Racial differences in triage assessment at rural vs urban Maine emergency departments.

Data continue to accumulate demonstrating that those belonging to racialized groups face implicit bias in the emergency care delivery system across many indices, including triage assessment. The Emergency Severity Index (ESI) was developed and widely implemented across the US to improve the objectivity of triage assessment and prioritization of care delivery; however, research continues to support the presence of subjective bias in triage assessment. We sought to assess the relationship between perceived race and/or need for translator and assigned ESI score and whether this was impacted by hospital geography. We performed retrospective EMR-based review of patients presenting to urban and rural emergency departments of a health system in Maine with one of the top ten most common chief complaints (CC) across a 5-year period, excluding psychiatric CCs. We used multivariable regression to analyze the relationships between perceived race, need for translator, and gender with ESI score, wait time, and hallway bed assignments. We found that patients perceived as non-white were more likely to receive lower acuity ESI scores and have longer wait times as compared to patients perceived as white. Patients perceived as female were more likely to receive lower acuity scores and wait longer to be seen than patients perceived as male. The need for an interpreter was associated with increased wait times but not significantly associated with ESI score. After stratification by hospital geography, evidence of subjective bias was limited to urban emergency departments and was not evident in rural emergency departments. Further investigation of subjective bias in emergency departments in Maine, particularly in urban settings, is warranted.

Resident Attitudes Toward Performing Pelvic Examinations in the Emergency Department.

Mounting evidence suggests that emergency physicians tend to avoid patients with gynecologic chief complaints, and that avoidance may be higher for male physicians compared to females. One underlying reason could be discomfort with performing pelvic examinations. The goal of this study was to assess whether male residents report greater discomfort with pelvic examinations than females. We performed a cross-sectional, Institutional Review Board-approved survey of residents at 6 academic emergency medicine programs. Of 100 residents who completed the survey, 63 self-identified as male, 36 female, and one selected "prefer not to say" and was excluded. Responses were compared between male and females using chi-square tests. In secondary analysis, t-tests were used to compare preferences for various chief complaints. Self-reported comfort with pelvic examinations did not differ significantly between males and females (p = 0.4249). Barriers for male respondents in performing pelvic examinations included lack of training, general dislike, and concern the patient would prefer female providers. Male residents had a statistically significant higher aversion ranking towards patients with vaginal bleeding than female residents (mean difference = 0.48, confidence interval = 0.11-0.87). Aversion ranking was the same between males and females on other chief complaints. There is a gender disparity among male and female residents in attitudes towards patients with vaginal bleeding. However, the results from this study do not demonstrate a significant difference in self-reported comfort amongst male and female residents in performing pelvic examinations. This disparity may be driven by other barriers, including self-reported lack of training and concern about patients' physician gender preferences.

Scheduling practices for pregnant emergency medicine residents.

Background: Night shift work is associated with adverse pathophysiologic effects on maternal and fetal well-being. Although emergency medicine (EM) residents work frequent night shifts, there is no existing guidance for residency program directors (PDs) regarding scheduling pregnant residents. Our study assessed scheduling practices for pregnant EM residents, differences based on program and PD characteristics, barriers and attitudes toward implementing a formal scheduling policy, and PDs' awareness of literature describing adverse effects of night shifts on maternal-fetal outcomes. Methods: We conducted an anonymous, web-based survey of U.S. EM residencies (N = 276). Quantitative data were summarized; chi-square analysis and logistic regression were used to assess relationships between program and PD characteristics and schedule accommodations. Qualitative description was used to analyze an open-ended question, organizing findings into major and minor themes. Results: Of the 167 completed surveys (response rate 61%), 67% of programs reported no formal policy for scheduling pregnant residents but made adjustments on an individual basis including block changes (85%), decreased (46%) or no night shifts (34%), and working shifts earlier in pregnancy to cover later shifts (20%). Barriers to adjustments included staffing constraints (60%), equity concerns (45%), or impact on wellness (41%) among all residents and privacy (28%). PDs endorsed scheduling adjustments as important (mean 8.1, 0-10 scale) and reported guidance from graduate medical education governance would be useful (60%). Larger program size, but not PD gender or proportion of female residents, was associated with an increased likelihood of scheduling modifications. Twenty-five percent of PDs reported little knowledge of literature regarding night shift work and pregnancy. Qualitative themes supported quantitative findings. Conclusions: Most EM residency programs do not have formal scheduling policies for pregnant residents, but most PDs support making adjustments and do so informally. More education and guidance for PDs are needed to promote the development of formal policies.

