IAP . They foThe study had a low risk of bias in all major domains, however there were critical limitations. Multiple statistical comparisons were conducted on a relatively small sample size increasing the probability of getting a significant effect due to chance. In addition to cerebral palsy, functional impairment, and bowel problems, the authors also investigated diabetes, behavioural problems, educational attainment, attention deficit hyperactivity disorder, and other developmental problems, and did not find any significant differences between any of the treatment and control groups. This is particularly important as the biological plausibility of IAP increasing the risk of cerebral palsy is unknown.In this systematic review, we presented the evidence on adverse events experienced by the mother and/or her child after treatment with intrapartum antibiotic prophylaxis (IAP). Despite a wide range of adverse outcomes reported from 17 observational studies and 13 RCTs, there was limited high quality information to determine the frequency of adverse events from IAP for neonatal GBS disease prevention. The evidence contains much uncertainty, with a substantial evidence gap around the long-term effects of IAP. The only RCT investigating the long-term effects of IAP reported a moderate effect of severe consequences such as cerebral palsy. This trial had limited applicability as it used a different drug, a longer drug regimen, and pre-term rather than term labour compared to IAP for GBS prevention. We also found consistent observational evidence that IAP for neonatal GBS prevention alters the infant microbiome, with some studies showing changes up to 90 days of life. However, these study populations were not followed through to clinical outcomes, therefore the short- and long-term clinical significance of the changes are unknown. Finally, there was evidence for increased antibiotic resistance in some, but not all studies, with no evidence of a reduction. However, this observational evidence was at high or unclear risk of bias due to confounding variables.Our review is the first systematic assessment of the literature on the adverse events from IAP. We had an extensive search with no date limit, and referencing checking of all included papers and relevant systematic reviews. We also had expert input, two reviewers conducting processes, including quality appraisal using validated tools, and we calculated summary measures for study outcomes where they were not available. However, as our search was broad and focused heavily on harms or adverse events search terms, we may not have found studies which investigated an outcome that would potentially be an adverse event, but may not have been indexed as such. Furthermore, as we only included studies for which full texts were available in English, adverse events reported in other languages may have been missed. We were also unable to conduct any meta-analyses due to the heterogeneity across the adverse events investigated.Previous literature has suggested that initial bacterial colonisation of the gut plays an important role in the development of the mucosal immune system of infants –23, 42. Evidence on the increase of antibiotic resistance after IAP was inconsistent. Literature on the trends of antibiotic resistance in countries offering IAP for neonatal GBS prevention has shown an increase in rates overtime. Resistance to clindamycin and erythromycin has increased in the last 20 years , with reKenyon et al.’s (2008) RCT had a low risk of bias and showed that IAP was associated with an increase in the severe consequences such as cerebral palsy . HoweverA Cochrane meta-analysis concluded that despite an 83% reduction in EOGBS incidence from IAP, IAP for maternal GBS is not supported by conclusive evidence due to a high risk of bias across RCTs . CombiniThe evidence on the adverse events from IAP treatment for neonatal GBS disease prevention is unclear, inconsistent, and/or at risk of bias. There is consistent evidence that GBS antibiotic prophylaxis alters the infant microbiome, and some inconsistent evidence that IAP increases antibiotic resistance. However, this evidence is at risk of bias, and the clinical consequences of the microbiome alterations are unknown. There is evidence from a single long-term RCT associating IAP in pre-term labour with potentially severe consequences such as cerebral palsy, however, it has applicability concerns, unclear biological plausibility, and was not replicated in a similar RCT. These limitations preclude the drawing of any accurate conclusions on the frequency of adverse events from IAP treatment for neonatal GBS disease prevention. Larger, better quality, and longer studies are needed to provide estimates of adverse events from IAP treatment for neonatal GBS disease prevention.


