Morbidity and healthcare use among mothers of children with cancer: A population-based study.

BACKGROUND: The impact of a child's cancer diagnosis on subsequent maternal physical health is unclear. METHODS: We identified all Ontario children diagnosed less than 18 years with cancer between 1992 and 2017. Linkage to administrative databases identified mothers who were matched to population controls. We identified physical health conditions, acute healthcare use, and preventive healthcare use through validated algorithms using healthcare data, and compared them between exposed (child with cancer) and unexposed mothers. Predictors of health outcomes were assessed among exposed mothers. RESULTS: We identified 5311 exposed mothers and 19,516 matched unexposed mothers. For exposed mothers, median age at last follow-up was 48 years, (interquartile range: 42-53). Exposed mothers had an increased risk of cancer (hazard ratio [HR] 1.2, 95% confidence interval [95% CI]: 1.0-1.5, p = .03), but not of any other adverse physical outcomes or of increased acute healthcare use. Exposed mothers were more likely to receive influenza vaccinations (odds ratio 1.4, 95% CI: 1.3-1.5, p < .0001), and underwent cancer screening at the same rate as unexposed mothers. Among exposed mothers, bereavement was associated with a subsequent increased risk of cancer (HR 1.7, 95% CI: 1.2-2.5, p = .004) and death (HR 2.2, 95% CI: 1.2-4.1, p = .01). CONCLUSION: Mothers of children with cancer are at increased risk of developing cancer, but not of other adverse physical health outcomes, and were equally or more likely to be adherent to preventive healthcare practices. Bereaved mothers were at increased risk of subsequent cancer and death. Interventions targeting specific subpopulations of mothers of children with cancer or focused on screening for specific cancers may be warranted.

Morbidity and health care use among siblings of children with cancer: A population-based study.

BACKGROUND: Childhood cancer impacts the entire family unit. We sought to investigate its impact on the long-term physical health outcomes of siblings of children with cancer. PROCEDURE: Pediatric cancer patients diagnosed in Ontario, Canada between 1988 and 2016 were linked to biological siblings. Sibling cases were matched to population controls based on sex, age, geographic location, and number of other children in the family. After individual linkage to health services data, we compared several outcomes between sibling cases and controls: (a) physical health conditions (such as diabetes, hypertension, and death); (b) acute health care use (hospitalization, low- and high-acuity emergency department [ED] visits); and (c) preventive health care use (periodic health checkups, influenza vaccinations). Cox proportional hazards, recurrent event, or logistic regression models were used as appropriate. RESULTS: We identified 8529 sibling cases and 30,364 matched controls (median age at index: 6 years, median age at last follow-up 17 years). Compared to controls, siblings were at increased risk of hypertension (hazard ratio [HR] 1.8; 95% confidence interval [CI] 1.1-2.9; p = .01), had higher rates of low- and high-acuity ED visits (rate ratio 1.1; 95% CI 1.1-1.2; p < .001), and increased risk of hospitalization (HR 1.1; 95% CI 1.1-1.2; p < .001). Sibling cases were also more likely to receive preventive health care (p < .05). CONCLUSION: Increased risk of hypertension, high-acuity ED visits, and hospitalizations suggest that siblings may experience poorer health compared to controls. Counseling families about this potential increased risk and long-term follow-up of siblings to monitor their physical health may be justified.

A Comparative Utility Score for Digital Health Tools.

Digital health tools (DHT) are increasingly poised to change healthcare delivery given the Coronavirus Disease 2019 (COVID-19) pandemic and the drive to telehealth. Establishing the potential utility of a given DHT could aid in identifying how it could be best used and further opportunities for healthcare improvement. We propose a metric, a Utility Factor Score, which quantifies the benefits of a DHT by explicitly defining adherence and linking it directly to satisfaction and health goals met. To provide data for how the comparative utility score can or should work, we illustrate in detail the application of our metrics across four DHTs with two simulated users. The Utility Factor Score can potentially facilitate integration of DHTs into various healthcare settings and should be evaluated within a clinical study.

Lymphedema evaluation using noninvasive 3T MR lymphangiography.

