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Objective: Opioid use disorder (OUD) can be effectively treated with buprenorphine maintenance. Recent changes in federal policy have removed the requirement for physicians to complete additional training to apply for a Drug Enforcement Administration (DEA) waiver to prescribe buprenorphine. At that time, few primary care providers (PCPs) had completed the training for a DEA waiver to prescribe buprenorphine. Our goal was to identify addressable barriers that may persist despite updates to federal legislation., Design: A 42-item survey was distributed to 662 physicians and nurse practitioners at two academic medical centers with 100 respondents., Setting: The survey was sent via email and administered anonymously through SurveyMonkey., Patients and Participants: All participants were PCPs, and all PCPs at the two academic medical centers were eligible to participate., Interventions: PCPs responded to the survey by answering questions online., Main Outcome Measures: PCPs answered questions regarding previous buprenorphine waiver training status, local OUD prevalence, the effectiveness of OUD treatment modalities, and previous barriers to training., Results: Respondents were compared using descriptive statistics and logistic regression. Of the 100 respondents (response rate: 15 percent), 69 percent had not completed the training. Ninety-nine percent of PCPs agreed that OUD was an issue in their area, 94 percent saw patients with OUD, and 91 percent rated buprenorphine maintenance as a very effective treatment for OUD. Previously waivered and nonwaivered providers did not differ in their responses to these questions. Those who had been waivered were less likely to say they did not see enough patients with OUD to justify training (odds ratio [OR] 0.267, p = 0.005) and were less likely to express concern about allowing patients with OUD into their practice (OR 0.348, p = 0.020) than PCPs who had applied for the DEA waiver., Conclusions: Despite nonwaivered PCPs recognizing OUD's prevalence, they were concerned about allowing patients with OUD into their practice and said there were not enough patients to justify training. This suggests that attitudinal barriers are the most appropriate target for current intervention.

Background: Increased left ventricular wall thickness is a hallmark of cardiac amyloidosis (CA). Several other disease states, including hypertrophic cardiomyopathy (HCM), share this common feature. Myocardial strain has emerged as a diagnostic and prognostic tool to differentiate causes of increased left ventricular wall thickness. We sought to determine if regional strain differences were present in CA when compared with HCM when indexed to wall thickness as well as adjusting for important factors such as ejection fraction (EF), age, sex, and hypertension., Methods: We performed a multicenter, retrospective analysis of 122 patients in 3 groups: CA (n=40), HCM (n=44), and controls (n=38). Using commercially available software, we determined peak systolic strain measurements in the base, mid, and apical segments in all 3 cardinal directions of radial strain, circumferential strain, and longitudinal strain. The regional strain was indexed to wall thickness to create a strain to wall thickness (STT) ratio. Analysis of Variance was performed to examine the association of each strain parameter with the disease group, adjusting for age, sex, hypertension, and EF. Multinomial logistic regression was performed to determine which combination of variables can potentially be used to best model the disease group., Results: Ratios of STT at all 3 levels were significantly different with respect to the cardinal directions of radial, circumferential, and longitudinal strain in a multivariable analysis adjusting for age, sex, and hypertension. Specifically, with respect to the basal segments, the STT ratio across CA, HCM, and normal were significantly different in radial (1.13±0.34 vs. 3.79±0.22 vs. 4.12±0.38; P <0.0001), circumferential (-0.79±0.10 vs. -1.62±0.07 vs. -2.25±0.11; P <0.0001), and longitudinal directions (-0.41±0.09 vs. -1.03±0.06 vs. -1.41±0.10; P <0.0001). When adjusting for age, sex, hypertension and EF, only the base was significantly different between the CA and HCM groups in the radial (1.49±0.37 vs. 3.53±0.24; P <0.0001), circumferential -1.04±0.10 vs. -1.44±0.06; P <0.005), and longitudinal (-0.55±0.10 vs -0.94±0.06; P =0.007) directions. Using multinomial logistic regression, the use of age, left ventricular EF, global longitudinal strain, and basal radial strain yielded a diagnostic model with an area under the receiver operating characteristic curve (AUC) of 0.98. A model excluding age, despite being likely an independent predictor in our cohort, yielded an overall AUC of 0.90. When excluding age, the overall AUC was 0.91 and specifically when discriminating CA from HCM was 0.95., Conclusions: Regional myocardial strain indexed to wall thickness with an STT ratio can differentiate between etiologies of increased left ventricular wall thickness. Differences in myocardial deformation may be independent of wall thickness. Differences in basal strain when indexed to wall thickness in all 3 cardinal directions between CA and HCM are independent of EF. Multinomial logistic regression analysis using strain parameters differentiates CA and HCM with excellent diagnostic accuracy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Chronic kidney disease (CKD) affects 37 million adults in the United States, and for patients with CKD, hypertension is a key risk factor for adverse outcomes, such as kidney failure, cardiovascular events, and death., Objective: To evaluate a computerized clinical decision support (CDS) system for the management of uncontrolled hypertension in patients with CKD., Design, Setting, and Participants: This multiclinic, randomized clinical trial randomized primary care practitioners (PCPs) at a primary care network, including 15 hospital-based, ambulatory, and community health center-based clinics, through a stratified, matched-pair randomization approach February 2021 to February 2022. All adult patients with a visit to a PCP in the last 2 years were eligible and those with evidence of CKD and hypertension were included., Intervention: The intervention consisted of a CDS system based on behavioral economic principles and human-centered design methods that delivered tailored, evidence-based recommendations, including initiation or titration of renin-angiotensin-aldosterone system inhibitors. The patients in the control group received usual care from PCPs with the CDS system operating in silent mode., Main Outcomes and Measures: The primary outcome was the change in mean systolic blood pressure (SBP) between baseline and 180 days compared between groups. The primary analysis was a repeated measures linear mixed model, using SBP at baseline, 90 days, and 180 days in an intention-to-treat repeated measures model to account for missing data. Secondary outcomes included blood pressure (BP) control and outcomes such as percentage of patients who received an action that aligned with the CDS recommendations., Results: The study included 174 PCPs and 2026 patients (mean [SD] age, 75.3 [0.3] years; 1223 [60.4%] female; mean [SD] SBP at baseline, 154.0 [14.3] mm Hg), with 87 PCPs and 1029 patients randomized to the intervention and 87 PCPs and 997 patients randomized to usual care. Overall, 1714 patients (84.6%) were treated for hypertension at baseline. There were 1623 patients (80.1%) with an SBP measurement at 180 days. From the linear mixed model, there was a statistically significant difference in mean SBP change in the intervention group compared with the usual care group (change, -14.6 [95% CI, -13.1 to -16.0] mm Hg vs -11.7 [-10.2 to -13.1] mm Hg; P = .005). There was no difference in the percentage of patients who achieved BP control in the intervention group compared with the control group (50.4% [95% CI, 46.5% to 54.3%] vs 47.1% [95% CI, 43.3% to 51.0%]). More patients received an action aligned with the CDS recommendations in the intervention group than in the usual care group (49.9% [95% CI, 45.1% to 54.8%] vs 34.6% [95% CI, 29.8% to 39.4%]; P < .001)., Conclusions and Relevance: These findings suggest that implementing this computerized CDS system could lead to improved management of uncontrolled hypertension and potentially improved clinical outcomes at the population level for patients with CKD., Trial Registration: ClinicalTrials.gov Identifier: NCT03679247.