Urbanization has challenged many humanitarian practices given the complexity of cities. Urban humanitarian crises have similarly made identifying vulnerable populations difficult. As humanitarians respond to cities with chronic deficiencies in basic needs stressed by a crisis, identifying and prioritizing the most in need populations with finite resources is critical.The full systematic review applied standard systematic review methodology that was described in detail, peer-reviewed, and published before the research was conducted.Results: While the science of humanitarian practice is still developing, a systematic review of targeting vulnerable populations in urban humanitarian crises shed some light on the evidence base to guide policy and practice. This systematic review, referenced and available online, led to further findings that did not meet the pre-defined inclusion and exclusion criteria for evidence set out in the full review but that the authors, in their expert opinion, believe provide valuable insight nonetheless given their recurrence.These additional findings that did not meet criteria for evidence and formal inclusion in the full manuscript, but deemed valuable by the subject expert authors, are discussed in this commentary This discussion compliments a full systematic review by the authors published by Oxfam on targeting in urban humanitarian crises: What practices are used to identify and prioritize vulnerable populations affected by urban humanitarian emergencies? A systematic review. Oxford: Oxfam GB.In addition to the studies and findings reported in the full review, we identified 16 reports that were relevant to the topic of the review by meeting criteria for initial screening, but fell short of meeting the criteria for inclusion in the formal evidence-based synthesis. The predefined inclusion criteria for inclusion in the systematic review required that reports a) described a targeting practice had been employed in an urban humanitarian crisis and; b) that the practice was evaluated in some form or another. Standard systematic review methodology was used and a protocol for the systematic review was reviewed and published prior to the research. For the detailed methodology used in the systematic review including key terms of reference please refer to the original publication. As expert authors, we believe repeated lessons within these 16 reports provide valuable insights, reinforce the full systematic review findings or represent promising areas of research for further study despite their lack of supporting evidence as defined by the full systematic review methodology. This editorial commentary on targeting was focused around these recurrent lessons identified through the same thematic analysis used in the full systematic review. These summary commentary lessons from the full systematic review and these additional 16 reports about targeting approaches and other features of targeting are summarized in Given the overall lack of study, we argue that the absence of evidence does not necessarily make these lessons untrue. In fact, their repeated nature would actually qualify them as valid findings according to other criteria and they may eventually be supported by evidence. We included examples from the 16 reports within the commentary to provide a clearer depiction of the content discussed, not as anecdotal evidence.Commentary from Recurrent LessonsTargeting ‘Affected’ vs. ‘Non-Affected’ populations does not work wellTargeting by 'disaster affected persons does not work well in urban areas to accurately identify all or the most persons in need of a specific humanitarian aid interventions services.In addition to targeting by displacement status, as highlighted in the full systematic review, targeting only persons affected by a crisis, those experiencing some loss as a result of the crisis, does not generally work well in the urban space even when resources are limited. Targeting only persons directly affected by the crisis such as those that suffer material or bodily harm directly by the crisis does not identify all or even the most vulnerable in urban humanitarian emergencies.Targeting upstream individuals and groups can enable recovery for the most vulnerableFocusing on employers or individuals who are responsible for the livelihoods of others can be a means of returning beneficiaries to baseline livelihoods more quickly.5Incorporating this form of upstream targeting can facilitate smooth exit strategies and shifts the focus of targeting to engaging local actors.After the January 2010 earthquake in Haiti, targeting in one program focused on small business owners in an effort to help businesses remain in operation. Targeting focused on both the low-income as well as the middle-income groups “for two reasons: first, the middle groups were also badly affected by the earthquake and secondly, the services and activities carried out by the middle groups play a vital role in the recovery [of] the economy.”Poverty is a useful but imperfect proxy for vulnerability when used aloneA snapshot of income or assets alone does not account for an accurate understanding of vulnerability. As identified by MacAuslan and Farhat, poverty measures alone do not account for current or anticipated needs or the impact of a crisis on various socio-economic groups.Urban areas constitute an economic environment with goods and services driven by markets and thus poverty is key but does not wholly reflect vulnerability, which is multidimensional.Targeting vulnerability more generally based on poverty alone as a proxy may be appropriate in urban settings but requires detailed understanding to target correctly. Protection concern may drive vulnerability more than other measures in some situationsTargeting approaches should add