Clinical Questions Research Articles

PATIENT FACTORS ASSOCIATED WITH NOVEL EAR-Q APPEARANCE, PSYCHOSOCIAL AND SOCIAL SCALES: A CROSS-SECTIONAL STUDY AND REGRESSION ANALYSIS

IntroductionThe EAR-Q is a rigorously validated patient-reported outcome measure which evaluates ear appearance and health-related quality of life (HRQL) in patients with congenital or acquired ear conditions. The aim of this study was to conduct an exploratory analysis to examine factors associated with EAR-Q appearance and HRQL scale scores. Methods862 participants, aged 8-29 years, with a congenital or acquired ear condition, completed the EAR-Q as part of an international field-test study. Patients responded to demographic and clinical questions as well as the EAR-Q. Univariable and multivariable linear regression analyses were used to determine which factors were significant predictors for scores on the EAR-Q Appearance, Psychological, and Social scales. ResultsMost participants were male (57.4%), awaiting treatment (55.0%), and had a microtia diagnosis (70.4%), with a mean age of 13 (±4) years. Worse ear appearance scores were associated (p<0.02) with male gender, microtia, no history of treatment, ear surgery within 6 months, unilateral involvement, and greater self-reported ear asymmetry. Decreased psychological scores were associated (p<0.01) with increasing participant age, no treatment history, recent ear surgery and dissatisfaction with ears matching/overall. Lower social scores were associated (p≤0.04) with no treatment history, those awaiting surgery, ear surgery within the last 6 months, bilateral involvement, and self-reported ears matching/appearance overall. ConclusionThis analysis identifies patient factors that may influence ear appearance and HRQL scale scores. The findings provide evidence of patient factors that should be adjusted for when undertaking future observational research designs using the EAR-Q in this patient population.

The Lived Experience of Patients with Vascular Malformations: A Qualitative Meta-synthesis

Objective: The purpose of this study was to synthesize the existing qualitative literature on the lived experience of patients with vascular malformations to identify emergent themes and new areas for clinical care and research. Methods: A formal meta-synthesis was conducted, which followed 4 steps: (1) form the clinical question and refine search criteria; (2) complete a literature review following Preferred Reporting Items for Reviews and Meta-Analysis; (3) quality appraisal of included literature with Lett’s Critical Review Form; and (4) completion of team-based reciprocal translation and thematic analysis to synthesize the literature. PubMed, CINAHL, Johanna Briggs, and Embase were used to retrieve English language, peer-reviewed qualitative, and mixed-method articles from 1996 to May 2023. Results: Six articles met the criteria for inclusion. A wide range of vascular malformations were represented, ranging from slow-flow malformation to high-flow or complex with associated overgrowth. Studies were conducted in the United States, France, and Germany, focusing mainly on the adult experience, with 1 article focusing solely on pediatrics. Three main themes emerged: social isolation, uncertainty and hope, and healthcare experiences. Conclusion: The overarching themes of social isolation, uncertainty and hope, and healthcare experiences each offer avenues to inform clinical practice, provide education for healthcare providers managing patients with vascular malformations, and future research to better understand how each of these themes affect patients. This qualitative meta-synthesis is a novel method for this field and provides new insights into the lived experience of those with vascular malformations.

Moving Immunotherapy Into the Treatment of Resectable Non-Small Cell Lung Cancer.

Clinical investigation of immune checkpoint inhibitors (ICIs) has expanded from indications in metastatic non-small cell lung cancer (NSCLC) to add to the treatment of early-stage or resectable NSCLC. Although completed randomized trials supported the approvals of some ICIs as perioperative therapies (ie, adjuvant, neoadjuvant, or neoadjuvant followed by adjuvant), ongoing trials are evaluating other anti-PD-(L)1 antibodies for similar indications, or in combination with stereotactic body radiotherapy (SBRT). The incorporation of immunotherapy brings potential to improve outcomes of patients with resectable NSCLC, but these advances have also increased the complexity of the treatment landscape and created important knowledge gaps. This article reviews the current standards for local therapies in NSCLC, describes the clinical trials exploring the combination of ICIs to SBRT, and explains the recent approvals of ICIs as perioperative therapies. A discussion follows to highlight three important areas of uncertainty: (1) the contribution of ICIs given in each treatment phase (neoadjuvant and adjuvant) to the overall effect of neoadjuvant chemoimmunotherapy followed by adjuvant ICIs; (2) the selection of regimens to serve as comparators in future randomized trials of perioperative therapies; and (3) the role of pathologic complete response as an intermediate end point and aid for selection of patients for adjuvant therapy. Moving forward, stakeholders will need to engage in concerted research efforts to address the relevant clinical questions regarding the optimal management of resectable NSCLC.

