A high-throughput approach to developing and optimizing mixed-mode membrane chromatography for protein purification.

Membrane chromatography has been established as a viable alternative to packed-bed column chromatography for the purification of therapeutic proteins. Purification via membrane chromatography offers key advantages, including higher productivity and reduced buffer usage. Unlike column chromatography purification, the utilization of high-throughput screening in order to reduce development times and material requirements has been a challenge for membrane chromatography. This research focused on the development of a new, high-throughput screening technique for use in screening membrane chromatography conditions for monoclonal antibody purification. The developed screen utilizes a 96-well plate format, thereby allowing for the screening of multiple different membrane conditions at once. For this study, four mixed-mode cation exchange membranes and one cation exchange membrane were evaluated on the plate. The screen is performed in a similar manner to that of a resin slurry plate screen, however, instead of a single loading step, the antibody feed was loaded in 50 mg/ml increments up to a maximum loading of 450 mg/ml. Performing a similar, incremental loading on a resin plate would be impractical, as mixing times are substantially longer due to pore diffusion limitations. However, due to the significantly faster rate of mass transfer for membranes relative to resin, mixing times could be reduced by up to a factor of sixty on the membrane plate. Additional optimization showed that higher hydrophobicity can potentially lead to slower kinetics and mixing times that may need to be adjusted accordingly. The end result is a screen that has been proven to provide results comparable to those obtained on larger-scale membrane purification runs while also enabling exploration of a much greater operating space and significantly reducing the feed materials required.

Teaching Undergraduate Medical Students Non-Technical Skills: An Evaluation Study of a Simulated Ward Experience.

Purpose: Research suggests that medical students in the UK report a need to be better prepared for the non-technical skills required for the role of a junior doctor. A Simulated Ward Experience was developed in an attempt to address this need. The purpose of this study was (1) to evaluate the effectiveness of the Simulated Ward Experiences by examining students' reactions regarding the quality of teaching and (2) to examine the main drivers of learning and the extent to which students felt it helped them prepare for their future training. Methods: A mixed method evaluation study was conducted using a questionnaire and focus groups. Final year students who participated in the Simulated Ward Experience were invited to contribute to the evaluation, out of which 25 completed the questionnaire and 13 took part in focus group interviews. Data analysis were conducted by means of descriptive statistics for questionnaire data and thematic analysis of focus group transcripts. Results: The median Likert scores for quality of teaching Non-Technical Skills were either very good or excellent, demonstrating that students were highly satisfied with the way in which these were taught. Qualitative data provided further insights into the aspects of the intervention that promoted learning, and these were categorised into four themes, including realism of the simulation; relevance for the role and responsibilities of the Foundation Year 1 Doctor (including Non-Technical Skills); learning from and with others; and supportive learning environment. Conclusion: This evaluation study provides further evidence of the value of learning in a simulated setting, particularly when it is closely aligned to the real clinical context and creates opportunities to practice skills that are perceived to be relevant by the learner. Study limitations are recognised and suggestions for further studies are provided.

Retrospective assessment of clonality of a legacy cell line by analytical subcloning of the master cell bank.

In recent years, assurance of clonality of the production cell line has been emphasized by health authorities during review of regulatory submissions. When insufficient assurance of clonality is provided, augmented control strategies may be required for a commercial production process. In this study, we conducted a retrospective assessment of clonality of a legacy cell line through analysis of subclones from the master cell bank (MCB). Twenty-four subclones were randomly selected based on a predetermined acceptance sampling plan. All these subclones share a conserved integration junction, thus providing a high level of assurance that the cell population in the MCB was derived from a single progenitor cell. However, Southern blot analysis indicates that at least four subpopulations possibly exist in the MCB. Additional characterization of these four subpopulations demonstrated that the resulting changes in product quality attributes of some subclones are not related to the genetic heterogeneity observed in Southern blot hybridization. Furthermore, process consistency, process comparability, and analytical comparability have been demonstrated in batches produced across varying manufacturing processes, scales, facilities, cell banks, and cell ages. Finally, process and product consistency together with a high level of assurance of clonal origin of the MCB helped clear the hurdle for regulatory approval without requirement of additional control strategies.

Breast Core Biopsy Information and Consent: Do we Prepare or do we Scare?