Our objective is to use computed tomography angiography (CTA) and computed tomography perfusion (CTP) to identify the ischemic significance of myocardial bridging (MB). We also seek to determine the long-term prognostication of MB in the presence or absence of obstructive coronary artery disease (CAD). The CORE320, a prospective, multicenter study including 381 patients with known or suspected CAD clinically referred for invasive coronary angiography who underwent combined (CTA-CTP) and single-photon emission computed tomography before conventional coronary angiography. The incidence of MB was identified in 135 patients (35.4%) with 93.9% identified in the left anterior descending artery. MB were divided as partially encased versus fully encased. There was no difference in ischemia identified between partially encased MB and fully encased MB (37 [40%] vs 25 [35%], p = 0.54]. Ischemia was identified at similar rates in partially versus fully encased MB by single-photon emission computed tomography at (8 [9%] vs 8 [11%], p = 0.57] and CTP (34 [37%] vs 21 [30%], p = 0.33]. There was no difference in the primary outcome of 5-year outcome of combined incidence of myocardial infarction or death. The restricted mean survival time in patients with CTA with <50% stenosis with or without a MB was 4.906 years (95% confidence interval 4.759 to 5.000) and 4.891 years (95% confidence interval 4.718 to 5.000), respectively (p = 0.824). Cardiac computed tomography perfusion imaging can assess both anatomic and functional significance of myocardial bridging with diagnostic accuracy similar to current standard imaging. Furthermore, 5-year cardiovascular events were not different with the presence of MB in both obstructive and non-obstructive CAD., Competing Interests: Declaration of Competing Interest Dr. George is an employee at AstraZeneca. Dr. Vavere is an employee at AstraZeneca. Dr. Chen is an employee of the Division of Intramural Research, Department of Health and Human Services, National Heart, Lung, and Blood Institute, National Institutes of Health. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Endovascular embolization has emerged as an effective treatment for intractable epistaxis. This systematic review and meta-analysis aimed to calculate the rates of success, rebleeds, and complications and to identify the etiologies and complications of patients who undergo endovascular embolization., Methods: This systematic review and meta-analysis was conducted per the guidelines set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles were extracted from Scopus, PubMed, Web of Science, and Cochrane Central and were filtered by a systematic review process using Rayyan software. A random-effects model was used to quantify the rates success, rebleeds, and complications., Results: Forty-two studies were included, totaling 1660 patients. The pooled success rate was 89% (95% confidence interval [CI] 86%-92%) and the pooled rebleed rate was 19% (95% CI 16%-22%). The pooled minor complication rate was 18% (95% CI 11%-27%). The most common major complication was soft tissue necrosis followed by stroke. The most common minor complication was facial pain. No minor complications were reported to be permanent. Of the patients who failed initial embolization, 42% underwent repeat embolization and 34% underwent surgical arterial ligation., Conclusions: Endovascular embolization is an effective treatment for intractable epistaxis. The decision to perform embolization should be carefully weighed given the rare but significant major complications.

