Risk of chemotherapy-induced febrile neutropenia in intermediate-risk regimens: Clinical and economic outcomes of granulocyte colony-stimulating factor prophylaxis.

BACKGROUND: Chemotherapy-induced neutropenia increases the risk of febrile neutropenia (FN) and infection with resultant hospitalizations, with substantial health care resource utilization (HCRU) and costs. Granulocyte-colony stimulating factor (GCSF) is recommended as primary prophylaxis for chemotherapy regimens having more than a 20% risk of FN. Yet, for intermediate-risk (10%-20%) regimens, it should be considered only for patients with 1 or more clinical risk factors (RFs) for FN. It is unclear whether FN prophylaxis for intermediate-risk patients is being optimally implemented. OBJECTIVE: To examine RFs, prophylaxis use, HCRU, and costs associated with incident FN during chemotherapy. METHODS: This retrospective study used administrative claims data for commercial and Medicare Advantage enrollees with nonmyeloid cancer treated with intermediate-risk chemotherapy regimens during January 1, 2009, to March 31, 2020. Clinical RFs, GCSF prophylaxis, incident FN, HCRU, and costs were analyzed descriptively by receipt of primary GCSF, secondary GCSF, or no GCSF prophylaxis. Multivariable Cox regression analysis was used to examine the association between number of RFs and cumulative FN risk. RESULTS: The sample comprised 13,937 patients (mean age 67 years, 55% female). Patients had a mean of 2.3 RFs, the most common being recent surgery, were aged 65 years or greater, and had baseline liver or renal dysfunction; 98% had 1 or more RFs. However, only 35% of patients received primary prophylaxis; 12% received secondary prophylaxis. The hazard ratio of incident FN was higher with increasing number of RFs during the first line of therapy, yet more than 54% of patients received no prophylaxis, regardless of RFs. Use of GCSF prophylaxis varied more by chemotherapeutic regimen than by number of RFs. Among patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone, 76% received primary prophylaxis, whereas only 22% of patients treated with carboplatin/paclitaxel received primary prophylaxis. Among patients with a first line of therapy FN event, 78% had an inpatient stay and 42% had an emergency visit. During cycle 1, mean FN-related coordination of benefits-adjusted medical costs per patient per month ($13,886 for patients with primary prophylaxis and $18,233 for those with none) were driven by inpatient hospitalizations, at 91% and 97%, respectively. CONCLUSIONS: Incident FN occurred more often with increasing numbers of RFs, but GCSF prophylaxis use did not rise correspondingly. Variation in prophylaxis use was greater based on regimen than RF number. Lower health care costs were observed among patients with primary prophylaxis use. Improved individual risk identification for intermediate-risk regimens and appropriate prophylaxis may decrease FN events toward the goal of better clinical and health care cost outcomes. DISCLOSURES: This work was funded by Sandoz Inc., which participated in the design of the study, interpretation of the data, writing and revision of the manuscript, and the decision to submit the manuscript for publication. The study was performed by Optum under contract with Sandoz Inc. The author(s) meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. The authors received no direct compensation related to the development of the manuscript. Dr Li is an employee of Sandoz Inc. Drs Bell and Lal and Mr Peterson-Brandt were employees of Optum at the time of the study. Ms Anderson and Dr Aslam are employees of Optum. Dr Lyman has been primary investigator on a research grant from Amgen to their institution and has consulted for Sandoz, G1 Therapeutics, Partners Healthcare, BeyondSpring, ER Squibb, Merck, Jazz Pharm, Kallyope, Teva; Fresenius Kabi, Seattle Genetics, and Samsung.

Healthcare Resource Utilization and Costs of Steroid-Associated Complications in Patients With Graft-Versus-Host Disease.

