Risk factors associated with venous thromboembolism in breast cancer: a narrative review.

PURPOSE: To date, there is no universally acceptable risk assessment tool in clinical practice that accurately estimates the risk of venous thromboembolism (VTE) in patients with breast cancer, despite the large number of published studies. Thus, the aim of this narrative review was to summarize the most relevant risk factors for VTE in these patients. METHODS: We searched Ovid Embase and Ovid MEDLINE, from inception to March 26, 2021, to identify all articles that focused on breast cancer and multiple thromboembolic diseases. We also searched the references section of relevant articles to identify studies. We did not include case reports or case series with small sample size, N < 20. RESULTS: VTE in patients with breast cancer was strongly associated with patient-, tumor-, and non-tumor-related risk factors, such as age, disease stage, central catheter placement, and chemotherapy and tamoxifen use, especially within 2 years of breast cancer diagnosis. CDK inhibitors are emerging factors that may also increase the risk of VTE. CONCLUSIONS: The risk of VTE in patients with breast cancer depends on various patient-, tumor-, and non-tumor-related risk factors. Identifying these risk factors during breast cancer diagnosis and treatment is essential in developing a practical dynamic predictive tool that can help individualize strategies to prevent VTE.

Attributes, Attitudes, and Practices of Clinicians Concerned with Opioid Prescribing.

BACKGROUND: Many clinicians who prescribe opioids for chronic noncancer pain (CNCP) express concerns about opioid misuse, addiction, and physiological dependence. We evaluated the association between the degree of clinician concerns (highly vs less concerned), clinician attributes, other attitudes and beliefs, and opioid prescribing practices. METHODS: A web-based survey of clinicians at a multispecialty medical practice. RESULTS: Compared with less concerned clinicians, clinicians highly concerned with opioid misuse, addiction, and physiological dependence were more confident prescribing opioids (risk ratio [RR] = 1.34, 95% confidence interval [CI] = 1.08-1.67) but were more reluctant to do so (RR = 1.13, 95% CI = 1.03-1.25). They were more likely to report screening patients for substance use disorder (RR = 1.18, 95% CI = 1.01-1.37) and to discontinue prescribing opioids to a patient due to aberrant opioid use behaviors (RR = 1.30, 95% CI = 1.13-1.50). They were also less likely to prescribe benzodiazepines and opioids concurrently (RR = 0.40, 95% CI = 0.25-0.65). Highly concerned clinicians were more likely to work in clinics which engage in "best practices" for opioid prescribing requiring urine drug screening (RR = 4.65, 95% CI = 2.51-8.61), prescription monitoring program review (RR = 2.90, 95% CI = 1.84-4.56), controlled substance agreements (RR = 4.88, 95% CI = 2.64-9.03), and other practices. Controlling for clinician concern, prescribing practices were also associated with clinician confidence, reluctance, and satisfaction. CONCLUSIONS: Highly concerned clinicians are more confident but more reluctant to prescribe opioids. Controlling for clinician concern, confidence in care and reluctance to prescribe opioids were associated with more conservative prescribing practices.

A systematic review and meta-analysis of endovascular versus open surgical revascularization for chronic mesenteric ischemia.

BACKGROUND: Despite the enthusiasm for endovascular revascularization for chronic mesenteric ischemia (CMI), it is not clear if early benefits offset long-term patency rates. This systematic review aimed to provide an up-to-date comprehensive evidence synthesis evaluating the two approaches. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through July 15, 2016, for studies that compared the endovascular with the open surgical approach for revascularization in CMI patients. We conducted a random-effects meta-analysis to pool outcomes of interest across studies. RESULTS: We included 100 observational studies (22 comparative, 78 noncomparative; 18,726 patients; mean age, 69 years). Open surgery was associated with a statistically significant increase in the risk of in-hospital complications (relative risk [RR], 2.2; 95% confidence interval [CI], 1.8-2.6) and a nonsignificant increase in mortality at 30 days (RR, 1.57; 95% CI, 0.84-2.93). Open surgery was associated with lower risk of 3-year recurrence rates (RR, 0.47; 95% CI, 0.34-0.66) and a similar 3-year survival. Data from noncomparative studies provided similar inferences. The quality of evidence was low. CONCLUSIONS: Observational evidence suggests that the endovascular approach for revascularization in patients with CMI may offer better early outcomes than open surgery, although this effect may not be durable. Long-term mortality appears to be similar.