Background: Left bundle branch pacing (LBBP) is a developing method of native conduction pacing, but cases of injury to the septal perforator arteries during implantation have been reported. Knowing the distance between the His bundle and the first septal perforator artery can help operators implant LBBP leads more safely., Methods: Using previously performed coronary CT angiography (CCTA) studies, the distance between the His bundle and the first septal perforator was measured., Results: A total of 50 CCTA studies were included. The mean distance from the His bundle to the first septal perforator (His-SP) along the line connecting the His bundle to the RV apex (His-RV apex) was 27.17 ± 7.7 mm with a range of 13.0 to 44.7 mm. The distance was greater than 2.0 cm in 84% of patients. To standardize this distance among patients with varying cardiac structures, the ratio between the His-SP distance and the His-RV Apex distance was also measured. The mean His-SP:His-RV Apex was 0.302 and the median was 0.298. Eighty-six percent of patients had a ratio of greater than 0.20., Conclusion: Using this information, operators can aim to implant LBBP leads within 2.0 cm of the His bundle or 20% of the distance between the His bundle and the RV apex with minimal risk of causing vascular injury., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Chronic kidney disease (CKD) is common and associated with adverse clinical outcomes. Most care for early CKD is provided in primary care, including hypertension (HTN) management. Computerized clinical decision support (CDS) can improve the quality of care for CKD but can also cause alert fatigue for primary care physicians (PCPs). Computable phenotypes (CPs) are algorithms to identify disease populations using, for example, specific laboratory data criteria., Objectives: Our objective was to determine the feasibility of implementation of CDS alerts by developing CPs and estimating potential alert burden., Methods: We utilized clinical guidelines to develop a set of five CPs for patients with stage 3 to 4 CKD, uncontrolled HTN, and indications for initiation or titration of guideline-recommended antihypertensive agents. We then conducted an iterative data analytic process consisting of database queries, data validation, and subject matter expert discussion, to make iterative changes to the CPs. We estimated the potential alert burden to make final decisions about the scope of the CDS alerts. Specifically, the number of times that each alert could fire was limited to once per patient., Results: In our primary care network, there were 239,339 encounters for 105,992 primary care patients between April 1, 2018 and April 1, 2019. Of these patients, 9,081 (8.6%) had stage 3 and 4 CKD. Almost half of the CKD patients, 4,191 patients, also had uncontrolled HTN. The majority of CKD patients were female, elderly, white, and English-speaking. We estimated that 5,369 alerts would fire if alerts were triggered multiple times per patient, with a mean number of alerts shown to each PCP ranging from 0.07-to 0.17 alerts per week., Conclusion: Development of CPs and estimation of alert burden allows researchers to iteratively fine-tune CDS prior to implementation. This method of assessment can help organizations balance the tradeoff between standardization of care and alert fatigue., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: As cardiovascular computed tomography (CCT) practice evolves, the demand for specialists continues to increase. However, CCT training remains variable globally with limited contemporaneous data to understand this heterogeneity. We sought to understand the role of CCT globally and the training available to underpin its use., Methods: We performed two consecutive surveys of cardiology and radiology physicians, two years apart, utilizing the Society of Cardiovascular Computed Tomography (SCCT) website, weblinks, social media platforms, and meeting handouts to maximize our response rate. We compared United States (US)-based vs. international responses to understand global similarities and differences in practice and training in the surveys., Results: 235 respondents (37% trainees and 63% educators/non-trainees) initiated the first survey with 174 (74%) completing the core survey, with 205 providing their work location (114 US and 91 international). Eighty-four percent (92/110) of educator respondents stated a need for increased training opportunities to meet growing demand. Dedicated training fellowships are heterogenous, with limited access to structural heart imaging training, despite structural scanning being performed within institutions. The lack of a standardized curriculum was identified as the main obstacle to effective CCT learning, particularly in the US, with web-based learning platforms being the most popular option for improving access to CCT training. 148 trainees initiated the second survey with 107 (72%) completing the core components (51% North America, 49% international). Only 68% said they would be able to meet their required CCT education needs via their training program. Obstacles in obtaining CCT training again included a lack of a developed curriculum (51%), a lack of dedicated training time (35%), and a lack of local faculty expertise (31%). There was regional variability in access to CCT training, and, in contrast to the first survey, most (89%) felt 1:1 live review of cases with trained/expert reader was most useful for improving CCT training alongside formal curriculum/live lectures (72%)., Conclusions: There is a need to expand dedicated CCT training globally to meet the demand for complex CCT practice. Access to CCT education (didactic and 1:1 case-based teaching from expert faculty), implementation of recently published global training curricula, and increased teaching resources (web-based) as an adjunct to existing experiential learning opportunities, are all deemed necessary to address current educational shortfalls., Competing Interests: Declaration of competing interest The authors declare no relevant competing interests. N. Madan: None. D. J. Hur: None. M. P. Gannon: None. S. Gupta: None. J. R. Weir-McCall: None. C. Johns: None. A. Kumar: None. P. Nagpal: None. E. Fentanes: None. J. Lee: None. A. D. Choi: None. M. Ferencik: None. C. D. Maroules: None. T. C. Villines: None. E. D. Nicol: None., (Published by Elsevier Inc.)

Glutamine (Gln) was FDA-approved in 2017 to reduce acute sickle cell disease (SCD) pain and acute chest syndrome. However, typical pediatric patients with SCD exhibit moderate adherence, measured by a medication possession ratio <80%. This study examined Gln utilization in a "real-world" clinical setting to determine factors influencing medication adherence and to characterize the impact of an interdisciplinary team approach at an institution with specialty pharmacy services. A retrospective chart review identified 40 patients prescribed Gln by sickle cell specialists over a 2-year period and met selection criteria. Gln medication possession ratio for pediatric (72%) and adult (76%) patients were higher than other SCD medications. Pediatric patients (74%) demonstrated significantly lower first-attempt insurance approval rate compared with adult patients (95%) ( P =0.0026), suggesting an initial access barrier for pediatric patients. Pediatric patients demonstrated significantly higher number of medication fills (9.11 fills) compared with adult patients (3.86 fills) ( P =0.007), which suggests interdisciplinary collaboration may facilitate sustainable management of a new therapy. The majority of pediatric (89%) and adult (90%) patients reported high satisfaction with Gln ("excellent") with minor or no side effects. Multidisciplinary health care provider collaborations and tracking medication adherence metrics can help address barriers to care for SCD patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Primary care providers face challenges in recognizing and controlling hypertension in patients with chronic kidney disease (CKD). Clinical decision support (CDS) has the potential to aid clinicians in identifying patients who could benefit from medication changes. This study designed an alert to control hypertension in CKD patients using an iterative human-centered design process., Methods: In this study, we present a human-centered design process employing multiple methods for gathering user requirements and feedback on design and usability. Initially, we conducted contextual inquiry sessions to gather user requirements for the CDS. This was followed by group design sessions and one-on-one formative think-aloud sessions to validate requirements, obtain feedback on the design and layout, uncover usability issues, and validate changes., Results: This study included 20 participants. The contextual inquiry produced 10 user requirements which influenced the initial alert design. The group design sessions revealed issues related to several themes, including recommendations and clinical content that did not match providers' expectations and extraneous information on the alerts that did not provide value. Findings from the individual think-aloud sessions revealed that participants disagreed with some recommended clinical actions, requested additional information, and had concerns about the placement in their workflow. Following each step, iterative changes were made to the alert content and design., Discussion: This study showed that participation from users throughout the design process can lead to a better understanding of user requirements and optimal design, even within the constraints of an EHR alerting system. While raising awareness of design needs, it also revealed concerns related to workflow, understandability, and relevance., Conclusion: The human-centered design framework using multiple methods for CDS development informed the creation of an alert to assist in the treatment and recognition of hypertension in patients with CKD., (© 2022. The Author(s).)

