Twelve tips for providing feedback to peers about their teaching.

When healthcare professionals provide feedback to peers after a teaching observation, there are benefits for both parties. In this article, we outline strategies to use before, during, and after teaching observations to engage in mutually-beneficial conversations that highlight best practices, identify solutions for teaching dilemmas, and initiate teaching relationships. We discuss the importance of choosing words wisely; giving feedback about teaching skills, not the teacher as a person; recognizing how colleagues view their teaching identities; and ensuring peers are emotionally ready for a post-observation conversation. We also explain how to use pronouns, questions, and active listening during feedback conversations. Finally, we explore the impact of biases on observations, how to establish peer observer credibility, and how to make the teaching observation process and feedback discussion valuable experiences for both parties so that it leads to long-lasting partnerships in the quest to improve educational quality.

Long-term outcomes of patent foramen ovale closure or medical therapy after cryptogenic stroke: A meta-analysis of randomized trials.

OBJECTIVES: To examine long-term clinical outcomes with transcatheter patent foramen ovale (PFO) closure versus medical therapy alone in patients with cryptogenic stroke. BACKGROUND: A long-standing debate regarding the optimal approach for the management of patients with PFO after a cryptogenic stroke exists. METHODS: An electronic search was performed for randomized clinical trials (RCTs) reporting clinical outcomes with PFO closure vs. medical therapy alone after stroke. Random effects DerSimonian-Laird risk ratios (RR) were calculated. The main outcome was recurrence of stroke. Other outcomes included transient ischemic attack (TIA), new-onset atrial fibrillation/flutter (AF/AFL), major bleeding, serious adverse events, and device-related complications. All-cause mortality was also examined. RESULTS: Five RCTs with a total of 3,440 patients were included. At a mean follow-up of 4.02 ± 1.57 years, PFO closure was associated with less recurrence of stroke (RR = 0.43; 95% CI 0.19-0.91; P = .027) compared with medical therapy alone. No difference was observed between both strategies for TIA (P = .21), major bleeding (P = .69), serious adverse events (P = .35), and all-cause death (P = .48). However, PFO closure, was associated with increased new-onset AF/AFL (P < .001), risk of pulmonary embolism (P = .04), and device-related complications (P < .001). On a subgroup analysis, stroke recurrence rate remained lower in PFO closure arm regardless of the type of closure device used (Pinteraction = .50), or the presence of substantial shunt in the majority of study population (Pinteraction = .13). CONCLUSIONS: Transcatheter PFO closure reduces the recurrence of stroke compared with medical therapy alone, with no significant safety concerns. Close follow-up of patients after PFO closure is recommended to detect new-onset atrial arrhythmias.

Transcatheter aortic valve implantation through a transcarotid approach under local anesthesia.

AIMS: We report the first experience of transcatheter aortic valve implantation through a transcarotid approach under local anesthesia. METHODS AND RESULTS: An 81-year-old gentleman with severe symptomatic aortic stenosis was referred for TAVI. He was not suitable for transfemoral, transapical, subclavian, or direct aortic approach. He had severe lung disease and was considered unsuitable for general anesthesia. We, therefore, performed the procedure under local anesthesia though the right common carotid artery (CCA) approach. Superficial cervical block was achieved with Levobupivacaine, and in addition, he also had a target controlled infusion of Remifentanil. Cerebral oximetry was monitored throughout the procedure. The CCA was accessed through surgical cut-down. Aortic valvuloplasty was performed through a 12-F sheath, and the CoreValve was deployed successfully through an 18-F sheath. CONCLUSION: TAVI is commonly performed through femoral access under local anesthesia. The right carotid artery approach under local anesthesia requires careful monitoring of cerebral oxygen levels but allowed us to perform successful TAVI in this high risk patient when all conventional approaches were contra-indicated. Compared with a right subclavian or left carotid access, the right carotid offers more direct angle of approach allowing precise valve placement with minimal readjustment during deployment.

Incidentally detected lung nodules: clinical predictors of adherence to Fleischner Society surveillance guidelines.