PURPOSE: To exploit the long 3.0T relaxation times and low flow velocity of lymphatic fluid to develop a noninvasive 3.0T lymphangiography sequence and evaluate its relevance in patients with lymphedema. MATERIALS AND METHODS: A 3.0T turbo-spin-echo (TSE) pulse train with long echo time (TEeffective = 600 msec; shot-duration = 13.2 msec) and TSE-factor (TSE-factor = 90) was developed and signal evolution simulated. The method was evaluated in healthy adults (n = 11) and patients with unilateral breast cancer treatment-related lymphedema (BCRL; n = 25), with a subgroup (n = 5) of BCRL participants scanned before and after manual lymphatic drainage (MLD) therapy. Maximal lymphatic vessel cross-sectional area, signal-to-noise-ratio (SNR), and results from a five-point categorical scoring system were recorded. Nonparametric tests were applied to evaluate study parameter differences between controls and patients, as well as between affected and contralateral sides in patients (significance criteria: two-sided P < 0.05). RESULTS: Patient volunteers demonstrated larger lymphatic cross-sectional areas in the affected (arm = 12.9 ± 6.3 mm2 ; torso = 17.2 ± 15.6 mm2 ) vs. contralateral (arm = 9.4 ± 3.9 mm2 ; torso = 9.1 ± 4.6 mm2 ) side; this difference was significant both for the arm (P = 0.014) and torso (P = 0.025). Affected (arm: P = 0.010; torso: P = 0.016) but not contralateral (arm: P = 0.42; torso: P = 0.71) vessel areas were significantly elevated compared with control values. Lymphatic cross-sectional areas reduced following MLD on the affected side (pre-MLD: arm = 8.8 ± 1.8 mm2 ; torso = 31.4 ± 26.0 mm2 ; post-MLD: arm = 6.6 ± 1.8 mm2 ; torso = 23.1 ± 24.3 mm2 ). This change was significant in the torso (P = 0.036). The categorical scoring was found to be less specific for detecting lateralizing disease compared to lymphatic-vessel areas. CONCLUSION: A 3.0T lymphangiography sequence is proposed, which allows for upper extremity lymph stasis to be detected in ∼10 minutes without exogenous contrast agents. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1349-1360.

Sonography of Responsive Versus Nonresponsive Ectopic Pregnancies.

This case series describes changes in size, vascularity, and cul-de-sac fluid in 30 patients with ectopic pregnancies who were treated with systemic methotrexate. Pretreatment and posttreatment transvaginal sonography of the ectopic pregnancies was performed with color Doppler imaging, and the images were assessed for changes in size, vascularity, and cul-de-sac free fluid. There was a trend for nonresponders to show increased vascularity on serial examinations, although this finding was also seen in a single responder. There was also a trend for nonresponders with increased vascularity to be associated with a greater increase in ß-human chorionic gonadotropin levels and responders with decreased vascularity to be associated with a greater decrease in ß-human chorionic gonadotropin levels.

Routine clinical evaluation of cerebrovascular reserve capacity using carbogen in patients with intracranial stenosis.

BACKGROUND AND PURPOSE: A promising method for identifying hemodynamic impairment that may serve as a biomarker for stroke risk in patients with intracranial stenosis is cerebrovascular reactivity (CVR) mapping using noninvasive MRI. Here, abilities to measure CVR safely in the clinic using hypercarbic hyperoxic (carbogen) gas challenges, which increase oxygen delivery to tissue, are investigated. METHODS: In sequence with structural and angiographic imaging, blood oxygenation level-dependent carbogen-induced CVR scans were performed in patients with symptomatic intracranial stenosis (n=92) and control (n=10) volunteers, with a subgroup of patients (n=57) undergoing cerebral blood flow-weighted pseudocontinuous arterial spin labeling CVR. Subjects were stratified for 4 substudies to evaluate relationships between (1) carbogen and hypercarbic normoxic CVR in healthy tissue (n=10), (2) carbogen cerebral blood flow CVR and blood oxygenation level-dependent CVR in intracranial stenosis patients (n=57), (3) carbogen CVR and clinical measures of disease in patients with asymmetrical intracranial atherosclerotic (n=31) and moyamoya (n=29) disease, and (4) the CVR scan and immediate and longer-term complications (n=92). RESULTS: Noninvasive blood oxygenation level-dependent carbogen-induced CVR values correlate with (1) lobar hypercarbic normoxic gas stimuli in healthy tissue (R=0.92; P<0.001), (2) carbogen-induced cerebral blood flow CVR in patients with intracranial stenosis (R=0.30-0.33; P<0.012), and (3) angiographic measures of disease severity both in atherosclerotic and moyamoya patients after appropriate processing. No immediate stroke-related complications were reported in response to carbogen administration; longer-term neurological events fell within the range for expected events in this patient population. CONCLUSIONS: Carbogen-induced CVR elicited no added adverse events and provided a surrogate marker of cerebrovascular reserve consistent with intracranial vasculopathy.

