High prevalence of iron deficiency and socioeconomic disparities in laboratory screening of non-pregnant females of reproductive age: A retrospective cohort study.

Iron deficiency anemia (IDA) and non-anemic iron deficiency (NAID) are highly prevalent among non-pregnant females of reproductive age. Canada has no national screening guidelines for this population. Screening, when performed, is often with a complete blood count alone without ferritin or iron indices. The primary objective was to determine the prevalence of screening for NAID and IDA over a 3-year period in non-pregnant females of reproductive age who had tests performed at outpatient laboratories in Ontario, Canada. Retrospective cohort study of non-pregnant females ages 15-54 in Ontario, from 2017 to 2019. NAID was defined as ferritin <30 µg/L, anemia as hemoglobin <120 g/L, and IDA as ferritin <30 µg/L and hemoglobin <120 g/L. Annual household income was estimated using patient postal codes. A total of 784 132 non-pregnant females were included. The 82.1% were screened for iron deficiency, 38.3% had NAID and 13.1% had IDA; 55.6% with IDA had normal mean corpuscular volumes. The median household income was $89454.80 compared with a provincial median of $65285.00. Patients in the lowest income quintile had the highest odds of being anemic, and the lowest odds of having a ferritin checked. A large proportion of non-pregnant females of reproductive age in this cohort were screened for iron deficiency. In this relatively privileged cohort, NAID affected nearly 40%, and IDA 13%. Most patients with IDA did not have microcytosis. Low household income was associated with the greatest odds of anemia and the lowest odds of being screened, highlighting inequitable access to screening for IDA in Ontario, Canada.

Technical Challenges for Laryngeal Electromyography.

BACKGROUND/OBJECTIVE: Laryngeal electromyography (LEMG) is a useful diagnostic test in the evaluation of vocal fold paralysis (VFP). This study investigates factors that can make LEMG challenging to perform. METHODS: Patients with subacute unilateral VFP presented for LEMG were prospectively enrolled. Demographic data including BMI, previous neck surgery, and anatomic factors were collected. Patient-reported pain related to the procedure was recorded on a visual analogue scale (VAS). Electromyographer and otolaryngologist recorded a consensus rating of the perceived difficulty in performing the test and confidence in using the results for clinical decision-making. RESULTS: A total of 111 patients (56.8% female) were enrolled between August 2015 and August 2018. The mean age was 55 ± 14 years, and the average body mass index (BMI) was 28.5 ± 6.4. The mean patient-reported VAS score for pain was 35 ± 24. Notably, 31.2% of the tests were considered "very easy," 32.1% were considered "mildly challenging" and 23.9% and 12.8% were considered "moderately challenging" and "extremely challenging," respectively, by the clinicians. Common factors affecting LEMG difficulty included poorly palpable surface anatomy (50.5%) and patient intolerance (15.6%). Clinicians felt confident in 76.1% of the test findings. Bivariate analyses showed that prior neck surgery is associated with elevated VAS (p = 0.02), but clinician-perceived difficulty of performing the test is not associated with elevated VAS scores (p = 0.55). CONCLUSIONS: Majority of LEMG tests are well tolerated by patients. Physicians reported more confidence using LEMG for clinical decision-making when the test was easier to perform. Difficult surface anatomy and patient intolerance affects clinician confidence in integrating the test results with clinical care. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:831-834, 2024.

Formation and Assessment of a Laryngology Pathology Video Atlas for Resident Education.

OBJECTIVE: Conventional reference images of laryngeal pathologies may provide educational value for Otolaryngology-Head & Neck Surgery (OHNS) residents, but observing dynamic vocal fold function is critical for diagnosis. Our aim was to develop and validate a video atlas of laryngeal pathologies for resident education in OHNS. DESIGN: A multi-institution, prospective case-control study. SETTING/PARTICIPANTS: Ten videos showing 10 representative laryngeal pathologies were verified by two laryngologists. Six videos per category with kappa>0.8 were included in the video database. A collection of the videos was shown to a group of OHNS residents in a quiz fashion to determine if senior trainees would score higher than junior trainees. Another group of residents in OHNS was recruited and randomized to control or intervention. The control group was shown a quiz of 10 laryngeal videos at baseline and 24 weeks later. The intervention group was shown quizzes at baseline and every 6 weeks, ending at 24 weeks. Free-text diagnoses were scored for accuracy. Descriptive statistics, two-tailed tests, and analysis of covariance were performed. RESULTS: Twenty-nine residents participated, with 14 (48.3%) randomized to control, and 15 (51.7%) to the intervention. The postgraduate year (PGY) level had a significant impact on diagnostic performance. PGY1 and 2 had a significantly lower score than PGY5 (P = 0.017 and P = 0.035, respectively). PGY3 and PGY4 scores were not statistically different from PGY5 scores. The mean score difference between groups decreases as the PGY level increases (mean difference between groups = 0.87, P = 0.153), but this was not significant. CONCLUSIONS: The current study has created a validated collection of videos that are representative of common laryngeal pathologies and can be easily incorporated into resident video-based learning. Future directions include larger multi-site studies to further elucidate whether repeated viewing of this video atlas can improve OHNS resident laryngology knowledge.