a protection lens to vulnerability analyses keeping in mind that safety and security can be paramount to wellbeing.10Despite having low vulnerability according to various indicators such as income or displacement status, concerns about safety may actually drive vulnerability in some cases. These protection concerns may override many other indicators of vulnerability.Geographical targeting requires more detailed analysis given the density and heterogeneity of cities, because many urban areas are not homogenous, care should be taken to identify geographic units that are smaller and not restricted to typical municipal or administrative boundaries.5,9,Geographic selection of urban areas to identify vulnerable populations by specific location, such as slums or low-lying coastal zones, can be a very effective process for targeting.8Community participation and community based targeting are key to effective response but must be used with caution,8,9,13 Incorporating community perspectives can lead to locally derived measures of vulnerability as described in the full systematic review. Such locally derived measures, however, take time and resources to develop. They may often lose comparability between contexts depending on their design. Yet comparable tools can be developed. For example, a scale based on local coping strategies can allow comparison if variations of coping can be applied to the same quantitative scale. These trade-offs must factor into their selection.Many of the reports point toward the importance of community perspectives to help ensure that vulnerable areas and populations are not overlooked.5 incorporating community knowledge is clearly vital to good targeting, but participation can take many forms.Community based targeting (CBT) or participatory targeting whereby the community directly identifies vulnerable persons or households is a growing practice in humanitarian interventions and compliments trends toward locally driven processes that are inclusive and suited for area based programming. The data from these practices is thin and of low quality but common lessons are repeated. In general,Lessons indicate the importance of having a nuanced understanding of the motivating factors driving individual participation in community-based targeting, as well as familiarity with local power dynamics and knowing whose voices are being heard.4,5,5,Community engagement that unwittingly reinforces any pre-existing marginalization will do more harm than good.Measuring food security an take many diverse forms but requires detailed analysisPapers on targeting for food insecurity were more numerous than other forms of sector-specific targeting, with 10 of the 21 evidence-based articles in the full systematic review dealing specifically with food security. Indeed, many of the evidence-based lessons and recurrent lessons above came from food security reports yet applied more generally as well. There was a lack of evidence directly comparing measures but a few insights are found in the various reports.To identify food insecure populations, understanding intra-household consumption patterns, capturing out of home consumption and the local coping strategies employed in additon to standard tools is key.Targeting for food aid can measure a variety of characteristics such as consumption, purchasing power, access, nutritional status or coping strategies. These measures take multiple forms from a universal composite index to a locally derived context specific scale. All of these approaches come with their own advantages and disadvantages.Involving local markets is important to targeting in urban areas while enhancing overall recoverya better understanding of crucial market chains can help lead to a more effective distribution of humanitarian resources, faster economic recovery and less risk of long term dependency on external assistance.” The program in Haiti relied upon an inter-agency Emergency Market Mapping Analysis (EMMA) as well as a 2009 baseline assessment of income groups within Port Au Prince to create wealth group profiles for households affected by the earthquake and to inform targeting.6Markets are important to addressing vulnerability in urban areas. Multiple reports point toward the importance of market analysis as urban food security is closely linked to commodity prices, income opportunities and wage rates.Programming aimed at improving market recovery post-crisis can also achieve the dual purpose of improving livelihoods as well as nutrition. The review uncovered several studies that provide specific examples of how effective targeting involving local markets improved livelihoods. In Bulawayo, Zimbabwe, a program aimed at improving the nutritional status of vulnerable households successfully used local millers to produce, and existing retailers to sell, a low-cost maize alternative—sorghum.6Vulnerability can be invisibleIt is important to acknowledge that the most vulnerable persons may be those who try to stay invisible to authorities and even their neighbors, and therefore may be missed by the targeting methods discussed in this review.Selection of targeting vulnerable populations in urban crises will have to weight the costs, benefits and feasibility of each approach and funding tied to evidence on how these three variables are assessed will be the best path moving forward.The current evidence and recurrent lessons above do not point to one single best approach for targeting vulnerable populations in urban crises. As humanitarian programs have a wide variety of goals and urban contexts and crises vary, the complex nature of vulnerability makes it impossible to have one best approach for each situation. Any approach will have strengths and limitations and none will be perfect as needs may often exceed available