Informed consent has important ethical considerations for invasive procedures. Anecdotal evidence suggests an informed consent policy could heighten anxiety. We evaluated whether detailed information about breast biopsy prior to appointment negatively impacted patient experiences. Phase 1 surveyed patients receiving a standard appointment letter who underwent core biopsy (group A). Phase 2 surveyed two groups receiving standard letter plus biopsy leaflets: those who underwent core biopsy (group B) and those who did not (group C). The analysis included descriptive statistics and qualitative thematic analysis. Hundred percent of group A felt they were given enough information prior to biopsy and 72% felt it would not be helpful having information to read in the clinic beforehand. Hundred percent of group B and 94.1% of group C found it helpful to receive information with their letter. Common themes were good service, verbal explanation, and appreciation of written information. Despite concerns that too much information would heighten anxiety, this has not resulted in negative clinic experiences. Most patients found detailed information included with their appointment letter helpful, regardless of whether they had a biopsy or not.

Streptococcal toxic shock syndrome in the setting of recent gynecologic surgery: A case report.

Toxic shock syndrome (TSS) is an acute, toxin-mediated disease process which is commonly caused by Staphylococcus aureus or Streptococcus pyogenes. A high level of clinical suspicion is imperative, with prompt antibiotic therapy with a penicillinase-resistant penicillin (vancomycin in areas with increased methicillin-resistant Staphylococcus aureus) and clindamycin, given the high morbidity and mortality. Here, a case is reported of streptococcal-mediated TSS in a 37-year-old woman with a history of endometriosis, four days after a laparoscopic cystectomy; an intrauterine device (IUD) was left in situ at the time of uterine manipulation and not removed until hospital day 3 of the patient's readmission. Although no specific guidelines exist for removing IUDs, it is a foreign body and therefore it is recommended that early removal be considered regardless of the level of suspicion that it is the source of sepsis.

Streamlining process characterization efforts using the high throughput ambr® crossflow system for ultrafiltration and diafiltration processing of monoclonal antibodies.

Commercial process development for biopharmaceuticals often involves process characterization (PC) studies to gain process knowledge and understanding in preparation for process validation. One common approach to conduct PC activities is by using design-of-experiment, which can help determine the impact process parameter deviations may have on product quality attributes. Qualified scale-down systems are typically used to conduct these studies. For an ultrafiltration/diafiltration (UF/DF) application, however, a traditional scale-down still requires hundreds of milliliters of material per run and can only conduct one experiment at a time. This poses a challenge in resources as there could be 20+ experiments required for a typical UF/DF PC study. One solution to circumvent this is the use of high-throughput systems, which enable parallel experimentation by only using a fraction of the resources. Sartorius Stedim Biotech has recently commercialized the ambr® crossflow high-throughput system to meet this need. In this study, the performance of this system during a monoclonal antibody UF/DF step was first compared with a pilot- and a manufacturing-scale tangential flow filtration (TFF) system at a single operating condition. Due to material limitations, it was then compared to only the pilot-scale TFF system across wider ranges of transmembrane pressure; crossflow rate; and diafiltration concentration in a PC study. Permeate flux, aggregate content, process yield, pH/conductivity traces, retentate concentration, axial pressure drop, and turbidity values were measured at both scales. A good agreement was attained across scales, further supporting its potential use as a scale-down system.

Twelve Tips for running in-situ simulation during a Coronavirus pandemic.

This article was migrated. The article was marked as recommended. The arrival of the coronavirus pandemic has caused massive disruption to medical education, with universities having to close and adopt new ways of teaching, ensuring social distancing as standard. Final year medical students from the University of Aberdeen graduated early and stepped up to start working as 'Foundation interim Year 1 doctors' (FiY1). With their final months of medical school and end of year examinations cancelled, we felt that an in-situ ward simulation would help them make that transition by giving them an opportunity to act up in a safe environment. Here we share our tips for designing and implementing an in-situ simulation aimed at junior doctors in the early stages of their training. We conclude by reflecting on what we have learnt and how we plan to take this method of simulation forward into future practice, once the pandemic is over.

Highland games: A benchmarking exercise in predicting biophysical and drug properties of monoclonal antibodies from amino acid sequences.

