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Item Ability of the National Surgical Quality Improvement Program Risk Calculator to Predict Complications Following Total Laryngectomy(JAMA, 2016-10) Schneider, Alexander L.; Deig, Christopher R.; Prasad, Kumar G.; Nelson, Benton G.; Mantravadi, Avinash V.; Brigance, Joseph S.; Langer, Mark P.; McDonald, Mark W.; Johnstone, Peter A.; Moore, Michael G.; Department of Otololaryngology-Head and Neck Surgery, School of MedicineImportance The accuracy of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) risk calculator has been assessed in multiple surgical subspecialties; however, there have been no publications doing the same in the head and neck surgery literature. Objective To evaluate the accuracy of the calculator’s predictions in a single institution’s total laryngectomy (TL) population. Design, Setting, and Participants Total laryngectomies performed between 2013 and 2014 at a tertiary referral academic center were evaluated using the risk calculator. Predicted 30-day outcomes were compared with observed outcomes for return to operating room, surgical site infection, postoperative pneumonia, length of stay, and venous thromboembolism. Main Outcomes and Measures Comparison of the NSQIP risk calculator’s predicted postoperative complication rates and length of stay to what occurred in this patient cohort using percent error, Brier scores, area under the receiver operating characteristic curve, and Pearson correlation analysis. Results Of 49 patients undergoing TL, the mean (SD) age at operation was 59 (9.3) years, with 67% male. The risk calculator had limited efficacy predicting perioperative complications in this group of patients undergoing TL with or without free tissue reconstruction or preoperative chemoradiation or radiation therapy with a few exceptions. The calculator overestimated the occurrence of pneumonia by 165%, but underestimated surgical site infection by 7%, return to operating room by 24%, and length of stay by 13%. The calculator had good sensitivity and specificity of predicting surgical site infection for patients undergoing TL with free flap reconstruction (area under the curve, 0.83). For all other subgroups, however, the calculator had poor sensitivity and specificity for predicting complications. Conclusions and Relevance The risk calculator has limited utility for predicting perioperative complications in patients undergoing TL. This is likely due to the complexity of the treatment of patients with head and neck cancer and factors not taken into account when calculating a patient’s risk.Item Acquisition of Relative Interstrand Crosslinker Resistance and PARP Inhibitor Sensitivity in Fanconi Anemia Head and Neck Cancers(American Association for Cancer Research, 2015-04-15) Lombardi, Anne J.; Hoskins, Elizabeth E.; Foglesong, Grant D.; Wikenheiser-Brokamp, Kathryn A.; Wiesmüller, Lisa; Hanenberg, Helmut; Andreassen, Paul R.; Jacobs, Allison J.; Olson, Susan B.; Keeble, Winifred W.; Hays, Laura E.; Wells, Susanne I.; Department of Medical & Molecular Genetics, IU School of MedicinePURPOSE: Fanconi anemia is an inherited disorder associated with a constitutional defect in the Fanconi anemia DNA repair machinery that is essential for resolution of DNA interstrand crosslinks. Individuals with Fanconi anemia are predisposed to formation of head and neck squamous cell carcinomas (HNSCC) at a young age. Prognosis is poor, partly due to patient intolerance of chemotherapy and radiation requiring dose reduction, which may lead to early recurrence of disease. EXPERIMENTAL DESIGN: Using HNSCC cell lines derived from the tumors of patients with Fanconi anemia, and murine HNSCC cell lines derived from the tumors of wild-type and Fancc(-/-) mice, we sought to define Fanconi anemia-dependent chemosensitivity and DNA repair characteristics. We utilized DNA repair reporter assays to explore the preference of Fanconi anemia HNSCC cells for non-homologous end joining (NHEJ). RESULTS: Surprisingly, interstrand crosslinker (ICL) sensitivity was not necessarily Fanconi anemia-dependent in human or murine cell systems. Our results suggest that the increased Ku-dependent NHEJ that is expected in Fanconi anemia cells did not mediate relative ICL resistance. ICL exposure resulted in increased DNA damage sensing and repair by PARP in Fanconi anemia-deficient cells. Moreover, human and murine Fanconi anemia HNSCC cells were sensitive to PARP inhibition, and sensitivity of human cells was attenuated by Fanconi anemia gene complementation. CONCLUSIONS: The observed reliance upon PARP-mediated mechanisms reveals a means by which Fanconi anemia HNSCCs can acquire relative resistance to the ICL-based chemotherapy that is a foundation of HNSCC treatment, as well as a potential target for overcoming chemoresistance in the chemosensitive individual.Item Adult BMI change and risk of Breast Cancer: National Health and