A Case Report of a Normal Pregnancy in a Bicornuate Uterus Through In Vitro Fertilization.

The case report has been done to examine the possibility of normal pregnancy achieved in the case of a rare congenital anomaly, the bicornuate uterus. A bicornuate uterus is a very rare congenital anomaly of the uterus, which falls in the class 4 category according to the classification of Mullerian duct anomalies given by the American Society of Reproductive Medicine and is associated with several obstetrics complications like malpresentation, recurrent abortions, and growth restrictions. However, to have a normal pregnancy in a bicornuate uterus, close antenatal monitoring is required, and, depending on the individual, surgical unification can be done. A 30-year-old woman with G3A2 with 34.3 weeks of gestational age with in vitro fertilization (IVF) conception came with cervical stitch in situ and oligohydramnios with liquor index 7 for safe confinement. At the time of admission, amenorrhea was present for nine months. Ultrasound at 33 weeks three days showed a single uterine live fetus weighing about 2187 grams. The interpretation of the color Doppler was also normal. Fetal heart sound was heard in the Doppler. She was operated on at 36 weeks as an emergency lower-section cesarean section procedure. The indication was that it was an IVF baby, and the female had presented with oligohydramnios on performing investigations. The patient was counseled accordingly and discharged on 22 February 2022. She was advised to come back after 15 days or SOS at the time of emergency. All the measures were suggested, including adequate rest, plenty of fluids, and a good protein diet. Most cases of the bicornuate uterus do not present with any symptoms, i.e., they are asymptomatic and can be detected during routine evaluation of the patient. However, some patients can also have symptoms like menstrual problems such as dysmenorrhea and menorrhagia. Also, along with this anomaly, associated anomalies may be present, including agenesis of the kidney and ureter. The first and foremost investigation to be done is ultrasonography, which tells about the diagnosis of the bicornuate uterus. Magnetic resonance imaging is the gold standard test for its diagnosis. However, the diagnosis in the case of asymptomatic patients is relatively tricky and requires aggressive prenatal monitoring and needs to be kept in observation to make the pregnancy successful.

Time on shift in the emergency department and decision to prescribe opioids to patients without chronic opioid use.

OBJECTIVE: To study the effect of time on shift on the opioid prescribing practices of emergency physicians among patients without chronic opioid use. METHODS: We analyzed pain-related visits for five painful conditions from 2010 to 2017 at a single academic hospital in Boston. Visits were categorized according to national guidelines as conditions for which opioids are "sometimes indicated" (fracture and renal colic) or "usually not indicated" (headache, low back pain, and fibromyalgia). Using conditional logistic regression with fixed effects for clinicians, we estimated the probability of opioid prescribing for pain-related visits as a function of shift hour at discharge, time of day, and patient-level confounders (age, sex, and pain score). RESULTS: Among 16,115 visits for which opioids were sometimes indicated, opioid prescribing increased over the course of a shift (28% in the first hour compared with 40% in the last hour; adjusted odds ratio, 1.06; 95% confidence interval, 1.02-1.10; adjusted P-trend <0.01). However, among visits for which opioids are usually not indicated, relative to the first hour, opioid prescriptions progressively fell (40% in the first hour compared with 23% in the last hour; adjusted odds ratio, 0.93; 95% confidence interval, 0.91-0.96; adjusted P-trend <0.01). CONCLUSION: As shift hour progressed, emergency physicians became more likely to prescribe opioids for conditions that are sometimes indicated, and less likely to prescribe opioids for nonindicated conditions. Our study suggests that clinical decision making in the emergency department can be substantially influenced by external factors such as clinician shift hour.

Design of placebo-controlled randomized trials of anticancer agents: Ethical considerations based on a review of published trials.