Evaluating a pilot, structured, face-to-face, antimicrobial stewardship, prospective audit-and-feedback program in emergency general surgery service in a community hospital.

Background: Prospective audit and feedback (PAF) is an established practice in critical care settings but not in surgical populations. We pilot-tested a structured face-to-face PAF program for our acute-care surgery (ACS) service. Methods: This was a mixed-methods study. For the quantitative analysis, the structured PAF period was from August 1, 2017, to April 30, 2019. The ad hoc PAF period was from May 1, 2019, to January 31, 2021. Interrupted time-series segmented negative binomial regression analysis was used to evaluate change in antimicrobial usage measured in days of therapy per 1,000 patient days for all systemic and targeted antimicrobials. Secondary outcomes included C. difficile infections, length of stay and readmission within 30 days. Each secondary outcome was analyzed using a logistic regression or negative binomial regression model. For the qualitative analyses, all ACS surgeons and trainees from November 23, 2015, to April 30, 2019, were invited to participate in an email-based anonymous survey developed using implementation science principles. Responses were measured using counts. Results: In total, 776 ACS patients were included in the structured PAF period and 783 patients were included in the in ad hoc PAF period. No significant changes in level or trend for antimicrobial usage were detected for all and targeted antimicrobials. Similarly, no significant differences were detected for secondary outcomes. The survey response rate was 25% (n = 10). Moreover, 50% agreed that PAF provided them with skills to use antimicrobials more judiciously, and 80% agreed that PAF improved the quality of antimicrobial treatment for their patients. Conclusion: Structured PAF showed clinical outcomes similar to ad hoc PAF. Structured PAF was well received and was perceived as beneficial by surgical staff.

Self-reported Human Papillomavirus Vaccination and Vaccine Effectiveness Among Men Who Have Sex with Men: A Quantitative Bias Analysis.

BACKGROUND: Self-report of human papillomavirus (HPV) vaccination has ~80-90% sensitivity and ~75-85% specificity. We measured the effect of nondifferential exposure misclassification associated with self-reported vaccination on vaccine effectiveness (VE) estimates. METHODS: Between 2017-2019, we recruited sexually active gay, bisexual, and other men who have sex with men aged 16-30 years in Canada. VE was derived as 1-prevalence ratio × 100% for prevalent anal HPV infection comparing vaccinated (≥1 dose) to unvaccinated men using a multivariable modified Poisson regression. We conducted a multidimensional and probabilistic quantitative bias analysis to correct VE estimates. RESULTS: Bias-corrected VE estimates were relatively stable across sensitivity values but differed from the uncorrected estimate at lower values of specificity. The median adjusted VE was 27% (2.5-97.5th simulation interval = -5-49%) in the uncorrected analysis, increasing to 39% (2.5-97.5th simulation interval = 2-65%) in the bias-corrected analysis. CONCLUSION: A large proportion of participants erroneously reporting HPV vaccination would be required to meaningfully change VE estimates.

Vaccine Effectiveness Against 12-Month Incident and Persistent Anal Human Papillomavirus Infection Among Gay, Bisexual, and Other Men Who Have Sex With Men.

BACKGROUND: Real-world evidence of human papillomavirus (HPV) vaccine effectiveness (VE) against longitudinal outcomes is lacking among gay, bisexual, and other men who have sex with men (GBM). We compared 12-month incidence and persistence of anal HPV infection between vaccinated and unvaccinated GBM. METHODS: We recruited GBM aged 16-30 years in Montreal, Toronto, and Vancouver, Canada, from 2017 to 2019. Participants were followed over a median of 12 months (interquartile range, 12-13 months). Participants self-reported HPV vaccination and self-collected anal specimens for HPV DNA testing. We calculated prevalence ratios (PR) for 12-month cumulative incidence and persistence with ≥1 quadrivalent vaccine type (HPV 6/11/16/18) between vaccinated (≥1 dose at baseline) and unvaccinated participants using a propensity score-weighted, modified Poisson regression. RESULTS: Among 248 participants, 109 (44.0%) were vaccinated at baseline, of whom 62.6% received 3 doses. PRs for HPV 6/11/16/18 were 0.56 (95% confidence interval [CI], .24-1.31) for cumulative incidence and 0.53 (95% CI, .25-1.14) for persistence. PRs were 0.23 (95% CI, .05-1.03) and 0.08 (95% CI, .01-.59) for incidence and persistence, respectively, among participants who received their first dose at age ≤23 years and 0.15 (95% CI, .03-.68) and 0.12 (95% CI, .03-.54) among participants who were sexually active for ≤5 years before vaccination. CONCLUSIONS: Findings support national recommendations for HPV vaccination at younger ages or soon after sexual debut.