Information-seeking behaviour of primary care clinicians in Singapore at the point-of-care: A qualitative study.

Clinicians' information-seeking behaviours impact patient care quality. Earlier studies indicated that barriers to accessing information deter clinicians from seeking answers to clinical questions. To explore primary care clinicians' information-seeking behaviour at point-of-care, focusing on when and how they seek answers to clinical questions. Semi-structured interviews were conducted with 45 clinicians after clinical sessions to investigate their information-seeking habits. Follow-up interviews were conducted after a week for those intending to address unanswered queries. Two thirds of clinicians encountered questions during care, with nearly three quarters resolving them during the session. Colleagues, guidelines and online platforms were common information sources, with smartphones being used to access Google, WhatsApp or UpToDate®. Facilitators included reliable sources and the drive to confirm knowledge, while barriers included ineffective search methods and high workload. Despite challenges, most clinicians expressed satisfaction with their information-seeking process. The findings underscore the increasing use of smartphones for accessing clinical information among Singaporean primary care clinicians and suggest the need for tailored training programmes and guidelines to optimise information-seeking practices. Insights from this study can inform the development of training programmes and guidelines aimed at improving information-seeking practices among primary care clinicians, potentially enhancing patient care quality.

Novel CAR T cell therapies for patients with large B cell lymphoma.

Approximately 60-70% of patients with large B cell lymphoma (LBCL) achieve long-term remission or a cure after initial treatment. However, patients who relapse or are refractory to initial treatment have a poor prognosis. Chimeric antigen receptor (CAR) T cell therapy has recently attracted attention for its potential to provide a cure or long-term remission even for LBCL that has relapsed or is refractory to conventional chemotherapy. Currently, three CAR T cell products are clinically available for LBCL: tisagenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel). These CAR T cell products were initially approved as third- or later-line therapies worldwide. Recently, axi-cel and liso-cel have become feasible as second-line therapies for patients with early relapsed or refractory disease after first-line chemotherapy. Although a large body of data on CAR T cell therapy has been accumulated, the clinical question of how to choose between these three available CAR T cell products has yet to be resolved. The appropriate approach to treatment selection for patients who relapse after CAR T cell therapy also remains unclear. This review discusses treatment strategies to maximize the benefits of CAR T cell therapy.

Meta-Analysis in Surgical Research: Methodology and Statistical Application.

In evidence-based medicine, systematic review continues to carry the highest weight in terms of quality and reliability, synthesizing robust information from previously published cohort studies to provide a comprehensive overview of a topic. Meta-analysis provides further depth by allowing for comparative analysis between the studied intervention and the control group, providing the most up-to-date evidence on their characteristics and efficacy. We discuss the principles and methodology of meta-analysis, and its applicability to the field of surgical research. The clinical question is defined using PICO framework (Problem, Intervention, Comparison, Outcome). Then a systematic article search is performed across multiple medical databases using relevant search terms, which are then filtered out based on appropriate screening tools. Pertinent data from the selected articles are collected and undergo critical appraisal by at least two independent reviewers. Additional statistical tests may be performed to identify the presence of any significant bias. The data are then synthesized to perform comparative analysis between the intervention and comparison groups. In this article, we discuss specifically the usage of R software (R Foundation for Statistical Computing, Vienna, Austria) for data analysis and visualization. Meta-analysis results of the pooled data are presented using forest plots. Concerns for potential bias may be addressed through the creation of funnel plots. Meta-analysis is a powerful tool to provide highly reliable medical evidence. It may be readily performed by independent researchers with minimal need for funding or institutional approval. The ability to conduct such studies is an asset to budding medical scholars.

A cross-sectional survey of clinical trials knowledge, participation, and perspectives in an underserved community of Washington, DC.

