Clinical Guideline Recommendations Research Articles

How consistent are the key recommendations, and what is the quality of guidelines and expert consensus regarding paediatric cow's milk protein allergy?

The objective of this study was to assess the quality and consistency of recommendations in clinical practice guidelines (CPGs) and expert consensus on paediatric cow's milk protein allergy (CMPA) to serve as a foundation for future revisions and enhancements of clinical guidelines and consensus documents. We conducted a comprehensive literature search across several databases, including the Chinese Biomedical Literature Database (CBM), PubMed, Embase, Web of Science, UpToDate, ClinicalKey, DynaMed Plus and BMJ Best Practice. We spanned the search period from the inception of each database through October 1, 2023. We integrated subject headings (MeSH/Emtree) and keywords into the search strategy, used the search methodologies of existing literature and developed it in collaboration with a librarian. Two trained researchers independently conducted the literature screening and data extraction. We evaluated methodological quality and recommendations by using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) and AGREE-Recommendations for Excellence (AGREE-REX) tools. Moreover, we compared and summarized key recommendations from high-quality CPGs. Our study included 27 CPGs and expert consensus documents on CMPA. Only four CPGs (14.8%) achieved a high-quality AGREE II rating. The four high-quality CPGs consistently provided recommendations for CMPA. The highest scoring domains for AGREE II were 'scope and purpose' (77 ± 12%) and 'clarity of presentation' (75 ± 22%). The lowest scoring domains were 'stakeholder involvement' (49 ± 21%), 'rigor of development' (34 ± 20%) and 'applicability' (12 ± 20%). Evaluation with AGREE-REX generally demonstrated low scores across its domains. Conclusion: Recommendations within high-quality CPGs for the paediatric CMPA showed fundamental consistency. Nevertheless, the methodology and recommendation content of CPGs and the expert consensus exhibited low quality, thus indicating a substantial scope for enhancement. Guideline developers should rigorously follow the AGREE II and AGREE-REX standards in creating CPGs or expert consensuses to guarantee their clinical efficacy in managing paediatric CMPA. What is Known: • The quality of clinical practice guidelines and expert consensus on paediatric cow's milk protein allergy (CMPA) remains uncertain. • There is a lack of clarity regarding the consistency of crucial recommendations for CMPA management. What is New: • Improving the methodological quality of guidelines and consensus on CMPA requires greater emphasis on stakeholder engagement, rigorous development processes, and practical applicability. • The recommendations from four high-quality guidelines align. However, addressing clinical applicability, integrating values and preferences, and ensuring actionable implementation are critical to improving the quality of all guidelines.

Clinical inertia in thyrotropin suppressive therapy for low-risk differentiated thyroid cancer: A real-world experience at an endocrine center in Bangkok.

The management of low-risk differentiated thyroid cancer (DTC) has evolved over time toward treatment de-escalation. However, overtreatment with supraphysiological dose of levothyroxine (LT4) continues to be observed despite current clinical guideline. This study aimed to assess the actual thyrotropin suppressive therapy for low-risk DTC patients at an endocrine center in Bangkok. This retrospective study included patients with low-risk DTC who were regularly follow-up for at least 18 months at Theptarin Hospital between 2016 and 2022. The serum thyroid stimulating hormone (TSH) levels were stratified as TSH < 0.1 mIU/L; TSH 0.1 to 0.5 mIU/L; TSH 0.5 to 2.0 mIU/L; and TSH > 2.0 mIU/L. The initial risk stratification (IRS) and dynamic risk stratification were determined at 12 months of follow-up after completing the initial treatment and at the last visit. The clinical factors associated with overtreatment with LT4 were analyzed. A total of 102 patients (83.3% female, age at diagnosis 41.8 ± 13.6 years, mean tumor size 1.6 ± 1.0 cm) were evaluated with a mean follow-up of 5.9 years. The IRS classified 92.2% of patients after the initial treatment and 93.1% of patients at the last follow-up visit into the excellent response category. The mean LT4 daily dosage at the last follow-up was 121.3 ± 44.8 µg/day. Serum TSH levels were in an appropriate target range according to IRS in only 8.8% (9/102) of the patients and then improved to 19.6% (20/102) at the last follow-up visit. Further analysis showed that treating physicians with ≥10 years of practice was associated with severe TSH suppression therapy (TSH < 0.1 mIU/L). Despite the current clinical guideline recommendations and scientific evidences, less than one-fifth of low-risk DTC patients achieved the appropriate serum TSH target. While the proportion of an optimum LT4 suppressive had improved during the study period, further efforts are needed to overcome this clinical inertia.

Clinical Practice Guideline-Inconsistent Management of Fertility Preservation in Pediatric Cancer Patients in Community Settings: A Children's Oncology Group Study.