Biopharmaceutical product and process development do not yet take advantage of predictive computational modeling to nearly the degree seen in industries based on smaller molecules. To assess and advance progress in this area, spirited coopetition (mutually beneficial collaboration between competitors) was successfully used to motivate industrial scientists to develop, share, and compare data and methods which would normally have remained confidential. The first "Highland Games" competition was held in conjunction with the October 2018 Recovery of Biological Products Conference in Ashville, NC, with the goal of benchmarking and assessment of the ability to predict development-related properties of six antibodies from their amino acid sequences alone. Predictions included purification-influencing properties such as isoelectric point and protein A elution pH, and biophysical properties such as stability and viscosity at very high concentrations. Essential contributions were made by a large variety of individuals, including companies which consented to provide antibody amino acid sequences and test materials, volunteers who undertook the preparation and experimental characterization of these materials, and prediction teams who attempted to predict antibody properties from sequence alone. Best practices were identified and shared, and areas in which the community excels at making predictions were identified, as well as areas presenting opportunities for considerable improvement. Predictions of isoelectric point and protein A elution pH were especially good with all-prediction average errors of 0.2 and 1.6 pH unit, respectively, while predictions of some other properties were notably less good. This manuscript presents the events, methods, and results of the competition, and can serve as a tutorial and as a reference for in-house benchmarking by others. Organizations vary in their policies concerning disclosure of methods, but most managements were very cooperative with the Highland Games exercise, and considerable insight into common and best practices is available from the contributed methods. The accumulated data set will serve as a benchmarking tool for further development of in silico prediction tools.

High throughput screening of ultrafiltration and diafiltration processing of monoclonal antibodies via the ambr® crossflow system.

As the biopharmaceutical industry moves toward high concentration of monoclonal antibody drug substance, additional development is required early on when material is still limited. A key constraint is the availability of predictive high-throughput low-volume filtration screening systems for bioprocess development. This particularly impacts final stages such as ultrafiltration/diafiltration steps where traditional scale-down systems need hundreds of milliliters of material per run. Recently, the ambr® crossflow system has been commercialized by Sartorius Stedim Biotech (SSB) to meet this need. It enables parallel high throughput experimentation by only using a fraction of typical material requirements. Critical parameters for predictive filtration systems include loading, mean transmembrane pressure (Δ P¯TMP ), and crossflow rate (QF ). While axial pressure drop (ΔPaxial ) across the cartridge is a function of these parameters, it plays a key role and similar values should result across scales. The ambr® crossflow system is first presented describing typical screening experiments. Its performance is then compared to a traditional pilot-scale tangential flow filtration (TFF) at defined conditions. The original ambr® crossflow (CF) cartridge underperformed resulting in ~20x lower ΔPaxial than the pilot-scale TFF flat-sheet cassette. With an objective to improve the scalability of the system, efforts were made to understand this scale difference. The ambr® CF cartridge was successfully modified by restricting the flow of the feed channel, and thus increasing its ΔPaxial . Additional studies across a range of loading (100-823 gm-2 ); Δ P¯TMP (12-18 psi); and QF (4-8 L/min/m2 ) were conducted in both scales. Comparable flux and aggregate levels were achieved.

Scale-down model qualification of ambr® 250 high-throughput mini-bioreactor system for two commercial-scale mAb processes.

Recent advances in high-throughput (HTP) automated mini-bioreactor systems have significantly improved development timelines for early-stage biologic programs. Automated platforms such as the ambr® 250 have demonstrated the ability, using appropriate scale-down approaches, to provide reliable estimates of process performance and product quality from bench to pilot scale, but data sets comparing to large-scale commercial processes (>10,000 L) are limited. As development moves toward late stages, specifically process characterization (PC), a qualified scale-down model (SDM) of the commercial process is a regulatory requirement as part of Biologics License Application (BLA)-enabling activities. This work demonstrates the qualification of the ambr® 250 as a representative SDM for two monoclonal antibody (mAb) commercial processes at scales >10,000 L. Representative process performance and product quality associated with each mAb were achieved using appropriate scale-down approaches, and special attention was paid to pCO2 to ensure consistent performance and product quality. Principal component analysis (PCA) and univariate equivalence testing were utilized in the qualification of the SDM, along with a statistical evaluation of process performance and product-quality attributes for comparability. The ambr® 250 can predict these two commercial-scale processes (at center-point condition) for cell-culture performance and product quality. The time savings and resource advantages to performing PC studies in a small-scale HTP system improves the potential for the biopharmaceutical industry to get products to patients more quickly.

Prediction of lab and manufacturing scale chromatography performance using mini-columns and mechanistic modeling.