Rationale & Objective: To design and implement clinical decision support incorporating a validated risk prediction estimate of kidney failure in primary care clinics and to evaluate the impact on stage-appropriate monitoring and referral., Study Design: Block-randomized, pragmatic clinical trial., Setting & Participants: Ten primary care clinics in the greater Boston area. Patients with stage 3-5 chronic kidney disease (CKD) were included. Patients were randomized within each primary care physician panel through a block randomization approach. The trial occurred between December 4, 2015, and December 3, 2016., Intervention: Point-of-care noninterruptive clinical decision support that delivered the 5-year kidney failure risk equation as well as recommendations for stage-appropriate monitoring and referral to nephrology., Outcomes: The primary outcome was as follows: Urine and serum laboratory monitoring test findings measured at one timepoint 6 months after the initial primary care visit and analyzed only in patients who had not undergone the recommended monitoring test in the preceding 12 months. The secondary outcome was nephrology referral in patients with a calculated kidney failure risk equation value of >10% measured at one timepoint 6 months after the initial primary care visit., Results: The clinical decision support application requested and processed 569,533 Continuity of Care Documents during the study period. Of these, 41,842 (7.3%) documents led to a diagnosis of stage 3, 4, or 5 CKD by the clinical decision support application. A total of 5,590 patients with stage 3, 4, or 5 CKD were randomized and included in the study. The link to the clinical decision support application was clicked 122 times by 57 primary care physicians. There was no association between the clinical decision support intervention and the primary outcome. There was a small but statistically significant difference in nephrology referral, with a higher rate of referral in the control arm., Limitations: Contamination within provider and clinic may have attenuated the impact of the intervention and may have biased the result toward null., Conclusions: The noninterruptive design of the clinical decision support was selected to prevent cognitive overload; however, the design led to a very low rate of use and ultimately did not improve stage-appropriate monitoring., Funding: Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award K23DK097187., Trial Registration: ClinicalTrials.gov Identifier: NCT02990897., (© 2022 The Authors.)

Introduction: The purpose of this study is to incorporate behavioural economic principles and user-centred design principles into a multicomponent intervention for the management of uncontrolled hypertension (HTN) in chronic kidney disease (CKD) in primary care., Methods and Analysis: This is a multicentre, pragmatic, controlled trial cluster-randomised at the clinician level at The Brigham and Women's Practice -Based Research Network of 15 practices. Of 220 total clinicians, 184 were eligible to be enrolled, and the remainder were excluded (residents and clinicians who see urgent care or walk-in patients); no clinicians opted out. The intervention consists of a clinical decision support system based in behavioural economic and user-centred design principles that will: (1) synthesise existing laboratory tests, medication orders and vital sign data; (2) increase recognition of CKD, (3) increase recognition of uncontrolled HTN in CKD patients and (4) deliver evidence-based CKD and HTN management recommendations. The primary endpoint is the change in mean systolic blood pressure between baseline and 6 months compared across arms. We will use the Reach Effectiveness Adoption Implementation Maintenance framework. At the conclusion of this study, we will have: (1) validated an intervention that combines laboratory tests, medication records and clinical information collected by electronic health records to recognise uncontrolled HTN in CKD patients and recommend a course of care, (2) tested the effectiveness of said intervention and (3) collected information about the implementation of the intervention that will aid in dissemination of the intervention to other practice settings., Ethics and Dissemination: The Human Subjects Institutional Review Board at Brigham and Women's Hospital provided an expedited review and approval for this study protocol, and a Data Safety Monitoring Board will ensure the ongoing safety of the trial., Trial Registration Number: NCT03679247., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Trivalent chromium has been proposed to be transported in vivo from the bloodstream to the tissues via endocytosis by transferrin (Tf), the major iron transport protein in the blood. While Cr(III) loss from the Tf/Tf receptor complex after acidification to pH 5.5 has recently been shown to be sufficiently rapid to be physiologically relevant, the released Cr(III) still must exit the endosome during the time of the endocytosis cycle (circa 15 min). Cr(III) binds too slowly to small ligands such as citrate or ascorbate, or even EDTA, for such complexes to form and be transported from the endosome, while no trivalent ion transporters are known. However, the apo form of the peptide low-molecular-weight chromium-binding substance (LMWCr) can remove Cr(III) from Cr(III) 2 -Tf at neutral pH, albeit slowly, and LMWCr is known to be transported from cells after binding Cr(III), although the transporter is not known. LMWCr subsequently carries Cr(III) to the bloodstream ultimately for removal from the body in the urine. The rate of binding of Cr(III) to apoLMWCr was significantly enhanced in the presence of the Tf/Tf receptor complex. These results suggest that apoLMWCr may function to bind Cr(III) released in the endosomes for ultimate removal from the body as part of a Cr(III) detoxification process., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Hypertrophic cardiomyopathy (HCM) has a variable clinical presentation due to the diversity of causative genetic mutations. Animal models allow in vivo study of genotypic expression through non-invasive imaging, pathologic sampling, and force analysis. This review focuses on the spontaneous and induced mutations in various animal models affecting mainly sarcomere proteins. The sarcomere is comprised of thick (myosin) filaments and related proteins including myosin heavy chain and myosin binding protein-C; thin (actin) filament proteins and their associated regulators including tropomyosin, troponin I, troponin C, and troponin T. The regulatory milieu including transcription factors and cell signaling also play a significant role. Animal models provide a layered approach of understanding beginning with the causative mutation as a foundation. The functional consequences of protein energy utilization and calcium sensitivity in vivo and ex vivo can be studied. Beyond pathophysiologic disruption of sarcomere function, these models demonstrate the clinical sequalae of diastolic dysfunction, heart failure, and arrhythmogenic death. Through this cascade of understanding the mutation followed by their functional significance, targeted therapies have been developed and are briefly discussed., (Copyright © 2019. Published by Elsevier Inc.)

Myocarditis encompasses both primary and secondary processes causing inflammation of the myocardium. Viral infections are a common secondary cause of myocarditis with important clinical relevance. Viral myocarditis has a varied clinical presentation, potentially resulting in significant morbidity and mortality. Acutely, systolic dysfunction and sudden cardiac death may ensue; chronically, myocarditis may result in a dilated cardiomyopathy requiring heart transplantation. Myocarditis is thought to be one of the most common causes of myocardial infarction with nonobstructive coronary arteries (MINOCA), with important consequences for cardiovascular outcomes. Patients with myocarditis are currently underdiagnosed. Cardiac MRI has evolved as the noninvasive test of choice, with cardiac MRI-specific diagnostic requirements defined in the Lake Louise Criteria (LLC). Detecting the presence of tissue edema, hyperemia, and necrosis in both acute and chronic stages form the foundation of the LLC. Cardiac MR for chronic myocarditis (greater than 8 weeks from symptom onset) has decreased sensitivity for diagnosis. Emerging sequences such as T 1 and T 2 parametric maps provide tissue characterization regarding inflammation without reliance on reference tissue, overcoming limitations of the LLC. Beyond diagnostic criteria, these imaging techniques have proven useful in further characterizing the diseased tissue, prognostication, and clinical decision-making. This review describes the utility and evolving use of cardiac MRI in clinical practice. Level of Evidence: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2018;47:1061-1071., (© 2019 International Society for Magnetic Resonance in Medicine.)

