Baseline labs predict adverse postoperative outcomes following metastatic brain tumor resection: Analysis of 5943 patients from a prospective surgical registry (2015-2019).

INTRODUCTION: The present study sought to evaluate the predictive accuracy of preoperative lab values (PLV) on postoperative metastatic brain tumor resection (MBTR) outcomes using data queried from a large prospective international surgical registry, representing over 700 hospitals in 11 countries. METHODS: Adult metastatic brain tumor patients (N = 5943) were queried from the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database, from 2015 to 2019, using diagnostic and procedural coding. The relationship between preoperative lab values and key indicators of adverse postoperative outcomes following metastatic brain tumor resection were assessed with univariate and multivariate analyses. Adverse postoperative outcomes of interest included: 30-day mortality, Clavien-Dindo Grade IV (CDIV) complications, extended length of stay (eLOS), and discharge to non-home destination (NHD), as well as secondary outcomes: non-Clavien-Dindo Grade IV complications, unplanned reoperation, and unplanned readmission. RESULTS: Independent PLV most strongly associated with 30-day mortality were hypernatremia, increased serum creatinine, and thrombocytopenia. Significant predictors of CDIV complications were hypoalbuminemia and thrombocytopenia. eLOS was associated with hypoalbuminemia, anemia, and hyponatremia. The strongest independent predictors of NHD were anemia, hyperbilirubinemia, and hypoalbuminemia. CONCLUSION: Several pre-operative lab values independently predicted worse outcomes for metastatic brain tumor resection patients. Hypoalbuminemia, thrombocytopenia, and anemia had the strongest association with the study's adverse postoperative outcomes. These baseline lab values may be considered for preoperative risk stratification of metastatic brain tumor patients.

Exploring the Solar Wind-Planetary Interaction at Mars: Implication for Magnetic Reconnection.

The Martian crustal magnetic anomalies present a varied, asymmetric obstacle to the imposing draped interplanetary magnetic field (IMF) and solar wind plasma. Magnetic reconnection, a ubiquitous plasma phenomenon responsible for transferring energy and changing magnetic field topology, has been observed throughout the Martian magnetosphere. More specifically, reconnection can occur as a result of the interaction between crustal fields and the IMF, however, the global implications and changes to the overall magnetospheric structure of Mars have yet to be fully understood. Here, we present an analysis to determine these global implications by investigating external conditions that favor reconnection with the underlying crustal anomalies at Mars. To do so, we plot a map of the crustal anomalies' strength and orientation compiled from magnetic field data collected throughout the Mars Atmosphere and Volatile EvolutioN (MAVEN) mission. Then, we create "shear maps" which calculate and plot the angle of shear between the crustal fields and a chosen external field orientation. From there we define a "shear index" to quantify the susceptibility of a region to undergo reconnection based on a given overlaid, external field orientation and the resulting shear map for that region. We demonstrate that the shear analysis technique augments analysis of local reconnection events and suggests southward IMF conditions should favor dayside magnetic reconnection on a more global scale at Mars.

Periostin as a blood biomarker of muscle cell fibrosis, cardiomyopathy and disease severity in myotonic dystrophy type 1.