The inclusion of participants from underrepresented and underserved groups is lagging in dermatology clinical trials. Through dissemination of a pilot survey at a community skin health fair, knowledge, participation, and perspectives of clinical trials were evaluated in an urban, medically underserved community in Washington, DC. Clinical trial-related questions were derived from the Health Information National Trends Survey 5 Cycle 4. This cross-sectional survey analyzed responses from 39/55 attendees (71% response rate). Most respondents were female (23/37 [62.2%]), between the ages of 25 and 54 (19/38, [50.0%]), and self-identified as non-white (35/39 [89.7%]) with a majority self-identifying as Black (16/31 [41%]). Most respondents self-reported knowing "little" to "nothing" about clinical trials (26/35 [74.3%]), and even more were unaware of the federal resource clinicaltrials.gov (30/37 [81.1%]). Few respondents discussed clinical trials as a treatment option with their healthcare provider (8/35 [22.9%]), yet having a discussion was significantly correlated with clinical trial participation (p = 0.0302). Self-reported level of knowledge was not significantly associated with participation in a clinical trial (p = 0.3035). Healthcare providers were the preferred first source of clinical trial information, followed by an internet search. Respondents rarely cited mistrust or skepticism as a barrier to participation (2/34 [5.9%]). Subjective positive healthcare experiences were significantly correlated to positive expectations with clinical trial participation (p = 0.0242). The findings of this study suggest the essential role healthcare providers, including dermatologists, play in clinical trial education and recruitment of underrepresented populations, and that patient mistrust may be present but is a rarely cited barrier to clinical trial participation.

Selecting Research Methods to Address Clinical Questions.

Selecting Research Methods to Address Clinical Questions.

Effect of a workplace-based learning program on clerkship students’ behaviors and attitudes toward evidence-based medicine practice

ABSTRACT In clinical clerkship (CC), medical students can practice evidence-based medicine (EBM) with their assigned patients. Although CC can be a valuable opportunity for EBM education, the impact of EBM training, including long-term behavioral changes, remains unclear. One hundred and nine fourth- and fifth-year medical students undergoing CC at a medical school in Japan attended a workplace-based learning program for EBM during CC (WB-EBM), which included the practice of the five steps of EBM. The program’s effect on the students’ attitudes toward EBM in CC was assessed through questionnaires. A total of 88 medical students participated in the program. Responses to the questionnaire indicated high satisfaction with the WB-EBM program. The most common theme in students’ clinical problems with their assigned patients was the choice of treatment, followed by its effect. Based on the responses in the post-survey for the long-term effects of the program, the frequency of problem formulation and article reading tended to increase in the ‘within six months’ group comprising 18 students who participated in the WB-EBM program, compared with the control group comprising 34 students who did not. Additionally, the ability to self-assess problem formulation was significantly higher, compared with the control group. However, among 52 students who participated in the WB-EBM program more than six months later, EBM-related behavioral habits in CC and self-assessments of the five steps of EBM were not significantly different from those in the control group. The WB-EBM program was acceptable for medical students in CC. It motivated them to formulate clinical questions and enhanced their critical thinking. Moreover, the WB-EBM program can improve habits and self-evaluations about EBM. However, as its effects may not last more than six months, it may need to be repeated across departments throughout CC to change behavior in EBM practice.

Using a flipped classroom in a veterinary systems physiology course increases student performance on basic knowledge and clinical applicability questions.

Flipped classrooms are being utilized more frequently in biomedical education in order to provide more active learning opportunities to students although there are mixed results on the benefits of the flipped classroom in biomedical education. In this study, the effects of using a flipped classroom with case-based learning in the endocrine section of a first-year veterinary integrated histology and physiology course was investigated. Results demonstrated that the flipped classroom improved performance on the endocrine section exam by 15.9% (Cohen's d = 1.08, p<0.001) with improvements on both clinically-applicable and basic-knowledge questions. Student satisfaction with the flipped-classroom was also investigated. Students reported high satisfaction with the in-class case-based learning opportunities but lower satisfaction with the asynchronous content delivery and the time required outside of class. Student perceptions of the flipped classroom were measured again after being exposed to the results of the flipped classroom on student learning. After seeing the results, students were significantly more likely to value the time spent in the flipped classroom and to desire more opportunities for flipped classrooms in the future.