resources. In addition to these technical limitations, the security situation and political context can also impact the selection of a targeting approach. While evidence to guide humanitarian practice accumulates further debates on the humanitarian system and financing will have to progress in ways that incentivize evidence based practice. We believe the most vulnerable in urban humanitarian crises are best targeted using a collection of socioeconomic indicators along with in depth contextual understanding.Vulnerability in urban areas is complex and interconnected such that assessing sector-specific vulnerability seems inappropriate or at least less useful. A person’s health and nutrition for instance is related to their shelter, access to sanitation, livelihood and surrounding security. Practices for targeting vulnerable populations in urban crises should leverage urban development practice and tools in rapidly growing cities that aim to alleviate poverty and build resilience.Given that local actors, including government, will play a larger role in humanitarian response and the knowledge that municipal authorities and pre-existing organizations have, leveraging pre-existing data will be valuable. Often these may be incomplete, outdated or biased but improving these sources of information beforehand could be prove useful and efficient. As development and humanitarian practice come closer together within a resilience framework, reducing urban vulnerability as part of development efforts could help inform targeting in the event of a humanitarian crisis. Targeting approaches should exploit local knowledge and community based approaches with a nuanced understanding of these communities and power relations.Additionally, as the local expertise of already established actors and the affected community itself can prove invaluable, community based targeting (CBT) should be developed and tested further. The success of such an approach will depend on local capacity and technical expertise. Entrenched biases and power-dynamics may also bend a very well-intentioned approach into exacerbating vulnerability and a nuanced understanding of this context is required. The recent focus on area-based programming leans toward using a CBT approach as a key component. Research and practice should focus on developing and testing rapidly tools that can be quickly contextualized to the local situation.Finally, the most promising approach may in fact be targeting based on methods that can be locally contextualized and rapidly so given the important of balancing accuracy with speedily delivering aid. As spaces within cities can be micro-environments that differ from neighbourhood to neighbourhood, locally contextualized tools should be further developed and expanded. Overall, the full systematic review and this commentary from recurrent lessons lay bare the general lack of evidence guiding practice in targeting the most vulnerable in urban crises. Focused research and funding for it, as discussed in the full systematic review, must be prioritized to ensure humanitarian practice is grounded in rigorous evidence.Ronak B. Patel, rbpatel@gmail.comAll relevant data are included within the paper.The authors declare the following interest: DS serves on the Editorial Board for PLOS Currents: Disasters. He has not influenced or played any role in the peer-review, editorial decision making or publication of the manuscript.


Primary care physicians believe they are delivering evidence-based care, understanding that adherence to evidence-based clinical guidelines results in tangible benefits in the populations for which they were developed. Unfortunately, most clinical guidelines are based on trial populations which are very different to primary care populations , and do To illustrate the point, allow me to present Mary, an 82-year-old, socially active woman living alone. Mary has been taking alendronate and calcium/vitamin C following a Colles fracture 5 years ago. She has difficulty walking as a result of osteoarthritis (for which she takes paracetamol and naproxen) and chronic obstructive pulmonary disease . Mary is visiting her GP today to discuss her recently diagnosed stage 2 hypertension (ambulatory blood pressure 162/92 mmHg), her fasting total:HDL (high-density lipoprotein cholesterol) of 5.3, and her newly diagnosed chronic kidney disease (CKD) stage 3aA2.With strict adherence to all the current evidence-based guidelines for her conditions, Mary would be leaving her appointment today with a prescription containing all of the following:Paracetamol 1 g four-times per day, as neededNaproxen 250 mg twice-daily, as neededCalcichew D3 Forte two tablets per dayAlendronate 70 mg once-weeklySalbutamol and/or ipratropium bromide inhalers, as neededSalmeterol/Fluticasone 50/500 mg inhaler, one puff twice-dailyAtorvastatin 20 mg, once dailyA calcium channel blocker, once dailyAn angiotensin-converting enzyme (ACE) inhibitor, possibly at the maximum dosePossibly a thiazide to achieve CKD blood pressure targets.Patients like Mary are now the norm – not the exception – in primary care .The Quality Outcomes Framework for general practice in the UK has resulted in more consistent use of evidence-based interventions, but has also led to far greater use of pharmacological therapies . This haIn Mary’s circumstances and for many other patients, we need to adopt a more rational, patient-centered approach to care, and consider deviating from the guidelines when it is safe and justifiable to do so. Most guidelines contain a statement encouraging clinicians to exercise “clinical judgement”; to do this we need to consider what the individual patient really wants, prioritize those conditions most likely to do harm, and initiate only those treatments most likely to confer