Anticoagulation reversal in vitamin K antagonist-associated intracerebral hemorrhage: a systematic review.

The effect of rapid anticoagulation reversal on mortality and functional outcome in vitamin K antagonist-associated intracerebral hemorrhage (VKA-ICH) is uncertain. Given the approval of idarucizumab for dabigatran reversal and pending approval for andexanet alfa for reversal of factor Xa inhibitors, a systematic appraisal of the effectiveness of reversal for VKA-ICH would provide a bench mark for current practice. We performed PubMed searches and reviewed current guidelines. Using pre-specified inclusion and exclusion criteria, studies were reviewed by two physicians independently. Data elements abstracted included study design, sample size, inclusion and exclusion criteria; patient characteristics at presentation; time to presentation and therapy; dose and timing of warfarin reversal agents; functional outcome and mortality. Studies were assessed for risk of bias. Twenty-one studies met the selection criteria. The overall quality of the studies was poor with small sample size for the majority and all studies being either case series or retrospective observational in design. Inclusion criteria were not uniform. Interpretation of the effectiveness of vitamin K antagonist reversal on functional outcome was not feasible due to lack of standard protocols in the management of VKA-ICH including choice, dose, and timing of reversal agent, timing of subsequent INR monitoring, and decision for repeat imaging. Confounding by indication, lack of universal reporting of functional outcome, and use of varied scales for the endpoint further limited a summary interpretation. Despite availability of reversal agents, mortality and morbidity remain high following VKA-ICH. Evidence for improvement in neurological outcome is limited.

Organizational factors associated with Health Care Provider (HCP) influenza campaigns in the Veterans health care system: a qualitative study.

BACKGROUND: It is an important goal to vaccinate a high proportion of health care providers (HCPs) against influenza, to prevent transmission to patients. Different aspects of how a HCP vaccination campaign is conducted may be linked to different vaccination rates. We sought to characterize organizational factors and practices that were associated with vaccination campaign success among six sites within the Veterans Health Administration, where receipt of flu-vaccination is voluntary. METHOD: We conducted a total of 31 telephone interviews with key informants who were involved with HCP flu vaccination campaigns at three sites with high-vaccination rates and three sites with low-vaccination rates. We compared the organization and management of the six sites' campaigns using constant comparison methods, characterzing themes and analyzing data iteratively. RESULTS: Three factors distinguished sites with high flu vaccination rates from those with low vaccination rates. 1) High levels of executive leadership involvement: demonstrating visible support, fostering new ideas, facilitating resources, and empowering flu team members; 2) Positive flu team characteristics: high levels of collaboration, sense of campaign ownership, sense of empowerment to meet challenges, and adequate time and staffing dedicated to the campaign; and 3) Several concrete strong practices emerged: advance planning, easy access to the vaccine, ability to track employee vaccination status, use of innovative methods to educate staff, and use of audit and feedback to promote targeted efforts to reach unvaccinated employees. CONCLUSION: Successful HCP flu campaigns shared several recognizable characteristics, many of which are amenable to adoption or emulation by programs hoping to improve their vaccination rates.

Effectiveness of Intermittent Pneumatic Compression Devices for Venous Thromboembolism Prophylaxis in High-Risk Surgical Patients: A Systematic Review.

BACKGROUND: Thromboprophylaxis regimens include pharmacologic and mechanical options such as intermittent pneumatic compression devices (IPCDs). There are a wide variety of IPCDs available, but it is uncertain if they vary in effectiveness or ease of use. This is a systematic review of the comparative effectiveness of IPCDs for selected outcomes (mortality, venous thromboembolism [VTE], symptomatic or asymptomatic deep vein thrombosis, major bleeding, ease of use, and adherence) in postoperative surgical patients. METHODS: We searched MEDLINE (via PubMed), Embase, CINAHL, and Cochrane CENTRAL from January 1, 1995, to October 30, 2014, for randomized controlled trials, as well as relevant observational studies on ease of use and adherence. RESULTS: We identified 14 eligible randomized controlled trials (2633 subjects) and 3 eligible observational studies (1724 subjects); most were conducted in joint arthroplasty patients. Intermittent pneumatic compression devices were comparable to anticoagulation for major clinical outcomes (VTE: risk ratio, 1.39; 95% confidence interval, 0.73-2.64). Limited data suggest that concurrent use of anticoagulation with IPCD may lower VTE risk compared with anticoagulation alone, and that IPCD compared with anticoagulation may lower major bleeding risk. Subgroup analyses did not show significant differences by device location, mode of inflation, or risk of bias elements. There were no consistent associations between IPCDs and ease of use or adherence. CONCLUSIONS: Intermittent pneumatic compression devices are appropriate for VTE thromboprophylaxis when used in accordance with current clinical guidelines. The current evidence base to guide selection of a specific device or type of device is limited.