Background: The primary objective was to measure adherence to clinical practice guideline (CPG) recommendations for fertility preservation (FP) in pediatric cancer patients treated in National Cancer Institute Community Oncology Research Program (NCORP) sites. Secondary objectives were to describe factors such as site size associated with CPG-inconsistent care delivery and cryopreservation completion. Methods: This retrospective, multicenter study included patients 15 to 21 years old with a first cancer diagnosis from January 2014 through December 2015 who were previously enrolled to a Children's Oncology Group (COG) study and received care at a participating NCORP site. Patients were randomly selected from a list generated by the COG for chart review by participating sites. Primary outcome was care delivery that was inconsistent with a strong CPG recommendation on FP, namely discussion and offering of FP options before cancer treatment initiation, as adjudicated centrally by a panel. Results: A total of 129 patients from 25 sites were included. Among these, 48% (62/129) received CPG-inconsistent care. Most CPG-inconsistent care was due to lack of FP discussion documentation (93.5%, 58/62). Small site size, treatment at a pediatric (vs mixed adult/pediatric) site, and female sex were associated with higher odds of CPG-inconsistent care delivery. Conclusions: Newly diagnosed pediatric cancer patients often received CPG-inconsistent care for FP, with disproportionate gaps noted for females, and those treated at smaller or pediatric NCORP sites. The primary reason for CPG-inconsistent care is lack of FP discussion from clinicians. Opportunities to improve FP CPG implementation are highlighted.

Recommendations of Clinical Practice Guidelines for the treatment of urinary incontinence in women: A methodological survey

Objective: This study described and analysed key recommendations from Clinical Practice Guidelines (CPGs) concerning urinary incontinence (UI) treatment in women. Materials and methods: We carried out searches in the following databases: MEDLINE, EMBASE, Web of Science, Virtual Health Library, among others. The reviewers, in duplicate and independently, selected the documents and extracted the data. The quality assessment of the guidelines was carried out, in triplicate, using the Appraisal of Guidelines REsearch and Evaluation (AGREE II) instrument. Results: Six CPGs were selected for analysis. Pelvic Floor Muscle Training (PFMT) is the primary treatment for UI, with adjunctive therapies (biofeedback, vaginal cones, dynamic lumbopelvic stabilisation, and electrical stimulation) recommended alongside PFMT. Discrepancies among CPG were noted in recommendations for drug treatments and invasive procedures, suggesting the need for individualised approaches. When conservative non-pharmacological treatments failed, drugs are recommended. Mid-urethral slings were endorsed, with alternatives like colposuspension or autologous rectus fascial slings considered when mid-urethral slings were unsuitable. Botulinum toxin type A was suggested for urge UI patients unresponsive to conservative therapy. Conclusion: UI treatment must prioritise the conservative non-pharmacological therapies and progressing to invasive options, as necessary. These evidence-based findings aim to guide patients, healthcare professionals, and policy managers in effectively managing UI. Level of evidence: Not applicable

Clinicians in the Veterans Health Administration initiate gender-affirming hormone therapy in concordance with clinical guideline recommendations.

Gender-affirming hormone therapy (GAHT) is a common medical intervention sought by transgender and gender diverse (TGD) individuals. Initiating GAHT in accordance with clinical guideline recommendations ensures delivery of high-quality care. However, no prior studies have examined how current GAHT initiation compares to recommended GAHT initiation. This study assessed guideline concordance around feminizing and masculinizing GAHT initiation in the Veterans Health Administration (VHA). The sample included 4,676 veterans with a gender identity disorder diagnosis who initiated feminizing (n=3,547) and masculinizing (n=1,129) GAHT between 2007 and 2018 in VHA. Demographics and health conditions on veterans receiving feminizing and masculinizing GAHT were assessed. Proportion of guideline concordant veterans on six VHA guidelines on feminizing and masculinizing GAHT initiation were determined. Compared to veterans receiving masculinizing GAHT, a higher proportion of veterans receiving feminizing GAHT were older (≥60 years: 23.7% vs. 6.3%), White non-Hispanic (83.5% vs. 57.6%), and had a higher number of comorbidities (≥7: 14.0% vs. 10.6%). A higher proportion of veterans receiving masculinizing GAHT were Black non-Hispanic (21.5% vs. 3.5%), had posttraumatic stress disorder (43.0% vs. 33.9%) and positive military sexual trauma (33.5% vs.16.8%; all p-values<0.001) than veterans receiving feminizing GAHT. Among veterans who started feminizing GAHT with estrogen, 97.0% were guideline concordant due to no documentation of contraindication, including venous thromboembolism, breast cancer, stroke, or myocardial infarction. Among veterans who started spironolactone as part of feminizing GAHT, 98.1% were guideline concordant as they had no documentation of contraindication, including hyperkalemia or acute renal failure. Among veterans starting masculinizing GAHT, 90.1% were guideline concordant due to no documentation of contraindications, such as breast or prostate cancer. Hematocrit had been measured in 91.8% of veterans before initiating masculinizing GAHT, with 96.5% not having an elevated hematocrit (>50%) prior to starting masculinizing GAHT. Among veterans initiating feminizing and masculinizing GAHT, 91.2% had documentation of a gender identity disorder diagnosis prior to GAHT initiation. We observed high concordance between current GAHT initiation practices in VHA and guidelines, particularly for feminizing GAHT. Findings suggest that VHA clinicians are initiating feminizing GAHT in concordance with clinical guidelines. Future work should assess guideline concordance on monitoring and management of GAHT in VHA.