BACKGROUND: Limited information exists about the design of placebo-controlled cancer trials. Through a systematic review of trials published in 2013, we describe placebo use in randomized trials testing anticancer agents and analyze strategies that increase exposure to the experimental regimen. METHODS: Trials were classified as add-on (placebo in combination with standard treatment) or placebo-only. Strategies to allow more than half of the participants to receive the experimental regimen were reviewed. The risk-benefit ratio of receiving the experimental agent was considered favorable if the difference in primary outcome was significant (p ≤ 0.05), neutral if there was no significant difference in the primary outcome and the experimental agent did not add substantial toxicity, and unfavorable otherwise. RESULTS: Eighty trials were included (32,694 participants). Most trials were add-on (69%). The risk-benefit outcome was favorable, neutral, and unfavorable to the experimental agent in 52%, 32%, and 16% of placebo-only trials and 25%, 53%, and 22%, respectively, of add-on trials. Four strategies increased exposure to the experimental regimen: one-way crossover (23%), uneven randomization (21%), three-arms (13%), and randomized discontinuation design (4%); these strategies were used more often in placebo-only trials. CONCLUSION: A minority of participants received placebo alone and strategies to increase experimental exposure were used commonly. Fewer than half of the studies had favorable outcomes, thus defending the use of placebo controls, when there is no established treatment. Strategies that increase patient exposure to experimental agents rather than placebo may expose them to non-beneficial, sometimes toxic, experimental agents.

Prediction of patient disposition: comparison of computer and human approaches and a proposed synthesis.

OBJECTIVE: To compare the accuracy of computer versus physician predictions of hospitalization and to explore the potential synergies of hybrid physician-computer models. MATERIALS AND METHODS: A single-center prospective observational study in a tertiary pediatric hospital in Boston, Massachusetts, United States. Nine emergency department (ED) attending physicians participated in the study. Physicians predicted the likelihood of admission for patients in the ED whose hospitalization disposition had not yet been decided. In parallel, a random-forest computer model was developed to predict hospitalizations from the ED, based on data available within the first hour of the ED encounter. The model was tested on the same cohort of patients evaluated by the participating physicians. RESULTS: 198 pediatric patients were considered for inclusion. Six patients were excluded due to incomplete or erroneous physician forms. Of the 192 included patients, 54 (28%) were admitted and 138 (72%) were discharged. The positive predictive value for the prediction of admission was 66% for the clinicians, 73% for the computer model, and 86% for a hybrid model combining the two. To predict admission, physicians relied more heavily on the clinical appearance of the patient, while the computer model relied more heavily on technical data-driven features, such as the rate of prior admissions or distance traveled to hospital. DISCUSSION: Computer-generated predictions of patient disposition were more accurate than clinician-generated predictions. A hybrid prediction model improved accuracy over both individual predictions, highlighting the complementary and synergistic effects of both approaches. CONCLUSION: The integration of computer and clinician predictions can yield improved predictive performance.

Association of resident characteristics with patterns of patient self-assignment.

OBJECTIVE: We hypothesized that resident characteristics impact patterns of patient self-assignment in the emergency department (ED). Our goal was to determine if male residents would be less likely than their female colleagues to see patients with sensitive (e.g. breast-related or gynecologic) chief complaints (CCs). We also investigated whether resident specialty was associated with preferentially choosing patients with more familiar chief complaints. METHODS: We performed a retrospective cross-sectional study at a tertiary academic medical center using data from all adult patients presenting to the ED between 2010 and 2019 with one of six CC categories (vaginal bleeding, breast-related concerns, male genitourinary [GU] concerns, gastrointestinal bleeding, epistaxis, and laceration). These CCs were chosen as they each require either an invasive medical exam or procedure, and cannot easily be evaluated with an exam in a hallway bed. We used logistic regression to assess the likelihood of being treated by a male resident compared to a female resident for each CC, adjusting for candidate variables of patient age, race, primary language, ESI score, bed location, time of day, day of week, calendar month, and resident specialty. We also similarly analyzed patterns of patient self-assignment according to resident specialty. RESULTS: Male residents were significantly less likely than female residents to treat patients with breast-related CCs (adjusted OR 0.67, 95% CI 0.54-0.83, p < 0.001) or vaginal bleeding (adjusted OR 0.73, 95% CI 0.63-0.84, p < 0.001, reference group: epistaxis). Off-service residents were more likely to assign themselves to familiar chief complaints, for example surgery residents were more likely to see patients with lacerations (adjusted OR 2.11, 95% CI 1.71-2.61, p < 0.001) and OB/GYN residents were less likely to see patients with male GU concerns (adjusted OR 0.21, 95% CI 0.05-0.85, p = 0.029), compared to emergency medicine residents. CONCLUSION: In a single facility, resident characteristics were associated with preferential patient self-assignment. Further work is necessary to determine the underlying reasons for patient avoidance, and to create work environments in which preferentially choosing patients is discouraged.