Awareness of strengths and weaknesses of Cardiovascular Magnetic Resonance Imaging (CMR) – Results from a questionnaire survey

Abstract Background Extensive research has established cardiovascular magnetic resonance (CMR) as a powerful tool for diagnosing and monitoring various cardiovascular diseases (CVD). However, CMR has yet to reach its full potential in routine clinical care, which is mainly due to reimbursement issues. Among other factors, overcoming this gap requires adequate awareness among healthcare professionals and potential patients, the extent of which is currently unknown. Therefore, we conducted a survey to assess awareness and identify knowledge gaps regarding the clinical role and socio-economic factors associated with CMR. Methods and results 144 subjects not involved in direct patient care were enrolled at a German health conference and completed a 24-item survey, including procedural, clinical and socio-economic questions about CMR. Respondents were well aware of the socio-economic impact of CVD. Common CMR indications were correctly identified by most participants, but only 22.9% knew the full spectrum. Participants underestimated the modality’s benefits, such as absence of ionizing radiation and rare allergic reactions to contrast agents (only 70.9% and 37.6% correct answers, respectively). Respondents estimated the therapeutic guidance of CMR to be high (50.7% voted impact &amp;gt;50%) and the annual demand to be increasing (89.9%). Attitudes towards CMR were generally positive, with 77.1% of participants willing to travel &amp;gt;25km and 60.4% willing to pay &amp;gt;125 Euros to have a CMR examination. Conclusion Despite great interest in CMR, significant knowledge gaps hinder its optimal use in clinical practice. The development and implementation of awareness and education strategies are needed to realize the full clinical potential of CMR.

#1608 Use of intraperitoneal hydration by peritoneal dialysis fluid as a complementary palliative therapy in peritoneal dialysis patients

Abstract Background and Aims End life care should manage pain, other distressing symptoms and guarantee sufficient hydration. It should also involve psychological, social and spiritual support. Palliative care in peritoneal dialysis is a new and growing clinical question. There are several open questions: Should we stop peritoneal dialysis totally? Should we go on with peritoneal dialysis in a reduced fashion? Hereby we report a new application of CAPD exchanges, intraperitoneal hydration, in end life care of peritoneal dialysis patients. Method In seven peritoneal dialysis patients (2 female, 3 male, age 82 to 90 years) affected by severe heart failure (3 patients), dementia (2 patients) and malnutrition-inflammation syndrome (2 patients) we applied the concept of intraperitoneal hydration as a complementary palliative care. Peritoneal dialysis was switched into a single CAPD bag therapy utilizing a glucose concentration of 1.36% or 1.5%. Depending on the clinical hydration status 1000 ml of dialysis fluid was loaded daily or each other day without prior drainage. None of the patients was on intravenous therapy. Results The duration of the intraperitoneal hydration therapy varied between 5 and 16 days. In two cases, therapy was performed initially at the hospital ward and hereafter at a nursing home, whereas in the latter 5 cases at the patient's home by family members. No case of hypervolemia occurred. The intraperitoneal hydration therapy was well accepted by the family members. Conclusion The transformation of peritoneal dialysis from ultrafiltration and depuration into hydration without depuration seems to be a feasible approach. This approach should be kept in mind in special conditions such as end life palliative care and hypohydration.

Case report: Early use of whole exome sequencing unveils HNRNPU-related neurodevelopmental disorder and answers additional clinical questions through reanalysis

This case report chronicles the diagnostic odyssey and resolution of a 27-year-old female with a complex neurodevelopmental disorder (NDD) using Whole Exome Sequencing (WES). The patient presented to a precision medicine clinic with multiple diagnoses including intellectual disability, autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD), tics, seizures, and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Although this patient previously had chromosomal microarray and several single-gene tests, the underlying cause of this patient’s symptoms remained elusive. WES revealed a pathogenic missense mutation in the HNRNPU gene, associated with HNRNPU-related neurodevelopmental disorder (HNRNPU-NDD) and developmental and epileptic encephalopathy-54 (DEE54, OMIM: # 617391). Following this diagnoses, other treating clinicians identified additional indications for genetic testing, however, as the WES data was readily available, the clinical team was able to re-analyze the WES data to address their inquiries without requiring additional tests. This emphasizes the pivotal role of WES in expediting diagnoses, reducing costs, and providing ongoing clinical utility throughout a patient’s life. Accessible WES data in primary care settings can enhance patient care by informing future genetic inquiries, enhancing coordination of care, and facilitating precision medicine interventions, thereby mitigating the burden on families and the healthcare system.

Evaluation of ChatGPT as a Tool for Answering Clinical Questions in Pharmacy Practice.