Perioperative continuous infusions of factor VIII versus factor IX for patients with hemophilia A or B undergoing major surgery.

Continuous factor VIII (FVIII) or factor IX (FIX) infusions are commonly used for patients with hemophilia A (HA) or B (HB) undergoing surgery to secure perioperative hemostasis. To describe differences between the initial recovery and subsequent FIX and FVIII levels, and describe clinical outcomes among HB and HA patients receiving perioperative continuous infusion (CI) of recombinant FVIII and FIX concentrates. Retrospective chart review was conducted on 8 consecutive patients with HB and 7 consecutive patients with HA who underwent major surgery between 2014 and 2018 and received continuous infusions of standard half-life factor concentrate. Median initial bolus dose per kilogram was higher for HB compared to HA patients [90.8 (IQR 78.0-98.7) vs. 52.1 (IQR 48.6-55.6) IU/kg], while initial CI dose-rates were similar [4.3 (IQR 3.8-4.6) vs. 4.2 (IQR 3.8-4.4) IU/kg/h]. Median post-bolus recovery was higher for FVIII compared to FIX [1.70 (IQR 1.23-1.75) vs. 0.88 (IQR 0.75-1.00) IU/mL]. Median factor levels also were higher for FVIII on post-operative days 1 to 3. HB patients had greater mean intraoperative estimated blood loss [285.7 (range 0-1000) vs. 142.8 (range 0-400) mL] and longer median length of hospital stay [9 (IQR 8-12) vs. 5 (IQR 4-6.5) days]. Our initial evidence suggests greater in vivo yield of rFVIII compared to rFIX in the perioperative setting. We identified poorer clinical outcomes in this small cohort of perioperative HB patients indicating that they may benefit from a higher CI rate for adequate surgical hemostatic coverage.

Increases in human papillomavirus vaccine coverage over 12 months among a community-recruited cohort of gay, bisexual, and other men who have sex with men in Canada.

BACKGROUND: Starting in 2015/16, most Canadian provinces introduced publicly-funded human papillomavirus (HPV) vaccination programs for gay, bisexual, and other men who have sex with men (GBM) aged ≤ 26 years. We estimated 12-month changes in HPV vaccine coverage among community-recruited GBM from 2017 to 2021 and identified baseline factors associated with vaccine initiation (≥1 dose) or series completion (3 doses) among participants who were unvaccinated or partially vaccinated at baseline. METHODS: We recruited sexually-active GBM aged ≥ 16 years in Montreal, Toronto, and Vancouver, Canada, from 02/2017 to 08/2019 and followed them over a median of 12 months (interquartile range = 12-13 months). We calculated the proportion who initiated vaccination (≥1 dose) or completed the series (3 doses) by 12-month follow-up. Analyses were stratified by city and age-eligibility for the publicly-funded programs at baseline (≤26 years or > 26 years). We used multivariable logistic regression to identify baseline factors associated with self-reported incident vaccine initiation or series completion. RESULTS: Among 165 unvaccinated participants aged ≤ 26 years at baseline, incident vaccine initiation (≥1 dose) during follow-up was 24.1% in Montreal, 33.3% in Toronto, and 38.9% in Vancouver. Among 1,059 unvaccinated participants aged > 26 years, incident vaccine initiation was 3.4%, 8.9%, and 10.9%, respectively. Higher education and trying to access pre-exposure prophylaxis for HIV were associated with incident vaccination among those aged ≤ 26 years, while younger age, residing in Vancouver (vs. Montreal), being diagnosed with anogenital warts, having both government and private extended medical insurance, and being vaccinated against influenza were associated with incident vaccination among those aged > 26 years. CONCLUSIONS: We observed substantial gains in HPV vaccine coverage among young GBM within 5 + years of targeted program implementation, but gaps remain, particularly among older men who are ineligible for publicly-funded programs. Findings suggest the need for expanded public funding or insurance coverage for HPV vaccines.

Gynecologic Symptoms among Hormone Receptor-Positive Breast Cancer Patients on Oral Endocrine Therapy: A Cross-Sectional Study.