Chromatography is a cornerstone of biologics downstream purification processes, and there is an ever increasing demand for improved speed and efficiency in process development. Scale-down models are used in process development to optimize operating conditions and study process robustness while expending as little time and material as possible. The advent of automated liquid handling systems and miniature columns has taken the efficiency of process development to another level by allowing up to eight column runs in parallel with column volumes under 1 ml. As expected, results between these miniature columns and typical lab/manufacturing scale columns can deviate due to scale dependent and/or configuration dependent differences. Regulatory guidelines do not require an exact match in scale-down and large scale data, but do require that small scale models account for scale effects, be representative of the commercial process, and be scientifically justified. Therefore, it is important to gain insight into what causes differences between scales and account for them during development. Mechanistic models can be used to understand the physics of the process (fluid flow, mass transfer, etc.) as a function of scale, and provide explanation for deviations that may be observed. We have used mechanistic modeling to study the factors leading to differences in pool sizes observed between scales, and to make predictions on lab scale pool sizes from miniature column data. Results indicate that changes in mass transfer parameters, specifically axial dispersion, between scales leads to the observed differences in pool size. Additionally, we have studied the effect of system differences between automated liquid handling systems and conventional preparative chromatography systems on elution pool volume. This work provides new insight into the fundamental differences observed between scales and overcomes the challenge of enabling the use of miniature column chromatography as a scale-down model for process characterization.

An ultra scale-down method to investigate monoclonal antibody processing during tangential flow filtration using ultrafiltration membranes.

The availability of material for experimental studies is a key constraint in the development of full-scale bioprocesses. This is especially true for the later stages in a bioprocess sequence such as purification and formulation, where the product is at a relatively high concentration and traditional scale-down models can require significant volumes. Using a combination of critical flow regime analysis, bioprocess modelling, and experimentation, ultra scale-down (USD) methods can yield bioprocess information using only millilitre quantities before embarking on highly demanding full-scale studies. In this study the performance of a pilot-scale tangential flow filtration (TFF) system based on a membrane flat-sheet cassette using pumped flow was predicted by devising an USD device comprising a stirred cell using a rotating disc. The USD device operates with just 2.1 cm2 of membrane area and, for example, just 1.7 mL of feed for diafiltration studies. The novel features of the design involve optimisation of the disc location and the membrane configuration to yield an approximately uniform shear rate. This is characterised using computational fluid dynamics for a defined layer above the membrane surface. A pilot-scale TFF device operating at ~500-fold larger feed volume and membrane area was characterised in terms of the shear rate derived from flow rate-pressure drop relationships for the cassette. Good agreement was achieved between the USD and TFF devices for the flux and resistance values at equivalent average shear rates for a monoclonal antibody diafiltration stage.

Differential Expression of MicroRNAs in Breast Cancers from Four Different Ethnicities.

INTRODUCTION: Breast cancer outcomes vary across different ethnic groups. MicroRNAs (miRs) are small non-coding RNA molecules that regulate gene expression across a range of pathologies, including breast cancer. The aim of this study was to evaluate the presence and expression of miRs in breast cancer samples from different ethnic groups. MATERIALS AND METHODS: Breast cancer tissue from 4 ethnic groups, i.e., British Caucasian, British Black, Nigerian, and Indian, were identified and matched for patients' age, tumour grade/type, and 10 × 10 µm sections taken. Tumour areas were macrodissected, total RNA was extracted, and cDNA was synthesised. cDNA was applied to human miScript PCR arrays allowing the quantification of 84 of the most abundantly expressed/best-characterised miRs. RESULTS: Differential expression of 9 miRs was seen across the 4 groups. Significantly higher levels of miR-140-5p, miR-194 and miR-423-5p (the last of which harbours the single-nucleotide polymorphism rs6505162) were seen in the breast tumours of Nigerian patients when compared with other ethnic groups (all p < 0.0001). miR-101 was overexpressed in breast cancers in the Indian patients. An in silico analysis of miR-423-5p showed that the AC genotype is mainly associated with Europeans (57%), while Asians display mostly CC (approx. 60%), and Africans mainly AA (approx. 60%). CONCLUSIONS: This study shows divergence in miR expression in breast cancers from different ethnic groups, and suggests that specific genetic variants in miR genes may affect breast cancer risk in these groups. Predicted targets of these miRs may uncover useful biomarkers that could have clinical value in breast cancers in different ethnic groups.

High-dose versus standard-dose amoxicillin/clavulanate for clinically-diagnosed acute bacterial sinusitis: A randomized clinical trial.