Background: In the healthcare field, there has been a growing interest in using artificial intelligence (AI)-powered tools to assist healthcare professionals, including pharmacists, in their daily tasks. Objectives: To provide commentary and insight into the potential for generative AI language models such as ChatGPT as a tool for answering practice-based, clinical questions and the challenges that need to be addressed before implementation in pharmacy practice settings. Methods: To assess ChatGPT, pharmacy-based questions were prompted to ChatGPT (Version 3.5; free version) and responses were recorded. Question types included 6 drug information questions, 6 enhanced prompt drug information questions, 5 patient case questions, 5 calculations questions, and 10 drug knowledge questions (e.g., top 200 drugs). After all responses were collected, ChatGPT responses were assessed for appropriateness. Results: ChatGPT responses were generated from 32 questions in 5 categories and evaluated on a total of 44 possible points. Among all ChatGPT responses and categories, the overall score was 21 of 44 points (47.73%). ChatGPT scored higher in pharmacy calculation (100%), drug information (83%), and top 200 drugs (80%) categories and lower in drug information enhanced prompt (33%) and patient case (20%) categories. Conclusion: This study suggests that ChatGPT has limited success as a tool to answer pharmacy-based questions. ChatGPT scored higher in calculation and multiple-choice questions but scored lower in drug information and patient case questions, generating misleading or fictional answers and citations.

Incorporating temporal dynamics of mutations to enhance the prediction capability of antiretroviral therapy's outcome for HIV-1.

In predicting HIV therapy outcomes, a critical clinical question is whether using historical information can enhance predictive capabilities compared with current or latest available data analysis. This study analyses whether historical knowledge, which includes viral mutations detected in all genotypic tests before therapy, their temporal occurrence, and concomitant viral load measurements, can bring improvements. We introduce a method to weigh mutations, considering the previously enumerated factors and the reference mutation-drug Stanford resistance tables. We compare a model encompassing history (H) with one not using this information (NH). The H-model demonstrates superior discriminative ability, with a higher ROC-AUC score (76.34%) than the NH-model (74.98%). Wilcoxon test results confirm significant improvement of predictive accuracy for treatment outcomes through incorporating historical information. The increased performance of the H-model might be attributed to its consideration of latent HIV reservoirs, probably obtained when leveraging historical information. The findings emphasize the importance of temporal dynamics in acquiring mutations. However, our result also shows that prediction accuracy remains relatively high even when no historical information is available. Supplementary material is available.

Comparison of the ABC and ACMG systems for variant classification.

The ABC and ACMG variant classification systems were compared by asking mainly European clinical laboratories to classify variants in 10 challenging cases using both systems, and to state if the variant in question would be reported as a relevant result or not as a measure of clinical utility. In contrast to the ABC system, the ACMG system was not made to guide variant reporting but to determine the likelihood of pathogenicity. Nevertheless, this comparison is justified since the ACMG class determines variant reporting in many laboratories. Forty-three laboratories participated in the survey. In seven cases, the classification system used did not influence the reporting likelihood when variants labeled as "maybe report" after ACMG-based classification were included. In three cases of population frequent but disease-associated variants, there was a difference in favor of reporting after ABC classification. A possible reason is that ABC step C (standard variant comments) allows a variant to be reported in one clinical setting but not another, e.g., based on Bayesian-based likelihood calculation of clinical relevance. Finally, the selection of ACMG criteria was compared between 36 laboratories. When excluding criteria used by less than four laboratories (<10%), the average concordance rate was 46%. Taken together, ABC-based classification is more clear-cut than ACMG-based classification since molecular and clinical information is handled separately, and variant reporting can be adapted to the clinical question and phenotype. Furthermore, variants do not get a clinically inappropriate label, like pathogenic when not pathogenic in a clinical context, or variant of unknown significance when the significance is known.