substantial benefits. We must make the best decisions we can in partnership with our patients.Let us imagine that Mary expresses concern about the number of medications that she is being offered. She will do what her doctor advises, but would rather only take what is really necessary and wants to minimize her risk of side effects. Her treatment priorities are to reduce her risk of having a disabling stroke (a great fear) but she takes a philosophical approach about mortality and is not especially interested in taking drugs to increase longevity at her age; “You’ve got to die of something”. What her doctor needs to know now to help her make a treatment decision is: exactly how much good these treatments are likely to do her, how much harm they might cause, exactly how much risk reduction are they conferring, and a reduction in risk of what, exactly? An exploration of the evidence behind her guideline recommended treatment might lead her and her doctor to make some more prudent choices about her medication regime:Treatment of stage 2 hypertension has been shown to reduce the risk of stroke from 5.2% to 3.3% over approximately 4 years , and a sAn ACE inhibitor is recommended in current NICE guidance for CKD in the presence of moderate albuminuria and hypertension. Examination of the evidence for this recommendation reveals that this intervention is based on trials of patients with diabetes or severe, progressive CKD, and has been shown to reduce biochemical deterioration of CKD and the chance of end-stage CKD . This isWhy should she remain on her Salmeterol/Fluticasone inhaler? In chronic obstructive pulmonary disease with an FEV1 (forced expiratory volume in 1 s) <50% of predicted, this is recommended to reduce her risk of exacerbations and hospital admissions . HoweverBisphosphonates have been shown to reduce the risk of osteoporotic fractures in a secondary prevention population , althougThere is little evidence about the benefit for her in continuing oral calcium and vitamin D supplements without bisphosphonates. A trial in a comparable population showed no benefit .The role of statins in the very elderly in a primary prevention context remains controversial. NICE guidance  recommenWith regard to her analgesia, paracetamol and naproxen are both recommended in current NICE guidance , but MarGiven all this extra information, it may well be that Mary and her doctor choose to rationalize her long-term medication so that she might remain on just paracetamol, a calcium channel blocker and salbutamol inhaler as needed. In doing so, she may not lose much in terms of risk reduction, but gain a lot in reduced treatment burden, risk of acute kidney injury, GI bleed, hypotension, falls, and possibly hospital admission.But how might we achieve this sort of personalized assessment in everyday practice? Gathering this amount of information is prohibitively time consuming and requires high levels of confidence on the part of the doctor interpreting it. Current clinical guidelines tend to be prescriptive and the evidence summaries behind them relatively inaccessible, do not consider the cumulative impact of treatment recommendations on people with multimorbidities, and do not state the potential risks and benefits of different treatments to the individual.Primary care professionals are becoming increasingly frustrated by the prescriptive and additive nature of current guidelines based on research that excluded most of the types of patients with multimorbidities we see every day , 26–28. Primary care physicians need rapid access to evidence that matters – expressed in a way that is useful for patients – that can be found quickly during a consultation. A framework for a web-based resource is being explored by the Royal College of General Practitioners Standing Group on Overdiagnosis , and we We have a long way to go before we are adequately equipped to provide evidence-based, patient-centered care for our patients with multimorbidity, but at least the issues of over-diagnosis and over-treatment are now on the agenda, and there is a palpable hunger for change in primary care in the UK.


In response to a central drive for evidence-based practice, there have been many research support schemes, setups, and other practices concentrating on facilitating access to external research, such as the Centre for Evidence Based Healthcare Aotearoa, the Cochrane Collaboration, and the York Centre for Reviews and Dissemination. Very little attention has been paid to supporting internal research in terms of local evidence and internal research capabilities. The whole evidence-based practice movement has alienated internal decision makers and, thus, very little progress has been made in the context of evidence informing local policy formation. Health and social policies are made centrally based on dubious claims and often evidence is sought after implementation. For example, on record, most health care practitioners appear to agree with the causal link between depression and mental illness  with suicide; off the record, even some psychiatrists doubt that such a link is applicable to the population as a whole. Therefore, be it through misplaced loyalty or a lack of support for internal researchers/decision makers, local evidence informing local decision making may have been ignored in favour of external evidence. In this paper, we present a practical holistic model to support local evidence-based decision making. This approach is more relevant in light of a new approach to primary health care of “local knowledge” complementing external evidence. One possible outcome would be to network with other regional programmes around the world to share information and identify “best” practices, such as the “Stop Youth Suicide Campaign”(www.stopyouthsuicide.com).