Acute and chronic graft-versus-host disease (aGVHD/cGVHD) are serious conditions occurring after allogeneic hematopoietic cell transplantation (HCT). Steroids are the most common first-line therapy; however, they are frequently associated with numerous morbid complications. To describe the healthcare resource utilization (HCRU) and costs of steroid-related complications in patients receiving systemic steroids for GVHD. This retrospective study used medical and pharmacy claims from the Optum Research database. Eligible patients were diagnosed with GVHD (aGVHD, cGVHD, or both) after HCT and were treated with systemic steroids between July 1, 2010, and August 31, 2019. The index date was the date of the first claim for systemic steroids after GVHD diagnosis. The baseline period was the 6 months before the index date, and the follow-up period was 2 years after the index date. Outcome variables included HCRU and costs associated with steroid complications, grouped into 4 categories: bone/muscle, gastrointestinal, infection, and metabolic/endocrine. A multivariate analysis was used to assess the cost ratio associated with the presence of each steroid complication; the linear model was adjusted for baseline patient characteristics and types of steroid conditions identified during follow-up. Another multivariate analysis assessed the hazard ratio for hospitalization associated with each steroid complication using a Cox proportional hazards regression model adjusted for the time-varying presence of each complication category. A total of 689 patients were studied (median age, 55 years; male, 60%); 22% had aGVHD only, 21% had cGVHD only, and 39% had both types of GVHD. After 2 years of follow-up, 97% had at least 1 steroid-associated complication. The most common complication category was infection (79.5%), followed by metabolic/endocrine (32.4%), gastrointestinal (29.2%), and bone/muscle conditions (19.7%). About two thirds (66%) of patients with any steroid complication had ≥1 hospitalization requiring a median (interquartile range [IQR]) of 20 (8-43) hospital days. Patients with an infection experienced the highest hospitalization rate (72%) and thus the highest associated costs. The total mean (median [IQR]) healthcare cost potentially related to steroid complications was $164,787 ($50,834 [$8865-$182,693]), and the largest expense was hospitalization (mean [median {IQR}], $140,637 [$26,782 {$0-$141,398}]). Of the different steroid complications, infections were associated with the highest cost (mean [median {IQR}], $167,473 [$57,680 {$16,261-$178,698}]). In addition, a significantly higher total adjusted cost was associated with the presence of an infection, gastrointestinal complication, or bone/muscle complication in patients with GVHD versus the absence of each complication (all P < .001). Complications occurring after steroid treatment for GVHD may add substantially to the HCRU and costs associated with GVHD management. Infections in particular required inpatient care and were associated with the highest economic burden.

Positive margins matter regardless of subsequent resection findings.

OBJECTIVES: In the resection of oral cavity squamous cell carcinoma (OCSCC), an intraoperative positive surgical margin (SM) communicated to the head and neck surgeon necessitates further resection of the area of identified involvement to achieve a final negative SM. The prognostic implication of initial positive SM when the final SM is negative is understudied. MATERIALS AND METHODS: We retrospectively reviewed 249 patients with non-metastatic (stage I-IVB) OCSCC who underwent a resection from 2010 to 2019 to assess the prognostic impact of an initial positive SM. Chi-squared analysis was used to evaluate the association between an initial positive SM and clinicopathologic parameters. A Kaplan-Meier analysis was performed to estimate patient outcomes with Cox regression analysis used to determine absolute hazards. RESULTS: At a median follow-up of 28.4 months, the 2-year freedom from local recurrence (FFLR), disease-free survival (DFS), and overall survival (OS) rates were 82.1%, 63.5%, and 78.5%, respectively. Fifty patients (20.1%) had an initial positive SM which was revised to a negative SM on frozen and permanent sections by resecting further tissue while 12 patients (4.8%) had a final positive SM. An initial positive SM was independently associated with a worse FFLR (HR: 2.696, p = 0.004), DFS (HR: 1.57, p = 0.044), and OS (HR: 1.72, p = 0.029). CONCLUSION: An initial positive SM is independently associated with worse disease control and patient survival. A positive SM may be a surrogate for diffusely infiltrative disease as further malignancy identified on the re-resection specimen was associated with worse outcomes.

Real-world characteristics, treatment experiences and corticosteroid utilisation of patients treated with tofacitinib for moderate to severe ulcerative colitis.