BACKGROUND AND PURPOSE: Myotonic dystrophy type 1 (DM1) is the most common form of adult-onset muscular dystrophy and is caused by an repeat expansion [r(CUG)exp] located in the 3' untranslated region of the DMPK gene. Symptoms include skeletal and cardiac muscle dysfunction and fibrosis. In DM1, there is a lack of established biomarkers in routine clinical practice. Thus, we aimed to identify a blood biomarker with relevance for DM1-pathophysiology and clinical presentation. METHODS: We collected fibroblasts from 11, skeletal muscles from 27, and blood samples from 158 DM1 patients. Moreover, serum, cardiac, and skeletal muscle samples from DMSXL mice were included. We employed proteomics, immunostaining, qPCR and ELISA. Periostin level were correlated with CMRI-data available for some patients. RESULTS: Our studies identified Periostin, a modulator of fibrosis, as a novel biomarker candidate for DM1: proteomic profiling of human fibroblasts and murine skeletal muscles showed significant dysregulation of Periostin. Immunostaining on skeletal and cardiac muscles from DM1 patients and DMSXL mice showed an extracellular increase of Periostin, indicating fibrosis. qPCR studies indicated increased POSTN expression in fibroblasts and muscle. Quantification of Periostin in blood samples from DMSXL mice and two large validation cohorts of DM1 patients showed decreased levels in animals and diseased individuals correlating with repeat expansion and disease severity and presence of cardiac symptoms identified by MRI. Analyses of longitudinal blood samples revealed no correlation with disease progression. CONCLUSIONS: Periostin might serve as a novel stratification biomarker for DM1 correlating with disease severity, presence of cardiac malfunction and fibrosis.

A single-arm, long-term efficacy and safety study of subcutaneous romiplostim in children with immune thrombocytopenia.

Romiplostim is a thrombopoietin (TPO) receptor agonist approved for children and adults with immune thrombocytopenia (ITP) for ≥6 months, recommended as second-line treatment. This phase 3b, single-arm, multicenter study investigated long-term efficacy and safety of romiplostim in children ≥1 to <18 years old with ≥6 months' ITP duration and platelet counts ≤30 × 109/L. Children received weekly subcutaneous romiplostim (1 µg/kg titrated to 10 µg/kg) to maintain platelets within 50 to 200 × 109/L. A subset underwent bone marrow examinations. The primary end point was percentage of time with platelet response during the first 6 months' treatment (counts ≥50 × 109/L without rescue medication within the preceding 4 weeks). Overall, 203 patients (median age, 10.0 years) received ≥1 dose of romiplostim, median treatment duration was ∼3 years, and median average weekly dose was 6.9 µg/kg. Ninety-five (46.8%) discontinued (lack of efficacy, n = 43 [21.2%]). Platelet responses were achieved a median (interquartile range) of 50.0% (16.7%-83.3%) of the time during the first 6 months, increasing to 78.2% (26.7%-90.4%) during the overall 36-month treatment period. Eleven patients (5.4%) achieved sustained responses (consecutive counts ≥50 × 109/L without ITP medications for ≥24 weeks). Treatment-related adverse events (AEs) occurred in 56 patients (27.6%), with 8 (3.9%) experiencing serious treatment-related AEs; all of these led to discontinuation, including 4 cases of neutralizing antibodies (romiplostim, n = 3; TPO, n = 1). Bleeding occurred in 141 patients (69.5%), decreasing over time; grade ≥3 bleeding events occurred in 20 (9.9%). At year 2, eight of 63 evaluable patients (12.7%) had grade 2 reticulin. Long-term romiplostim resulted in sustained on-treatment platelet responses with an overall safety profile consistent with previous studies. This trial was registered at www.clinicaltrials.gov as #NCT02279173.

A Statistical Investigation of Factors Influencing the Magnetotail Twist at Mars.

The Martian magnetotail exhibits a highly twisted configuration, shifting in response to changes in polarity of the interplanetary magnetic field's (IMF) dawn-dusk (B Y) component. Here, we analyze ∼6000 MAVEN orbits to quantify the degree of magnetotail twisting (θ Twist) and assess variations as a function of (a) strong planetary crustal field location, (b) Mars season, and (c) downtail distance. The results demonstrate that θ Twist is larger for a duskward (+B Y) IMF orientation a majority of the time. This preference is likely due to the local orientation of crustal magnetic fields across the surface of Mars, where a +B Y IMF orientation presents ideal conditions for magnetic reconnection to occur. Additionally, we observe an increase in θ Twist with downtail distance, similar to Earth's magnetotail. These findings suggest that coupling between the IMF and moderate-to-weak crustal field regions may play a major role in determining the magnetospheric structure at Mars.

Coronary microvascular function and visceral adiposity in patients with normal body weight and type 2 diabetes.