OBJECTIVE: The objective of this study was to determine adherence to incidentally detected lung nodule computed tomographic (CT) surveillance recommendations and identify demographic and clinical factors that increase the likelihood of CT surveillance. MATERIALS AND METHODS: A total of 419 patients with incidentally detected lung nodules were included. Recorded data included patient demographic, radiologic, and clinical characteristics and outcomes at a 4-year follow-up. Multivariate logistic regression models determined the factors associated with likelihood of recommended CT surveillance. RESULTS: At least 1 recommended surveillance chest CT was performed on 48% of the patients (148/310). Computed tomographic result communication to the patient (odds ratio [OR], 2.2; P = 0.006; confidence interval [CI], 1.3-4.0) or to the referring physician (OR, 2.8; P = 0.001; CI, 1.7-4.5) and recommendation of a specific surveillance time interval (OR, 1.7; P = 0.023; CI, 1.08-2.72) increased the likelihood of surveillance. Other demographic, radiologic, and clinical factors did not influence surveillance. CONCLUSIONS: Documented physician and patient result communication as well as the recommendation of a specific surveillance time interval increased the likelihood of CT surveillance of incidentally detected lung nodules.

Twelve tips for overnight teaching.

BACKGROUND: The European Working Time Directive and the United States' duty hour restrictions have changed resident physicians' schedules, specifically increasing overnight shifts and decreasing overall time spent in the hospital. As residents' perception of night shifts is that they have little educational value, efforts to improve educational opportunities and night attending teaching are desirable. However, resources about and recommendations for best practices for overnight teaching by faculty are scarce. AIM: To provide 12 tips to highlight strategies intended to optimize attending physicians' overnight teaching skills and strategies. METHOD: The tips provided are based on our experiences and reflections as in-house faculty supervising residents working overnight, by our experience and group discussions as medical educators, and the available literature. RESULTS: The 12 tips presented offer specific strategies to optimize attending physicians' overnight teaching for resident physicians, specifically highlighting the unique logistics, pedagogy and follow-up of overnight teaching. CONCLUSION: Preparation for teaching is important in any environment, but understanding the unique timing and circumstances associated with overnight teaching is vital to ensure that overnight teaching is effective. Acknowledging and addressing the physical and cognitive obstacles associated with overnight teaching and learning is necessary to maximize the educational value of overnight teaching.

Dynamic expiratory tracheal collapse in morbidly obese COPD patients.

Morbid obesity may influence several aspects of airway function. However, the effect of morbid obesity on expiratory tracheal collapse in COPD patients is unknown. We thus prospectively studied 100 COPD patients who underwent full pulmonary function tests (PFTs), 6-minute walk test (6MWT), Saint George's Respiratory Questionnaire (SGRQ), and low-dose CT at total lung capacity and during dynamic exhalation with spirometric monitoring. We examined correlations between percentage dynamic expiratory tracheal collapse and body mass index (BMI). The association between tracheal collapse and BMI was compared to a control group of 53 volunteers without COPD. Patients included 48 women and 52 men with mean age 65 ± 7 years; BMI 30 ± 6; FEV1 64 ± 22% predicted and percentage expiratory collapse 59 ± 19%. Expiratory collapse was significantly associated with BMI (69 ± 12% tracheal collapse among 20 morbidly obese patients with BMI ≥ 35 compared to 57 ± 19% in others, p = 0.002, t-test). In contrast, there was no significant difference in collapse between healthy volunteers with BMI ≥ 35 and < 35. COPD patients with BMI ≥ 35 also demonstrated shorter 6MWT distances (340 ± 139 m vs. 430 ± 139 m, p = 0.003) and higher (worse) total SGRQ scores (48 ± 19 vs. 36 ± 20, p = 0.013) compared to those with BMI < 35. In light of these results, clinicians should consider evaluating for excessive expiratory tracheal collapse when confronted with a morbidly obese COPD patient with greater quality of life impairment and worse exercise performance than expected based on functional measures.

Effect of therapeutic hyperoxia on maximal oxygen consumption and perioperative risk stratification in chronic obstructive pulmonary disease.