Effect of Uncomplicated Cataract Surgery on Central Macular Thickness in Diabetic and Non-diabetic Subjects.

PURPOSE: To assess the quantitative changes of macula in diabetic and non-diabetic eyes after uncomplicated cataract surgery. METHODS: In this prospective interventional study being performed in a tertiary healthcare hospital, a total of 660 eyes were divided into two groups. Group 1 included 330 eyes from healthy subjects and group 2 included 330 eyes from well-controlled diabetic subjects with no diabetic retinopathy planned for phacoemulsification with foldable IOL implantation by the same surgeon under similar settings. Optical Coherence Tomography (Heidelberg Spectralis SD-OCT) was used to assess preoperative and postoperative central macular thickness (CMT) at weeks 1 and 6. RESULTS: The mean CMT in group 1 preoperatively, at postoperative week 1, and at post-operative week 6 was 257.03 ± 20.904, 262.82 ± 17.010, and 265.15 ± 20.078 µm, respectively. The corresponding values in group 2 were 255.36 ± 17.852, 259.15 ± 16.644, and 266.09 ± 18.844 µm, respectively. There was no significant difference in the mean CMT values between the two groups on any of the three occasions when the CMT was measured (P = 0.374 and P = 0.313 at weeks 1 and 6, respectively). CONCLUSION: There was no statistically significant difference in CMT between normal subjects and diabetic subjects without diabetic retinopathy preoperatively and in early postoperative period after uncomplicated phacoemulsification surgery.

Idiopathic Isolated Acquired Steroid Dependent SO Palsy: A Rare Case Report.

15-year-old boy presented with sudden onset, stable, nonprogressive painless diplopia (greatest in right gaze and inferior field of view) and hyperdeviation of left eye for a year. On ophthalmic examination, the patient had uncrossed diplopia with tilt and separation maximum in dextrodepression. On Park's three step test, left eye hypertropia increased on right gaze and left tilt suggestive of left superior oblique (SO) palsy. On prism bar cover test (PBCT), deviation was more than 25 PD base-down over the left eye for both distance and near in all gazes. MRI head and orbit revealed a normal study while the myasthenia and inflammatory work-up was unremarkable. A provisional diagnosis of "Idiopathic Acquired Left Superior Oblique Palsy" was made and the patient was given trial of oral steroids at 1 mg/kg body weight. At 6 weeks, patient's diplopia resolved and PBCT neutralised at 6PD. Oral steroids were gradually tapered off by 10 mg per week with weekly follow-up. Upon decreasing the dose of prednisolone to 5 mg, intermittent diplopia and 18 PD left hypertropia reappeared. When patient was again restarted on oral steroids at 1 mg/kg body weight, diplopia-hypertropia disappeared at 10 mg OD prednisolone only to reappear at 5 mg OD dosage, leading to the final diagnosis of a "Steroid Dependent Isolated Superior Oblique Palsy". Presently, the patient is maintained on a daily dose of 10 mg oral prednisolone.

Multimedia Appendix Removal and Editorial Warning Regarding the MMAS Scale (Two-Way Social Media Messaging in Post-Operative Cataract Surgical Patients: A Prospective Interventional Study).

[This corrects the article DOI: 10.2196/jmir.8330.].

Impact of a dedicated palliative radiation oncology service on the use of single fraction and hypofractionated radiation therapy among patients with bone metastases.