Trends of Antihypertensive Prescription Among US Adults From 2010 to 2019 and Changes Following Treatment Guidelines: Analysis of Multicenter Electronic Health Records.

Guidelines for the use of antihypertensives changed in 2014 and 2017. To understand the effect of these guidelines, we examined trends in antihypertensive prescriptions in the United States from 2010 to 2019 using a repeated cross-sectional design. Using electronic health records from 15 health care institutions for adults (20-85 years old) who had ≥1 antihypertensive prescription, we assessed whether (1) prescriptions of beta blockers decreased after the 2014 Eighth Joint National Committee (JNC 8) report discouraged use for first-line treatment, (2) prescriptions for calcium channel blockers and thiazide diuretics increased among Black patients after the JNC 8 report encouraged use as first-line therapy, and (3) prescriptions for dual therapy and fixed-dose combination among patients with blood pressure ≥140/90 mm Hg increased after recommendations in the 2017Hypertension Clinical Practice Guidelines. The study included 1 074 314 patients with 2 133 158 prescription episodes. After publication of the JNC 8 report, prescriptions for beta blockers decreased (3% lower in 2018-2019 compared to 2010-2014), and calcium channel blockers increased among Black patients (20% higher in 2015-2017 and 41% higher in 2018-2019, compared to 2010-2014), in accordance with guideline recommendations. However, contrary to guidelines, dual therapy and fixed-dose combination decreased after publication of the 2017 Hypertension Clinical Practice Guidelines(9% and 11% decrease in 2018-2019 for dual therapy and fixed-dose combination, respectively, compared to 2015-2017), and thiazide diuretics decreased among Black patients after the JNC8 report (6% lower in 2018-2019 compared to 2010-2014). Adherence to guidelines on prescribing antihypertensive medication was inconsistent, presenting an opportunity for interventions to achieve better blood pressure control in the US population.

Induced abortion in Africa: A systematic review and meta-analysis.

One of the main factors contributing to maternal morbidity and mortality is induced abortion. The WHO estimates that over 44 million induced abortions take place annually around the world. The majority of these abortions-about 50%-are unsafe, significantly increasing maternal morbidity and contributing to 13% of maternal deaths. Thus, this review aimed to estimate the pooled prevalence of induced abortion and its associated factors in Africa. To find literature on the prevalence of induced abortion and its associated factors, a thorough search of the internet databases such as PubMed/MEDLINE, African Journals Online, and Google Scholar was conducted. The data were extracted using a structured method of data collection. Software called STATA 14 was used to do the analysis. funnel plot and Egger regression test were used to evaluate potential publication bias. I2 statistics and Cochrane's Q were used to measure the heterogeneity at a p-value < 0.05. 976 studies were found through a thorough search of electronic databases. Finally, 46 full-text abstract papers were included in this study. The estimated pooled prevalence of induced abortion was 16% (95% CI: 13%-19%). According to the sub-group analysis, most studies were conducted in Ethiopia, and the pooled prevalence was 19% (95% CI: 10%-30%). Similarly, the subgroup analysis by year of study showed that the prevalence of induced abortion was 39% (95% CI: 17%-64%) among studies conducted in 2019. The results of this study thus imply that the pooled prevalence of induced abortion is higher than that of earlier studies that were published in some nations. the data from this study are needed to support reproductive and adolescent health programmers and policymakers and to formulate recommendations for future clinical practice and guidelines.

Abstract PO5-27-01: Comparison between the 7th and the 8th edition of TNM Staging System of American joint committee on Cancer(AJCC) for Breast Cancer Patients, diagnosed and treated at King Abdulaziz Medical City