In their day-to-day practice, pharmacists, graduate (pre-registration) pharmacists, pharmacy technicians, dispensing assistants and medicines counter assistants use widely available office, retail and management information systems alongside dedicated pharmacy management and electronic health  applications. The ability of pharmacy staff to use these applications at home and at work, also known as digital literacy or digital competence or e-skills, depends on personal experience and related education and training. The aim of this research was to gain insight into the self-reported digital literacy of the pharmacy workforce in the North East of Scotland. A purposive case sample survey was conducted across NHS Grampian in the NE of Scotland. Data collection was based on five items: sex, age band, role, pharmacy experience plus a final question about self-reported digital literacy. The study was conducted between August 2012 and March 2013 in 17 community and two hospital pharmacies. With few exceptions, pharmacy staff perceived their own digital literacy to be at a basic level. Secondary outcome measures of role, age, gender and work experience were not found to be clear determinants of digital literacy. Pharmacy staff need to be more digitally literate to harness technologies in pharmacy practice more effectively and efficiently. Pharmacy staff across all practice settings are increasingly reliant on information technology ,2,3,4. PThe British Computer Society defines digital literacy as, “being able to make use of technologies to participate in and contribute to modern social, cultural, political and economic life” . A similA government commissioned report into digital literacy in Australia concluded that “both citizen and worker will need to be digitally literate for the digital economy to work effectively” while a report from New Zealand argues “that technology can change the nature of work faster than people can change their skills” ,14. In tHealthcare in the UK is politically devolved to its national parliaments. The Scottish Government’s policy driven National Health Service (NHS) is regionalised to 14 local Health Boards. Each Board manages the delivery of pharmacy services within hospitals and contracts community pharmacies to offer a range of core services most of which are technology based. In Scotland, community and hospital pharmacies are sited in remote and rural or urban settings with a diverse level of technology implemented, from the minimum required to facilitate electronic transfer of prescriptions (ETP) starting from a broadband networked single computer with linked printer and barcode reader through to advanced robotic medicines management systems .The regulatory body for the pharmacy profession in the UK, which also sets standards for education and training, is the General Pharmaceutical Council (GPhC) . Unlike However, the way ahead for the pharmacy workforce is a central issue in the most recent “Review of NHS Pharmaceutical Care of Patients in the Community in Scotland” . It recoThe aim of this research was to gain insight into the self-reported digital literacy of the pharmacy workforce in the North East (NE) of Scotland.A purposive case sample survey was conducted across NHS Grampian in the NE of Scotland as part of a larger study.NHS Grampian health board manages eight hospitals (two main in Aberdeen and Elgin) and 131 community pharmacies  that serve a population of over half a million across the North East of Scotland .urban, remote and rural geographical settings;technology infrastructures;pharmacy management systems implemented; andhospital pharmacy  and community pharmacy , 67 small (1–4 pharmacies) to medium (5–25 pharmacies) chain multiples, and 41 national chain multiples) .Experts from the local health board and practicing academic pharmacists were engaged to assist with stratified purposive sampling taking into account the range of:Professional networks of academic pharmacists based at Robert Gordon University (RGU), one of two centres offering graduate level pharmacy courses in Scotland, made the initial approach to local area network of pharmacy owners and managers. They outlined the proposed study and those who expressed an interest were emailed an information sheet and consent form by the research team. Management consent included facilitating contact with the wider pharmacy team.Where distance allowed, the researcher arranged a preliminary site visit as a follow up to email contact. This served multiple purposes of introducing the researcher to potential participants, familiarising the researcher with the pharmacy location and layout and for distribution of information sheets and consent forms. It was emphasised that consent was both voluntary and individual. Where the preliminary visit was not possible a study pack was posted to the pharmacy.The study was conducted between August 2012 and March 2013 in 17 community and two hospital pharmacies across the NHS Grampian area. Preliminary site vetting during sampling provided data on pharmacy setting , type , rural/urban, high/low technology and pharmacy management system. Categorisation as a “low tech” pharmacy was allocated where the minimum specification necessary to operate was implemented. For example, single or multiple PCs connected to a network server with secure N3 broadband connection, barcode scanner(s), label dispenser(s), printer(s) and, very often, a fax machine. If the pharmacy had robotic medicines management capability it was categorised as “high tech.”During the consent process, participants provided five further items of data: sex, age band, role, pharmacy