A left ventricular (LV) false tendon is a frequently visualized structure in echocardiography with unclear clinical significance. We present the case of a false tendon serving as a nidus for thrombus in a post-orthotopic heart transplantation patient. Three-dimensional transthoracic echocardiography (3DTTE) was utilized to visualize a LV mass and facilitate its identification as a thrombus as well as the surrounding structures. Using datasets from 3DTTE, the lack of ventricular wall attachment and circumferential formation of the thrombus around the false tendon was identified. Serial imaging demonstrated resolution of the thrombus with anticoagulation., (© 2018 Wiley Periodicals, Inc.)

A 75-year-old man with a history of mechanical aortic valve replacement with aortic conduit for severe aortic insufficiency underwent routine screening computed tomography evaluation revealing right coronary anastomosis endoleak and proximal aortic root pseudoaneurysm.

Uterine rupture in pregnancy is a rare and catastrophic complication with a high incidence of fetal and maternal morbidity. Very few cases have been reported in the literature., Case Presentation: A 28-year-old fifth gravid woman with a history of one caesarean section presented to our department at 39 weeks and 6 days gestation with complaints of headache, epigastric pain and nausea. Her blood pressure was elevated and there was proteinuria. Emergency caesarean section was performed in view of symptoms. Uterine rupture was found during the surgery. A live male infant was delivered in good condition. Postnatal recovery was unremarkable and the woman discharged on postoperative day 5., Conclusion: Rupture of the uterus can present in third trimester even before labour with minimal or no symptoms.

Objectives: This study assessed the impact of adjunct delivery techniques on the deployment success of distal protection filters in saphenous vein grafts (SVGs)., Background: Despite their proven clinical benefit, distal protection devices are underutilized in SVG interventions. Deployment of distal protection filters can be technically challenging in the presence of complex anatomy. Techniques that facilitate the delivery success of these devices could potentially improve clinical outcomes and promote greater use of distal protection., Methods: Outcomes of 105 consecutive SVG interventions with attempted use of a FilterWire distal protection device (Boston Scientific) were reviewed. In patients in whom filter delivery initially failed, the success of attempted redeployment using adjunct delivery techniques was assessed. Two strategies were utilized sequentially: (1) a 0.014" moderate-stiffness hydrophilic guidewire was placed first to function as a parallel buddy wire to support subsequent FilterWire crossing; and (2) if the buddy-wire approach failed, predilation with a 2.0 mm balloon at low pressure was performed followed by reattempted filter delivery., Results: The study population consisted of 80 men and 25 women aged 73 ± 10 years. Mean SVG age was 14 ± 6 years. Complex disease (American College of Cardiology/American Heart Association class B2 or C) was present in 92%. Initial delivery of the FilterWire was successful in 82/105 patients (78.1%). Of the 23 patients with initial failed delivery, 8 (35%) had successful deployment with a buddy wire alone, 7 (30%) had successful deployment with balloon predilation plus buddy wire, 4 (17%) had failed reattempt at deployment despite adjunct maneuvers, and in 4 (17%) no additional attempts at deployment were made at the operator's discretion. Deployment failure was reduced from 21.9% initially to 7.6% after use of adjunct delivery techniques (P<.01). No adverse events were observed with these measures., Conclusions: Deployment of distal protection devices can be technically difficult with complex SVG disease. Adjunct delivery techniques are important to optimize deployment success of distal protection filters during SVG intervention.

Objective: Commotio cordis, sudden death with chest impact, occurs clinically despite chest wall protectors worn in sports. In an experimental model of commotio cordis, commercially available chest wall protectors failed to prevent ventricular fibrillation (VF). The goal of the current investigation was to develop a chest wall protector effective in the prevention of commotio cordis., Design: In the Tufts experimental model of commotio cordis the ability of chest protectors to prevent VF was assessed. Impacts were delivered with a 40-mph lacrosse ball, timed to the vulnerable period for VF., Intervention: A chest wall protector or no chest wall protector (control) was randomly assigned to be placed over the chest. Four iterative series of 2 to 4 different chest wall material combinations were assessed. Materials included 3 different foams (Accelleron [Unequal Technologies, Glen Mills, PA], closed cell high density foam; Airilon [Unequal Technologies, Glen Mills, PA], closed cell low density soft foam; and an open cell memory foam) that were adhered to a layer of TriDur (Unequal Technologies, Glen Mills, PA), a flexible elastomeric coated aramid that was bonded to a semirigid polypropylene polymer (ImpacShield, Unequal Technologies, Glen Mills, PA)., Main Outcome Measure: Induction of VF by chest wall impact was the primary outcome., Results: Of 80 impacts without chest protectors, 43 (54%) resulted in VF. Ventricular fibrillation with chest protectors ranged from a high of 60% to a low of 5%. Of 12 chest protectors assessed, only 3 significantly lowered the risk of VF compared with impacts without chest protectors. These 3 chest protectors were combinations of Accelleron, Airilon, TriDur, and ImpacShield of different thicknesses. Protection increased linearly with the thicker combinations., Conclusions: Effective protection against VF with chest wall protection can be achieved in an experimental model of commotio cordis., Clinical Relevance: Chest protector designs incorporating these novel materials will likely be effective in the prevention of commotio cordis on the playing field., Competing Interests: The authors report no conflicts of interest.