Abstract Breast cancer is a heterogeneous disease with different biological and molecular characteristics that affect local recurrence, metastases, prognoses, and response to available therapies. The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for breast cancer has incorporated the biological and molecular characteristics, tumor grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor status(Her-2)and tumor grade, into the traditional anatomical 7th edition that only considers tumor size, lymph nodes status, and distant metastases. The aim of this study is to compare the 7th to 8th editions of the AJCC staging system for prognostic impact, assess the effect of the new edition on the treatment and treatment outcome Method A retrospective cohort study was performed for all breast cancer patients, diagnosed between (2013 -2019) and underwent upfront surgery at King Abdulaziz Medical City (KAMC).Patients’ clinicopathological, immunohistochemical, surgical, therapeutic, and follow-up data were retrieved. Overall survival (OS) and breast cancer-specific survival (BCSS) were estimated using the Kaplan–Meier method. Univariate analysis using Fisher's exact test was used to compare staging systems' prognostic accuracy. Multivariable analysis using Cox proportional hazards regression analysis was performed to identify factors independently associated with disease outcome Results A total of 169 female patients were included, the 8th AJCC staging system resulted in a reallocation of 108 (63.9%) of the patients to a different stage group. The majority were downstaged(60.9%) while only 3% were upstaged, most of the upstaged patients had a triple-negative subtype (80%). The change in overall stage for the 8th edition was most significant in stage I (an increase by 140.3%), followed by stage II (downstaged by 74.3%) and stage III (downstaged by 49.7%) compared to the 7th edition. Critically 42.8% of all downstaged patients treated with adjuvant chemotherapy were found to have received unnecessary chemotherapy after applying the 8th AJCC staging system as per National Comprehensive Cancer Network (NCCN) clinical practice guidelines recommendations. The 8th AJCC staging system was a better prognostic predictor of disease survival, patients in 8th AJCC stage 3 had a higher tendency to develop metastases and die because of their disease (P-value 0.03, 0.051, respectively). Conclusions: Our comparison revealed that the AJCC 8th edition staging system is superior and more comprehensive than the 7th, in term of prognostic value, and in defining the precise adjuvant therapy Figure 1 Comparison of the 7th AJCC and the 8th AJCC staging system Citation Format: Nafisa Abdelhafiez, Abdulmohsen Alkushi, Lolwah Alriyees, Mohammad Arabi, Faris Alsalamah, Emad Masuadi, Ahmad Omair, Mohammad Alkaiyat, Hussam Shehata. Comparison between the 7th and the 8th edition of TNM Staging System of American joint committee on Cancer(AJCC) for Breast Cancer Patients, diagnosed and treated at King Abdulaziz Medical City [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-01.

Abstract PO4-04-03: Empowering Oncologists to Develop Individualized Management Strategies for HER2+ Metastatic Breast Cancer: Findings from a Quality Improvement Initiative

Abstract Background: Rapidly evolving evidence in the treatment of metastatic HER2+ metastatic breast cancer (MBC) can present challenges in aligning practice with the latest clinical data and guideline recommendations. In this ongoing quality improvement initiative, we identify and address real-world challenges healthcare professionals (HCPs) face in individualizing treatment plans, adverse event management, and patient-centered care for HER2+ MBC. Methods: From 9/2022 to 12/2022, 22 HCPs who treat patients with breast cancer (BC) along with 52 patients with HER2+ MBC from 2 large US community oncology clinics completed tethered surveys assessing practice patterns, challenges, and attitudes related to individualized and patient-centered care for HER2+MBC. Patient charts (n=100) were audited to assess current practice patterns and to track changes over time. Inclusion criteria included a confirmed HER2+ MBC diagnosis, prescription for two or more lines of HER2+ breast cancer treatment, and ≥ 1 visit in the one-year chart abstraction period. HCPs participated in audit-feedback sessions to assess site-specific challenges and gaps and developed action plans for improvement. Follow-up chart audits and HCP surveys will evaluate changes in practice patterns 6 months after the educational intervention. Results: The most frequently reported HCP challenges included coordination of care (41%) and individualizing treatment plans (32%). The most frequently reported patient challenges included feeling confident in treatment plan (30%) and being unable to meet work or home responsibilities (22%). In tethered surveys, there were discordant findings between patient and HCP perceptions related to goals for treatment, patient education, and patient-centered care. For example, 82% of HCPs reported often or always asking patients about treatment preferences, but only 8% of patients reported their doctor asked. While HCPs overwhelmingly thought surviving as long as possible was their patients’ top goal (82%), patients reported their top goals for treatment were improving quality of life (57%) and controlling symptoms (41%). Additionally, while HCPs thought patients had the most difficulty managing nausea/vomiting (68%) and diarrhea (59%), patients reported they have the most difficulty managing fatigue (46%) and hair loss (44%). Baseline chart audits highlighted several areas for improvement in guideline-aligned care, including treatment selection, sequencing, and supportive care. Based on identified gaps, providers developed and implemented action plans, such as increasing use of patient navigators, referring patients for palliative care at time of diagnosis, improving multidisciplinary team-based approaches, and implementing tools and resources to stay up-to-date on clinical evidence and guidelines. Full findings from baseline surveys and chart audits will be presented, along with follow-up surveys and chart audits to measure impact. Conclusions: Through this QI initiative, we identified gaps in individualized, guideline-aligned, patient-centered care for patients with HER2+ MBC, and HCPs developed and are implementing action plans for improvement. The methods and findings from this initiative demonstrate key opportunities to improve outcomes for patients with HER2+ MBC in community oncology clinics. Citation Format: Reshma Mahtani, Erika Hamilton, Ilona Dewald, Chelsie Anderson, Jeffrey Carter, Cherilyn Heggen, Kelly McKinnon. Empowering Oncologists to Develop Individualized Management Strategies for HER2+ Metastatic Breast Cancer: Findings from a Quality Improvement Initiative [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-03.