BACKGROUND: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. We aimed to describe the real-world treatment experience and corticosteroid utilisation of patients treated with tofacitinib in a US claims database. METHODS: Patients with a UC diagnosis who initiated tofacitinib, vedolizumab or tumour necrosis factor inhibitor (TNFi) treatment between May 2018 and July 2019 were identified from the Optum Research Database. Demographic and clinical characteristics of patients who initiated tofacitinib, vedolizumab or TNFi were described. Oral corticosteroid use prior to and following tofacitinib initiation was evaluated. Tofacitinib adherence (proportion of days covered) and continuation was assessed for 6 months following initiation. Analyses were descriptive and stratified by prior biologic use (naïve, 1 or ≥ 2; minimum of 12 months prior to tofacitinib initiation). RESULTS: Among patients initiating tofacitinib (N = 225), mean age was 45.6 (SD 16.5) years and 50.2% were female. Of these, 43 (19.1%) patients were biologic-naïve and 182 (80.9%) had prior biologic use (92 [40.9%], 1 prior biologic; 90 [40.0%], ≥ 2 prior biologics). Among patients with 1 prior biologic, 82.6% were previously treated with a TNFi. Among patients with ≥ 2 prior biologics, 54.4% were previously treated with vedolizumab and a TNFi, 16.7% with two TNFi and 28.9% with ≥ 3 prior biologics. In the 6 months prior to tofacitinib initiation, 65.8% of patients had received oral corticosteroids (74.4%, 60.9% and 66.7% for biologic-naïve, 1 and ≥ 2 prior biologics, respectively). The proportion of patients with ongoing oral corticosteroid use 3-6 months after tofacitinib initiation decreased to 13.3% (9.3%, 18.5% and 10.0% for biologic-naïve, 1 and ≥ 2 prior biologics, respectively), and 19.6% of patients discontinued oral corticosteroid use during the 6 months after tofacitinib initiation. Overall, tofacitinib adherence, as determined by the mean proportion of days covered during the 6-month follow-up, was 0.7 (median 0.8). During the 6-month follow-up, 84.9% of patients continued tofacitinib. CONCLUSIONS: Among patients with UC initiating tofacitinib, the majority had prior biologic use. Tofacitinib adherence was high, discontinuation was low and oral corticosteroid utilisation decreased irrespective of prior biologic use. Further research with longer follow-up and a larger sample size is required.

The Impact of Adverse Events on Health Care Resource Utilization, Costs, and Mortality Among Patients Treated with Immune Checkpoint Inhibitors.

BACKGROUND: We investigated the association between adverse events (AEs) suspected to be immune-related and health care resource utilization, costs, and mortality among patients receiving programmed cell death 1/programmed cell death ligand 1 immune checkpoint inhibitor (ICI) monotherapy for urothelial carcinoma, renal cell carcinoma, non-small cell lung cancer, or Merkel cell carcinoma. PATIENTS AND METHODS: We conducted a retrospective cohort study using medical and pharmacy claims and enrollment information from U.S. commercial and Medicare Advantage with Part D enrollees in the Optum Research Database from March 1, 2014, through April 30, 2019. Claims were linked with mortality data from the Social Security Death Index and the National Death Index. Eligible patients had at least one ICI claim between September 1, 2014, and April 30, 2019. RESULTS: After adjusting for potential confounding variables, we found patients with AEs had more than double the risk of an inpatient stay (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.9-2.5) and an 80% higher risk of an emergency visit (HR, 1.8; 95% CI, 1.6-2.1) than patients without AEs. Adjusted 6-month total costs were $24,301 higher among patients with an AE versus those without ($99,037 vs. $74,736; 95% CI, $18,828-29,774; p < .001). Mean ± SD AE-related medical costs averaged $2,359 ± $7,496 per patient per month, driven by inpatient visits, which accounted for 89.9% of AE-related costs. Adjusted risk of mortality was similar in patients with and without AEs. CONCLUSION: Patients with AEs had higher risks of hospitalizations, emergency room visits, and higher health care costs, driven by inpatient stays, than patients without AEs. The adjusted risk of mortality was similar between the two cohorts. IMPLICATIONS FOR PRACTICE: Patients taking immune checkpoint inhibitors (ICIs) who had adverse events (AEs) had significantly higher health care costs and utilization, driven by inpatient stays, compared with patients who did not. Given this high cost associated with AEs and the differences in the side effect profile of ICIs versus traditional chemotherapy, it is important for physicians to be cognizant of these differences when treating patients with ICIs. Ongoing evaluation, earlier recognition, and more effective, multidisciplinary management of AEs may improve patient outcomes and reduce the need for costly inpatient stays.