Hidden hearing loss in hereditary demyelinating neuropathies: insights from Charcot-Marie-Tooth mouse models.

Hidden hearing loss (HHL) is a recently described auditory neuropathy characterized by normal audiometric thresholds but reduced sound-evoked potentials. It has been proposed that HHL contributes to hearing difficulty in noisy environments in people with normal audiometric thresholds, a widespread complaint. While most studies on HHL pathogenesis have focused on inner hair cell (IHC) synaptopathy, recent research suggests that transient auditory nerve (AN) demyelination may also cause HHL. To test the impact of myelinopathy in a clinically relevant model, we studied a mouse model of Charcot-Marie-Tooth type 1A (CMT1A), the most prevalent hereditary peripheral neuropathy in humans. CMT1A mice exhibit the functional hallmarks of HHL, together with disorganization of AN heminodes near the IHCs with minor loss of AN fibers. Our results support the hypothesis that mild disruptions of AN myelination can cause HHL, and that heminodal defects contribute to the alterations in action potential amplitudes and latencies seen in these models. Also, these findings suggest that patients with CMT1A or other mild peripheral neuropathies are likely to suffer from HHL. Furthermore, these results suggest that studies of hearing in CMT1A patients might help develop robust clinical tests for HHL, which are currently lacking.

Evaluating the Clinical Performance of a Novel, Precision Oral Appliance Therapy Medical Device Made Wholly From a Medical Grade Class VI Material for the Treatment of Obstructive Sleep Apnea.

Objective The objective of this study is to evaluate the clinical performance of a novel, precision, oral appliance therapy (OAT) medical device made entirely from a US Pharmacopeia (USP) medical grade class VI qualified material for the treatment of obstructive sleep apnea (OSA). Methods This was a multi-center, single-arm, chart-based, retrospective study of 91 patients diagnosed with OSA, treated utilizing a novel, precision, OAT medical device. Performance criteria were overall efficacy (reduction of OSA events to less than 10 per hour); efficacy for patients with severe OSA (reduction of OSA events to less than 20 per hour and a 50% improvement); and compliance (the rate of continuation of treatment after at least a one-year follow-up, or, conversely, the rate of discontinuation of treatment due to material-related adverse events or side effects after one year).  Results Eighty-nine percent of all subjects diagnosed with all levels of OSA severity were successfully treated to an apnea hypopnea index ("AHI") < 10 events per hour. Ninety-eight percent of subjects diagnosed with mild to moderate OSA were successfully treated to an AHI < 10. Eighty percent of subjects with severe OSA, without screening or excluding subjects for airway collapse profile, were successfully treated to an AHI < 20 with a 50% improvement in AHI. After a minimum one-year follow-up period, 96% of patients were confirmed to remain in active treatment. No subjects were reported to discontinue treatment due to adverse events or side effects. Conclusions This novel, precision OAT medical device made from the USP Class VI qualified material demonstrated efficacy and safety for the treatment of patients with OSA.

Initial development and testing of an exhaled microRNA detection strategy for lung cancer case-control discrimination.

For detecting field carcinogenesis non-invasively, early technical development and case-control testing of exhaled breath condensate microRNAs was performed. In design, human lung tissue microRNA-seq discovery was reconciled with TCGA and published tumor-discriminant microRNAs, yielding a panel of 24 upregulated microRNAs. The airway origin of exhaled microRNAs was topographically "fingerprinted", using paired EBC, upper and lower airway donor sample sets. A clinic-based case-control study (166 NSCLC cases, 185 controls) was interrogated with the microRNA panel by qualitative RT-PCR. Data were analyzed by logistic regression (LR), and by random-forest (RF) models. Feasibility testing of exhaled microRNA detection, including optimized whole EBC extraction, and RT and qualitative PCR method evaluation, was performed. For sensitivity in this low template setting, intercalating dye-based URT-PCR was superior to fluorescent probe-based PCR (TaqMan). In application, adjusted logistic regression models identified exhaled miR-21, 33b, 212 as overall case-control discriminant. RF analysis of combined clinical + microRNA models showed modest added discrimination capacity (1.1-2.5%) beyond clinical models alone: all subjects 1.1% (p = 8.7e-04)); former smokers 2.5% (p = 3.6e-05); early stage 1.2% (p = 9.0e-03), yielding combined ROC AUC ranging from 0.74 to 0.83. We conclude that exhaled microRNAs are qualitatively measureable, reflect in part lower airway signatures; and when further refined/quantitated, can potentially help to improve lung cancer risk assessment.