Aspirin as Venous Thromboembolism Prophylaxis in Arthroplasty Patients: An Analysis of Clinical Practice Guidelines Recommendations

BackgroundVenous thromboembolism (VTE) is a recognized postoperative complication of hip or knee arthroplasty and incurs major morbidity and mortality. While anticoagulants are the mainstay of chemoprophylaxis, aspirin has recently emerged as a popular prophylactic agent. However, there is a lack of high-quality evidence comparing aspirin to anticoagulants as a method of VTE prophylaxis, and current guidelines are conflicting regarding using aspirin as first-line chemoprophylaxis. We aimed to investigate guideline characteristics that are associated with the recommendation for or against aspirin as a first-line agent. MethodsMedLine, EMBASE, CINAHL, and PubMed databases were searched from 1966 to January 2024 to identify clinical practice guidelines for VTE prophylaxis in adult hip or knee arthroplasty inpatients of average risk. The characteristics of the guideline were collected by two independent reviewers. Logistic regression was used to test the association between the recommendation for or against aspirin and guideline characteristics. ResultsThere were 26 guidelines published from February 2003 to September 2023 and included in this study. There were five guidelines that recommended aspirin and 11 guidelines that recommended against aspirin as first-line therapy. With a more recent year of publication, aspirin was more likely to be recommended (odds ratio (OR) 1.72, 95% confidence interval (CI): 1.05 to 2.84) and less likely to be recommended against (OR 0.61, 95% CI: 0.41 to 0.90). No other variables, including the level of evidence used, the composition of the guideline working group, or the objective of the guideline were associated with the recommendation for or against aspirin. ConclusionGuidelines were inconsistent in their recommendations regarding aspirin as first-line therapy as VTE prophylaxis in arthroplasty patients. Adequately powered randomised controlled trials (RCTs) using modern practices, such as early postoperative mobilization, are needed to better inform clinical practice guidelines.

Physicians found an interactive tool displaying structured evidence summaries for multiple comparisons understandable and useful: A qualitative user-testing study

ObjectiveTo evaluate and improve MATCH-IT – a digital, interactive decision support tool displaying structured evidence summaries for multiple comparisons – to help physicians interpret and apply evidence from network meta-analysis (NMA) for their clinical decision-making. Study design and SettingWe conducted a qualitative user-testing study, applying principles from user centred design in an iterative development process. We recruited a convenience sample of practicing physicians in Norway, Belgium and Canada, and asked them to interpret structured evidence summaries for multiple comparisons – linked to clinical guideline recommendations – displayed in MATCH-IT. User-testing included (a) introduction of a clinical scenario, (b) a think aloud session with participant-tool-interaction and (c) a semi-structured interview. We video recorded, transcribed, and analysed user-tests using directed content analysis. The results informed new updates in MATCH-IT. ResultsDistributed across five development cycles we tested MATCH-IT with 26 physicians. Of these, 24 (94%) reported either no or sparse prior experience with interpretation of NMA. Physicians perceived MATCH-IT as easy to interpret, navigate and appreciated its ability to provide an overview of the evidence. Visualization of effects in pictograms and inclusion of information on burden of treatment (“practical issues”) were highlighted as potentially useful features in interacting with patients. We also identified problems, including undiscovered functionalities (drag and drop), suboptimal tutorial, and cumbersome navigation of the tool. In addition, physicians wanted definition/explanation of key terms (e.g., outcomes and “certainty”) and there were concerns that overwhelming evidence from a large NMA would complicate applicability to clinical practice. This led to several updates with development of a new start page, tutorial, updated user-interface for more efficient manoeuvring, solutions to display definition of key terms and a FAQ section. To facilitate interpretation of large networks, we improved categorization of results using colour coding and added filtering functionality. These modifications allowed physicians to focus on interventions of interest and reduce information overload. ConclusionsThis study provides proof of concept that physicians can use MATCH-IT to understand NMA evidence. Key features of MATCH-IT in a clinical context include providing an overview of the evidence, visualization of effects and the display of information on burden of treatments. However, unfamiliarity with GRADE concepts, time constraints and accessibility at the point of care may be challenges for use. To what extent our results are transferable to real-world clinical contexts remains to be explored.