Green Salad Intake Is Associated with Improved Oral Cancer Survival and Lower Soluble CD44 Levels.

Deficiencies in fruit and vegetable intake have been associated with oral cancer (oral cavity and oropharyngeal). Salivary rinses contain measurable biomarkers including soluble CD44 (solCD44) and total protein, which are known markers of oral cancer risk. This study investigates the effect of nutritional factors on solCD44 and protein levels to evaluate oral cancer risk and survival. We evaluated solCD44 and protein levels from 150 patients with oral and oropharyngeal squamous cell carcinoma and 150 frequency-matched controls. We subsequently characterized the effect of food group consumption and these biomarkers on progression-free survival (PFS) and overall survival (OS). Patients reported eating fewer servings of salad (p = 0.015), while controls reported eating fewer servings of potatoes (p < 0.001). Oral cancer patients who consumed at least one serving per week of green salad were found to have significantly lower CD44 levels than those who ate salad less frequently (mean of log2[solCD44]1.73 versus 2.25, p = 0.014). Patients who consumed at least one serving per week of "salad or other vegetables" had significantly longer PFS (median 43.5 versus 9.1 months, p = 0.003, adjusted hazard ratio (HR) = 0.39 p = 0.014) and OS (median 83.6 versus 10 months, p = 0.008, adjusted HR = 0.04 p = 0.029). These findings suggest that dietary factors, namely greater green salad and vegetable intake, may be associated with lower CD44 levels and better prognosis in oral cancer patients.

Benign and Malignant Granular Cell Tumor of the Hypopharynx: Two Faces of a Rare Entity.

Granular cell tumors (GCT) are rare soft tissue tumors that involve the head and neck in 50% of patients. Two distinct variants of GCT, one benign (bGCT) and the other malignant (mGCT), involving the hypopharynx, a subsite of the larynx, are presented here. The clinical presentations, radiographic features, pathologic diagnosis in these two variants of GCT are discussed. The mGCT was diagnosed only after complete tumor excision. This report highlights the importance of complete excision of the tumor mass, as diagnosis of mGCT can be exceedingly difficult to make on a small biopsy specimen. Therefore, complete excision is recommended for definitive diagnosis and treatment of GCTs.

Risk Factors for Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Homeless Shelters in Chicago, Illinois-March-May, 2020.

BACKGROUND: People experiencing homelessness are at increased risk of coronavirus disease 2019 (COVID-19), but little is known about specific risk factors for infection within homeless shelters. METHODS: We performed widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction testing and collected risk factor information at all homeless shelters in Chicago with at least 1 reported case of COVID-19 (n = 21). Multivariable, mixed-effects log-binomial models were built to estimate adjusted prevalence ratios (aPRs) for SARS-CoV-2 infection for both individual- and facility-level risk factors. RESULTS: During March 1 to May 1, 2020, 1717 shelter residents and staff were tested for SARS-CoV-2; 472 (27%) persons tested positive. Prevalence of infection was higher for residents (431 of 1435, 30%) than for staff (41 of 282, 15%) (prevalence ratio = 2.52; 95% confidence interval [CI], 1.78-3.58). The majority of residents with SARS-CoV-2 infection (293 of 406 with available information about symptoms, 72%) reported no symptoms at the time of specimen collection or within the following 2 weeks. Among residents, sharing a room with a large number of people was associated with increased likelihood of infection (aPR for sharing with >20 people compared with single rooms = 1.76; 95% CI, 1.11-2.80), and current smoking was associated with reduced likelihood of infection (aPR = 0.71; 95% CI, 0.60-0.85). At the facility level, a higher proportion of residents leaving and returning each day was associated with increased prevalence (aPR = 1.08; 95% CI, 1.01-1.16), whereas an increase in the number of private bathrooms was associated with reduced prevalence (aPR for 1 additional private bathroom per 100 people = 0.92; 95% CI, 0.87-0.98). CONCLUSIONS: We identified a high prevalence of SARS-CoV-2 infections in homeless shelters. Reducing the number of residents sharing dormitories might reduce the likelihood of SARS-CoV-2 infection. When community transmission is high, limiting movement of persons experiencing homelessness into and out of shelters might also be beneficial.