Endocrine therapy (ET) for hormone receptor-positive (HR+) breast cancer can contribute to gynecologic symptoms (GS) that impact vaginal health, sexual function, and quality of life (QoL). A cross-sectional study was conducted at St. Michael's Hospital in Toronto, Canada between July 2017 and June 2018 to examine the occurrence and frequency of GS among HR+ breast cancer patients on ET, patient-provider communication, female sexual dysfunction (FSD), and QoL. A Treatment Experience questionnaire was developed for this study and the Female Sexual Function Index (FSFI) and Menopause-Specific Quality of Life questionnaire (MENQOL) were also administered. Of 151 patients surveyed, 77 (51.0%) were on tamoxifen and 74 (49.0%) on an aromatase inhibitor. Most patients (84.1%, 95% confidence interval [CI] 77.3% to 89.5%) experienced at least one GS "all the time" or "often", or one or more infections, in the past year. Only 44 (31.9%) patients reported that their oncologist had ever previously asked them about experiencing GS. The prevalence of FSD was 61.2% (95% CI 46.2% to 74.8%) among 49 sexually active patients that completed the FSFI. Symptoms captured in the MENQOL's vasomotor domain were deemed most bothersome. Side effect management and patient-provider communication should be prioritized to optimize GS, vaginal health, and sexual function of ET users.

Challenges in Cross-Cultural Communication in Breast Cancer Surgery: Is there a Gender Gap?

The aim of this study is to identify [1] facilitators and barriers to cross-cultural communication with Canadian immigrants during the breast cancer (BC) surgical consultation and [2] the impact of cultural sensitivity training on the perception of cross-cultural communication barriers. A 29-item questionnaire mailed to 450 surgeons was developed based on the Ottawa Decision Support Framework, informed by interviews with BC practitioners and a literature review. The inclusion criteria are English-speaking general surgeons practicing in Vancouver, Montréal, and Toronto, home to > 60% of Canada's immigrant population. The association between surgeon characteristics and barriers to communication was assessed using the chi-square or Fisher's exact test. Univariate and multivariable logistic regression models estimated odds ratios and 95% confidence intervals for the association between frequent perception of each barrier to communication and gender, career stage, and percentage of foreign-born patients. Between June and September 2017, 130 surveys were returned for a 29% response rate. The majority of practitioners reported experiencing language barriers in consultation with immigrant patients (71.4%). In the patient-provider relationship, the most commonly reported barrier was the patient's lack of medical understanding (81.4%). At the system level, the absence of a relative for translation was the most frequently encountered challenge (77.1%). On multivariable analysis adjusting for career stage and percentage of foreign-born patients, female gender of a surgeon was associated with more frequent perception of barriers related to language (OR 4.91, [95% CI 1.43, 16.82; p = 0.0114]), the patient's desired role in decision-making (OR 3.000 [95% CI 1.116-8.059; p = 0.0294]), and poor access to interpreters (OR 3.63 [95% CI 1.24, 10.64; p = 0.0189]). Furthermore, on multivariable analysis adjusting for gender and career stage, surgeons identified as having < 25% foreign-born patients in their practice were less likely to identify communication barriers due to the patients' perception and understanding of their healthcare (OR 0.32 [95% CI 0.11, 0.95; p = 0.041]). Cultural sensitivity training did not appear to be an influential factor though this may be due to the low number of surgeons who received training (5.7%). There are multiple cross-cultural communication challenges. Gender, years in practice, and the cultural diversity of a practice might play significant roles in the identification and perception of these barriers.

Suboptimal iron deficiency screening in pregnancy and the impact of socioeconomic status in a high-resource setting.

Iron deficiency (ID) anemia in pregnancy is associated with poor maternal and childhood outcomes, yet ferritin testing, the standard test for ID, is not considered part of routine prenatal bloodwork in Canada. We conducted a retrospective cohort study of 44 552 pregnant patients with prenatal testing at community laboratories in Ontario, Canada, to determine the prevalence of ferritin testing over 5 years. Secondary objectives were to determine the prevalence and severity of ID and to identify clinical and demographic variables that influence the likelihood of ID screening. A total of 59.4% of patients had a ferritin checked during pregnancy; 71.4% were ordered in the first trimester, when the risk of ID is lowest. Excluding patients with abnormally elevated ferritins, 25.2% were iron insufficient (30-44 µg/L) and 52.8% were iron deficient (≤29 µg/L) at least once in pregnancy. A total of 8.3% were anemic (hemoglobin <105 g/L). The proportion of anemic patients with a subsequent ferritin test in pregnancy ranged from 22% to 67% in the lowest and highest anemia severity categories, respectively. Lower annual household income was negatively associated with the odds of a ferritin test; compared with those in the fifth (ie, highest) income quintile, the odds of ferritin testing for patients in the first, second, and fourth quintiles were 0.83 (95% confidence interval [CI], 0.74-0.91), 0.82 (95% CI, 0.74-0.91), and 0.86 (95% CI, 0.77-0.97), respectively. These data highlight gaps in prenatal care and issues of health equity that warrant harmonization of obstetrical guidelines to recommend routine ferritin testing in pregnancy.