Recommendations for pharmacogenetic testing in clinical practice guidelines in the US.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Pharmacogenetic testing can identify patients who may benefit from personalized drug treatment. However, clinical uptake of pharmacogenetic testing has been limited. Clinical practice guidelines recommend biomarker tests that the guideline authors deem to have demonstrated clinical utility, meaning that testing improves treatment outcomes. The objective of this narrative review is to describe the current status of pharmacogenetic testing recommendations within clinical practice guidelines in the US. Guidelines were reviewed for pharmacogenetic testing recommendations for 21 gene-drug pairs that have well-established drug response associations and all of which are categorized as clinically actionable by the Clinical Pharmacogenetics Implementation Consortium. The degree of consistency within and between organizations in pharmacogenetic testing recommendations was assessed. Relatively few clinical practice guidelines that provide a pharmacogenetic testing recommendation were identified. Testing recommendations for HLA-B*57:01 before initiation of abacavir and G6PD before initiation of rasburicase, both of which are included in drug labeling, were mostly consistent across guidelines. Gene-drug pairs with at least one clinical practice guideline recommending testing or stating that testing could be considered included CYP2C19-clopidogrel, CYP2D6-codeine, CYP2D6-tramadol, CYP2B6-efavirenz, TPMT-thiopurines, and NUDT15-thiopurines. Testing recommendations for the same gene-drug pair were often inconsistent between organizations and sometimes inconsistent between different guidelines from the same organization. A standardized approach to evaluating the evidence of clinical utility for pharmacogenetic testing may increase the inclusion and consistency of pharmacogenetic testing recommendations in clinical practice guidelines, which could benefit patients and society by increasing clinical use of pharmacogenetic testing.

Malignancy and "Violated Neck" Rates in Consecutive Cohort of 79 Adult Patients With Solitary Cystic Neck Mass-Lessons Learned and Recommendations for Clinical Practice Guidelines.

The neck region is a common site for solitary cystic neck mass (SCNM) of various etiologies, including congenital, inflammatory, and neoplastic. In adults, the primary focus is excluding malignancy. The objective of this study was to retrospectively analyze the accuracy of available diagnostic technologies for the differentiation of benign and malignant SCNM in adult patients. The study aimed to develop new clinical practice guidelines for evaluating and managing SCNM. The primary predictive variables were the diagnostic utilities of fine-needle aspiration cytology (FNAC), ultrasound (U/S), multislice computed tomography, and magnetic resonance imaging. The study's endpoint was the overall diagnostic accuracy in differentiating between benign and malignant SCNM. The final diagnosis was based on histopathology. The study included 79 adult patients: 55 (69.62%) male and 24 (30.38%) female (P<0.05). The mean age at presentation was 42.1 years (range: 18-84 years). Solitary cystic neck mass was distributed in the anterior neck region in 30 (37.97%) patients and the posterolateral neck regions in 49 (62.03%) patients (P<0.05). The posterolateral neck regions had a significantly higher rate of malignant SCNM than the anterior neck region [19/49 (38.78%) versus 1/30 (3.33%)] (P<0.05). There was no statistically significant difference between the U/S+FNAC and U/S+FNAC+multislice computed tomography and/or magnetic resonance imaging groups in differentiating benign and malignant SCNM (40/42 versus 36/37, P>0.05). "Violated neck" was recorded in 2 cases. A systematic investigation protocol should be applied to evaluate adult patients with SCNM.

A practical guide to living evidence: Reducing the knowledge-to-practice gap.

Living evidence involves continuous evidence surveillance to incorporate new relevant evidence into systematic reviews and clinical practice guideline recommendations as soon as it becomes available. Thus, living evidence may improve the timeliness of recommendation updates and reduce the knowledge-to-practice gap. When considering a living evidence model, several processes and practical aspects need to be explored. Some of these include identifying the need for a living evidence model, funding, governance structure, time, team skills and capabilities, frequency of updates, approval and endorsement and publication and dissemination.

Why all clinical guideline recommendations are ‘Conditional’

Highlights The impact of clinical guidelines on practitioner behaviour and clinical care remains in doubt. The acceptability of a 5‐ or 10‐year delay in producing a ‘strong’ clinically important recommendation is unlikely to hold. Practitioners think holistically, in contrast to the analytical thinking that characterizes clinical research. Rapidly accessible, flexible, ‘knowledge‐in‐practice‐in‐context’ cannot be simply replaced by a focused piece of new research or guideline.

Tratamiento de la enfermedad inflamatoria del tracto intestinal, manejo individualizado. Tratamiento de inducción de la remisión y del mantenimiento

Inflammatory bowel disease (IBD) encompasses a group of chronic disorders characterized by immune-mediated inflammation of the gastrointestinal tract. The most notable entities are Crohn's disease and ulcerative colitis. IBD treatment focuses on achieving measurable goals that are agreed upon with the patient that allow for clinical remission, mucosal healing, and improvement in quality of life. The therapeutic approach to IBD is multidisciplinary and individualized according to the patient's characteristics, severity of the flare, extent and phenotype of the disease, treatment response, and cost of treatment.Currently, a wide variety of drugs are available for treating IBD: aminosalicylates, corticosteroids, immunomodulators, biologic drugs, or new small molecule drugs. Surgery is reserved for severe flare-ups that do not respond to medical treatment or complications such as bowel obstruction or perforation. In addition, nutritional support plays an essential role managing this disease. This document lists the different treatments available in the approach to IBD and proposes a treatment sequence based on the available clinical evidence and clinical practice guidelines recommendations.