“My attending really wants it!” Manual clinical decision support adjudicating the “better look” inpatient MRI at an academic medical center

ObjectiveMRI utilization in the United States is relatively higher than in other parts of the world and inpatient MRI utilization is particularly difficult to manage given the lack of direct reimbursement. Body MRI studies present an opportunity to reduce inpatient MRI utilization since they are generally the least emergent. Our objective was to use a targeted questionnaire to probe the necessity of inpatient body MRI orders and present an opportunity to either cancel them or transition them to the outpatient realm MethodsA 9-item questionnaire was devised asking questions about the urgency of the inpatient MRI order including the urgent management question, an inpatient procedure or whether it was recommended by a consultant. Peer-to-peer discussion walking through each of the questions was conducted by radiology housestaff with the ordering clinicians and responses recorded. Results845 recorded responses reported a lack of specific clinical question in 23.9% of orders, 68.9% were recommended by a non-radiology consulting service and 16.1% were recommended by radiology studies. 17.0% orders were felt to be outpatient appropriate and 23.3% were considered possibly appropriate for the outpatient setting. 3.9% were canceled and 4.9% were transitioned to outpatient orders. DiscussionEngaging in a focused discussion about the urgency and appropriateness of an inpatient MRI body order following a list of scripted questions has the potential to reduce utilization. This approach also highlights the relatively high rate of indication uncertainty among ordering clinicians and the central role of consultants in prompting orders.

Adverse tumor events induced by ranitidine: an analysis based on the FAERS database

ABSTRACT Background Ranitidine induced tumor adverse events remains a contradictory clinical question, due to the limited evidence of tumor risk associated with ranitidine in the real world. The purpose of this study was to evaluate the association of ranitidine with all types of tumors through the FAERS database and to provide a reference for clinical use. Research design and methods Cancer cases associated with ranitidine in the FAERS database from the first quarter of 2004 to the fourth quarter of 2023 were extracted to analyze demographic characteristics, and a disproportion analysis was performed. Result A total of 662,998 ranitidine-related cancer cases were screened, and the 50–59 and 60–69 groups accounted for the largest proportion. In PT signal detection, ranitidine was associated with 98 PT, including penal cancer stage II, gastric cancer stage II, et al. In terms of outcome events, adverse events were higher in men (20.65%) than in women (18.47%). Conclusions Ranitidine may induce various tumor-related adverse reactions, especially in long-term users and elderly patients. For these patients, tumor screening should be strengthened, and long-term use of ranitidine should be avoided. Since this study cannot prove causality, further evidence is needed for prospective studies with a larger sample size.

A Delphi Approach to Define Lucid Episodes in People Living With Dementia.

Lucid episodes (LEs: unexpected episodes of spontaneous, meaningful, and relevant communication or behavior) in Alzheimer disease and related dementias are a new area of scientific inquiry that lacks clinical consensus and require more conceptual attention. We aimed to measure consensus from an expert group on: (1) potential medical or clinical explanations for LEs; (2) necessary medical and clinical context to LEs; and (3) interpretation of LEs. We convened 13 experts from different disciplines (neurology, psychiatry, psychology, pharmacy, palliative care, hospice, nursing, social work, primary care, geriatrics, and professional home caregivers) to identify elements of LEs. Experts provided a range of opinions on medical and clinical explanations and questions to understand LEs. Consensus on LEs when presented with clinical vignettes was not reached. Panelists highlighted key medical and contextual factors needed to make a definitive judgement about LEs. There is variability in how LEs are interpreted by clinical experts, which complicates the identification of LEs in Alzheimer disease and related dementias.

Selection of Germline Genetic Testing Panels in Patients With Cancer: ASCO Guideline.

To guide use of multigene panels for germline genetic testing for patients with cancer. An ASCO Expert Panel convened to develop recommendations on the basis of a systematic review of guidelines, consensus statements, and studies of germline and somatic genetic testing. Fifty-two guidelines and consensus statements met eligibility criteria for the primary search; 14 studies were identified for Clinical Question 4. Patients should have a family history taken and recorded that includes details of cancers in first- and second-degree relatives and the patient's ethnicity. When more than one gene is relevant based on personal and/or family history, multigene panel testing should be offered. When considering what genes to include in the panel, the minimal panel should include the more strongly recommended genes from Table 1 and may include those less strongly recommended. A broader panel may be ordered when the potential benefits are clearly identified, and the potential harms from uncertain results should be mitigated. Patients who meet criteria for germline genetic testing should be offered germline testing regardless of results from tumor testing. Patients who would not normally be offered germline genetic testing based on personal and/or family history criteria but who have a pathogenic or likely pathogenic variant identified by tumor testing in a gene listed in Table 2 under the outlined circumstances should be offered germline testing.Additional information is available at www.asco.org/molecular-testing-and-biomarkers-guidelines.