experience, plus answering a final question, “As a gauge of your current information technology experience which of the following would be the most appropriate challenge for you?”, followed by titles of six digital literacy courses listed in order of difficulty , which fThe site data was collated and tabulated  to show This study was approved by the Ethics Review Panel of Robert Gordon University School of Pharmacy and Life Sciences and deemed service evaluation by the Research & Development office of NHS Grampian.Two of the community pharmacies that had expressed an initial interest in taking part in the study withdrew before the consent process due to staff illness and holiday commitments. No potential participants withheld consent or subsequently withdrew from the study. The figures given reflect the number in each role available and willing to participate on the arranged day and time which is not necessarily the number employed at that pharmacy.Although prescriptions and item quantities dispensed are not directly comparable, it provided an impression of dispensing volume per pharmacy. These ranged from approximately 850 prescriptions per month in a small, rural community pharmacy to over 800 items per day in a large, hospital pharmacy dispensary. Three community pharmacies withheld dispensing volume information citing commercial confidentiality reasons and the information was not available from one of the hospital.n = 8), Positive Solutions (n = 3), ProScript (n = 5) and Nexphase (n = 1).Fourteen of the community pharmacies and one hospital pharmacy were categorised as “low tech” with three community and one hospital pharmacy deemed “high tech.” Neither hospital had introduced HEPMA . A range of commercially available pharmacy management software applications were implemented. Two ran the specialist hospital pharmacy software, JAC, while the community pharmacy systems included Cegidem  followed by “Computing for the Terrified” (n = 19). These two least difficult courses together accounted for the selections of nearly two-thirds of participants. The remainder selected “European Computer Driving Licence” , “Computing for the Courageous” (n = 13), “ECDL Advanced” (n = 5) or “Degree or Diploma” (n = 4).As previously described, participants self-selected from six IT course titles listed in order of difficulty  as a seln = 8) in the “29 or younger” age band self-selected “ECDL” as their appropriate IT challenge, the predominance of the lower level courses, indicative of basic levels of digital literacy, was clear across all roles and age bands , the evidence seems to counter the commonly held perception that younger, professional people are more digitally literate. Although there were notable exceptions, most pharmacies had the minimum level of technology implemented with unaddressed usability issues acting as barriers, or additional restraining forces. Changing roles may also lead to the pharmacist spending less time with the pharmacy team depriving the team of the cascading of knowledge. The decisions of individuals to adopt technology may be influenced by their use of technology outside work but Adair and Lewin would also argue that leadership and group acceptance of technology are influential in the change management needed to counter the restraining forces [If policy is the driver bringing technology into pharmacy practice, the main restraining forces are the pharmacy team, its leadership and the individuals within the pharmacy team. Findings depict a workforce who self-reported their digital literacy levels as basic. Although a small sample (g forces ,38.In “Human Relations in Curriculum Change,” Lewin outlined the conditions for change, the tensions at play in his Force Field theory and combinations of educational and organisational measures to “change the strength of opposing forces” ,38. LewiTo the best of our knowledge, this is the only study to consider the digital literacy of the whole pharmacy team in both community and hospital settings. An observational case study is underway which will build on these findings. National surveys of digital literacy amongst not just the pharmacy workforce but also the broader healthcare workforce would provide a benchmark for evaluation of educational interventions and inform curricula design. Evaluation of progress towards implementation of policy around adoption of technology to support role development across the pharmacy team is also indicated.Although this was a local study, the findings hold implications at the national level. Evidence from the findings suggests there is a policy driven intention to support changing roles in pharmacy by increasing and improving the provision of technology and providing the associated education and training of all pharmacy staff. With few exceptions, pharmacy staff in the NHS Grampian area work with minimum levels of technology and self-report their own digital literacy levels as basic. This tends to indicate organisational and social factors may act as restraining factors against the driving forces for technology in pharmacy and associated digital literacy training. Aspirational national and international policies have been shown to need local solutions for adoption to be successful . Grudin’With few exceptions, pharmacy staff in the NHS Grampian area work with minimum levels of technology and perceive their own digital literacy to be at a basic level.Role, age, gender and work experience were not clear determinants of digital literacy.Pharmacy staff need to be trained to harness pharmacy technologies effectively and efficiently in support of their role development.