We hypothesized that evolution of salivary gland secretory proteome has been important in adaptation to insectivory, the most common dietary strategy among Chiroptera. A submandibular salivary gland (SMG) transcriptome was sequenced for the little brown bat, Myotis lucifugus. The likely secretory proteome of 23 genes included seven (RETNLB, PSAP, CLU, APOE, LCN2, C3, CEL) related to M. lucifugus insectivorous diet and metabolism. Six of the secretory proteins probably are endocrine, whereas one (CEL) most likely is exocrine. The encoded proteins are associated with lipid hydrolysis, regulation of lipid metabolism, lipid transport, and insulin resistance. They are capable of processing exogenous lipids for flight metabolism while foraging. Salivary carboxyl ester lipase (CEL) is thought to hydrolyze insect lipophorins, which probably are absorbed across the gastric mucosa during feeding. The other six proteins are predicted either to maintain these lipids at high blood concentrations or to facilitate transport and uptake by flight muscles. Expression of these seven genes and coordinated secretion from a single organ is novel to this insectivorous bat, and apparently has evolved through instances of gene duplication, gene recruitment, and nucleotide selection. Four of the recruited genes are single-copy in the Myotis genome, whereas three have undergone duplication(s) with two of these genes exhibiting evolutionary 'bursts' of duplication resulting in multiple paralogs. Evidence for episodic directional selection was found for six of seven genes, reinforcing the conclusion that the recruited genes have important roles in adaptation to insectivory and the metabolic demands of flight. Intragenic frequencies of mobile- element-like sequences differed from frequencies in the whole M. lucifugus genome. Differences among recruited genes imply separate evolutionary trajectories and that adaptation was not a single, coordinated event.

Background: The present paper describes the implementation of a novel, web-based, comprehensive national information hub for trainees in obstetrics and gynecology in Ireland. This was a unique development in the context of an entire medical specialty and was aligned with the communication strategy of the governing professional body. To date, trainee doctors working in Ireland undergo an incoherent and inconsistent new-staff induction and handover. In the healthcare setting, staff integration can have a major impact on the quality of patient care., Methods: A free wiki software platform (PBworks) was used for the website, and freely available software (Google Analytics) was used to determine user interaction and level of engagement., Results: In the first year, 442 user visits were recorded. The average duration of site visits was 4 minutes 39 seconds, which compared favorably with the 4-minute duration for visits to Wikipedia., Conclusion: The project was successful as a proof concept and in practice. Other medical faculties have expressed an interest in adopting the concept and developing it for their trainees. The concept is widely applicable to other countries, with the negligible cost relevant to resource-poor areas., (Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Tumor necrosis factor (TNF)-alpha inhibitors and other biologic response modifiers (BRMs) are frequently used to treat a variety of inflammatory diseases. Use of these agents may increase risk of serious infections, malignancies, and other complications such as worsening symptoms of heart failure or demyelinating disease. Because of these risks, a baseline assessment and routine monitoring have been recommended, but standardized guidelines for monitoring have yet to be established., Objective: To measure the compliance with the recommended safety monitoring in the Clinical Care Guidelines for BRMs at the University of Illinois Hospitals and Health Sciences System (UI Health)., Methods: The Clinical Care Guidelines for BRMs was developed by a committee of pharmacists, nurses, and physicians based on an assessment of published literature and medication labeling. The guidelines included recommendations for safety monitoring prior to BRM therapy, such as the tuberculosis (TB) test, Hepatitis B surface Antigen (HBsAg) test, liver function test (LFT), complete blood count (CBC), up-to-date vaccinations, risk assessment for cancer, pregnancy testing, monitoring for contraindications with concomitant medications, concomitant disease state risk assessment, and patient education. The guidelines were introduced to UI Health in February 2012 by a systemwide email and by in-services given by the health system's Specialty Pharmacy Service. In-services were given in the clinics known to generate large numbers of BRM orders (e.g., gastroenterology and rheumatology) and at the outpatient center for infused therapies. The purpose of the in-services was to introduce providers to the guidelines and encourage their compliance. To ensure that guideline requirements were met when BRMs were ordered, a process was established to identify BRM orders, assess the orders for compliance with 4 of the safety monitoring tests from the guidelines (TB, HBsAg, LFT, and CBC), and make interventions. When necessary, Specialty Pharmacy Services coordinated with the pharmacists and other providers in the clinic to order lab tests and ensure they were completed prior to the start of therapy. Feedback was provided during the study to proactively improve compliance with the guidelines. After completion of the study, a report containing outpatient prescription orders for BRMs (abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, and tocilizumab) from August 2011 through July 2012 was generated from the electronic medical record. Retrospective analyses of completion of safety monitoring were conducted for patients administered BRM treatment. Completion rates were compared before and after implementation of guidelines in February 2012. Completion was considered to have occurred when all 4 safety monitoring tests had been conducted -TB (unless known to be positive from a previous test), HBsAg, LFT, and CBC. Completion data from August 2011 through January 2012 were before the guidelines were implemented, and data from February 2012 through July 2012 were after the guidelines. Chi square analyses were performed on completion frequencies in the patients before and after the guidelines were implemented., Results: Of the 320 unique patient BRM orders evaluated in this study, 195 (61%) were generated in the Rheumatology clinic, 99 (31%) in the Gastroenterology clinic, 21 (6.5%) in the Dermatology clinic, and 5 (1.5%) in the Transplant clinic. Before the guidelines were implemented, 54 ( 31%) of 173 patient orders complied with the safety monitoring by having all 4 clinical tests performed at the appropriate time points. After guideline implementation, 88 (60%) of 147 patient orders were compliant and had all 4 clinical tests conducted, which represents a statistically significant improvement in the rate of compliance (Pearson chi square = 26.43, degrees of freedom (df) = 1, P  less than  0.0001). This significant improvement in compliance rates after guideline implementation was observed in both the new patient group and the patients with continuing prescription orders/treatment changes. There was also an improvement in patients whose prescriptions were dispensed by UI Health and to a lesser degree those whose prescriptions were dispensed by an outside pharmacy. When the new patient group was analyzed separately (n = 92), 50 patients were treated before the guidelines were implemented, and 42 patients were treated after the guidelines were implemented. Compliance rates with safety monitoring in these 2 groups were 52% pre-implementation and 83% post-implementation, which represented a statistically significant improvement in compliance (Pearson chi square = 10.03, df=1, P = 0.0015). Similar results were observed in the second patient subgroup with continuing prescription orders/treatment change (n = 228). A total of 123 patients were treated before the guidelines were implemented, and 105 were treated after the guidelines were implemented. Compliance rates were 23% pre-implementation compared with 50% post-implementation, which represented a statistically significant improvement in compliance (Pearson chi square = 18.99, df = 1, P  less than  0.0001)., Conclusion: Given the widespread and long-term use of BRMs, safety monitoring and management should be an important part of a comprehensive medication management program for their use. A coordinated effort may have a significant impact on compliance with safety monitoring guidelines.