Free tissue reconstruction of the anterior skull base: A review.

OBJECTIVE: There has been a significant shift from open craniofacial resection of the anterior skull base to endoscopic approaches that accomplish the same outcomes in tumor ablation. However, when open resection is required, free flap reconstruction is often necessary to provide sufficient well-vascularized tissue for optimal wound healing as well as providing adequate tissue bulk for cosmesis. This articleaims to providea focused review of free flaps most commonly used in anterior skull base reconstruction. METHODS: This is a state-of-the-art review based on expert opinion and previously published reviews and journal articles, queried using PubMed and Google Scholar. RESULTS & CONCLUSION: Anterior skull base reconstruction via free tissue transfer is imperative in limiting complications and promoting healing, particularly with large defects, post-radiation, and in at-risk patients. The type of free flap utilized for a particular anterior skull base reconstruction should be tailored to the patient and nature of the disease. This review offers insight into the numerous reconstructive options for the free flap surgeon.

Increased hepatocyte growth factor levels over 2 years are associated with coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA)

Hepatocyte growth factor (HGF) is associated with subclinical and clinical atherosclerosis. However, the significance of change in HGF and development of atherosclerotic disease is unknown. In a large and diverse population-based cohort, we report that change in the biomarker HGF is an independent predictor of incident CHD.

Hepatocyte growth factor is associated with progression of atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Hepatocyte growth factor (HGF) has previously been associated with risk of stroke, coronary heart disease, and atherosclerosis. We hypothesized that higher circulating HGF is associated with greater progression of measures of atherosclerosis: coronary artery calcium (CAC) and carotid plaque. METHODS: Participants aged 45-84 years from the prospective cohort study Multi-Ethnic Study of Atherosclerosis had HGF measured at baseline (between 2000 and 2002) and were followed for progression of atherosclerosis for up to 12 years. CAC was measured at all five exams using the Agatston method. Mixed-effects models were used to examine the association of HGF and CAC progression among 6695 participants with available data. Relative risk regression was used to assess the association between HGF and new or additional carotid plaque between exams 1 and 5 in 3400 participants with available data. All point estimates were adjusted for potential confounding variables. RESULTS: Each standard deviation higher HGF at baseline was associated with 2.9 Agatston units/year greater CAC progression (95% CI: 1.6-4.2, p < 0.0001), and the magnitude of this association differed by race/ethnicity (p value for interaction by race = 0.003). Each standard deviation higher HGF at baseline was associated with a 4% higher risk of new or additional carotid plaque (95% CI: 1.01-1.08, p = 0.005). CONCLUSIONS: Higher levels of HGF were significantly associated with greater progression of atherosclerosis in this large and diverse population. Circulating HGF continues to show promise as a potential clinical biomarker for cardiovascular disease.

Hepatocyte growth factor demonstrates racial heterogeneity as a biomarker for coronary heart disease.