Nutrition Examination Survey (NHANES) 2005-2010(Springer-Verlag, 2015-11) Gathirua-Mwangi, Wambui G.; Zollinger, Terrell W.; Murage, Mwangi J.; Pradhan, Kamnesh R.; Champion, Victoria L.; Department of Epidemiology, Richard M. Fairbanks School of Public HealthOBJECTIVE: Breast cancer is the second leading cause of cancer mortality among women in the developed world. This study assessed the association between occurrence of breast cancer and body mass index (BMI) change from age 25 to age closest to breast cancer diagnosis while exploring the modifying effects of demographic variables. METHODS: The National Health and Nutrition Examination Survey data were used. Women included were ≥50 years, not pregnant and without a diagnosis of any cancer but breast. The total sample included 2895 women (172 with breast cancer and 2723 controls with no breast cancer diagnosis). Multivariate logistic regression was used to estimate the OR and 95 % CIs and interaction evaluated by including an interaction term in the model. RESULTS: Women whose BMI increased from normal or overweight to obese compared to those who remained at a normal BMI were found to have a 2 times higher odds (OR = 2.1; 95 % CI 1.11-3.79) of developing breast cancer. No significant association was observed for women who increased to overweight. However, a more pronounced association was observed in non-Hispanic black women (OR = 6.6; 95 % CI 1.68-25.86) and a significant association observed when they increased from normal to overweight (OR = 4.2; 95 % CI 1.02-17.75). CONCLUSIONS: Becoming obese after age 25 is associated with increased risk of breast cancer in women over 50 years old, with non-Hispanic black women being at greatest risk.Item Confirmatory factor analysis of the Pittsburgh Sleep Quality Index in women with hot flashes(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2015-11) Otte, Julie L.; Rand, Kevin L.; Landis, Carol A.; Paudel, Misti L.; Newton, Katherine M.; Woods, Nancy; Carpenter, Janet S.; IU School of NursingOBJECTIVE: Women, especially those with hot flashes, report poor sleep quality during various stages of the menopausal transition and postmenopause. Sleep measurements vary widely because of the copious instruments available. The Pittsburgh Sleep Quality Index (PSQI) is a frequently used questionnaire that produces a single score for sleep quality. This one-factor structure has not received consistent support in the literature. The goal of this analysis was to determine the best factor structure of the PSQI in women with hot flashes. METHODS: A confirmatory factor analysis was conducted on PSQI baseline data from three randomized controlled clinical trials enrolling perimenopausal and postmenopausal women with hot flashes (N = 849) from the Menopause Strategies: Finding Lasting Answers for Symptoms and Health network. Several a priori factor models were compared. RESULTS: One-factor and two-factor models did not fit the data. A three-factor model comprising sleep efficiency, perceived sleep quality, and daily disturbance showed good fit; however, the sleep medication item was dropped because of poor fit and low rates of sleep medication use. The three-factor model was examined in African-American and white subsamples and was found to be similar in both groups; however, two items showed small group differences in strength as indicators. CONCLUSIONS: Sleep quality in midlife women with hot flashes, as measured by the PSQI, seems to comprise three correlated factors. Minor measurement differences detected between groups are of research interest but do not necessitate different scoring practices. Additional research is needed to further define sleep quality and its associations with health-related outcomes.Item Cost effectiveness of telecare management for pain and depression in patients with cancer: results from a randomized trial(Elsevier, 2014-11) Choi Yoo, Sung J.; Nyman, John A.; Cheville, Andrea L.; Kroenke, Kurt; Department of Medicine, IU School of MedicineOBJECTIVE: Pain and depression are prevalent and treatable symptoms among patients with cancer, yet they are often undetected and undertreated. The Indiana Cancer Pain and Depression (INCPAD) trial demonstrated that telecare management can improve pain and depression outcomes. This article investigates the incremental cost effectiveness of the INCPAD intervention. METHODS: The INCPAD trial was conducted in 16 community-based urban and rural oncology practices in Indiana. Of the 405 participants, 202 were randomized to the intervention group and 203 to the usual-care group. Intervention costs were determined, and effectiveness outcomes were depression-free days and quality-adjusted life years. RESULTS: The intervention group was associated with a yearly increase of 60.3 depression-free days (S.E. = 15.4; P < 0.01) and an increase of between 0.033 and 0.066 quality-adjusted life years compared to the usual care group. Total