OBJECTIVE: This study sought to assess whether diabetes affects coronary microvascular function in individuals with normal body weight. METHODS: Seventy-five participants (30 patients with type 2 diabetes [T2D] who were overweight [O-T2D], 15 patients with T2D who were lean [LnT2D], 15 healthy volunteers who were lean [LnHV], and 15 healthy volunteers who were overweight [O-HV]) without established cardiovascular disease were recruited. Participants underwent magnetic resonance imaging for assessment of subcutaneous, epicardial, and visceral adipose tissue areas, adenosine stress myocardial blood flow (MBF), and cardiac structure and function. RESULTS: Stress MBF was reduced only in the O-T2D group (mean [SD], LnHV = 2.07 [0.47] mL/g/min, O-HV = 2.08 [0.42] mL/g/min, LnT2D = 2.16 [0.36] mL/g/min, O-T2D = 1.60 [0.28] mL/g/min; p ≤ 0.0001). Accumulation of visceral fat was evident in the LnT2D group at similar levels to the O-HV group (LnHV = 127 [53] cm2 , O-HV = 181 [60] cm2 , LnT2D = 182 [99] cm2 , O-T2D = 288 [72] cm2 ; p < 0.0001). Only the O-T2D group showed reductions in left ventricular ejection fraction (LnHV = 63% [4%], O-HV = 63% [4%], LnT2D = 60% [5%], O-T2D = 58% [6%]; p = 0.0008) and global longitudinal strain (LnHV = -15.1% [3.1%], O-HV= -15.2% [3.7%], LnT2D = -13.4% [2.7%], O-T2D = -11.1% [2.8%]; p = 0.002) compared with both control groups. CONCLUSIONS: Patients with T2D and normal body weight do not show alterations in global stress MBF, but they do show significant increases in visceral adiposity. Patients with T2D who were overweight and had no prior cardiovascular disease showed an increase in visceral adiposity and significant reductions in stress MBF.

Assessment of romiplostim immunogenicity in pediatric patients in clinical trials and in a global postmarketing registry.

Development of first-generation thrombopoietins (TPOs) was halted due to antibodies that neutralized endogenous TPO, causing protracted thrombocytopenia in some patients. The second-generation TPO receptor agonist romiplostim, having no homology to TPO, was developed to circumvent potential immunogenicity. We examined the development of binding and neutralizing antibodies to romiplostim and TPO among pediatric patients with primary immune thrombocytopenia (ITP) in 5 clinical trials and a global postmarketing registry. In the trials, 25 of 280 (8.9%) patients developed anti-romiplostim binding antibodies. The first positive result was detected 67 weeks (median) after romiplostim treatment was initiated. The median romiplostim dose was 8 µg/kg, and the median platelet count was 87 × 109/L. Most patients who developed anti-romiplostim binding antibodies (18 of 25 [72%]) had ≥90% of platelet assessments showing a response. Anti-romiplostim neutralizing antibodies developed in 8 of 280 (2.9%) patients. The development of anti-romiplostim neutralizing antibodies was unrelated to the romiplostim dose, and most patients who developed the antibodies (7 of 8 [88%]) had platelet response. Nine of 279 (3.2%) patients developed anti-TPO binding antibodies, and 1 (0.4%) developed transient anti-TPO neutralizing antibodies. In 8 patients who developed anti-romiplostim neutralizing antibodies, no TPO cross-reactivity was observed. In the postmarketing registry, 3 of 19 (15.8%) patients developed anti-romiplostim binding antibodies; 1 (5.3%) patient developed anti-romiplostim neutralizing antibodies. These results suggest that immunogenicity to romiplostim occurs infrequently in pediatric patients with ITP and is generally not associated with loss of platelet response or other negative clinical sequelae.

Febrile neutropenia-related care and associated costs in elderly patients with breast cancer, lung cancer, or non-Hodgkin lymphoma.