Percent Time in Range with Warfarin as a Performance Measure: How Long a Sampling Frame Is Needed?

BACKGROUND: Warfarin is received by millions of patients in the United States and elsewhere and will remain the most commonly used anticoagulant for the foreseeable future. Percent time in therapeutic range (TTR) with warfarin is increasingly used as a performance measure. However, stakeholders have expressed concern that TTR lags behind changes in performance. Work in a larger study focused on the impact of shortening the conventional measurement period for TTR. METHODS: Some 124 sites within the Department of Veterans Affairs (VA) were examined during a seven-year period (fiscal years [FYs] 2008-2014 (April 1, 2007-September 30, 2014). The duration of time segments (2, 3, 4, 6 months) used to calculate TTR were varied, and these four durations were compared in terms of the number of patients retained per site, mean and median site TTR, and site performance rankings. RESULTS: Data were obtained on 295,237 unique patients who received anticoagulation. As the calculation window shortened, patients with better control (that is, higher TTR) were selectively excluded from the measurement because their laboratory values were more widely spaced. Site mean TTR was highest when the most patients were included (6 months: 950 patients; TTR 65.2%) and lowest when the fewest patients were included (2 months: 567 patients; TTR 60.0%). However, the 3-, 4-, and 6-month segments achieved similar results, each of which included more than 800 patients per site, with mean TTR across a narrow range (64.9%-65.2%). Site rankings were less highly correlated between the 2-month period and longer periods (r = 0.7- 0.8) but were otherwise 0.95 or higher, with a nearly perfect correlation (0.985) between the 4- and 6-month periods. CONCLUSIONS: When TTR is used to measure site-level performance, comparable results can be achieved using a 4- or a 6-month measurement period. On the basis of these results, the use of a 4-month period for future measurement efforts is recommended.

A Qualitative Study of Knowledge of Metabolic Syndrome, Attitudes about Lifestyle Modifications, and Preferences for Lifestyle Interventions among Patients with Cancer and Metabolic Syndrome.

Background: Nearly 60% of patients with cancer have metabolic syndrome, which increases the risk of mortality, but there is no clear guidance for oncology providers about its management. Here, we report on the qualitative component of a larger mixed methods study that aimed to understand cancer patients' knowledge, attitudes, and preferences regarding metabolic syndrome. Methods: Adult cancer patients with metabolic syndrome were recruited during 2022-2023 in the MD Anderson General Internal Medicine clinic and participated in semistructured interviews focused on metabolic syndrome and lifestyle interventions. Interviews were audio-recorded and transcribed verbatim. Participants' demographic information was collected. Interviews were analyzed using hybrid thematic analysis and constant comparison involving deductive and inductive coding. Researcher triangulation and debriefing were used to ensure rigor. Results: There were 19 participants, 12 female and 12 White. Eighteen had solid tumors, including gynecologic (n = 5), genitourinary (n = 4), colorectal (n = 3), and breast (n = 2). Analysis yielded 5 major themes: 1) patients' understanding of metabolic syndrome; 2) attitudes about and approaches to managing metabolic syndrome; 3) capacity and limitations regarding managing metabolic syndrome; 4) patient-led care; and 5) tailored intervention plans. Participants had limited knowledge of metabolic syndrome and its cancer-related consequences; most desired additional education. Many participants reported that their cancer or diabetes diagnosis motivated them to prioritize lifestyle Modifications. Participants expressed strong interest in personalized care plans focused on healthy lifestyle rather than simply weight loss. As part of their tailored intervention plans, participants desired clear communication with their medical team, coordination of care among team members, and collaboration with providers about treatment decisions. Conclusion: Cancer patients with metabolic syndrome want collaborative, patient-centered care. Shared decision-making based on respect for patients' distinctive needs and preferences is an essential component of the development of such collaborative care. Tailored interventions, practical implementation strategies, and personalized care plans are needed for cancer patients with metabolic syndrome. The study findings contribute to filling the gap in knowledge regarding clear guidance for oncology providers on managing metabolic syndrome and will inform the development of future lifestyle interventions for patients diagnosed with metabolic syndrome.