Changes in mammography screening in Ontario and Alberta following national guideline dissemination: an interrupted time series analysis.

Background: In November 2011, the Canadian Task Force on Preventive Health Care released guidelines for screening women at average breast cancer risk. Weak recommendations (framed using GRADE methodology) were made for screening women aged 50 to 74 years every two to three years, and for not screening women aged 40 to 49 years. Methods: We conducted an interrupted time series analysis using administrative data to examine bilateral mammography use before and after a release of a national breast screening guideline. Women aged 40 to 74 years living in Ontario or Alberta from 30th November 2008 to 30th November 2014 were included. Strata included age, region of residence, neighbourhood income quintile, immigration status, and education level. Results: In both provinces, mammography use rates were lower in the post-intervention period (527 vs. 556 and 428 vs. 465/1000 women in Ontario and Alberta, respectively). In Ontario, mammography trends decreased following guideline release to align with recommendations for women aged 40 to 74 (decrease of 2.21/1000 women, SE 0.26/1000, p<0.0001). In Alberta, mammography trends decreased for women aged 40 to 49 years (3/1000 women, SE 0.32, p<0.001) and 50 to 69 (2.9/1000 women, SE 0.79, p<0.001), but did not change for women aged 70 to 74 (0.7/1000 women, SE 1.23, p=0.553). In both provinces, trends in mammography use rates were sustained for up to three years after guideline release. Conclusions: We observed a decrease in screening for women aged 40-49. Additional research to explore whether shared decision making was used to optimize guideline-concordant screening for women aged 50-74 is needed.

Effect of a Housing Intervention on Selected Cardiovascular Risk Factors Among Homeless Adults With Mental Illness: 24-Month Follow-Up of a Randomized Controlled Trial.

Background Cardiovascular disease is a leading cause of mortality among people experiencing homelessness. This study investigated whether housing intervention affects cardiovascular disease risk factors among homeless adults with mental illnesses over a 24-month period. Methods and Results We conducted a randomized controlled trial of a Housing First intervention that provided community-based scattered-site housing and support services. Five hundred seventy-five participants were randomized to the intervention (n=301) or treatment as usual (TAU) (n=274). Analyses were performed according to the intention-to-treat principle using generalized estimating equations. There were no differences in change over 24 months between the 2 groups for blood pressure, tobacco, and cocaine/crack use. However, the intervention had an impact on reducing the number of days of alcohol intoxication by 1.58 days compared with TAU (95% CI, -2.88 to -0.27, P=0.0018). Over the 24-month period, both the intervention and TAU groups had significant reductions in tobacco and cocaine use. Conclusions The intervention, compared with TAU, did not result in greater improvements in many of the selected cardiovascular risk factors. Since the study took place in a service-rich city with a range of pre-existing supportive services and universal health insurance, the high level of usual services available to the TAU group may have contributed to reductions in their cardiovascular disease risk factors. Further research is needed to develop interventions to reduce risk factors of cardiovascular disease among people experiencing homelessness and mental illness beyond existing treatments. REGISTRATION www.isrctn.comURL: www.isrctn.com. Unique Identifier: ISRCTN42520374.

Antibiotics: easier to start than to stop? Predictors of antimicrobial stewardship recommendation acceptance.