Escherichia coli dihydrofolate reductase (ecDHFR) has one surface cysteine, C152, located opposite and distal to the active site. Here, we show that the enzyme spontaneously assembles on an ultraflat gold surface as a homogeneous, covalently bound monolayer. Surprisingly, the activity of the gold-immobilized ecDHFR as measured by radiographic analysis was found to be similar to that of the free enzyme in solution. Molecular recognition force spectroscopy was used to study the dissociation forces involved in the rupture of AFM probe-tethered methotrexate (MTX, a tight-binding inhibitor of DHFR) from the gold-immobilized enzyme. Treatment of the ecDHFR monolayer with free MTX diminished the interaction of the functionalized tip with the surface, suggesting that the interaction was indeed active-site specific. These findings demonstrate the viability of a simple and direct enzymatic surface-functionalization without the use of spacers, thus, opening the door to further applications in the area of biomacromolecular force spectroscopy.

We have examined 46 tetramethylrosamine/rhodamine derivatives with structural diversity in the heteroatom of the xanthylium core, the amino substituents of the 3- and 6-positions, and the alkyl, aryl, or heteroaryl group at the 9-substituent. These compounds were examined for affinity and ATPase stimulation in isolated MDR3 CL P-gp and human P-gp-His(10), for their ability to promote uptake of calcein AM and vinblastine in multidrug-resistant MDCKII-MDR1 cells, and for transport in monolayers of MDCKII-MDR1 cells. Thioamide 31-S gave K(M) of 0.087 microM in human P-gp. Small changes in structure among this set of compounds affected affinity as well as transport rate (or flux) even though all derivatives examined were substrates for P-gp. With isolated protein, tertiary amide groups dictate high affinity and high stimulation while tertiary thioamide groups give high affinity and inhibition of ATPase activity. In MDCKII-MDR1 cells, the tertiary thioamide-containing derivatives promote uptake of calcein AM and have very slow passive, absorptive, and secretory rates of transport relative to transport rates for tertiary amide-containing derivatives. Thioamide 31-S promoted uptake of calcein AM and inhibited efflux of vinblastine with IC(50)'s of approximately 2 microM in MDCKII-MDR1 cells.

The DNA binding efficacy and preferred mode of binding of a series of rhodamine-related chalcogenoxanthylium dyes was investigated by isothermal titration calorimetry (ITC) using ctDNA, [poly(dCdG)](2) and [poly(dAdT)](2), and by a topoisomerase I DNA unwinding (Topo I) assay. The dyes of this study showed tight binding to ctDNA with binding constants, K(b), on the order of 10(6)-10(7)M(-1). The ITC and Topo I assay studies suggested that the 9-substituent has a strong impact on binding modes ranging from an apparent preference for intercalation with a 9-2-thienyl substituent (similar binding to [poly(dCdG)](2) and [poly(dAdT)](2), re-supercoiling of DNA in the Topo I assay at <10(-5)M dye), to mixed binding modes with 9-phenyl derivatives (2- to 3-fold preference for binding to [poly(dAdT)](2), re-supercoiling of DNA in the Topo I assay at approximately 2 x 10(-5)M dye), to minor groove binding in a 9-(2-thienyl-5-diethylcarboxamide) derivative (strong preference for binding to [poly(dAdT)](2), did not show complete re-supercoiling in the Topo I assay). No binding to ctDNA was observed in one derivative with a 9-(3-thienyl-2-diethylcarboxamide) substituent, which cannot be co-planar with the xanthylium core. In series of dyes where the chalcogen atom was varied, the selenoxanthylium derivatives had 2- to 3-fold higher values of K(b) than the corresponding xanthylium, thioxanthylium, or telluroxanthylium derivatives, which all showed comparable values of K(b). The chalcogen atom appeared to have little influence on binding mode.

The multidrug efflux pump P-glycoprotein (Pgp) couples drug transport to ATP hydrolysis. Previously, using a synthetic library of tetramethylrosamine ( TMR) analogues, we observed significant variation in ATPase stimulation ( V m (D)). Concentrations required for half-maximal ATPase stimulation ( K m (D)) correlated with ATP hydrolysis transition-state stabilization and ATP occlusion (EC 50 (D)) at a single site. Herein, we characterize several TMR analogues that elicit modest turnover ( k cat

Aim: The aim of our study was to evaluate the understanding of lower urinary tract symptom (LUTS) terminology used by patients., Materials and Methods: Women attending urodynamic clinics in United Kingdom, Australia, and Italy were asked to complete a questionnaire testing the women's understanding of stress urinary incontinence, urge urinary incontinence, frequency, urgency, nocturia, and hesitancy. Five possible explanations for the meaning of each symptom were given., Results: A total of 138 consecutive women were prospectively recruited. The terms of daytime frequency, nocturia, urgency, urge urinary incontinence, stress urinary incontinence, and hesitancy were defined correctly, according to the International Continence Society terminology, only by 33% (45/138), 44% (61/138), 46% (64/138), 39% (54/138), 37% (51/138), and 41% (57/138) of women, respectively. Over 20% of women were unsure about the meaning of each symptom. We did not find any statistical difference between the three groups in determining the correct definition (P = 0.5)., Conclusions: Our findings showed that most women do not know the correct meaning of LUTS terminology currently used by physicians.

2,4-Bis(4-dimethylaminophenyl)-6-alkylthiopyrylium and selenopyrylium dyes are essentially nonfluorescent (phi F < 0.001) and are poor generators of singlet oxygen in aqueous solution. However, upon complexation to calf thymus DNA, quantum yields for both fluorescence and generation of singlet oxygen increased dramatically. Irradiation of the dye-DNA complexes produced strand breaks in the DNA. The photodamage is not observed in the absence of oxygen and is suppressed by the addition of the singlet oxygen quencher imidazole. The inactivation of the pseudo-rabies virus upon treatment of oxygenated leukodepleted 20% hematocrit red blood cell suspensions with the chalcogenopyrylium dyes and light followed the same trend observed with quantum yields for the generation of singlet oxygen in the dye-DNA complexes.