PURPOSE: Limited information is available regarding elderly patients experiencing febrile neutropenia (FN). This study evaluated FN-related care among elderly cancer patients who received high/intermediate FN-risk chemotherapy and experienced ≥ 1 FN episodes. METHODS: We used Medicare data to identify patients aged ≥ 66 years who initiated high/intermediate FN-risk chemotherapy between 1 January 2008 and 31 August 2015 to treat breast cancer (BC), lung cancer (LC), or non-Hodgkin lymphoma (NHL) and had ≥ 1 FN episodes. We identified within-cycle FN episodes for each chemotherapy cycle on Part A inpatient claims or outpatient or Part B claims. We described the FN-related care setting (inpatient hospital, outpatient emergency department [ED], or outpatient non-ED) and reported mean total cost of FN-related care per episode overall and by care setting (adjusted to 2015 US$). RESULTS: We identified 2138, 3521, and 2862 patients with BC, LC, and NHL, respectively, with ≥ 1 FN episodes (total episodes: 2407, 3840, 3587, respectively). Most FN episodes required inpatient care (BC, 88.1%; LC, 93.0%; NHL, 93.2%) with mean hospital length of stay (LOS) 6.2, 6.5, and 6.8 days, respectively. Intensive care unit admission was required for 20.4% of BC, 29.0% of LC, and 25.7% of NHL hospitalizations (mean LOS: 4.7, 4.7, 5.5 days, respectively). The mean total cost of FN care per episode was $11,959 BC, $14,388 LC, and $15,006 NHL, with inpatient admission the costliest care component ($11,826; $14,294; and $14,873; respectively). CONCLUSIONS: Among elderly patients with BC, LC, or NHL who experienced FN, most FN episodes required costly hospital care, highlighting the FN burden on healthcare systems.

Prophylaxis of febrile neutropenia with colony-stimulating factors: the first 25 years.

Filgrastim prophylaxis, both primary and secondary, was rapidly incorporated into clinical practice in the 1990s. When pegfilgrastim became available in 2002, it quickly replaced filgrastim as the colony-stimulating factor (CSF) of choice for prophylaxis. Use of prophylaxis increased markedly in the first decade of this century and has stabilized during the present decade. Data concerning real-world CSF prophylactic practice patterns are limited but suggest that both primary and secondary prophylaxis are common, and that use is frequently inappropriate according to guidelines. The extent of inappropriate use is controversial, as are issues concerning the cost-effectiveness of prophylaxis versus no prophylaxis and the cost-effectiveness of primary prophylaxis versus secondary prophylaxis. Nevertheless, CSF prophylaxis is firmly established as a valuable adjunct to chemotherapy and will almost certainly continue to be widely used for the foreseeable future. In this article, we chronicle the use and impact of CSF prophylaxis in US patients receiving myelosuppressive chemotherapy for non-myeloid malignancies. We emphasize the interplay of expert opinion, clinical evidence, and economic factors in shaping the use of CSFs in clinical practice over time, and, with the recent introduction of new CSF agents and options, we aim to provide useful clinical and economic information for healthcare decision makers.

The long-term social value of granulocyte colony-stimulating factors.