OBJECTIVES: Acceptance of prospective audit and feedback antimicrobial stewardship programme (ASP) recommendations has been shown to vary, but the drivers of recommendation acceptance are not well understood. We sought to identify the factors associated with recommendation acceptance at a large community teaching hospital. METHODS: Data from an ASP recommendation registry were collected from 2010 to 2018. Variables included data about the infection, the prescriber, and the recommendation, categorized by whether they increase, decrease, or are neutral to antibiotic exposure. The primary outcome was acceptance of ASP recommendations. Adjusted odds ratios and 95% confidence intervals were estimated using logistic regression models with random intercepts in order to account for clustering by prescriber. RESULTS: Over the 8-year period, a total of 11 014 evaluable recommendations were made to 146 prescribers, and 9058 (82.2%) were accepted. The most common recommendations were: reduce duration (n = 2796; 25%), stop antibiotics (n = 2184; 20%), de-escalate (n = 1876; 17%) and increase duration (n = 1176; 11%). Acceptance by service ranged from 70% (n = 843/1196) (surgery) to 86% (n = 6378/7444) (general medicine). In the multivariable analysis, compared to recommendations that have a neutral impact on antibiotic exposure, recommendations to decrease antibiotic exposure had lower odds of acceptance (aOR 0.73; 95%CI 0.64-0.84) while recommendations to increase exposure were associated with greater acceptance (aOR 2.00; 95%CI 1.62-2.45). Other factors associated with increased acceptance included the presence of the ASP physician during rounds and making the recommendation verbally. CONCLUSIONS: Recommendations to decrease antibiotic exposure had lower odds of acceptance than those to increase antibiotic exposure. This study presents important considerations for ASPs with prospective audit and feedback programmes aiming to evaluate and increase the impact of their recommendations.

Development of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM): A toxicity subscale to measure quality of life in patients with cancer who are treated with ICMs.

BACKGROUND: Patients with cancer who are treated with immune checkpoint modulators (ICMs) have their health-related quality of life (HRQOL) measured using general patient-reported outcome (PRO) tools. To the authors' knowledge, no instrument has been developed to date specifically for patients treated with ICMs. The objective of the current study was to develop a toxicity subscale PRO instrument for patients treated with ICMs to assess HRQOL. METHODS: Input was collected from a systematic review as well as patients and physicians experienced with ICM treatment. Descriptive thematic analysis was used to evaluate the qualitative data obtained from patient focus groups and interviews, which informed an initial list of items that described ICM side effects and their impact on HRQOL. These inputs informed item generation and/or reduction to develop a toxicity subscale. RESULTS: Focus groups and individual interviews with 37 ICM-treated patients generated an initial list of 176 items. After a first round of item reduction that produced a shortened list of 76 items, 16 physicians who care for patients who are treated with ICMs were surveyed with a list of 49 patient-reported side effects and 11 physicians participated in follow-up interviews. A second round of item reduction was informed by the physician responses to produce a list of 25 items. CONCLUSIONS: To the authors' knowledge, this 25-item list is the first HRQOL-focused toxicity subscale for patients treated with ICMs and was developed in accordance with US Food and Drug Administration guidelines, which prioritize patient input in developing PRO tools. The subscale will be combined with the Functional Assessment of Cancer Therapy-General (FACT-G) to form the FACT-ICM. Prior to recommending the formal use of this PRO instrument, the authors will evaluate its validity and reliability in longitudinal studies involving substantially more patients.

Development and implementation of a quality improvement toolkit, iron deficiency in pregnancy with maternal iron optimization (IRON MOM): A before-and-after study.

BACKGROUND: Iron deficiency (ID) in pregnancy is a common problem that can compromise both maternal and fetal health. Although daily iron supplementation is a simple and effective means of treating ID in pregnancy, ID and ID anemia (IDA) often go unrecognized and untreated due to lack of knowledge of their implications and competing clinical priorities. METHODS AND FINDINGS: In order to enhance screening and management of ID and IDA in pregnancy, we developed a novel quality-improvement toolkit: ID in pregnancy with maternal iron optimization (IRON MOM), implemented at St. Michael's Hospital in Toronto, Canada. It included clinical pathways for diagnosis and management, educational resources for clinicians and patients, templated laboratory requisitions, and standardized oral iron prescriptions. To assess the impact of IRON MOM, we retrospectively extracted laboratory data of all women seen in both the obstetrics clinic and the inpatient delivery ward settings from the electronic patient record (EPR) to compare measures pre- and post-implementation of the toolkit: a process measure of the rates of ferritin testing, and outcome measures of the proportion of women with an antenatal (predelivery) hemoglobin value below 100 g/L (anemia), the proportion of women who received a red blood cell (RBC) transfusion during pregnancy, and the proportion of women who received an RBC transfusion immediately following delivery or in the 8-week postpartum period. The pre-intervention period was from January 2012 to December 2016, and the post-intervention period was from January 2017 to December 2017. From the EPR, 1,292 and 2,400 ferritin tests and 16,603 and 3,282 antenatal hemoglobin results were extracted pre- and post-intervention, respectively. One year after implementation of IRON MOM, we found a 10-fold increase in the rate of ferritin testing in the obstetric clinics at our hospital and a lower risk of antenatal hemoglobin values below 100 g/L (pre-intervention 13.5% [95% confidence interval (CI) 13.0%-14.11%]; post-intervention 10.6% [95% CI 9.6%-11.7%], p < 0.0001). In addition, a significantly lower proportion of women received an RBC transfusion during their pregnancy (1.2% pre-intervention versus 0.8% post-intervention, p = 0.0499) or immediately following delivery and in the 8 weeks following (2.3% pre-intervention versus 1.6% post-intervention, p = 0.0214). Limitations of this study include the use of aggregate data extracted from the EPR, and lack of a control group. CONCLUSIONS: The introduction of a standardized toolkit including diagnostic and management pathways as well as other aids increased ferritin testing and decreased the incidence of anemia among women presenting for delivery at our site. This strategy also resulted in reduced proportions of women receiving RBC transfusion during pregnancy and in the first 8 weeks postpartum. The IRON MOM toolkit is a low-tech strategy that could be easily scaled to other settings.

