A Revised Markov Model Evaluating Oophorectomy at the Time of Hysterectomy for Benign Indication: Age 65 Years Revisited.

OBJECTIVE: To perform an updated Markov modeling to assess the optimal age for bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy for benign indication. METHODS: We performed a literature review that assessed hazard ratios (HRs) for mortality by disease, age, hysterectomy with or without BSO, and estrogen therapy use. Base mortality rates were derived from national vital statistics data. A Markov model from reported HRs predicted the proportion of the population staying alive to age 80 years by 1-year and 5-year age groups at time of surgery, from age 45 to 55 years. Those younger than age 50 years were modeled as either taking postoperative estrogen or not; those 50 and older were modeled as not receiving estrogen. Computations were performed with R 3.5.1, using Bayesian integration for HR uncertainty. RESULTS: Performing salpingo-oophorectomy before age 50 years for those not taking estrogen yields a lower survival proportion to age 80 years than hysterectomy alone before age 50 years (52.8% [Bayesian CI 40.7-59.7] vs 63.5% [Bayesian CI 62.2-64.9]). At or after age 50 years, there were similar proportions of those living to age 80 years with hysterectomy alone (66.4%, Bayesian CI 65.0-67.6) compared with concurrent salpingo-oophorectomy (66.9%, Bayesian CI 64.4-69.0). Importantly, those taking estrogen when salpingo-oophorectomy was performed before age 50 years had similar proportions of cardiovascular disease, stroke, and people living to age 80 years as those undergoing hysterectomy alone or those undergoing hysterectomy and salpingo-oophorectomy at age 50 years and older. CONCLUSION: This updated Markov model argues for the consideration of concurrent salpingo-oophorectomy for patients who are undergoing hysterectomy at age 50 and older and suggests that initiating estrogen in those who need salpingo-oophorectomy before age 50 years mitigates increased mortality risk.

Longitudinal assessment of post-surgical physical activity in endometrial and ovarian cancer patients.

OBJECTIVE: Physical activity plays a key role in cancer survivorship. The purpose of this investigation was to (a) describe the post-surgical physical activity trajectories of endometrial (n = 65) and ovarian (n = 31) cancer patients and (b) identify clinical and demographic predictors of physical activity over time. METHODS: 96 participants wore an Actiwatch accelerometer for three days at each of three time points (one week, one month and four months) after surgical intervention for their endometrial or ovarian cancer diagnosis. Analyses were conducted using linear mixed effects regression modeling in SAS 9.4. RESULTS: For both tumor types, although physical activity levels increased with time after surgery, even at four months patients were performing only a small fraction of the 150 minutes of recommended weekly moderate to vigorous physical activity. At 1 week, subjects were completing on average 14 minutes/week (SD = 4) of moderate-to-vigorous physical activity, compared to 14 minutes/week (SD = 2) of moderate-to-vigorous physical activity at four months post-surgery (p < .05). Better self-rated health was associated with higher physical activity (p = 0.02) in endometrial cancer survivors only. BMI, age, surgery type and use of neoadjuvant chemotherapy were not associated with activity over time. CONCLUSIONS: Our findings suggest that physical activity levels are different for those with better self-rated health, but those individuals are still insufficiently active. This study adds new information describing the trajectories and variables that influence physical activity in gynecologic cancer survivors after surgery and highlights the need for health promotion interventions in this population.

The impact of physician burnout on clinical and academic productivity of gynecologic oncologists: A decision analysis.

OBJECTIVE: Physician burnout is associated with mental illness, alcohol abuse, and job dissatisfaction. Our objective was to estimate the impact of burnout on productivity of gynecologic oncologists during the first half of their career. METHODS: A decision model evaluated the impact of burnout on total relative value (RVU) production during the first 15years of practice for gynecologic oncologists entering the workforce from 2011 to 2015. The SGO practice survey provided physician demographics and mean annual RVUs. Published data were used to estimate probability of burnout for male and female gynecologic oncologists, and the impact of depression, alcohol abuse, and early retirement. Academic productivity was defined as annual PubMed publications since finishing fellowship. RESULTS: Without burnout, RVU production for the cohort of 250 gynecologic oncologists was 26.2 million (M) RVUs over 15years. With burnout, RVU production decreased by 1.6 M (5.9% decrease). Disproportionate rates of burnout among females resulted in 1.1 M lost RVUs for females vs. 488 K for males. Academic production without burnout was estimated at 9277 publications for the cohort. Burnout resulted in 1383 estimated fewer publications over 15years (14.9%). CONCLUSIONS: The impact of burnout on clinical and academic productivity is substantial across all specialties. As health care systems struggle with human resource shortages, this study highlights the need for effective burnout prevention and wellness programs for gynecologic oncologists. Unless significant resources are designated to wellness programs, burnout will increasingly affect the care of our patients and the advancement of our field.