BACKGROUND: Maximal consumption of oxygen ( ̇VO(2)max) during exercise is used in patients with chronic obstructive pulmonary disease (COPD) to stratify perioperative risk. However, the impact of therapeutic hyperoxia (i.e., use of supplemental oxygen to prevent hypoxemia during exercise) on ( ̇VO(2)max and other ventilatory parameters during maximal exercise in the resting normoxic COPD population is poorly defined. METHODS: A randomized, double-blind crossover study was performed in which resting normoxic subjects (n=16) with COPD underwent two standard symptom-limited, ramped-protocol bicycle ergometry cardiopulmonary exercise tests >5 days apart with FiO(2) of 0.21 (control) and ~0.28 (therapeutic hyperoxia). ̇VO(2)max and other ventilatory parameters were compared using a paired two-sample t-test. RESULTS: Therapeutic hyperoxia significantly increased ̇VO(2)max (12.2 ± 2.9 vs. 13.6 ± 3.8 ml/kg/min, P = 0.03), partial pressure of end-tidal carbon dioxide, and oxygen saturation and significantly decreased ̇VE-̇VCO(2) slope, but it did not affect exercise time, maximum watts achieved, maximum minute ventilation, or change in end-expiratory lung volume. Three of four subjects with ̇VO(2)max <10 ml/kg/min without supplemental oxygen increased ̇VO(2)max to ≥10 ml/kg/min on therapeutic hyperoxia and potentially changed perioperative risk category. CONCLUSIONS: Therapeutic hyperoxia in a resting normoxic COPD population significantly improves ̇VO(2)max and may change perioperative risk stratification by conventional criteria. Further studies are needed to determine if this change in stratification is appropriate.

Pulmonary zygomycosis in a non-neutropenic patient with myelodysplastic syndrome on lenalidomide.

Pulmonary zygomycosis is an uncommon infection that occurs mostly in immunocompromised patients. We report the case of a 75-year-old man with myelodysplastic syndrome, treated with lenalidomide for 3 months, who developed respiratory failure and a rapidly progressive left upper lobe consolidation. An extensive workup was unrevealing of the etiology, and the patient expired. A full autopsy was declined, but an in situ post-mortem transbronchial lung biopsy revealed pulmonary zygomycosis. This unique case illustrates the potential risks of lenalidomide therapy in patients with myelodysplastic syndrome and the difficulties in diagnosing pulmonary zygomycosis. To our knowledge this is the first report of a diagnostic in situ post-mortem transbronchial lung biopsy.

Twelve tips for facilitating Millennials' learning.

BACKGROUND: The current, so-called "Millennial" generation of learners is frequently characterized as having deep understanding of, and appreciation for, technology and social connectedness. This generation of learners has also been molded by a unique set of cultural influences that are essential for medical educators to consider in all aspects of their teaching, including curriculum design, student assessment, and interactions between faculty and learners. AIM: The following tips outline an approach to facilitating learning of our current generation of medical trainees. METHOD: The method is based on the available literature and the authors' experiences with Millennial Learners in medical training. RESULTS: The 12 tips provide detailed approaches and specific strategies for understanding and engaging Millennial Learners and enhancing their learning. CONCLUSION: With an increased understanding of the characteristics of the current generation of medical trainees, faculty will be better able to facilitate learning and optimize interactions with Millennial Learners.

Reaching the limits of mandated self-reporting: clinical logbooks do not predict clerkship performance.

BACKGROUND: Logbooks are used by US medical schools to evaluate curricular objectives and meet accreditation requirements, but research supporting their utility is conflicting. AIMS: The goal of our study was to examine the relationship between volume of clinical rotation experiences as reported in a logbook and clerkship grades within a longitudinal integrated clerkship. METHODS: We conducted a retrospective cohort study of third-year (clinical) medical students during academic year 2008-2009. We tracked student entries in a pocket-sized logbook (number of clinical encounters per clerkship, total number of exams, and procedures over the academic year). We performed correlation analyses between logbook entries and clerkship grades. RESULTS: We enrolled 36 students, who reported a total of 2992 encounters, 2262 exams, and 2342 procedures. Correlation coefficients between volume of clinical experience and clerkship grades were less than 0.4, indicating low correlation. We found borderline statistical significance for the Neurology, OB/Gyn, and Surgery clerkships. Sensitivity analyses showed little correlation between low-reporting activity and clerkship grades. CONCLUSIONS: Even within an integrated longitudinal clerkship framework, our findings are consistent with previous studies showing a negligible relationship between logbooks as an educational process measure and how they relate to educational outcomes.

Training Future International Clinical Academic Leaders Through a Structured Observership Program: Impact and Outcomes from the Initial Cohort.