BACKGROUND: Radiation therapy (RT) is frequently used to palliate symptomatic bone metastases. While high quality literature has shown that for uncomplicated bone metastases, shorter radiotherapy courses are just as effective as longer courses for the treatment of pain, shorter courses remain under-utilized. We aimed to assess the impact of a dedicated palliative radiation oncology service on the frequency of single fraction RT (SF-RT) and hypofractionated radiation (hypo-RT) (≤5 fractions) among patients with bone metastases. METHODS: We identified 2,086 instances of palliative radiation (RT) for complicated and uncomplicated bone metastases between April 10, 2008 and September 17, 2014. We used multivariable logistic regression analysis (MVA) to estimate the association of the Supportive and Palliative Radiation Oncology (SPRO) service with the likelihood of receiving SF-RT or hypo-RT after controlling for age, sex, tumor type, and treatment site. RESULTS: Prior to SPRO's implementation on July 1, 2011, the proportion of SF-RT and hypo-RT for bone metastases was 6.4% and 27.6% respectively. After SPRO's implementation, the proportion of SF-RT and hypo-RT increased to 22.3% (P<0.001) and 53.5% (P<0.001) respectively. In MVA, patients were more likely to receive SF-RT [odds ratio (OR) =3.3, 95% confidence interval (CI) =2.4-4.7, P<0.001], and hypo-RT (OR =2.5, 95% CI =2.0-3.1, P<0.001) after SPRO's implementation. Compared to sites without a dedicated palliative service, patients receiving care at the SPRO affiliated department were more likely to receive SF-RT (OR =1.9, 95% CI =1.1-3.2, P=0.02) and hypo-RT (OR =1.5, 95% CI =1.1-2.0, P=0.004) for bone metastases. After SPRO's implementation, the average number of RT courses delivered for bone metastases increased from 17.4 to 25.6 per month, (+8.3, 95% CI =4.99-11.55, P<0.001). Despite greater SF-RT and hypo-RT, the average total fractions per month of palliative RT for bone metastases increased from 163.5 pre-SPRO to 166.8 post-SPRO, though not significantly (+3.22, P=NS). CONCLUSIONS: Implementation of a dedicated palliative radiation oncology service was associated with increased use of SF and hypo-RT and with greater courses of RT delivered for bone metastases.

Two-Way Social Media Messaging in Postoperative Cataract Surgical Patients: Prospective Interventional Study.

BACKGROUND: Social media offers a new way to provide education, reminders, and support for patients with a variety of health conditions. Most of these interventions use one-way, provider-patient communication. Incorporating social media tools to improve postoperative (postop) education and follow-up care has only been used in limited situations. OBJECTIVE: The aim of this study was to determine the feasibility and efficacy of two-way social media messaging to deliver reminders and educational information about postop care to cataract patients. METHODS: A total of 98 patients undergoing their first eye cataract surgery were divided into two groups: a no message group receiving usual pre- and postop care and a message group receiving usual care plus messages in a mobile social media format with standardized content and timing. Each patient in the message group received nine messages about hand and face hygiene, medication and postop visit adherence, and links to patient education videos about postop care. Patients could respond to messages as desired. Main outcome measures included medication adherence, postop visit adherence, clinical outcomes, and patients' subjective assessments of two-way messaging. The number, types, content, and timing of responses by patients to messages were recorded. RESULTS: Medication adherence was better in the message group at postop day 7, with high adherence in 47 patients (96%, 47/49) versus 36 patients (73%, 36/49) in the no message group (P=.004), but no statistically significant differences in medication adherence between the groups were noted at preop and postop day 30. Visit adherence was higher at postop day 30 in the message group (100%, 49/49) versus the no message group (88%, 43/49; P=.03) but was 100% (49/49) in both groups at postop day 1 and 7. Final visual outcomes were similar between groups. A total of 441 standardized messages were sent to the message group. Out of 270 responses generated, 188 (70%) were simple acknowledgments or "thank you," and 82 (30%) responses were questions that were divided into three general categories: administrative, postop care, and clinical issues. Out of the 82 question responses, 31 (11%) were about administrative issues, 28 (10%) about postop care, and 23 (9%) about clinical symptoms. All the messages about symptoms were triaged by nurses or ophthalmologists and only required reassurance or information. Patients expressed satisfaction with messaging. CONCLUSIONS: Two-way social media messaging to deliver postop information to cataract patients is feasible and improves early medication compliance. Further design improvements can streamline work flow to optimize efficiency and patient satisfaction.

Cost-effectiveness of the polypill versus risk assessment for prevention of cardiovascular disease.