OBJECTIVE: To determine if hepatocyte growth factor (HGF), a promising biomarker of coronary heart disease (CHD) given its release into circulation in response to endothelial damage, is associated with subclinical and clinical CHD in a racial/ethnic diverse population. METHODS: HGF was measured in 6738 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Highest mean HGF values (pg/mL) were observed in Hispanic, followed by African, non-Hispanic white, then Chinese Americans. RESULTS: In all races/ethnicities, HGF levels were associated with older age, higher systolic blood pressure (SBP) and body mass index, lower high-density lipoprotein, diabetes and current smoking. In fully adjusted models, each SD higher HGF was associated with an average increase in coronary artery calcium (CAC) of 55 Agatston units for non-Hispanic whites (p<0.001) and 51 Agatston units for African-Americans (p=0.007) but was not in the other race/ethnic groups (interaction p=0.02). There were 529 incident CHD events, and CHD risk was 41% higher in African (p<0.001), 17% in non-Hispanic white (p=0.026) and Chinese (p=0.36), and 6% in Hispanic Americans (p=0.56) per SD increase in HGF. CONCLUSION: In a large and diverse population-based cohort, we report that HGF is associated with subclinical and incident CHD. We demonstrate evidence of racial/ethnic heterogeneity within these associations, as the results are most compelling in African-Americans and non-Hispanic white Americans. We provide evidence that HGF is a biomarker of atherosclerotic disease that is independent of traditional risk factors.

A Randomized, Single-Blind, Crossover Trial of Recovery Time in High-Flux Hemodialysis and Hemodiafiltration.

BACKGROUND: The choice between hemodiafiltration (HDF) or high-flux hemodialysis (HD) to treat end-stage kidney disease remains a matter of debate. The duration of recovery time after treatment has been associated with mortality, affects quality of life, and may therefore be important in informing patient choice. We aimed to establish whether recovery time is influenced by treatment with HDF or HD. STUDY DESIGN: Randomized patient-blinded crossover trial. SETTINGS & PARTICIPANTS: 100 patients with end-stage kidney disease were enrolled from 2 satellite dialysis units in Glasgow, United Kingdom. INTERVENTION: 8 weeks of HD followed by 8 weeks of online postdilution HDF or vice versa. OUTCOMES: Posttreatment recovery time, symptomatic hypotension events, dialysis circuit clotting events, and biochemical parameters. MEASUREMENTS: Patient-reported recovery time in minutes, incidence of adverse events during treatments, hematology and biochemistry results, quality-of-life questionnaire. RESULTS: There was no overall difference in recovery time between treatments (medians for HDF vs HD of 47.5 [IQR, 0-240] vs 30 [IQR, 0-210] minutes, respectively; P=0.9). During HDF treatment, there were significant increases in rates of symptomatic hypotension (8.0% in HDF vs 5.3% in HD; relative risk [RR], 1.52; 95% CI, 1.2-1.9; P<0.001) and intradialytic tendency to clotting (1.8% in HDF vs 0.7% in HD; RR, 2.7; 95% CI, 1.5-5.0; P=0.002). Serum albumin level was significantly lower during HDF (3.2 vs 3.3g/dL; P<0.001). Health-related quality-of-life scores were equivalent. LIMITATIONS: Single center; mean achieved HDF convection volume, 20.6L. CONCLUSIONS: Patients blinded to whether they were receiving HD or HDF in a randomized controlled crossover study reported similar posttreatment recovery times and health-related quality-of-life scores.

Defining myocardial tissue abnormalities in end-stage renal failure with cardiac magnetic resonance imaging using native T1 mapping.