BACKGROUND: The recommended treatment for acute bacterial sinusitis in adults, amoxicillin with clavulanate, provides only modest benefit. OBJECTIVE: To see if a higher dose of amoxicillin will lead to more rapid improvement. DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized trial in which, from November 2014 through February 2017, we enrolled 315 adult outpatients diagnosed with acute sinusitis in accordance with Infectious Disease Society of America guidelines. INTERVENTIONS: Standard-dose (SD) immediate-release (IR) amoxicillin/clavulanate 875 /125 mg (n = 159) vs. high-dose (HD) (n = 156). The original HD formulation, 2000 mg of extended-release (ER) amoxicillin with 125 mg of IR clavulanate twice a day, became unavailable half way through the study. The IRB then approved a revised protocol after patient 180 to provide 1750 mg of IR amoxicillin twice a day in the HD formulation and to compare Time Period 1 (ER) with Time Period 2 (IR). MAIN MEASURE: The primary outcome was the percentage in each group reporting a major improvement-defined as a global assessment of sinusitis symptoms as "a lot better" or "no symptoms"-after 3 days of treatment. KEY RESULTS: Major improvement after 3 days was reported during Period 1 by 38.8% of ER HD versus 37.9% of SD patients (P = 0.91) and during Period 2 by 52.4% of IR HD versus 34.4% of SD patients, an effect size of 18% (95% CI 0.75 to 35%, P = 0.04). No significant differences in efficacy were seen at Day 10. The major side effect, severe diarrhea at Day 3, was reported during Period 1 by 7.4% of HD and 5.7% of SD patients (P = 0.66) and during Period 2 by 15.8% of HD and 4.8% of SD patients (P = 0.048). CONCLUSIONS: Adults with clinically diagnosed acute bacterial sinusitis were more likely to improve rapidly when treated with IR HD than with SD but not when treated with ER HD. They were also more likely to suffer severe diarrhea. Further study is needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02340000.

High throughput chromatography strategies for potential use in the formal process characterization of a monoclonal antibody.

High throughput experimental strategies are central to the rapid optimization of biologics purification processes. In this work, we extend common high throughput technologies towards the characterization of a multi-column chromatography process for a monoclonal antibody (mAb). Scale-down strategies were first evaluated by comparing breakthrough, retention, and performance (yields and clearance of aggregates and host cell protein) across miniature and lab scale columns. The process operating space was then evaluated using several integrated formats, with batch experimentation to define process testing ranges, miniature columns to evaluate the operating space, and comparison to traditional scale columns to establish scale-up correlations and verify the determined operating space. When compared to an independent characterization study at traditional lab column scale, the high throughput approach identified the same control parameters and similar process sensitivity. Importantly, the high throughput approach significantly decreased time and material needs while improving prediction robustness. Miniature columns and manufacturing scale centerpoint data comparisons support the validity of this approach, making the high throughput strategy an attractive and appropriate scale-down tool for the formal characterization of biotherapeutic processes in the future if regulatory acceptance of the miniature column data can be achieved. Biotechnol. Bioeng. 2016;113: 1273-1283. © 2015 Wiley Periodicals, Inc.

Scholarly productivity for nursing clinical track faculty.

Recent years have yielded substantial advancement by clinical track faculty in cohort expansion and collective contributions to the discipline of nursing. As a result, standards for progression and promotion for clinical faculty need to be more fully developed, articulated, and disseminated. Our school formed a task force to examine benchmarks for the progression and promotion of clinical faculty across schools of nursing, with the goal of guiding faculty, reviewers, and decision makers about what constitutes excellence in scholarly productivity. Results from analyses of curriculum vitae of clinical professors or associate professors at six universities with high research activity revealed a variety of productivity among clinical track members, which included notable diversity in the types of scholarly products. Findings from this project help quantify types of scholarship for clinical faculty at the time of promotion. This work provides a springboard for greater understanding of the contributions of clinical track faculty to nursing practice.

A practical strategy for using miniature chromatography columns in a standardized high-throughput workflow for purification development of monoclonal antibodies.

The emergence of monoclonal antibody (mAb) therapies has created a need for faster and more efficient bioprocess development strategies in order to meet timeline and material demands. In this work, a high-throughput process development (HTPD) strategy implementing several high-throughput chromatography purification techniques is described. Namely, batch incubations are used to scout feasible operating conditions, miniature columns are then used to determine separation of impurities, and, finally, a limited number of lab scale columns are tested to confirm the conditions identified using high-throughput techniques and to provide a path toward large scale processing. This multistep approach builds upon previous HTPD work by combining, in a unique sequential fashion, the flexibility and throughput of batch incubations with the increased separation characteristics for the packed bed format of miniature columns. Additionally, in order to assess the applicability of using miniature columns in this workflow, transport considerations were compared with traditional lab scale columns, and performances were mapped for the two techniques. The high-throughput strategy was utilized to determine optimal operating conditions with two different types of resins for a difficult separation of a mAb monomer from aggregates. Other more detailed prediction models are cited, but the intent of this work was to use high-throughput strategies as a general guide for scaling and assessing operating space rather than as a precise model to exactly predict performance.