OBJECTIVES: Febrile neutropenia (FN) is a life-threatening complication of chemotherapy that can lead to hospitalizations, chemotherapy dose reductions or delays, and mortality. Granulocyte colony-stimulating factor (G-CSF) prophylaxis reduces the incidence of FN, enabling patients to undergo and remain on myelosuppressive chemotherapy. We estimate the benefits of continuing current G-CSF use patterns and an alternative that aligns prophylactic G-CSF use with guideline recommendations. STUDY DESIGN: Using The Health Economics Medical Innovation Simulation microsimulation, we estimated lifetime social value (SV) of prophylactic G-CSF for a nationally representative US population with breast, lung, and gynecological cancers and non-Hodgkin lymphoma. METHODS: SV estimates included the cost of G-CSF, FN, chemotherapy relative dose intensity (RDI) less than 85% (RDI<85%), medical spending, and deaths for 3 scenarios: current use (current G-CSF use), targeted use (100% G-CSF use among patients with high FN risk), and reduced use (current G-CSF use reduced by 20% across all FN risk categories). RESULTS: Over 10 years, current use, compared with no G-CSF use, would decrease cases of FN by 3.3 million, prevent 354,000 cases of RDI<85%, and generate $96 billion in SV. Compared with current use, targeted use would decrease cases of FN by an additional 3.3 million, prevent 355,000 more cases of RDI<85%, and generate another $119 billion in SV. Reduced use would increase FN and RDI<85%, lowering SV by $18 billion compared with current use. CONCLUSIONS: Current use of G-CSF prophylaxis would provide $96 billion in SV over the next 10 years. Targeting G-CSF prophylaxis to align with guidelines would more than double SV, highlighting the substantial value of appropriate FN risk assessment and targeted G-CSF prophylaxis.

Use and effectiveness of pegfilgrastim prophylaxis in US clinical practice:a retrospective observational study.

BACKGROUND: Febrile neutropenia (FN) is a serious complication of myelosuppressive chemotherapy. Clinical practice guidelines recommend routine prophylactic coverage with granulocyte colony-stimulating factor (G-CSF)-such as pegfilgrastim-for most patients receiving chemotherapy with an intermediate to high risk for FN. Patterns of pegfilgrastim prophylaxis during the chemotherapy course and associated FN risks in US clinical practice have not been well characterized. METHODS: A retrospective cohort design and data from two commercial healthcare claims repositories (01/2010-03/2016) and Medicare Claims Research Identifiable Files (01/2007-09/2015) were employed. Study population included patients who had non-metastatic breast cancer or non-Hodgkin's lymphoma and received intermediate/high-risk regimens. Pegfilgrastim prophylaxis use and FN incidence were ascertained in each chemotherapy cycle, and all cycles were pooled for analyses. Adjusted odds ratios for FN were estimated for patients who did versus did not receive pegfilgrastim prophylaxis in that cycle. RESULTS: Study population included 50,778 commercial patients who received 190,622 cycles of chemotherapy and 71,037 Medicare patients who received 271,944 cycles. In cycle 1, 33% of commercial patients and 28% of Medicare patients did not receive pegfilgrastim prophylaxis, and adjusted odds of FN were 2.6 (95% CI 2.3-2.8) and 1.6 (1.5-1.7), respectively, versus those who received pegfilgrastim prophylaxis. In cycle 2, 28% (commercial) and 26% (Medicare) did not receive pegfilgrastim prophylaxis; corresponding adjusted FN odds were comparably elevated (1.9 [1.6-2.2] and 1.6 [1.5-1.8]). Results in subsequent cycles were similar. Across all cycles, 15% of commercial patients and 23% of Medicare patients did not receive pegfilgrastim prophylaxis despite having FN in a prior cycle, and prior FN increased odds of subsequent FN by 2.1-2.4 times. CONCLUSIONS: Notwithstanding clinical practice guidelines, a large minority of patients did not receive G-CSF prophylaxis, and FN incidence was substantially higher among this subset of the population. Appropriate use of pegfilgrastim prophylaxis may reduce patient exposure to this potentially fatal but largely preventable complication of myelosuppressive chemotherapy.

Risks and consequences of travel burden on prophylactic granulocyte colony-stimulating factor administration and incidence of febrile neutropenia in an aged Medicare population.