Noninvasive quantification of myocardial fibrosis in end-stage renal disease is challenging. Gadolinium contrast agents previously used for cardiac magnetic resonance imaging (MRI) are contraindicated because of an association with nephrogenic systemic fibrosis. In other populations, increased myocardial native T1 times on cardiac MRI have been shown to be a surrogate marker of myocardial fibrosis. We applied this method to 33 incident hemodialysis patients and 28 age- and sex-matched healthy volunteers who underwent MRI at 3.0T. Native T1 relaxation times and feature tracking-derived global longitudinal strain as potential markers of fibrosis were compared and associated with cardiac biomarkers. Left ventricular mass indices were higher in the hemodialysis than the control group. Global, Septal and midseptal T1 times were all significantly higher in the hemodialysis group (global T1 hemodialysis 1171 ± 27 ms vs. 1154 ± 32 ms; septal T1 hemodialysis 1184 ± 29 ms vs. 1163 ± 30 ms; and midseptal T1 hemodialysis 1184 ± 34 ms vs. 1161 ± 29 ms). In the hemodialysis group, T1 times correlated with left ventricular mass indices. Septal T1 times correlated with troponin and electrocardiogram-corrected QT interval. The peak global longitudinal strain was significantly reduced in the hemodialysis group (hemodialysis -17.7±5.3% vs. -21.8±6.2%). For hemodialysis patients, the peak global longitudinal strain significantly correlated with left ventricular mass indices (R = 0.426), and a trend was seen for correlation with galectin-3, a biomarker of cardiac fibrosis. Thus, cardiac tissue properties of hemodialysis patients consistent with myocardial fibrosis can be determined noninvasively and associated with multiple structural and functional abnormalities.

Long-term Health Outcomes in Survivors of Childhood Cancer Diagnosed Between 1990 and 2000 in a Large US Integrated Health Care System.

We evaluated the long-term health outcomes of childhood cancer survivors (CCS) using data from the Kaiser Permanente Southern California (KPSC) health plan, whose members have similar health care coverage. Five-year survivors of invasive cancer diagnosed at ages 0 to 18 years between 1990 and 2000 at KPSC were identified and followed to December 31, 2010. A group of KPSC members without history of cancer were 10:1 matched to each CCS for comparison. Health outcomes of interest included mortality, second cancer, and chronic comorbidities. Incidence rate ratio (IRR) was estimated using multivariable Poisson regression. Cumulative incidence of each health condition over time was calculated. A total of 652 CCS and 6520 noncancer subjects were included. Compared with the noncancer subjects, IRR was significantly elevated among CCS for mortality (IRR=14.1), second cancer (IRR=10.0), cerebrovascular disease (IRR=10.1), dyslipidemia (IRR=1.9), hearing/vision loss (IRR=5.1), heart disease (IRR=3.9), hypogonadism (IRR=4.2), renal failure (IRR=13.4), and thyroid disorder (IRR=6.4). Approximately 40% of CCS developed at least 1 chronic health condition within 15 years of cancer diagnosis. Cumulative incidence curves showed different risk trajectories of various comorbidities which may inform screening schedule. These data suggested that CCS treated in a more contemporary era continued to experience substantial disease burden in their adolescent and young adulthood.

Disposition of elderly patients after head and neck reconstruction.

IMPORTANCE: A patient's needs at discharge, particularly the need for nursing facility placement, may affect hospital length of stay and health care costs. The association between age and disposition after microvascular reconstruction of the head and neck has yet to be reported in the literature. OBJECTIVE: To determine whether elderly patients are more likely to be discharged to a nursing or other care facility as opposed to returning home after microvascular reconstruction of the head and neck. DESIGN, SETTING, AND PARTICIPANTS: From January 1, 2001, through December 31, 2010, patients undergoing microvascular reconstruction at an academic medical center were identified and their medical records systematically reviewed. During the study period, 457 patients were identified by Current Procedural Terminology codes for microvascular free tissue transfer for a head and neck defect regardless of cause. Seven patients were excluded for inadequate data on the postoperative disposition or American Society of Anesthesiologists (ASA) score. A total of 450 were included for analysis. MAIN OUTCOMES AND MEASURES: Demographic and surgical data were collected, including the patient age, ASA score, and postoperative length of stay. These variables were then compared between groups of patients discharged to different posthospitalization care facilities. RESULTS: The mean age of participants was 59.1 years. Most patients (n = 386 [85.8%]) were discharged home with or without home health services. The mean age of those discharged home was 57.5 years; discharge to home was the reference for comparison and odds ratio (OR) calculation. For those discharged to a skilled nursing facility, mean age was 67.1 years (OR, 1.055; P < .001). Mean age of those discharged to a long-term acute care facility was 71.5 years (OR, 1.092; P = .002). Length of stay also affected the disposition to a skilled nursing facility (OR, 1.098), as did the ASA score (OR, 2.988). CONCLUSIONS AND RELEVANCE: Elderly patients are less likely to be discharged home after free flap reconstruction. Age, ASA score, and length of stay are independent factors for discharge to a nursing or other care facility.