A Population Health Approach to Clinical Social Work with Complex Patients in Primary Care.

Chronic diseases disproportionately occur among people from disadvantaged backgrounds. These backgrounds correlate with poor health in adulthood. Capacity for patients' to collaborate in their care tends to be lower than among other patients, leading to inefficient uses in medical services and higher risk of adverse events. In the course of this study, social workers engaged patients with increased inpatient and emergency department (ED) use and barriers to self-management, and evaluated them for lifetime exposure to material disadvantage and violence. Intervention focused on creating a primary care team that improved patients' self-efficacy, increased locus of control, and improved capacity for engagement. Results include a 49 percent decrease in admissions and a 5 percent decrease in ED utilization with significant cost savings. Authors recommend further study to analyze social, clinical, and financial risk in a larger sample, which may yield information about a health care provider's most at-risk patients for early targeted intervention.

Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions.

BACKGROUND: Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. AIM: The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. METHODS: Data of 50 children with unilateral CP caused by periventricular white matter lesions (5-17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7-16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm(2)) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment-AHA) was assessed in connections that showed significant differences in FA compared to CTD. RESULTS: FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r(2) = 0.16-0.44; p < 0.05). CONCLUSION: This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention.

Lesion segmentation from multimodal MRI using random forest following ischemic stroke.

Understanding structure-function relationships in the brain after stroke is reliant not only on the accurate anatomical delineation of the focal ischemic lesion, but also on previous infarcts, remote changes and the presence of white matter hyperintensities. The robust definition of primary stroke boundaries and secondary brain lesions will have significant impact on investigation of brain-behavior relationships and lesion volume correlations with clinical measures after stroke. Here we present an automated approach to identify chronic ischemic infarcts in addition to other white matter pathologies, that may be used to aid the development of post-stroke management strategies. Our approach uses Bayesian-Markov Random Field (MRF) classification to segment probable lesion volumes present on fluid attenuated inversion recovery (FLAIR) MRI. Thereafter, a random forest classification of the information from multimodal (T1-weighted, T2-weighted, FLAIR, and apparent diffusion coefficient (ADC)) MRI images and other context-aware features (within the probable lesion areas) was used to extract areas with high likelihood of being classified as lesions. The final segmentation of the lesion was obtained by thresholding the random forest probabilistic maps. The accuracy of the automated lesion delineation method was assessed in a total of 36 patients (24 male, 12 female, mean age: 64.57±14.23yrs) at 3months after stroke onset and compared with manually segmented lesion volumes by an expert. Accuracy assessment of the automated lesion identification method was performed using the commonly used evaluation metrics. The mean sensitivity of segmentation was measured to be 0.53±0.13 with a mean positive predictive value of 0.75±0.18. The mean lesion volume difference was observed to be 32.32%±21.643% with a high Pearson's correlation of r=0.76 (p<0.0001). The lesion overlap accuracy was measured in terms of Dice similarity coefficient with a mean of 0.60±0.12, while the contour accuracy was observed with a mean surface distance of 3.06mm±3.17mm. The results signify that our method was successful in identifying most of the lesion areas in FLAIR with a low false positive rate.

Assessment of structural connectivity in the preterm brain at term equivalent age using diffusion MRI and T2 relaxometry: a network-based analysis.