INTRODUCTION: Clinical observership programs have existed for many years as both formal initiatives organized at the institutional or professional society level and informal arrangements between individual physicians and prospective mentors. However, few programs longitudinally assess their impact on patient care and require implementation of a postobservership project to demonstrate learning. In 2018, the Harvard Medical School Office for External Education launched the International Clinical Leaders Observership Program (ICLOP) as an opportunity for midcareer physicians to shadow Harvard Medical School faculty in one of three specialty areas: oncology, cardiology, or diabetology. The culminating activity for each participant was presentation of a capstone project and commitment to implement it on returning home. METHODS: We summarize here the initial cohort and results from a follow-up survey measuring the impact of the program on their subsequent patient care, academic activities, and achievements. RESULTS: At 1 year of follow-up, 90% of survey respondents had implemented their project. Improvements were reported in areas of clinical, surgical, therapeutic, system, patient education, and team innovation, as well as personal benefits to the participants. DISCUSSION: ICLOP is a robust and reproducible initiative that resulted in meaningful improvements in patient care and physician-related outcomes for the first cohort of participants.

Quality of Life Assessment in Patients Undergoing Trans-Catheter Aortic Valve Implantation Using MacNew Questionnaire.

The MacNew questionnaire is a disease-specific quality of life measure that has been used in patients with myocardial infarction and heart failure. We aimed to investigate the impact of transcatheter aortic valve implantation (TAVI) on health-related quality of life (HRQoL) using MacNew Questionnaire and identify predictors associated with a change in its score. This was a prospective multi-center study performed across 5 National Health Service hospitals in the United Kingdom performing TAVI between 2016 and 2018. HRQoL was assessed using MacNew Questionnaire, Euro Quality of Life-5D-5L, and Short Form 36 questionnaires collected at baseline, 3-, 6- and 12 months after the procedure. Out of 225 recruited patients, 19 did not have TAVI and 4 withdrew their consent, and hence 202 patients were included. HRQoL was assessed in 181, 161, and 147 patients at 3, 6, and 12 months, respectively. Using MacNew, there was a significant improvement in all domains of HRQoL as early as 3 months after TAVI which was sustained up to 12 months with improved discrimination of change in HRQoL compared with other scales. Poor mobility at baseline and history of myocardial infarction were independent predictors of reduced improvement in HRQoL at 3 months. HRQoL increased in all subgroups of patients including frail ones. In conclusion, the MacNew assessment tool performed well in a representative TAVI cohort and could be used as an alternative disease-specific method for assessing HRQoL change after TAVI.

Teaching medical students about obesity: a pilot program to address an unmet need through longitudinal relationships with bariatric surgery patients.

BACKGROUND: Despite obesity's relevance and impact, curricula addressing obesity are underrepresented in clinical medical education. A novel pilot program to begin teaching medical students about care of the obese patient was developed and student attitudes toward obesity and bariatric surgery were assessed. METHODS: The authors paired third-year students with obese patients undergoing bariatric surgery. Students established a longitudinal patient relationship, received faculty mentorship, and kept a reflections journal. An attitude assessment survey was administered before and after third year. Reflections were analyzed for common themes. RESULTS: Baseline student responses differed from those previously reported for practicing physicians on many survey statements, including more strongly agreeing with the relationship between obesity and serious medical conditions (P < .001), the need to educate patients about obesity risks (P < .001), and willingness to recommend bariatric surgery evaluation (P = .004). These differences were maintained after clinical clerkships. Reflection themes included recognition of obesity stereotypes, improved estimation of body mass index, and awareness of physicians' attitudes about obesity. CONCLUSION: Development and assessment of a novel pilot program to teach third-year medical students about obesity and bariatric surgery suggests a potential impact on student attitudes and understanding of obesity and obesity surgery. Students today may have different attitudes toward obesity than those reflected in prior data for physicians in practice, and programs such as this may help maintain positive attitudes.

Optimizing Remote Learning: Leveraging Zoom to Develop and Implement Successful Education Sessions.

Virtual meeting platforms, such as Zoom, have become essential to medical education during the SARS-CoV-2 pandemic. However, many medical educators do not have experience planning or leading these sessions. Despite the prevalence of Zoom learning, there has been little published on best practices. In this article we describe best practices for using Zoom for remote learning, acknowledging technical considerations, and recommending workflows for designing and implementing virtual sessions. Furthermore, we discuss the important role of cognitive learning theory and how to incorporate these key pedagogical insights into a successful virtual session. While eventually in-person classrooms will open, virtual teaching will remain a component of medical education. If we utilize these inventive tools creatively and functionally, then virtual learning can augment and elevate the practice of medical education.

ACTIVATION (PercutAneous Coronary inTervention prIor to transcatheter aortic VAlve implantaTION): A Randomized Clinical Trial.