OBJECTIVE: Granulocyte colony-stimulating factors (G-CSFs) decrease the incidence of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. This study examines the impact patient travel burden has on administration of prophylactic G-CSFs and the subsequent impact on FN incidence. METHODS: Medicare claims data were used to identify a cohort of beneficiaries age 65+ with non-myeloid cancers at high risk for FN between January 2012 and December 2014. Driving distance and time were calculated from patient residence ZIP code to the location of G-CSF and/or chemotherapy administration. Regression models were used to estimate the odds of G-CSF prophylaxis relative to patient driving distance and time, and odds of FN incidence relative to timing of G-CSF administration (optimal [days 2-4 after chemotherapy], sub-optimal [same day], or none). RESULTS: The 52,389 study patients had a mean age of 73.5 years, and were 82% female and 89% white race; 49% had female breast cancer, 12% lung cancer, 15% ovarian cancer, and 24% non-Hodgkin's lymphoma. Of these high FN risk patients, 69% had at least one prophylactic G-CSF administration within at least one chemotherapy cycle. The percentage of patients receiving prophylactic G-CSFs in the first cycle was 56%. Median travel time was slightly longer for patients who did not receive G-CSFs and patients receiving short-acting vs long-acting G-CSFs. The odds of receiving no G-CSFs were 26-52% higher (depending on cancer type) for patients with a >80-min one-way travel time, compared to patients traveling <20-min. Concurrently, the odds of FN (using a "narrow" definition) were 18-93% higher for patients who did not receive G-CSFs in the first cycle of chemotherapy. CONCLUSIONS: Travel burden, linked to clinic visits for G-CSF administration following myelosuppressive chemotherapy, is associated with sub-optimal use of G-CSF prophylaxis, which may result in a higher incidence of FN.

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis: a retrospective evaluation using Medicare claims.

BACKGROUND: Two recent evaluations reported that many cancer chemotherapy patients discontinue pegfilgrastim prophylaxis (PP) following the first cycle, and that these patients have a higher subsequent risk of febrile neutropenia (FN). Such evidence is based principally on the experience of younger adults with private healthcare coverage, and the generalizability of results to elderly Medicare patients is unknown. METHODS: A matched-cohort design and data from the Medicare Claims Research Identifiable Files were employed. The source population comprised cancer patients aged ≥65 years who received chemotherapy with intermediate/high-risk for FN and first-cycle PP. From the source population, beginning with the second cycle, all patients who received PP in all previous cycles were identified. From this sub-set, patients who did not receive PP in the cycle of interest ("comparison patients") were matched to those who received PP in that cycle ("PP patients"); the same process was repeated for subsequent cycles. Odds ratios (OR) for FN (broad and narrow definitions) were estimated using generalized estimating equations. RESULTS: Among 77,616 elderly patients in the source population, 5.3% did not receive second-cycle PP and were matched to those who did. In cycle 2, FN odds were significantly higher among comparison patients vs PP patients when employing the broad definition (OR = 1.9, p < .001) and the narrow definition (OR = 2.1, p < .001). Results for subsequent cycles (broad definition: OR = 2.0, p < .001; narrow definition: OR = 2.1, p < .001) and for the last cycle (broad definition: OR = 1.4, p = .060; narrow definition: OR = 1.7, p = .055) were largely comparable. CONCLUSIONS: In this large-scale evaluation of elderly Medicare patients who received myelosuppressive chemotherapy and first-cycle PP in recent US clinical practice, FN risk was substantially lower among patients who continued to receive PP in subsequent cycles vs those who discontinued PP.

Risk of chemotherapy-induced febrile neutropenia with same-day versus next-day pegfilgrastim prophylaxis among patients aged ≥65 years: a retrospective evaluation using Medicare claims.