Preterm birth is associated with a high prevalence of adverse neurodevelopmental outcome. Non-invasive techniques which can probe the neural correlates underpinning these deficits are required. This can be achieved by measuring the structural network of connections within the preterm infant's brain using diffusion MRI and tractography. We used diffusion MRI and T2 relaxometry to identify connections with altered white matter properties in preterm infants compared to term infants. Diffusion and T2 data were obtained from 9 term neonates and 18 preterm-born infants (born <32 weeks gestational age) at term equivalent age. Probabilistic tractography incorporating multiple fibre orientations was used in combination with the Johns Hopkins neonatal brain atlas to calculate the structural network of connections. Connections of altered diffusivity or T2, as well as their relationship with gestational age at birth and postmenstrual age at the time of MRI, were identified using the network based statistic framework. A total of 433 connections were assessed. FA was significantly reduced in 17, and T2 significantly increased in 18 connections in preterm infants, following correction for multiple comparisons. Cortical networks associated with affected connections mainly involved left frontal and temporal cortical areas: regions which are associated with working memory, verbal comprehension and higher cognitive function--deficits which are often observed later in children and adults born preterm. Gestational age at birth correlated with T2, but not diffusion in several connections. We found no association between diffusion or T2 and postmenstrual age at the time of MRI in preterm infants. This study demonstrates that alterations in the structural network of connections can be identified in preterm infants at term equivalent age, and that incorporation of non-diffusion measures such as T2 in the connectome framework provides complementary information for the assessment of brain development.

Move it to improve it (Mitii): study protocol of a randomised controlled trial of a novel web-based multimodal training program for children and adolescents with cerebral palsy.

INTRODUCTION: Persons with cerebral palsy require a lifetime of costly and resource intensive interventions which are often limited by equity of access. With increasing burden being placed on health systems, new methods to deliver intensive rehabilitation therapies are needed. Move it to improve it (Mitii) is an internet-based multimodal programme comprising upper-limb and cognitive training with physical activity. It can be accessed in the client's home at their convenience. The proposed study aims to test the efficacy of Mitii in improving upper-limb function and motor planning. Additionally, this study hopes to further our understanding of the central neurovascular mechanisms underlying the proposed changes and determine the cost effectiveness of Mitii. METHODS AND ANALYSIS: Children with congenital hemiplegia will be recruited to participate in this waitlist control, matched pairs, single-blind randomised trial. Children be matched at baseline and randomly allocated to receive 20 weeks of 30 min of daily Mitii training immediately, or waitlisted for 20 weeks before receiving the same Mitii training (potential total dose=70 h). Outcomes will be assessed at 20 weeks after the start of Mitii, and retention effects tested at 40 weeks. The primary outcomes will be the Assessment of Motor and Process Skills (AMPS), the Assisting Hand Assessment (AHA) and unimanual upper-limb capacity using the Jebsen-Taylor Test of Hand Function (JTTHF). Advanced brain imaging will assess use-dependant neuroplasticity. Measures of body structure and functions, activity, participation and quality of life will be used to assess Mitii efficacy across all domains of the International Classification of Functioning, Disability and Health framework. ETHICS AND DISSEMINATION: This project has received Ethics Approval from the Medical Ethics Committee of The University of Queensland (2011000608) and the Royal Children's Hospital Brisbane (HREC/11/QRCH/35). Findings will be disseminated widely through conference presentations, seminars and peer-reviewed scientific journals. TRIAL REGISTRATION: ACTRN12611001174976.

Prolonged postoperative venous thrombo-embolism prophylaxis is cost-effective in advanced ovarian cancer patients.

OBJECTIVE: The purpose of this study was to investigate the cost-effectiveness of prolonged prophylaxis with enoxaparin in high-risk surgical patients with ovarian cancer. In addition, we sought to quantify the impact of prolonged prophylaxis (PP) on the incidence of venous thromboembolism (VTE), its related complications, and overall patient survival. METHODS: A Markov decision analytic model was used to estimate the costs, resource allocation and outcomes associated with the prolonged use of enoxaparin, for a total of four weeks after surgery, in patients undergoing primary debulking surgery for stage IIIC ovarian cancer. We estimated incremental cost per quality-adjusted life-year (QALY) at one and five year intervals; the estimated reduction in VTE episodes, bleeding episodes, and survival at the five year interval for a simulated cohort of 10,000 women. RESULTS: The incremental cost effectiveness ratio (ICER) for prolonged prophylaxis (PP) was $5236/QALY and $-1462/QALY at one and five years respectively. For patients receiving PP, the model estimated a 12% reduction in the clinically evident VTE episodes and a higher five-year survival (31.61% vs. 29.96%; p<0.0001). Resource allocation analysis reveals that 95% of initial investment cost of prolonged enoxaparin is recovered within one year. CONCLUSIONS: In ovarian cancer patients undergoing open abdominal surgery, prolonged VTE prophylaxis not only improves patient outcomes, but is also a cost saving strategy when modeled over five years. A significant reduction in the episodes of VTE and a higher overall survival warrants consideration for the routine use of PP in this patient population.