The modern evidence-based practice movement owes a lot to librarians; in fact, some would say that it could not have happened without them. Yet the library profession still has not totally embraced the concept of evidence-based practice in its own field, nor fully utilized it as a source for decision making. In this work, Koufogiannakis and Brettle bring together “recent theory, research and case studies from practice environments across the broad field of librarianship to illustrate how librarians can incorporate the principles of evidence-based library and information practice (EBLIP) into their work” (p. 3).While the EBLIP movement was mentioned in 1995 by Haines and Roddham, Bradley, and Marshall, it was Eldredge who in 1997 not only first used the term “evidence-based librarianship,” but also firmly planted and started the movement in earnest. In 2000, the Medical Library Association Research Section created an Evidence-Based Librarianship Implementation Committee to promote EBLIP as both a practice and a part of the professional culture.Evidence-based practice in libraries has evolved over the years and has become known as EBLIP. The model used in this book is based on Koufogiannakis’s doctoral research results. Koufogiannakis and Brettle refer to Eldredge’s original model for EBLIP from 2000, as well as Booth and Brice’s 2004 work. Koufogiannakis’s “revised model for EBLIP” is described as one that takes a “holistic approach,” “incorporating research evidence as well as local evidence and professional knowledge” (p. 13).An essential part of EBP is research that builds a body of knowledge, but “within librarianship…we also need to consider local context and circumstances, because the decision being made is specific to those circumstances. The populations we serve and their needs are not necessarily the same in all instances” (p. 14).This work is divided into two parts. In part 1, the authors devote chapters to each of the five elements of their new model for EBLIP. Table 2.1: “Elements of the EBLIP process” (p. 15) outlines the five elements:Articulate: A clear understanding of the problem or question must be reached. Part of articulating the problem includes working out what is known already and why the information is needed, as well as ensuring that the problem is set in the appropriate context.Assemble: Evidence should be assembled from multiple sources that are the most appropriate to the question or problem at hand and should include research evidence, local evidence, and professional knowledge.Assess: Evidence should be assessed for its quality , determining what the evidence says as a whole.Agree: Determine a course of action and begin implementation of the decision. If working with a group, try to achieve consensus based on the evidence and organizational goals.Adapt: Evaluate the decision and how it has worked in practice. Revisit goals and reflect on the success of implementation.Part 2 of this work, “EBLIP in Action,” offers all-important “real life” examples of EBLIP in all types of libraries. Wilson discusses “Practitioner-Researchers & EBLIP” and describes, among other issues, the challenges, motivation, funding, and ultimate benefits of conducting research as a practicing librarian, and their deep connection to EBLIP as they bridge the gap between research and practice.Somerville and Kloda speak to EBLIP in “Academic Libraries.” They briefly summarize three widely diverse examples of EBLIP in academic libraries from around the world that “support the customization of EBLIP principles and practices to local circumstances.”Eldredge, Marshall, Brettle, Holmes, Haglund, and Wallace devote a chapter to EBLIP in “Health Libraries,” where the movement found its genesis: “The EBLIP movement has helped to move research and its application into the practice realm…Health librarians will, no doubt, continue to pursue EBP in a way that includes the priorities and approaches common to the health settings in which they work” (p. 131). Other chapters speak to EBLIP in public libraries, school libraries, and special libraries. A number of figures and tables effectively amplify the text.Koufogiannakis and Brettle present an excellent overview of the history and evolution of library evidence-based practice along with the current state of EBLIP. The model they have presented is demonstrated to be usable across the library spectrum. This work is highly recommended.