Cochlear Neurotrophin-3 overexpression at mid-life prevents age-related inner hair cell synaptopathy and slows age-related hearing loss.

Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly. This progressive pathology often has psychological and medical comorbidities, including social isolation, depression, and cognitive decline. Despite ARHL's enormous societal and economic impact, no therapies to prevent or slow its progression exist. Loss of synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs), a.k.a. IHC synaptopathy, is an early event in cochlear aging, preceding neuronal and hair cell loss. To determine if age-related IHC synaptopathy can be prevented, and if this impacts the time-course of ARHL, we tested the effects of cochlear overexpression of neurotrophin-3 (Ntf3) starting at middle age. We chose Ntf3 because this neurotrophin regulates the formation of IHC-SGN synapses in the neonatal period. We now show that triggering Ntf3 overexpression by IHC supporting cells starting in middle age rapidly increases the amplitude of sound-evoked neural potentials compared with age-matched controls, indicating that Ntf3 produces a positive effect on cochlear function when the pathology is minimal. Furthermore, near the end of their lifespan, Ntf3-overexpressing mice have milder ARHL, with larger sound-evoked potentials along the ascending auditory pathway and reduced IHC synaptopathy compared with age-matched controls. Our results also provide evidence that an age-related decrease in cochlear Ntf3 expression contributes to ARHL and that Ntf3 supplementation could serve as a therapeutic for this prevalent disorder. Furthermore, these findings suggest that factors that regulate synaptogenesis during development could prevent age-related synaptopathy in the brain, a process involved in several central nervous system degenerative disorders.

Spica MRI after closed reduction for developmental dysplasia of the hip.

Spica MRI is a fast and effective tool to assess morphology after closed reduction for developmental dysplasia of the hip (DDH) without the need for sedation. The multiplanar capabilities allow depiction of coronal and axial reduction of the hips. Due to MRI's inherent ability to delineate soft tissue structures, both intrinsic and extrinsic obstacles to failed reduction may be identified. Technical and interpretative challenges of spica MRI are discussed.

Microarray-based characterization of a colony assay used to investigate endothelial progenitor cells and relevance to endothelial function in humans.

OBJECTIVE: An assay proposed to quantify endothelial progenitor cell (EPC) colonies in humans was investigated to determine the phenotype of recovered cells and their relevance to in vivo endothelial function. METHODS AND RESULTS: Twelve sedentary subjects participating in a worksite wellness program underwent endothelial flow-mediated dilation (FMD) testing of the brachial artery and blood sampling for EPC colony assay. Microarray-based genotypic characterization of colonies showed surface markers consistent with T lymphocyte phenotype, but not with an EPC (CD34, CD133, VEGFR-2) or endothelial (CD146) phenotype. Gene expression patterns more closely matched T lymphocytes (r=0.87) than endothelial cells (r=0.66) in our microarray database. Flow cytometry of colonies confirmed large populations of CD3+CD45+ T cells (>75%) and few CD146+CD45- endothelial cells (<1%). Further, there was no correlation between colony number and the magnitude of FMD (r=-0.1512, P=0.6389). After exercise training, subjects improved FMD, from 6.7+/-2.0 to 8.7+/-1.9% (P=0.0043). Colonies also increased (P=0.0210), but without relation to FMD (r=0.1074, P=0.7396). T lymphocyte phenotype persisted after exercise (r=0.87). CONCLUSIONS: Cells in a commonly used EPC colony assay have a gene expression and cell surface marker profile consistent with a predominance of T lymphocytes and have an unclear relevance to endothelial function, either before or after exercise training.

A Contemporary Review of Neurological Sequelae of COVID-19.