OBJECTIVE: There is an international trend towards recommending medication to prevent cardiovascular disease (CVD) in individuals at increasingly lower cardiovascular risk. We assessed the cost-effectiveness of a population approach with a polypill including a statin (simvastatin 20 mg) and three antihypertensive agents (amlodipine 2.5 mg, losartan 25 mg and hydrochlorothiazide 12.5 mg) and periodic risk assessment with different risk thresholds. METHODS: We developed a microsimulation model for lifetime predictions of CVD events, diabetes, and death in 259 146 asymptomatic UK Biobank participants aged 40-69 years. We assessed incremental costs and quality-adjusted life-years (QALYs) for polypill scenarios with the same combination of agents and doses but differing for starting age, and periodic risk assessment with 10-year CVD risk thresholds of 10% and 20%. RESULTS: Restrictive risk assessment, in which statins and antihypertensives were prescribed when risk exceeded 20%, was the optimal strategy gaining 123 QALYs (95% credible interval (CI) -173 to 387) per 10 000 individuals at an extra cost of £1.45 million (95% CI 0.89 to 1.94) as compared with current practice. Although less restrictive risk assessment and polypill scenarios prevented more CVD events and attained larger survival gains, these benefits were offset by the additional costs and disutility of daily medication use. Lowering the risk threshold for prescription of statins to 10% was economically unattractive, costing £40 000 per QALY gained. Starting the polypill from age 60 onwards became the most cost-effective scenario when annual drug prices were reduced below £240. All polypill scenarios would save costs at prices below £50. CONCLUSIONS: Periodic risk assessment using lower risk thresholds is unlikely to be cost-effective. The polypill would become cost-effective if drug prices were reduced.

Comparing smartphone camera adapters in imaging post-operative cataract patients.

Introduction The goal of this study is to compare image quality and clinical confidence for managing post-operative cataract patients based on anterior segment smartphone images obtained in real-world settings using four types of adapters: (a) macro lens (ML), (b) ML with augmented light-emitting diode (LED) illumination (ML-LED), (c) no adapter (NA) and (d) slit lamp (SL) adapter. Methods Anterior segment images were obtained from 190 eyes after cataract surgery using an eight-megapixel iPhone 6 smartphone camera with four adapters: ML, ML-LED, NA, and SL. Smartphone images were subjectively rated by ophthalmologists as acceptable or not acceptable for: (a) image quality for evaluating the anterior segment structures and (b) reader confidence in clinically managing post-operative patients based on smartphone images. Results NA, ML-LED, and SL had the highest scores for image quality with 100%, 93.7%, and 86.3% judged as acceptable, respectively. NA, SL, and ML-LED were also rated highest in clinical confidence with 100%, 98%, and 93.2% having acceptable levels, respectively. ML was judged lowest in both image quality (61.1% acceptable) and clinical confidence (37.4% acceptable). Discussion This study represents the first effort to compare different smartphone camera adapters' ability to image the anterior segment of the eye in a real-world setting. Our study shows that ML-LED, NA, and SL adapters were acceptable for visualizing anterior segment structures to physician readers in 86-100% of cases. When coupled with visual acuity, intro-ocular pressure and history, these images can result in acceptable clinical confidence in 93-100% of cases.

Associations between metabolic dysregulation and circulating biomarkers of fibrosis: the Cardiovascular Health Study.

AIM: Fibrosis is one postulated pathway by which diabetes produces cardiac and other systemic complications. Our aim was to determine which metabolic parameters are associated with circulating fibrosis-related biomarkers transforming growth factor-ß (TGF-ß) and procollagen type III N-terminal propeptide (PIIINP). METHODS: We used linear regression to determine the cross-sectional associations of diverse metabolic parameters, including fasting glucose, fasting insulin, body mass index, fatty acid binding protein 4, and non-esterified fatty acids, with circulating levels of TGF-ß (n = 1559) and PIIINP (n = 3024) among community-living older adults in the Cardiovascular Health Study. RESULTS: Among the main metabolic parameters we examined, only fasting glucose was associated with TGF-ß (P = 0.03). In contrast, multiple metabolic parameters were associated with PIIINP, including fasting insulin, body mass index, and non-esterified fatty acids (P<0.001, P<0.001, P=0.001, respectively). These associations remained statistically significant after mutual adjustment, except the association between BMI and PIIINP. CONCLUSIONS: Isolated hyperglycemia is associated with higher serum concentrations of TGF-ß, while a broader phenotype of insulin resistance is associated with higher serum PIIINP. Whether simultaneous pharmacologic targeting of these two metabolic phenotypes can synergistically reduce the risk of cardiac and other manifestations of fibrosis remains to be determined.

Fibrosis-related biomarkers and large and small vessel disease: the Cardiovascular Health Study.