The value of archival tissue blocks in understanding breast cancer biology.

Pathological reporting of breast cancer has evolved alongside scientific advances. Such advances have led to recognition of different molecular classes of breast cancer resulting in improved disease management. The aim of this study was to establish whether these advances could be applied to archival breast cancer cases dating from the 1940s to assess historical trends. Important observations included the marked differences in pathological reporting, size of tumour and in ERα expression throughout the decades.

[The concept of equity when developing clinical practice guidelines]. / Equidad en el desarrollo de guías de práctica clínica.

This systematic literature review sought to identify methodologies and technical strategies emphasising healthcare services and outcomes when incorporating the concept of equity into Clinical Practice Guidelines (CPG). 940 references were identified, of which 20 fulfilling the inclusion criteria were selected. While no reports were found describing or evaluating an explicit methodology for incorporating considerations of equity into CPG, some studies revealed related strategies or processes, summarised as follows: 1. Target population involvement during all phases of designing, implementing and evaluating CPG; 2. "Cultural capacity" seen as being necessary in CPGs' "cultural translation" for interventions to have less disparity regarding their application and results; 3. Considering psycho-social factors which could affect implementing CPG, and; 4. Considering system inequities so that any health intervention would also confront risks and obstacles to health care due to socioeconomic status. It was concluded that CPGs could be a potential route for promoting more equitable healthcare effects by standardising health interventions if, by incorporating some of the processes described above, they actively seek to avoid unjust differences in access to and/or the quality of the interventions that they prescribe.

Equidad en el desarrollo de guías de práctica clínica / The concept of equity when developing clinical practice guidelines

Con el objetivo de identificar las metodologías para incorporar las consideraciones de equidad durante el desarrollo de una Guía de Practica Clínica (GPC) se realizó una revisión sistemática de la literatura. De 940 artículos identificados 24 cumplieron los criterios de selección. No se encontraron artículos metodológicos que describieran o evaluaran una metodología explicita para incorporar las consideraciones de equidad. Algunos estudios dan recomendaciones generales con algunas estrategias de acuerdo a la etapa del desarrollo de las guías. Se consideran factores importantes para la incorporación de consideraciones de equidad: 1. vincular la población objetivo durante todas las fases desarrollo de GPC, 2. el análisis y adaptación al contexto cultural que propendan por la aplicación de intervenciones sin disparidades por barreras culturales y con resultados clínicos más equitativos, 3. considerar los factores psicosociales que podrían afectar la implementación y los resultados de las GPC, 4. considerar las inequidades del sistema de salud en su conjunto de modo que se promueva intervenciones dirigidas a conductas de riesgo y barreras para la salud debidas a factores socioeconómicos. Se concluye que las GPC pueden favorecer la equidad en la atención en salud, si se incorporan los procesos mencionados, mediante la promoción de la estandarización de intervenciones y evitando diferencias innecesarias, evitables o injustas en la cantidad y calidad de la atención.

This systematic literature review sought to identify methodologies and technical strategies emphasising healthcare services and outcomes when incorporating the concept of equity into Clinical Practice Guidelines (CPG). 940 references were identified, of which 20 fulfilling the inclusion criteria were selected. While no reports were found describing or evaluating an explicit methodology for incorporating considerations of equity into CPG, some studies revealed related strategies or processes, summarised as follows: 1. Target population involvement during all phases of designing, implementing and evaluating CPG; 2. "Cultural capacity" seen as being necessary in CPGs' "cultural translation" for interventions to have less disparity regarding their application and results; 3. Considering psycho-social factors which could affect implementing CPG, and; 4. Considering system inequities so that any health intervention would also confront risks and obstacles to health care due to socioeconomic status. It was concluded that CPGs could be a potential route for promoting more equitable healthcare effects by standardising health interventions if, by incorporating some of the processes described above, they actively seek to avoid unjust differences in access to and/or the quality of the interventions that they prescribe.