BACKGROUND: Two recent evaluations reported that risk of febrile neutropenia (FN) may be higher when pegfilgrastim prophylaxis (PP) is administered on same day as chemotherapy rather than per recommendation (1-3 days following chemotherapy). Such evidence is based largely on the experience of younger privately insured adults and may not be generalizable to older patients in US clinical practice. METHODS: A retrospective cohort design and data from Medicare Claims Research Identifiable Files (January 2008-September 2015) were employed. Patients were aged ≥65 years, had breast cancer or non-Hodgkin's lymphoma, received chemotherapy with intermediate/high risk for FN, and received PP in ≥1 cycle; cycles with PP were stratified based on administration day (same-day ["Day 0"] vs. 1-3 days following chemotherapy ["Days 1-3"]) and were pooled for analyses. Adjusted odds ratios (ORs) for FN during the cycle were estimated for patients who received PP on Day 0 versus Days 1-3. RESULTS: Study population included 65,003 patients who received PP in 261,184 cycles; in 5% of cycles, patients received PP on Day 0. Incidence proportion for FN in cycle 1 was 11.4% for Day 0 versus 8.4% for Days 1-3; adjusted OR was 1.4 (p < .001). Incidence proportion for FN when considering all cycles was 7.7% for Day 0 and 6.0% for Days 1-3; adjusted OR was 1.3 (p < .001). Adjusted ORs when considering all cycles and only inpatient FN episodes (1.3, p < .001) and the narrow definition for FN (1.5, p < .001) were similar. CONCLUSIONS: Among Medicare patients receiving chemotherapy and PP in US clinical practice, PP was administered before the recommended timing in 5% of cycles and FN incidence was significantly higher in these cycles. Along with prior research, study findings support recently updated US practice guidelines indicating that PP should be administered the day after chemotherapy.

Travel burden associated with granulocyte colony-stimulating factor administration in a Medicare aged population: a geospatial analysis.

OBJECTIVE: Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) is recommended for patients receiving myelosuppressive chemotherapy regimens with a high risk of febrile neutropenia (FN). G-CSFs should be administered starting the day after chemotherapy, necessitating return trips to the oncology clinic at the end of each cycle. We examined the travel burden related to prophylactic G-CSF injections after chemotherapy in the US. METHODS: We used 2012-2014 Medicare claims data to identify a national cohort of beneficiaries age 65+ with non-myeloid cancers who received both chemotherapy and prophylactic G-CSFs. Patient travel origin was based on residence ZIP code. Oncologist practice locations and hospital addresses were obtained from the Medicare Physician Compare and Hospital Compare websites and geocoded using the Google Maps Application Programming Interface (API). Driving distance and time to the care site from each patient ZIP code tabulation area (ZCTA) were calculated using Open Street Maps road networks. Geographic and socio-economic characteristics of each ZCTA from the US Census Bureau's American Community Survey were used to stratify and analyze travel estimates. RESULTS: The mean one-way driving distance to the G-CSF provider was 23.8 (SD 30.1) miles and the mean one-way driving time was 33.3 (SD 37.8) minutes. When stratified by population density, the mean one-way travel time varied from 12.1 (SD 10.1) minutes in Very Dense Urban areas to 76.7 (SD 72.1) minutes in Super Rural areas. About 48% of patients had one-way travel times of <20 minutes, but 19% of patients traveled ≥50 minutes one way for G-CSF prophylaxis. Patients in areas with above average concentrations of aged, poor or disabled residents were more likely to experience longer travel. CONCLUSIONS: Administration of G-CSF therapy after chemotherapy can present a significant travel burden for cancer patients. Technological improvements in the form and methods of drug delivery for G-CSFs might significantly reduce this travel burden.

Sports Nutrition Knowledge among Mid-Major Division I University Student-Athletes.

Competitive athletes have goals to optimize performance and to maintain healthy body composition. Sports nutrition is a component of training programs often overlooked by student-athletes and their coaches. The purpose of this study was to examine student-athletes' sports nutrition knowledge across sex, class level, team, and completion of prior nutrition coursework. Participants included 123 mid-major Division I university student-athletes (47 females and 76 males) from baseball, softball, men's soccer, track and field, and tennis. The student-athletes completed a survey questionnaire to determine adequate sports nutrition knowledge (mean ≥ 75%). The overall mean sports nutrition knowledge score for the student-athletes was 56.9% which was considered inadequate sports nutrition knowledge (mean < 75%). Only 12 student-athletes achieved adequate sports nutrition knowledge score of 75% or higher. There were no differences by sex, class level, team, and completion of prior nutrition coursework. Student-athletes' inadequate sports nutrition knowledge may place them at nutrition risk, lead to impaired performance, and affect their lean body mass and energy levels. Athletics personnel should not assume student-athletes have adequate sports nutrition knowledge. Athletic departments may make available a board certified Sports Dietitian or Registered Dietitian and offer classroom or online courses facilitating student-athletes to optimize nutrition knowledge and behaviors.