Co-design workshops to develop evidence synthesis summary formats for use by clinical guideline development groups

BackgroundEvidence synthesis is used by decision-makers in various ways, such as developing evidence-based recommendations for clinical guidelines. Clinical guideline development groups (GDGs) typically discuss evidence synthesis findings in a multidisciplinary group, including patients, healthcare providers, policymakers, etc. A recent mixed methods systematic review (MMSR) identified no gold standard format for optimally presenting evidence synthesis findings to these groups. However, it provided 94 recommendations to help produce more effective summary formats for general evidence syntheses (e.g., systematic reviews). To refine the MMSR recommendations to create more actionable guidance for summary producers, we aimed to explore these 94 recommendations with participants involved in evidence synthesis and guideline development.MethodsWe conducted a descriptive qualitative study using online focus group workshops in February and March 2023. These groups used a participatory co-design approach with interactive voting activities to identify preferences for a summary format's essential content and style. We created a topic guide focused on recommendations from the MMSR with mixed methods support, ≥ 3 supporting studies, and those prioritized by an expert advisory group via a pragmatic prioritization exercise using the MoSCoW method (Must, Should, Could, and Will not haves). Eligible participants must be/have been involved in GDGs and/or evidence synthesis. Groups were recorded and transcribed. Two independent researchers analyzed transcripts using directed content analysis with 94 pre-defined codes from the MMSR.ResultsThirty individuals participated in six focus groups. We coded 79 of the 94 pre-defined codes. Participants suggested a “less is more” structured approach that minimizes methodological steps and statistical data, promoting accessibility to all audiences by judicious use of links to further information in the full report. They emphasized concise, consistently presented formats that highlight key messages, flag readers to indicators of trust in the producers (i.e., logos, websites, and conflict of interest statements), and highlight the certainty of evidence (without extenuating details).ConclusionsThis study identified guidance based on the preferences of guideline developers and evidence synthesis producers about the format of evidence synthesis summaries to support decision-making. The next steps involve developing and user-testing prototype formats through one-on-one semi-structured interviews to optimize evidence synthesis summaries and support decision-making.

Abstract 2552: Real-world analysis of biomarker testing and use of targeted therapies in metastatic non-small cell lung cancer (mNSCLC) in the United States (US)

Abstract Background: Between 1998 and 2022, over 40% of new oncology drugs approved by the US FDA were precision therapies. In nonsquamous mNSCLC, detecting biomarkers where targeted therapies exist (EGFR, ALK, ROS1, BRAF V600E variant, MET exon 14 skipping variant, RET and PD-L1) has become essential for adequate clinical care. This study investigated real-world use of these biomarker tests, their characteristics, and associated use of targeted therapies in mNSCLC patients in the US. Methods: Adults ≥18 years old with stage IV mNSCLC from the nationwide Flatiron Health electronic health record-derived de identified database (01/2011 - 04/2023). The proportion of patients receiving biomarker tests, timing, characteristics, test type (single, multiple or next-generation sequencing), and proportion of patients receiving guideline recommended associated targeted therapies (i.e. actionable treatment) was assessed. Actionable treatment was defined in study years where at least one actionable therapy was FDA approved (biomarker, therapy, date: ALK, crizotinib, Aug 2011; BRAF V600E, dabrafenib+trametinib, Jul 2015; EGFR, afatinib, Jul 2013; MET exon 14 skipping, capmatinib, May 2020; PD-L1, pembrolizumab, Oct 2015; RET, pralsetinib, Sep 2020; ROS-1, crizotinib, Mar 2016). Results: In 42,037 patients with mNSCLC, the proportion of patients receiving each test were: ALK: 71.6%, BRAF: 48.8%, EGFR: 74.9%, MET: 41.4%, PD-L1: 49.3%, RET: 42.3%, and ROS1: 54.2%. Median (Q1, Q3) time from mNSCLC diagnosis to first biomarker result was 21 (12, 37) days. Tissue was the most common sample type for biomarker testing, although sampling by blood has increased in recent years. Multiple testing methods were more common in ALK and PD-L1 (48.1% and 50.3%, respectively) and next generation sequencing was more common in the other biomarkers (BRAF: 77.7%, EGFR: 57.1%, MET: 74.1%, RET: 70.7%, ROS1: 54.0%). Testing rates increased from 2011 through 2023 for each biomarker, with the highest rates in 2023: ALK (87.7%), BRAF (85.2%), EGFR (88.7%), MET (85.7%), PDL1 (78.7%), RET (84.8%), and ROS1 (86.9%). Testing rates were similar when timing was restricted to a 1-year window from mNSCLC diagnosis. Receipt of actionable treatment varied by biomarker, in order of increasing frequency: RET+ (23.0%), MET+ (34.0%), BRAF+ (42.7%), PDL1+ (56.3%), ROS1+ (59.8%), EGFR+ (70.6%), and ALK+ (89.0%). Generally, across all biomarkers, receipt of actionable therapy increased in more recent years. Conclusion: Current real-world biomarker testing rates and use of actionable treatments may reflect increased adoption of clinical guideline recommendations. Despite increased testing, use of actionable therapy remains low for certain biomarkers. Further improvements in the implementation of robust biomarker testing to use appropriate therapies are needed, which can lead to better patient outcomes. Citation Format: Michael J. Dennis, Devin Abrahami, Maria Cecilia Vieira, Darrin Benjumea, Marley Boyd, Anran Shao, Kirsten Duncan, John Kelton, Sandip P. Patel. Real-world analysis of biomarker testing and use of targeted therapies in metastatic non-small cell lung cancer (mNSCLC) in the United States (US) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2552.