Clinical Factors Associated with Non-Obese Nonalcoholic Fatty Liver Disease Detected among US Adults in the NHANES 2017-2018.

NAFLD can occur in non-obese individuals with BMI < 25 kg/m2. Our goal was to examine the prevalence and clinical factors associated with non-obese NAFLD using vibration-controlled transient elastography (VCTE) with controlled attenuation parameter which estimates steatosis and fibrosis among US adults. We aggregated data from the 2017−2018 cycle of NHANES and included adults (age ≥ 20 years) with BMI < 25 kg/m2 with complete data for the survey, medical examination, and VCTE along with controlled attenuation parameter (CAP). We excluded participants with risks of other liver diseases. We considered patients to have non-obese NAFLD if CAP was >285 dB/m, or non-obese NAFLD fibrosis if this CAP criteria was met and liver stiffness was >8.6 kPa. We calculated the adjusted OR and 95% CI for associations with non-obese NAFLD using multivariable logistic regression. The prevalence of non-obese NAFLD was 6.2% and Asian Americans (12.2%) had the highest non-obese NAFLD prevalence. Clinical factors associated with non-obese NAFLD were advanced age and metabolic syndrome (ORadjusted = 6.8, 95% CI 3.0−15.5). In a separate model, we found elevated glucose (ORadjusted = 4.1, 95% CI 2.1−7.9), triglycerides (ORadjusted = 3.8, 95% CI 1.7−8.5), and truncal fat (100-unit increase ORadjusted = 1.07, 95% CI: 1.04−1.10) were associated with higher odds of non-obese NAFLD. Meanwhile, low physical activity (ORadjusted = 2.9, 95% CI 1.2−7.1) was also positively associated with non-obese NAFLD. Non-obese NAFLD is prevalent in the US and is highly associated with metabolic conditions and syndrome. Our results support the importance of considering racial/ethnic differences when investigating NAFLD in a clinical setting.

A Systematic Review of Patient- and Family-Level Inhaled Corticosteroid Adherence Interventions in Black/African Americans.

BACKGROUND: Inhaled corticosteroid (ICS) adherence rates are suboptimal among adult black/African Americans. Comprehensive studies characterizing the effectiveness and the methodological approaches to the development of interventions to improve ICS adherence in adult black/African Americans have not been performed. OBJECTIVES: Conduct a systematic review of patient/family-level interventions to improve ICS adherence in adult black/African Americans. METHODS: We searched MEDLINE, EMBASE, Web of Science, and CINAHL from inception to August 2017 for English-language US studies enrolling at least 30% black/African Americans comparing patient/family-level ICS adherence interventions with any comparator. Two investigators independently selected, extracted data from, and rated risk of bias. We collected information on intervention characteristics and outcomes, and assessed whether studies were informed by behavior theory, stakeholder engagement, or both. RESULTS: Among 1661 abstracts identified, we reviewed 230 full-text articles and identified 4 randomized controlled trials (RCTs) and 1 quasi-experimental (pre-post design) study meeting criteria. Study participants (N range, 17-333) varied in mean age (22-47 years), proportion black/African Americans studied (71%-93%), and sex (69%-82% females). RCTs evaluated problem-solving classes, self-efficacy training, technology-based motivational interviewing program, and the use of patient advocates. The RCT testing self-efficacy training was the only intervention informed by both behavior theory and stakeholder engagement. All 4 RCTs compared interventions with active control and rated as medium risk of bias. No RCTs found a statistically significant improvement in adherence. CONCLUSIONS: Few studies assessing asthma adherence interventions focused on adult black/African-American populations. No RCTs demonstrated improved ICS adherence in participants. Future studies that are informed by behavior change theory and stakeholder engagement are needed.

Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions: A Meta-Epidemiologic Study.