Assessment of left ventricular function by CMR versus MUGA scans in breast cancer patients receiving trastuzumab: a prospective observational study.

Little is known about the comparison of multiple-gated acquisition (MUGA) scanning with cardiovascular magnetic resonance (CMR) for serial monitoring of HER2+ breast cancer patients receiving trastuzumab. The association of cardiac biomarkers with CMR left ventricular (LV) function and volume is also not well studied. Our objectives were to compare CMR and MUGA for left ventricular ejection fraction (LVEF) assessment, and to examine the association between changes in brain natriuretic peptide (NT-BNP) and troponin-I and changes in CMR LV function and volume. This prospective longitudinal two-centre cohort study recruited HER2+ breast cancer patients between January 2010 and December 2013. MUGA, CMR, NT-BNP and troponin-I were performed at baseline, 6, 12, and 18 months after trastuzumab initiation. In total, 41 patients (age 51.7 ± 10.8 years) were enrolled. LVEF comparison between MUGA and CMR demonstrated weak agreement (Lin's correlation coefficient r = 0.46, baseline; r = 0.29, 6 months; r = 0.42, 12 months; r = 0.39, 18 months; all p < 0.05). Bland-Altman plots demonstrated wide LVEF agreement limits (pooled agreement limits 3.0 ± 6.2). Both modalities demonstrated significant LVEF decline at 6 and 12 months from baseline, concomitant with increased LV volumes on CMR. Changes in NT-BNP correlated with changes in LV diastolic volume at 12 and 18 months (p < 0.05), and LV systolic volume at 18 months (p < 0.05). Changes in troponin-I did not correlate with changes in LV function or volume at any timepoint. In conclusion, CMR and MUGA LVEF are not interchangeable, warranting selection and utility of one modality for serial monitoring. CMR is useful due to less radiation exposure and accuracy of LV volume measurements. Changes in NT-BNP correlated with changes in LV volumes.

Exploring the effect of factor Xa inhibitors on rotational thromboelastometry: a case series of bleeding patients.

Direct oral anticoagulants (DOACs) have become the standard for thromboembolic risk management. In cases of major bleeding, trauma, or urgent surgery, accurate monitoring of DOAC activity is desirable; however, there is often no rapid, readily available test. We therefore explored the degree to which DOAC activity correlated with two coagulation assays: rotational thromboelastometry (ROTEM) and a standard coagulation assay in bleeding patients. We conducted a retrospective review of patients who experienced bleeding while on DOAC therapy from 2015 to 2017 at a Level 1 trauma center. ROTEM (EXTEM-clotting time {CT} in seconds), activated partial thromboplastin time (aPTT) (in seconds), prothrombin time (PT) (in seconds), DOAC specific drug test (anti-Xa and Hemoclot in ng/mL), and relevant clinical parameters were recorded. Descriptive statistics (median, range) and Spearman correlation coefficients were estimated. Differences between correlations were tested using Williams' t test. Twelve cases were reviewed (13 separate bleeding episodes). Sixteen measurements of DOAC activity, EXTEM-CT, and PT were obtained. The correlations with rivaroxaban activity were 0.96 and 0.86 (p = 0.2062) for PT and EXTEM-CT, respectively. The correlations with apixaban activity were 0.63 and 0.56 (p = 0.7175) for PT and EXTEM-CT, respectively. Analyses were not conducted for dabigatran due to limited data. Although not statistically significant, PT appears to have a higher correlation with direct Xa inhibitor activity than EXTEM-CT. Further research with larger samples is necessary to clarify the differences between ROTEM and standard assays in detecting DOAC activity.

Aqueous Humor Cytokine Levels and Anatomic Response to Intravitreal Ranibizumab in Diabetic Macular Edema.