Dynamic corticospinal white matter connectivity changes during stroke recovery: a diffusion tensor probabilistic tractography study.

PURPOSE: To investigate corticospinal tract connectivity changes at the cortical surface using diffusion tensor imaging (DTI) tractography during recovery from stroke. MATERIALS AND METHODS: Using data from 10 stroke patients (four subcortical) and six elderly controls, we developed an automated method to quantify altered motor connectivity that involves the use of a simplified cortical surface model as a seed mask with target regions defined within the corticospinal tracts to initiate a probabilistic tractography algorithm. RESULTS: We found no change in volume overlap of the generated corticospinal tracts in the stroke patients compared to controls, but significant connectivity changes at the boundary of the simplified cortical surface mask, especially within the ipsilesional hemisphere of stroke patients over time. Using the cortical regions with significantly enhanced connectivity as a seed mask on the patient data, tracts that are directly associated with stroke recovery can be delineated. Measures of uncertainty in fiber orientation within these fiber tracts significantly correlated with functional outcome. CONCLUSION: The novel findings from this study highlight the usefulness of this methodology to study white matter repair/reorganization during stroke recovery.

Assessment of dynamic susceptibility contrast cerebral blood flow response to amphetamine challenge: a human pharmacological magnetic resonance imaging study at 1.5 and 4 T.

Pharmacological MRI (phMRI) techniques can be used to monitor the neurophysiological effects of central nervous system (CNS) active drugs. In this study, we investigated whether dynamic susceptibility contrast (DSC) perfusion imaging employing the use of superparamagnetic iron oxide nanoparticles (Resovist) could be used to measure hemodynamic response to d-amphetamine challenge in human subjects at both 1.5 and 4 T. Significant changes in cerebral blood flow (CBF) were found in focal regions associated with the nigrostriatal circuit and mesolimbic and mesocortical dopaminergic pathways. More significant CBF responses were found at higher field strength, mainly within striatal structures. The results from this study indicate that DSC perfusion imaging using Resovist can be used to assess the efficacy of CNS-active drugs and may play a role in the development of novel psychiatric therapies at the preclinical level.

Impact of scar thickness on the assessment of viability using dobutamine echocardiography and thallium single-photon emission computed tomography: a comparison with contrast-enhanced magnetic resonance imaging.

OBJECTIVES: We sought to determine whether the transmural extent of scar (TES) explains discordances between dobutamine echocardiography (DbE) and thallium single-photon emission computed tomography (Tl-SPECT) in the detection of viable myocardium (VM). BACKGROUND: Discrepancies between DbE and Tl-SPECT are often attributed to differences between contractile reserve and membrane integrity, but may also reflect a disproportionate influence of nontransmural scar on thickening at DbE. METHODS: Sixty patients (age 62 +/- 12 years; 10 women and 50 men) with postinfarction left ventricular dysfunction underwent standard rest-late redistribution Tl-SPECT and DbE. Viable myocardium was identified when dysfunctional segments showed Tl activity >60% on the late-redistribution image or by low-dose augmentation at DbE. Contrast-enhanced magnetic resonance imaging (ceMRI) was used to divide TES into five groups: 0%, <25%, 26% to 50%, 51% to 75%, and >75% of the wall thickness replaced by scar. RESULTS: As TES increased, both the mean Tl uptake and change in wall motion score decreased significantly (both p < 0.001). However, the presence of subendocardial scar was insufficient to prevent thickening; >50% of segments still showed contractile function with TES of 25% to 75%, although residual function was uncommon with TES >75%. The relationship of both tests to increasing TES was similar, but Tl-SPECT identified VM more frequently than DbE in all groups. Among segments without scar or with small amounts of scar (<25% TES), >50% were viable by SPECT. CONCLUSIONS: Both contractile reserve and perfusion are sensitive to the extent of scar. However, contractile reserve may be impaired in the face of no or minor scar, and thickening may still occur with extensive scar.