OBJECTIVE: To determine whether the early trials in chronic medical conditions demonstrate an effect size that is larger than that in subsequent trials. METHODS: We identified randomized controlled trials (RCTs) evaluating a drug or device in patients with chronic medical conditions through meta-analyses (MAs) published between January 1, 2007, and June 23, 2015, in the 10 general medical journals with highest impact factor. We estimated the prevalence of having the largest effect size or heterogeneity in the first 2 published trials. We evaluated the association of the exaggerated early effect with several a priori hypothesized explanatory variables. RESULTS: We included 70 MAs that had included a total of 930 trials (average of 13 [range, 5-48] RCTs per MA) with average follow-up of 24 (range, 1-168) months. The prevalence of the exaggerated early effect (ie, proportion of MAs with largest effect or heterogeneity in the first 2 trials) was 37%. These early trials had an effect size that was on average 2.67 times larger than the overall pooled effect size (ratio of relative effects, 2.67; 95% CI, 2.12-3.37). The presence of exaggerated effect was not significantly associated with trial size; number of events; length of follow-up; intervention duration; number of study sites; inpatient versus outpatient setting; funding source; stopping a trial early; adequacy of random sequence generation, allocation concealment, or blinding; loss to follow-up or the test for publication bias. CONCLUSION: Trials evaluating treatments of chronic medical conditions published early in the chain of evidence commonly demonstrate an exaggerated treatment effect compared with subsequent trials. At the present time, this phenomenon remains unpredictable. Considering the increasing morbidity and mortality of chronic medical conditions, decision makers should act on early evidence with caution.

Improving Anticoagulation Measurement Novel Warfarin Composite Measure.

BACKGROUND: Percent time in therapeutic range (TTR) and international normalized ratio (INR) variability both measure warfarin control and are associated with outcomes independently. Here, we examine the advantages of a warfarin composite measure (WCM), which summarizes the 2 when measuring patient outcomes. We also examine how the measure chosen would affect anticoagulation clinic performance rankings. METHODS AND RESULTS: We constructed WCM using an equally weighted method, adding standardized TTR to standardized log-transformed INR variability using 103 897 warfarin-experienced patients from 100 anticoagulation clinics. We examined the association of WCM with ischemic stroke, major bleeding, and fatal bleeding, using a subset of patients with atrial fibrillation (n=40 404). We divided patients into quintiles based on their level of control for TTR, log INR variability, and WCM. We calculated the hazard ratios for ischemic stroke, major bleeding, and fatal bleeding stratified by these quintiles. WCM hazard ratios for stroke and fatal bleeding showed the largest difference between excellent control and poorest control quintile compared with TTR and log INR variability, but not for major bleeding. In addition, we compared site rankings obtained using each of our 3 performance measures. Kappa scores for identifying outlier and nonoutlier clinics between WCM and its components were moderate (κ=0.56 for TTR and κ=0.62 for log INR variability) but was weak between TTR and log INR variability (κ=0.13). CONCLUSIONS: WCM produces the largest range of risk for warfarin complications, widening the floor ceiling effects that limit the use of TTR and INR variability as separate measures. Anticoagulation clinics ranking changed considerably according to the anticoagulation measure that was selected.

Improving quality measurement for anticoagulation: adding international normalized ratio variability to percent time in therapeutic range.

BACKGROUND: Among patients receiving warfarin, percent time in therapeutic range (TTR) and international normalized ratio (INR) variability predict adverse events individually. Here, we examined what is added to the prediction of adverse events by using both measures together. METHODS AND RESULTS: We included 40 404 patients anticoagulated for atrial fibrillation, aged 65+, within the Veterans Health Administration. TTR and log-transformed INR variability were calculated for each patient. Our study outcomes were ischemic stroke and major bleeding, defined using International Classification of Diseases-9 codes. We estimated the hazard ratios (HRs) for the study outcomes using 3 nested Cox regression models, including (1) TTR or log INR variability separately; (2) TTR and log INR variability together; and (3) both predictors together plus an interaction term. We divided TTR into 3 categories (high, >70%; moderate, 50% to 70%; low, <50%) and log INR variability into 2 categories (stable and unstable). The reference groups high TTR and stable anticoagulation each denote good control. Higher log INR variability (ie, unstable control) predicted ischemic stroke (HR=1.45, P<0.001) and major bleeding (HR=1.57, P<0.001) independently, regardless of TTR levels. Our model with interaction terms showed that High log INR variability predicted a significantly higher risk for ischemic stroke and major bleeding compared with low log INR variability, at moderate TTR levels (HR= 1.27 and HR=1.29, respectively) and at high TTR levels (HR=1.55 and HR=1.56, respectively), but not at low TTR levels. CONCLUSIONS: Unstable anticoagulation predicts warfarin adverse effects independent of TTR. Moreover, knowledge about anticoagulation stability further stratifies the risk for adverse events at given levels of TTR.