Deprotonation and lithium-bromine exchange in 5- or 3-bromothiophene-2-carboxylic acids with t-BuLi form the corresponding dianion, which reacts highly regioselectively in the presence of 0.25 equiv of tetramethyl-1,2-ethylenediamine with 3,6-bis(dimethylamino) chalcogenoxanthones to give S- and Se-containing rhodamines. Quenching studies with D2O indicate that an extra equivalent of t-BuLi is not necessary in these reactions. Deprotonation is faster than metal-halogen exchange with the bromothiophene-2-carboxylic acids using t-BuLi.

9-formyljulolidine was oxidized via a microwave-assisted Willgerodt-Kindler reaction to the N-piperidine or N-morpholine julolidine-9-thioamide. 9-formyl-1,1,7,7-tetramethyljulolidine gave the corresponding N-piperidine tetramethyljulolidine-9-thioamide. The thioamides were converted to the corresponding carboxamides with trifluoroacetic anhydride. The amide group directed ortho-metalation in the julolidine system, but not in the tetramethyljulolidine system. The resulting anion was captured by dichalcogenide electrophiles. The resulting products were converted to chalcogenoxanthones with phosphorus oxychloride and triethylamine (POCl3/Et3N).

The multidrug resistance efflux pump P-glycoprotein (Pgp) couples drug export to ATP binding and hydrolysis. Details regarding drug trajectory, as well as the molecular basis for coupling, remain unknown. Nearly all drugs exported by Pgp have been assayed for competitive behavior with rhodamine123 transport at a canonical "R" drug binding site. Tetramethylrosamine (TMR) displays a relatively high affinity for Pgp when compared to other rhodamines. Here, we present the construction and characterization of a library of compounds based upon the TMR scaffold and use this set to assess the determinants of drug binding to the "R" site of Pgp. This set contained modifications in (1) the number, location, and conformational mobility of hydrogen-bond acceptors; (2) the heteroatom in the xanthylium core; and (3) the size of the substituent in the 9-position of the xanthylium core. Relative specificity for coupling to the distal ATP catalytic site was assessed by ATPase stimulation. We found marked ( approximately 1000-fold) variation in the ATPase specificity constant within the library of TMR analogues. Using established methods involving ADP-Vi trapping by wild-type Pgp and ATP binding by catalytic carboxylate mutant Pgp, these effects can be extended to ATP hydrolysis transition-state stabilization and ATP occlusion at a single site. These data support the idea that drugs trigger the engagement of ATP catalytic site residues necessary for hydrolysis. Further, the nature of the drug binding site and coupling mechanism may be dissected by variation of a drug-like scaffold. These studies may facilitate development of novel competitive inhibitors at the "R" drug site.

Although ambulatory hysteroscopy is well established in dedicated centres, there is a delay in its general implementation. One reason for this may be the lack of consensus regarding a protocol for analgesia and anaesthesia in ambulatory hysteroscopy. This review looks at the various methods in use. These include the paracervical or intracervical injection of anaesthetic to establish a block. Topical anaesthetic may be applied to the surface of the endometrium in the uterine cavity or to the cervix. Oral analgesia is also used. A vaginoscopic approach to the uterine cavity without any anaesthesia is also becoming popular. Finally, combinations of the above methods have been employed for hysteroscopic surgical procedures, including the newer generation of endometrial ablation methods.

Between April and October 1997, 689 bats representing seven species were captured at Pennsylvania's Canoe Creek State Park. Each bat was sampled for ectoparasitic arthropods, and four species were collected from 13.2% of the host individuals. Ectoparasites include the bat flea Myodopsylla insignis (Rothschild), the wing mite Spinturnix americanus (Banks), the bed bug Cimex adjunctus Barber, and the soft tick Ornithodoros kelleyi Cooley & Kohls. Prevalence, relative density, and mean intensity were calculated for ectoparasites of Myotis lucifugus (Le Conte), which harbored all four ectoparasite species and was the most commonly captured host. Patterns of ectoparasite associations were examined with respect to host sex and habitat (roost characteristics). Female M. lucifugus hosted higher densities of ectoparasites than did males. Moreover, relative densities of ectoparasites from M. lucifugus were dependent on the proximate roost; hosts captured near Bat Church were more heavily parasitized than those captured near Hartman Mine. Two other bat species were infested with at least one ectoparasite, but sample sizes were too small to analyze statistically. These bat species included Myotis septentrionalis (Trouessart), harboring M. insignis, S. americanus, and O. kelleyi, and Eptesicus fuscus (Beauvois), which harbored M. insignis and O. kelleyi.

Objective: To explore the relation between pre-operative psychiatric morbidity, menstrual blood loss and psychiatric outcome in women receiving endometrial ablation for heavy periods., Design: A prospective cohort study., Setting: The menorrhagia clinic at Leeds General Infirmary., Population: One hundred and twenty consecutive women referred to the Clinic for endometrial ablation., Methods: Psychiatric interview and actual menstrual blood loss measurements at presentation pre-operatively and one year post endometrial ablation., Main Outcome Measure: Psychiatric status using the semi-structured interview, Present State Examination, with measurement of menstrual blood loss., Results: Endometrial ablation was performed on 92 women. Of the 87 women evaluated 51 (59%) had clinically significant psychiatric symptoms, mainly depression and anxiety. Psychiatric morbidity fell to 21.8% at one year after endometrial ablation. Women with the best psychiatric outcome (6% post-operative psychiatric morbidity) were those with genuine menorrhagia (> or =80 mL) and low psychiatric morbidity pre-operatively. Those who fared worst (39% post-operative psychiatric morbidity) were women with high pre-operative psychiatric morbidity and low menstrual blood loss. Of seven women with very low losses [mean 19 mL (SD 17)] who did not proceed to surgery after counselling, six (86%) had significant psychiatric morbidity., Conclusions: Pre-operative psychiatric status and menstrual blood loss are predictors of outcome of surgery for women with reported heavy periods.