OBJECTIVES: This study sought to determine if percutaneous coronary intervention (PCI) prior to transcatheter aortic valve replacement (TAVR) in patients with significant coronary artery disease would produce noninferior clinical results when compared with no PCI (control arm). BACKGROUND: PCI in patients undergoing TAVR is not without risk, and there are no randomized data to inform clinical practice. METHODS: Patients with severe symptomatic aortic stenosis and significant coronary artery disease with Canadian Cardiovascular Society class ≤2 angina were randomly assigned to receive PCI or no PCI prior to TAVR. The primary endpoint was a composite of all-cause death or rehospitalization at 1 year. Noninferiority testing (prespecified margin of 7.5%) was performed in the intention-to-treat population. RESULTS: At 17 centers, 235 patients underwent randomization. At 1 year, the primary composite endpoint occurred in 48 (41.5%) of the PCI arm and 47 (44.0%) of the no-PCI arm. The requirement for noninferiority was not met (difference: -2.5%; 1-sided upper 95% confidence limit: 8.5%; 1-sided noninferiority test P = 0.067). On analysis of the as-treated population, the difference was -3.7% (1-sided upper 95% confidence limit: 7.5%; P = 0.050). Mortality was 16 (13.4%) in the PCI arm and 14 (12.1%) in the no-PCI arm. At 1 year, there was no evidence of a difference in the rates of stroke, myocardial infarction, or acute kidney injury, with higher rates of any bleed in the PCI arm (P = 0.021). CONCLUSIONS: Observed rates of death and rehospitalization at 1 year were similar between PCI and no PCI prior to TAVR; however, the noninferiority margin was not met, and PCI resulted in a higher incidence of bleeding. (Assessing the Effects of Stenting in Significant Coronary Artery Disease Prior to Transcatheter Aortic Valve Implantation; ISRCTN75836930).

Tai chi exercise for patients with chronic obstructive pulmonary disease: a pilot study.

OBJECTIVE: To determine the feasibility of a randomized controlled trial of the effect of a tai chi program on quality of life and exercise capacity in patients with COPD. METHODS: We randomized 10 patients with moderate to severe COPD to 12 weeks of tai chi plus usual care (n = 5) or usual care alone (n = 5). The tai chi training consisted of a 1-hour class, twice weekly, that emphasized gentle movement, relaxation, meditation, and breathing techniques. Exploratory outcomes included disease-specific symptoms and quality-of-life, exercise capacity, pulmonary function tests, mood, and self-efficacy. We also conducted qualitative interviews to capture patient narratives regarding their experience with tai chi. RESULTS: The patients were willing to be randomized. Among 4 of the 5 patients in the intervention group, adherence to the study protocol was excellent. The cohort's baseline mean ± SD age, percent-of-predicted FEV1, and ratio of FEV1 to forced vital capacity were 66 ± 6 y, 50 ± 12%, and 0.63 ± 0.14, respectively. At 12 weeks there was significant improvement in Chronic Respiratory Questionnaire score among the tai chi participants (1.4 ± 1.1), compared to the usual-care group (-0.1 ± 0.4) (P = .03). There were nonsignificant trends toward improvement in 6-min walk distance (55 ± 47 vs -13 ± 64 m, P = .09), Center for Epidemiologic Studies Depression Scale (-9.0 ± 9.1 vs -2.8 ± 4.3, P = .20), and University of California, San Diego Shortness of Breath score (-7.8 ± 3.5 vs -1.2 ± 11, P = .40). There were no significant changes in either group's peak oxygen uptake. CONCLUSIONS: A randomized controlled trial of tai chi is feasible in patients with moderate to severe COPD. Tai chi exercise as an adjunct to standard care warrants further investigation.

Meta-Analysis Comparing Percutaneous to Surgical Access in Trans-Femoral Transcatheter Aortic Valve Implantation.