Association between cardiovascular disease risk factors and occurrence of venous thromboembolism. A time-dependent analysis.

Apart from obesity, it remains controversial whether atherosclerosis and its cardiovascular risk disease (CVD) factors are associated with risk of venous thromboembolism (VTE). Using data from the Atherosclerosis Risk in Communities study (ARIC), we evaluated associations between CVD risk factors and incident VTE in a cohort of 15,340 participants who were free a history of VTE and/or anticoagulant use on enrolment. The CVD risk factors were updated during the follow-up period. Over a mean follow-up time of 15.5 years (237,375 person-years), 468 participants had VTE events. Adjusting for demographic variables and body mass index (BMI), current smokers were at greater risk [HR of 1.44 (95% CI: 1.12-1.86)] compared to non-smokers. There was a positive monotonic association between BMI and VTE risk. Individuals with a BMI ≥35 kg/m² had a HR for VTE of 3.09 (95%CI: 2.26-4.23) compared to those with normal BMI (<25 kg/m²). Greater physical activity was associated with lower VTE risk in a demographic adjusted model; however, this association became non-significant following adjustment for BMI. Alcohol intake, diabetes, hypertension, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides were not associated with VTE risk. In conclusion, among the well-established CVD risk factors, only current smoking and obesity were independently associated with VTE risk in this large cohort where risk factors were updated serially during follow-up. This finding corroborates that the pathogenesis of venous disease differs from that of atherosclerotic disease.

Our inability to predict thromboembolic events after prosthetic valve surgery.

BACKGROUND AND AIM OF THE STUDY: Thromboembolic and bleeding complications detract from outcome for patients with prosthetic heart valves. The study aim was to investigate whether measurement of coagulation activation markers and transcranial Doppler ultrasound microembolic signals (MES) could identify patients at subsequent higher risk of thromboembolism or bleeding events. METHODS: A total of 526 patients (mean age 66 years; 266 males, 260 females) who underwent elective valve replacement surgery was enrolled between April 1999 and October 2002. Clinical assessment and blood sampling for coagulation activation markers was performed preoperatively and at three and 12 months postoperatively. Transcranial Doppler MES were recorded in the first 144 patients. Status was reviewed between 21st April and 9th June 2005, with 99.4% follow up. RESULTS: Among patients, 62% had an aortic valve replaced, and mechanical valves constituted 60% of all implants. The mean follow up was 3.61 years; total follow up was 1,899.2 patient-years (pt-yr). In total, 115 patients died, while 61 experienced a total of 80 thromboembolic events: linearized event rates were 3.94% (mechanical valves) and 4.4% (bioprostheses). There was no difference between mitral and aortic implants, or among bileaflet, tilting-disc mechanical and porcine valves. Atrial fibrillation was not influential. Coagulation activation markers were not associated with thromboembolic events, except for an elevated von Willebrand factor (vWF), which was associated with a five-fold increase in embolic event rate. Fifty-one patients experienced 59 bleeding events; eight patients experienced multiple events. Linearized event rates were 3.37% (mechanical valves) and 2.49% (bioprostheses). The INR was suboptimal in 44-58% of patients. Transcranial Doppler MES were not associated with blood coagulation markers or thromboembolic events. CONCLUSION: Coagulation activation markers (except vWF) and MES did not predict thromboembolic events in valve replacement patients. Thromboembolic and bleeding event rates for West of Scotland patients generally exceeded reported rates: suboptimal anticoagulation appeared common and most likely influenced thromboembolic and bleeding event rates more than any other factor.