Compliance with Australian Orthopaedic Association guidelines does not reduce the risk of venous thromboembolism after total hip and knee arthroplasty.

Preventing avoidable venous-thrombo-embolism (VTE) is a priority to improve patient and service outcomes after total hip and total knee arthroplasty (THA, TKA), but compliance with relevant clinical guidelines varies. This study aims to determine the degree to which prophylaxis was compliant with Australian Orthopaedic Association (AOA) VTE prophylaxis guidelines and whether non-compliance is associated with increased risk of VTE. A prospective multi-centre cohort study of adults with osteoarthritis undergoing primary TKA/THA was completed at 19 high-volume public and private hospitals. Data were collected prior to surgery and for one-year post-surgery. Logistic regression was undertaken to explore associations between non-compliance with AOA VTE prophylaxis guidelines and symptomatic 90-day VTE outcomes. Data were analysed for 1838 participants from 19 sites. The rate of non-compliance with all clinical guideline recommendations was 20.1% (N = 369), with 14.1% (N = 259) non-compliance for risk-stratified prophylaxis, 35.8% (N = 658) for duration, and 67.8% (N = 1246) for other general recommendations. Symptomatic VTE was experienced up to 90-days post-surgery by 48 people (2.6%). Overall guideline non-compliance (AOR = 0.93, 95%CI = 0.4 to 1.3, p = 0.86) was not associated with a lower risk of symptomatic 90-day VTE. Results were consistent when people with high bleeding risk were excluded (AOR = 0.94, 95%CI = 0.44 to 2.34, p = 0.89). Non-compliance with the AOA VTE prophylaxis guidelines was not associated with risk of 90-day VTE after arthroplasty. This counterintuitive finding is concerning and necessitates a rigorous review of the AOA VTE prevention clinical guideline.

The Role of Pharmaceutical Innovation in Clinical Practice Guidelines for Chronic Diseases.

Over the last 25 years, clinical practice guidelines have emerged as a means to standardize and improve care. As pharmaceutical innovations develop, guidelines are updated to incorporate new interventions. However, the extent to which pharmacotherapies are represented as treatment options in guideline recommendations has not been well elucidated. This study aimed to quantify the role pharmacotherapy has played in clinical practice guidelines across a range of chronic diseases over the past 20 years. Clinical practice guidelines published from 2000 to 2021 were identified for five chronic diseases: ischemic heart disease (IHD), non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD), Alzheimer's disease (AD), and type 2 diabetes (T2D). Guidelines were reviewed and data on treatment recommendations were collected, including the type of intervention, line of therapy, and, for pharmacotherapies, year of regulatory approval and year of inclusion in guidelines. In total, 92 clinical practice guidelines were reviewed. Among the 184 discrete recommended interventions across the five disease areas, 146 (79.3%) were pharmacotherapies, 21 (11.4%) were behavioral modifications, 6 (3.3%) were surgical interventions, and 11 (6%) were other interventions. Across guidelines, when a line of therapy was specified, behavioral modifications and pharmacotherapies were most frequently recommended as first-line interventions, whereas surgical interventions were more often recommended for subsequent lines of treatment. The time from regulatory approval of novel pharmacotherapies to inclusion in guideline recommendations varied considerably by disease area and geography. Across the reviewed disease areas, behavioral interventions and pharmacotherapies are shown to be critical components of clinical practice. Over the last 20 years, novel pharmaceutical innovations have been incorporated into clinical practice guideline recommendations; however, with varying speeds of adoption. Given the increasing pace of pharmacologic innovation, timely updates of clinical practice guidelines are critical to evolving the standard of care and practicing evidence-based medicine.