Management of dysfunctional uterine bleeding based on endometrial thickness.

OBJECTIVE: To manage patients with dysfunctional uterine bleeding (DUB) according to endometrial thickness. METHODS: A retrospective chart review of 49 patients who reported 8 or more days of bleeding was performed. They were then divided into three groups based on endometrial thickness (mm): less than 6, 6-11, and greater than 11. These three groups were treated with combined oral contraceptive pills (OCP), conjugated estrogen plus progesterone and megestrol respectively. Patients given megestrol also underwent endometrial biopsy before treatment. Patients recorded the degree of bleeding each day for one month after starting treatment. RESULTS: Mean endometrial thickness in the combined OCPs, conjugated estrogen plus progesterone and megestrol groups were 4, 8 and 14 mm, respectively. Combined OCPs decreased bleeding from 46 to 8 days (P < 0.05, n = 8). Conjugated estrogen plus progesterone decreased the number of days of bleeding from a mean of 41 to 9 (P < 0.01, n = 16). Megestrol decreased bleeding from 54 to 3 days (P < 0.001, n = 25). 52% of patients given megestrol had endometrial hyperplasia. CONCLUSION: These results support the effectiveness of treating patients with DUB according to endometrial thickness.

Type 2 11beta-hydroxysteroid dehydrogenase activity in human fallopian tube and correlation of enzyme levels with endometrial histopathology.

PROBLEM: The inter-conversion of hormonally active cortisol and inactive cortisone is catalyzed by 11beta-hydroxysteroid dehydrogenase (11beta-HSD). This conversion controls the level of active glucocorticoid concentration in tissues. As the fallopian tube plays a major role in the process of fertilization, we wanted to investigate whether 11beta-HSD is present in the human fallopian tube to control the glucocorticoid levels as in other tissues. METHOD OF STUDY: Isthmic, ampullary and fimbrial portions of the fallopian tube are obtained from patients undergoing hysterectomy and salpingo-oopherectomy for symptomatic leomyomata uteri. 11beta-HSD activities were measured in the homogenates of the tube, cortisol as the steroid substrate. The enzyme activity was expressed as nanomolar cortisone formed per minute per gram of tissue (mean +/- S.D.). RESULTS: A significant level of 11beta-HSD activity in oxidation direction was found in all three parts of the tube. There is no significant difference in the distribution of the enzyme activity throughout the tube. When tubal 11beta-HSD activity was compared with endometrial histology, the enzyme activity is significantly lower in proliferative endometrium when compared with secretory endometrium (P = 0.002). The enzyme activity in inactive endometrium is significantly higher than the active endometrium (P = 0.05). CONCLUSION: The presence of 11beta-HSD throughout the fallopian tube and its correlation to endometrial histology is indicative of its probable role in controlling the glucocorticoid levels in the tissue, which in turn may influence the fertilization process.

Diversity selection for phase-diverse phase retrieval.

Wavefront-sensing performance is assessed for focus-diverse phase retrieval as the aberration spatial frequency and the diversity defocus are varied. The analysis includes analytical predictions for optimal diversity values corresponding to the recovery of a dominant spatial-frequency component in the pupil. The calculation is shown to be consistent with the Cramér-Rao lower bound by considering a sensitivity analysis of the point-spread function to the spatial frequency being estimated. A maximum value of diversity defocus is also calculated, beyond which wavefront-sensing performance decreases as diversity defocus is increased. The results are shown to be consistent with the Talbot imaging phenomena, explaining multiple periodic regions of maximum and minimum contrast as a function of aberration spatial frequency and defocus. Wavefront-sensing performance for an iterative-transform phase-retrieval algorithm is also considered as diversity defocus and aberration spatial frequency are varied.