OBJECTIVE: Fibrosis has been implicated in a number of pathological, organ-based conditions of the liver, kidney, heart, and lungs. The objective of this study was to determine whether biomarkers of fibrosis are associated with vascular disease in the large and/or small vessels. METHODS: We evaluated the associations of two circulating biomarkers of fibrosis, transforming growth factor-ß (TGF-ß) and procollagen type III N-terminal propeptide (PIIINP), with incident peripheral artery disease (PAD) and subclinical macrovascular (carotid intima-media thickness, flow-mediated vasodilation, ankle-brachial index, retinal vein diameter), and microvascular (retinal artery diameter and retinopathy) disease among older adults in the Cardiovascular Health Study. We measured TGF-ß and PIIINP from samples collected in 1996 and ascertained clinical PAD through 2011. Measurements of large and small vessels were collected between 1996 and 1998. RESULTS: After adjustment for sociodemographic, clinical, and biochemical risk factors, TGF-ß was associated with incident PAD (hazard ratio [HR] = 1.36 per doubling of TGF-ß, 95% confidence interval [CI] = 1.04, 1.78) and retinal venular diameter (1.63 µm per doubling of TGF-ß, CI = 0.23, 3.02). PIIINP was not associated with incident PAD, but was associated with carotid intima-media thickness (0.102 mm per doubling of PIIINP, CI = 0.029, 0.174) and impaired brachial artery reactivity (-0.20% change per doubling of PIIINP, CI = -0.39, -0.02). Neither TGF-ß nor PIIINP were associated with retinal arteriolar diameter or retinopathy. CONCLUSIONS: Serum concentrations of fibrosis-related biomarkers were associated with several measures of large vessel disease, including incident PAD, but not with small vessel disease. Fibrosis may contribute to large vessel atherosclerosis in older adults.

Novel metabolic biomarkers of cardiovascular disease.

Coronary heart disease (CHD) accounts for one in every six deaths in US individuals. Great advances have been made in identifying important risk factors for CHD, such as hypertension, diabetes mellitus, smoking and hypercholesterolaemia, which have led to major developments in therapy. In particular, statins represent one of the greatest successes in the prevention of CHD. While these standard risk factors are important, an obvious opportunity exists to take advantage of ongoing scientific research to better risk-stratify individuals and to identify new treatment targets. In this Review, we summarize ongoing scientific research in a number of metabolic molecules or features, including lipoproteins, homocysteine, calcium metabolism and glycaemic markers. We evaluate the current state of the research and the strength of evidence supporting each emerging biomarker. We also discuss whether the associations with CHD are strong and consistent enough to improve current risk stratification metrics, and whether these markers enhance our understanding of the underlying biology of CHD and thus point towards new treatment options.

Fibrosis-related biomarkers and incident cardiovascular disease in older adults: the cardiovascular health study.

BACKGROUND: Fibrotic changes in the heart and arteries have been implicated in a diverse range of cardiovascular diseases (CVD), but whether circulating biomarkers that reflect fibrosis are associated with CVD is unknown. METHODS AND RESULTS: We determined the associations of 2 biomarkers of fibrosis, transforming growth factor- ß (TGF-ß), and procollagen type III N-terminal propeptide (PIIINP), with incident heart failure, myocardial infarction, and stroke among community-living older adults in the Cardiovascular Health Study. We measured circulating TGF-ß (n=1371) and PIIINP (n=2568) from plasma samples collected in 1996 and ascertained events through 2010. Given TGF-ß's pleiotropic effects on inflammation and fibrogenesis, we investigated potential effect modification by C-reactive protein in secondary analyses. After adjustment for sociodemographic, clinical, and biochemical risk factors, PIIINP was associated with total CVD (hazard ratio [HR] per SD=1.07; 95% confidence interval [CI], 1.01-1.14) and heart failure (HR per SD=1.08; CI, 1.01-1.16) but not myocardial infarction or stroke. TGF-ß was not associated with any CVD outcomes in the full cohort but was associated with total CVD (HR per SD=1.16; CI, 1.02-1.31), heart failure (HR per SD=1.16; CI, 1.01-1.34), and stroke (HR per SD=1.20; CI, 1.01-1.42) among individuals with C-reactive protein above the median, 2.3 mg/L (P interaction <0.05). CONCLUSIONS: Our findings provide large-scale, prospective evidence that circulating biomarkers of fibrosis, measured in community-living individuals late in life, are associated with CVD. Further research on whether TGF-ß has a stronger fibrogenic effect in the setting of inflammation is warranted.