Coronavirus 2019 (COVID-19) is currently the center of what has become a public health crisis. While the virus is well-known for its trademark effects on respiratory function, neurological damage has been reported to affect a considerable proportion of severe cases. To characterize the neuro-invasive potential of this disease, a contemporary review of COVID-19 and its neurological sequelae was conducted using the limited, but growing, literature that is available. These neurological squeal are based on the manifestations that the virus has on normal central and peripheral nervous system function. The authors present the virology of the SARS-CoV-2 agent by analyzing its classification as an enveloped, positive-stranded RNA virus. A comprehensive timeline is then presented, indicating the progression of the disease as a public health threat. Furthermore, underlying chronic neurological conditions potentially lead to more adverse cases of COVID-19. SARS-CoV-2 may reach ACE2 receptors on neuronal tissue through mode of the general circulation. The CNS may also be susceptible to an immune response where a "cytokine storm" can manifest into neural injury. Histological evidence is provided, while symptoms such as headache and vertigo are highlighted as CNS manifestations of COVID-19. Treatment of these symptoms is addressed with paracetamol being recommended as a possible, but not conclusive, treatment to some CNS symptoms. The authors then discuss the peripheral nervous system sequelae and COVID's impact on causing chemosensory dysfunction starting with viral attack on olfactory sensory neurons and cells types within the lining of the nose. Histological evidence is also provided while symptoms such as anosmia and ageusia are characterized as PNS manifestations. Possible treatment options for these symptoms are then addressed as a major limitation, as anecdotal, and not conclusive evidence can be made. Finally, preventive measures of the neurological sequelae are addressed using a multidirectional approach. Postmortem examinations of the brains of COVID-19 patients are suggested as being a possible key to formulating new understandings of its neuropathology. Lastly, the authors suggest a more comprehensive neurological follow-up of recovered patients, in order to better characterize the neurological sequelae of this illness.

Ophthalmic Timolol and Hospitalization for Symptomatic Bradycardia and Syncope: A Case Series.

Topical beta-blockers are commonly used for the management of primary open angle glaucoma (POAG). One of the rare but serious side effects of the topical beta-blockers is bradycardia, defined as a heart rate below 60 beats per minute. In few cases, the heart rate drops to much lower level resulting in syncope or symptomatic bradycardia. Topical beta-blockers are still widely used for POAG even though there are much better medications available. We present a series of four cases of symptomatic bradycardia resulting from the use of timolol eye drops and after discontinuation of the eye drops, heart rate improved to normal range (60-100 beats per minute).

Key factors for implementing mindfulness-based burnout interventions in surgery.

BACKGROUND: Burnout and distress are widespread issues in surgical training. While effective interventions are slowly coming to light, little has been published regarding the sustainable implementation of such interventions, including the critical need to identify barriers and enablers. METHODS: Enhanced Stress Resilience Training (ESRT), a mindfulness-based cognitive intervention for surgical trainees, was delivered and studied on three separate occasions. For each, focus groups, field notes, surveys and interviews were collected involving leadership, administrators and participants. Thematic analysis was used in each instance, and across instances, to explore concepts and themes, which were used to identify critical influences effecting implementation. RESULTS: Culture (surrounding the intervention), infrastructure (supporting the intervention) and adaptability (of the intervention) were repeatedly critical influences, guiding iterative adaptation of the intervention, and resulting in sustainability across groups and over time. CONCLUSIONS: Identifying critical influences on intervention feasibility and acceptability can guide intervention refinement and shift sustainable implementation barriers to become enablers, as was the case at our institution. This approach may be useful in other settings.

The obstetrician and gynaecologist and the European Computer Driving Licence.

The European Computer Driving Licence (ECDL) has been adopted as the reference standard for all NHS staff for basic IT skills. The objective of the study was to determine awareness of the ECDL amongst members of the Royal College of Obstetricians and Gynaecologists. An anonymous postal survey was conducted with members and fellows of the College in three UK regions. A total of 720 questionnaires were posted, and the response rate was 47.9 per cent. A fifth of all respondents were not aware of the ECDL at all, and only 10 per cent were trained in the ECDL. However, more than third had some other formal training in IT skills. Half the respondents suggested that the questionnaire had prompted them to train for the ECDL. Much needs to be done to increase awareness of the ECDL and offer incentives for its takeup.

Afferent Loop Syndrome Due to Volvulus of the Afferent Limb.

A 78-year-old woman with a history of stage IIB gastric adenocarcinoma with previous Billroth II subtotal gastrectomy was admitted with pancreatitis, with subsequent development of fevers and acute jaundice. Transabdominal ultrasound demonstrated bile duct obstruction. An endoscopic retrograde cholangiopancreatography was attempted, but the lumen of the afferent limb appeared distorted without an obstructing lesion. A computed tomography scan demonstrated volvulus of the afferent limb near the gastrojejunal anastomosis, with afferent limb dilation and significant biliary dilation.

Endoscopic Ultrasound-Guided Hepaticogastrostomy With Lumen-Apposing Metal Stent for Management of Pyogenic Liver Abscess.