Importance: Variability in response to anti-vascular endothelial growth factor (VEGF) treatment in diabetic macular edema (DME) remains a significant clinical challenge. Biomarkers could help anticipate responses to anti-VEGF therapy. Objectives: To investigate aqueous humor cytokine level changes in response to intravitreal ranibizumab therapy for the management of DME, and to determine the association between baseline aqueous levels and anatomic response. Design, Setting, and Participants: In this prospective multicenter cohort study, 49 participants with diabetes mellitus complicated by center-involving DME, with a central subfield thickness of 310 µm or greater on spectral-domain optical coherence tomography (SD-OCT), were recruited from December 22, 2011, to June 13, 2013 and statistical analysis were performed from March 1, 2017, to June 1, 2017. A total of 48 participants proceeded to follow-up. Interventions: Participants received monthly injections of ranibizumab, 0.5 mg, for 3 months. Aqueous fluid for cytokine analysis was obtained at baseline and repeated at the 2-month visit. Multiplex immunoassay was carried out in duplicate for VEGF, placental growth factor, transforming growth factor beta 2, intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), IL-8, IL-10, vascular intercellular adhesion molecule, and monocyte chemoattractant protein 1. Main Outcomes and Measures: Baseline and 2-month change in aqueous cytokine levels, 3-month change in SD-OCT central subfield thickness and macular volume (MV), and the statistical association between baseline aqueous cytokine levels and these measures of anatomic response to ranibizumab in center-involving DME. Results: Among the 48 participants, the mean (SD) age was 61.9 (7.1) years and 36 participants (75.0%) were men. The following cytokines were lower at month 2 vs baseline: ICAM-1 (median change, -190.88; interquartile range [IQR], -634.20 to -26.54; P < .001), VEGF (median change, -639.45; IQR, -1040.61 to -502.61; P < .001), placental growth factor (median change, -1.31; IQR, -5.99 to -0.01; P < .001), IL-6 (median change, -38.61; IQR, -166.72 to -2.80; P < .001), and monocyte chemoattractant protein 1 (median change, -90.13; IQR, -382.74 to 109.47; P = .01). When controlling for age, foveal avascular zone size, and severity of retinopathy, multiple linear regression determined that increasing baseline aqueous ICAM-1 was associated with a favorable anatomic response, in terms of reduced SD-OCT MV at 3 months (every additional 100 pg/mL of baseline ICAM-1 was associated with a reduction of 0.0379 mm3; P = .01). Conversely, increasing baseline aqueous VEGF was associated with a less favorable SD-OCT MV response at 3 months (every additional 100 pg/mL of baseline VEGF was associated with an increase of 0.0731 mm3; P = .02) and was associated with lower odds of being a central subfield thickness responder (odds ratio, 0.868; 95% CI, 0.755-0.998). Conclusions and Relevance: Elevated aqueous ICAM-1 and reduced VEGF levels at baseline are associated with a favorable anatomic response to ranibizumab in DME, although there is not always direct correlation between anatomic and visual acuity response.

AQUEOUS HUMOR CYTOKINE LEVELS AS BIOMARKERS OF DISEASE SEVERITY IN DIABETIC MACULAR EDEMA.

PURPOSE: To determine whether aqueous cytokine levels correlate with disease severity in diabetic macular edema. METHODS: A prospective cross-sectional study of 49 adults with diabetes mellitus, centre-involving diabetic macular edema and central subfield macular thickness ≥310 µm on spectral domain optical coherence tomography. Clinical examination and aqueous sampling were carried out before an initial injection of ranibizumab. Multiplex immunoassay of sample was carried out for vascular endothelial growth factor, placental growth factor, transforming growth factor beta, intercellular adhesion molecule-1, interleukin (IL)-2, IL-3, IL-6, IL-8, IL-10, IL-17, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and epidermal growth factor. Multivariate robust regression models were constructed, and adjusted for age, lens status, or severity of retinopathy, and size of foveal avascular zone. RESULTS: Spectral domain optical coherence tomography macular volume was an excellent measure of disease severity, correlating strongly with central subfield macular thickness (P < 0.001), best-corrected Snellen visual acuity (P < 0.001), and baseline diabetic retinopathy severity (P = 0.01). Elevated aqueous intercellular adhesion molecule-1 correlated with greater macular volume (P = 0.002). No aqueous cytokine, including VEGF, correlated with central subfield macular thickness. There was an association between IL-10 levels and best-corrected Snellen visual acuity (P = 0.03). CONCLUSION: Aqueous intercellular adhesion molecule-1 correlates with disease severity as measured by macular volume on spectral domain optical coherence tomography, and IL-10 is associated with BCVA. Intercellular adhesion molecule-1 may be a clinically useful biomarker for diabetic macular edema severity.