To compare the outcomes in trans-femoral transcatheter aortic valve implantation (TF-TAVI) performed with percutaneous approach (PC) versus surgical cut-down (SC). In 13 trials including 5,859 patients (PC = 3447, SC = 2412), the outcomes based on Valve Academic Research Consortium criteria were compared between PC and SC in TF-TAVI. Compared with SC, PC was associated with similar major vascular complications (VCs) (8.7% vs 8.5%; odds ratio [OR] = 0.93, 95% confidence interval [CI] = 0.76 to 1.15, p = 0.53), major bleeding (OR = 1.09, 95% CI = 0.66 to 1.8, p = 0.73), perioperative mortality (5.7% vs 5.2%; OR = 1.13, 95% CI = 0.85 to 1.49, p = 0.4), urgent surgical repair (OR = 1.27, 95% CI = 0.81 to 2.02, p = 0.3), stroke (3.3% vs 3.9%; OR = 0.85, 95% CI = 0.53 to 1.36, p = 0.5), myocardial infarction (1.3% vs 1.1%; OR = 1.06, 95% CI = 0.53 to 2.12, p = 0.86), and renal failure (5.2% vs 5.9%; OR = 0.68, 95% CI = 0.38 to 1.22, p = 0.2), but shorter hospital stay (9.1 ± 8.5 vs 9.6 ± 9.5 days; mean difference = -1.07 day, 95% CI = -2.0 to -0.15, p = 0.02) and less blood transfusion (18.5% vs 25.7%; OR = 0.61, 95% CI = 0.43-0.86, p = 0.005). Minor VCs occurred more frequently in PC compared to SC (11.9% vs 6.9%; OR = 1.67, 95% CI = 1.04-2.67, p = 0.03). In conclusion, in TF-TAVI, PC is a safe and feasible alternative to SC, and adopting either approach depends on operator experience after ensuring that vascular access could be safely achieved with that specific technique.

Ice-stream demise dynamically conditioned by trough shape and bed strength.

Ice sheet mass loss is currently dominated by fast-flowing glaciers (ice streams) terminating in the ocean as ice shelves and resting on beds below sea level. The factors controlling ice-stream flow and retreat over longer time scales (>100 years), especially the role of three-dimensional bed shape and bed strength, remain major uncertainties. We focus on a former ice stream where trough shape and bed substrate are known, or can be defined, to reconstruct ice-stream retreat history and grounding-line movements over 15 millennia since the Last Glacial Maximum. We identify a major behavioral step change around 18,500 to 16,000 years ago-out of tune with external forcing factors-associated with the collapse of floating ice sectors and rapid ice-front retreat. We attribute this step change to a marked geological transition from a soft/weak bed to a hard/strong bed coincident with a change in trough geometry. Both these factors conditioned and ultimately hastened ice-stream demise.

Aspirin for Primary Prevention of Cardiovascular Events.

BACKGROUND: The efficacy and safety of aspirin for primary prevention of cardiovascular disease (CVD) remain debatable. OBJECTIVES: The purpose of this study was to examine the clinical outcomes with aspirin for primary prevention of CVD after the recent publication of large trials adding >45,000 individuals to the published data. METHODS: Randomized controlled trials comparing clinical outcomes with aspirin versus control for primary prevention with follow-up duration of ≥1 year were included. Efficacy outcomes included all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke, transient ischemic attack (TIA), and major adverse cardiovascular events. Safety outcomes included major bleeding, intracranial bleeding, fatal bleeding, and major gastrointestinal (GI) bleeding. Random effects DerSimonian-Laird risk ratios (RRs) for outcomes were calculated. RESULTS: A total of 15 randomized controlled trials including 165,502 participants (aspirin n = 83,529, control n = 81,973) were available for analysis. Compared with control, aspirin was associated with similar all-cause death (RR: 0.97; 95% confidence interval [CI]: 0.93 to 1.01), CV death (RR: 0.93; 95% CI: 0.86 to 1.00), and non-CV death (RR: 0.98; 95% CI: 0.92 to 1.05), but a lower risk of nonfatal MI (RR: 0.82; 95% CI: 0.72 to 0.94), TIA (RR: 0.79; 95% CI: 0.71 to 0.89), and ischemic stroke (RR: 0.87; 95% CI: 0.79 to 0.95). Aspirin was associated with a higher risk of major bleeding (RR: 1.5; 95% CI: 1.33 to 1.69), intracranial bleeding (RR: 1.32; 95% CI: 1.12 to 1.55), and major GI bleeding (RR: 1.52; 95% CI: 1.34 to 1.73), with similar rates of fatal bleeding (RR: 1.09; 95% CI: 0.78 to 1.55) compared with the control subjects. Total cancer and cancer-related deaths were similar in both groups within the follow-up period of the study. CONCLUSIONS: Aspirin for primary prevention reduces nonfatal ischemic events but significantly increases nonfatal bleeding events.