A 45-year-old man presented with abdominal pain, fever with chills, nonproductive cough, mild pleurisy, and anorexia. Computed tomography scan showed a heterogeneously enhancing mass in the left hepatic lobe with leukocytosis and elevated C-reactive protein. Interval growth of the lesion was noted on magnetic resonance imaging obtained several days after admission. Given the clinical suspicion for pyogenic liver abscess and favorable location in the left hepatic lobe, endoscopic ultrasound-guided drainage was pursued. The patient underwent endoscopic ultrasound-guided hepaticogastrostomy with a lumen-apposing metal stent. His symptoms gradually abated after procedure. Radiographic resolution of the abscess was noted 1 week after stent placement, and the stent was subsequently removed. He had no clinical or radiographic evidence of recurrence at 1-month follow-up.

Relation of endothelial function to cardiovascular risk in women with sedentary occupations and without known cardiovascular disease.

Our purpose was to determine predictors of endothelial function and potential association with cardiovascular risk in women with sedentary occupations, in whom obesity-associated risk factors may contribute to excess morbidity and mortality. Ninety consecutive women (age range 22 to 63 years, 22 overweight (body mass index [BMI] > or =25 to 29.9 kg/m(2)) and 42 obese (BMI > or = 30 kg/m(2)), had vital signs, lipids, insulin, glucose, high-sensitivity C-reactive protein, and sex hormones measured. Endothelial function was determined using brachial artery flow-mediated dilation after 5 minutes of forearm ischemia. Treadmill stress testing was performed with gas exchange analysis at peak exercise (peak oxygen consumption [Vo(2)]) to assess cardiorespiratory fitness. Brachial artery reactivity was negatively associated with Framingham risk score (r = -0.3542, p = 0.0007). Univariate predictors of endothelial function included peak Vo(2) (r = 0.4483, p <0.0001), age (r = -0.3420, p = 0.0010), BMI (r = -0.3065, p = 0.0035), and high-sensitivity C-reactive protein (r = -0.2220, p = 0.0400). Using multiple linear regression analysis with stepwise modeling, peak Vo(2) (p = 0.0003) was the best independent predictor of brachial artery reactivity, with age as the only other variable reaching statistical significance (p = 0.0436) in this model. In conclusion, endothelial function was significantly associated with cardiovascular risk in women with sedentary occupations, who were commonly overweight or obese. Even in the absence of routine exercise, cardiorespiratory fitness, rather than conventional risk factors or body mass, is the dominant predictor of endothelial function and suggests a modifiable approach to risk.

Predictors of endothelial function in employees with sedentary occupations in a worksite exercise program.

A sedentary workforce may be at increased risk for future cardiovascular disease. Exercise at the work site has been advocated, but effects on endothelium as a biomarker of risk and relation to weight loss, lipid changes, or circulating endothelial progenitor cells (EPCs) have not been reported. Seventy-two office and laboratory employees (58 women; average age 45 years, range 22 to 62; 26 with body mass index values >30 kg/m(2)) completed 3 months of participation in the National Heart, Lung, and Blood Institute's Keep the Beat program, with the determination of vital signs, laboratory data, and peak oxygen consumption (VO(2)) during treadmill exercise. Brachial artery endothelium was tested by flow-mediated dilation (FMD), which at baseline was inversely associated with Framingham risk score (r = -0.3689, p <0.0001). EPCs were quantified by colony assay. With exercise averaging 98 +/- 47 minutes each workweek, there was improvement in FMD (from 7.8 +/- 3.4% to 8.5 +/- 3.0%, p = 0.0096) and peak VO(2) (+1.2 +/- 3.1 ml O(2)/kg/min, p = 0.0028), with reductions in diastolic blood pressure (-2 +/- 8 mm Hg, p = 0.0478), total cholesterol (-8 +/- 25 mg/dl, p = 0.0131), and low-density lipoprotein cholesterol (-7 +/- 19 mg/dl, p = 0.0044) but with a marginal reduction in weight (-0.5 +/- 2.1 kg, p = 0.0565). By multiple regression modeling, lower baseline FMD, greater age, reductions in total and low-density lipoprotein cholesterol and diastolic blood pressure, and increases in EPC colonies and peak VO(2) were jointly statistically significant predictors of change in FMD and accounted for 47% of the variability in FMD improvement with program participation. Results were similar when modeling was performed for women only. In contrast, neither adiposity at baseline nor change in weight was a predictor of improved endothelial function. In conclusion, daily exercise achievable at their work sites by employees with sedentary occupations improves endothelial function, even with the absence of weight loss, which may decrease cardiovascular risk, if sustained.