cost of the intervention per patient was US$1189, which included physician, nurse care manager and automated monitoring set-up and maintenance costs. Incremental cost per depression-free day was US$19.72, which yields a range of US$18,018 to US$36,035 per quality-adjusted life year when converted to that metric. When measured directly, the incremental cost per quality-adjusted life year ranged from US$10,826 based on the modified EQ-5D to US$73,286.92 based on the SF-12. CONCLUSION: Centralized telecare management, coupled with automated symptom monitoring, appears to be a cost effective intervention for managing pain and depression in cancer patients.Item Francisella philomiragia Bacteremia in a Patient with Acute Respiratory Insufficiency and Acute-on-Chronic Kidney Disease(American Society for Microbiology, 2015-12) Relich, Ryan F.; Humphries, Romney M.; Mattison, H. Reid; Miles, Jessica E.; Simpson, Edward R.; Corbett, Ian J.; Schmitt, Bryan H.; May, M.; Department of Pathology & Laboratory Medicine, IU School of MedicineFrancisella philomiragia is a very uncommon pathogen of humans. Diseases caused by it are protean and have been reported largely in near-drowning victims and those with chronic granulomatous disease. We present a case of F. philomiragia pneumonia with peripheral edema and bacteremia in a renal transplant patient and review the diverse reports of F. philomiragia infections.Item HIV Infection Linked to Injection Use of Oxymorphone in Indiana, 2014-2015(New England Journal of Medicine, 2016-07-21) Peters, Philip J.; Pontones, Pamela; Hoover, Karen W.; Patel, Monita R.; Galang, Romeo R.; Shields, Jessica; Blosser, Sara J.; Spiller, Michael W.; Combs, Brittany; Switzer, William M.; Conrad, Caitlin; Gentry, Jessica; Khudyakov, Yury; Waterhouse, Dorothy; Owen, S. Michele; Chapman, Erika; Roseberry, Jeremy C.; McCants, Veronica; Weidle, Paul J.; Broz, Dita; Samandari, Taraz; Mermin, Jonathan; Walthall, Jennifer; Brooks, John T.; Duwve, Joan M.; Indiana HIV Outbreak Investigation Team; Department of Health Policy and Management, Richard M. Fairbanks School of Public HealthBACKGROUND: In January 2015, a total of 11 new diagnoses of human immunodeficiency virus (HIV) infection were reported in a small community in Indiana. We investigated the extent and cause of the outbreak and implemented control measures. METHODS: We identified an outbreak-related case as laboratory-confirmed HIV infection newly diagnosed after October 1, 2014, in a person who either resided in Scott County, Indiana, or was named by another case patient as a syringe-sharing or sexual partner. HIV polymerase (pol) sequences from case patients were phylogenetically analyzed, and potential risk factors associated with HIV infection were ascertained. RESULTS: From November 18, 2014, to November 1, 2015, HIV infection was diagnosed in 181 case patients. Most of these patients (87.8%) reported having injected the extended-release formulation of the prescription opioid oxymorphone, and 92.3% were coinfected with hepatitis C virus. Among 159 case patients who had an HIV type 1 pol gene sequence, 157 (98.7%) had sequences that were highly related, as determined by phylogenetic analyses. Contact tracing investigations led to the identification of 536 persons who were named as contacts of case patients; 468 of these contacts (87.3%) were located, assessed for risk, tested for HIV, and, if infected, linked to care. The number of times a contact was named as a syringe-sharing partner by a case patient was significantly associated with the risk of HIV infection (adjusted risk ratio for each time named, 1.9; P<0.001). In response to this outbreak, a public health emergency was declared on March 26, 2015, and a syringe-service program in Indiana was established for the first time. CONCLUSIONS: Injection-drug use of extended-release oxymorphone within a network of persons who inject drugs in Indiana led to the introduction and rapid transmission of HIV. (Funded by the state government of Indiana and others.).Item Infectious Complications in Obese Patients Following Trauma(Elsevier, 2016-04) Bell, Teresa Maria; Bayt, Demetria R.; Siedlecki, Charles B.; Stokes, Samantha M.; Yoder, Joseph; Jenkins, Peter; Fecher, Alison M.; Department of Surgery, IU School of MedicineBackground Obesity is a public health concern in the United States due to its increasing prevalence, especially in younger age groups. Trauma is the most common cause of death for people under aged 40 y. The purpose of this study is to determine the association between obesity and specific infectious complications after traumatic injury. Materials and methods A retrospective analysis was conducted using data from the 2012 National Trauma Data Bank. The National Trauma Data Bank defined obesity as having a body mass index of 30 or greater. Descriptive statistics were calculated and stratified by obesity status. A hierarchical regression model was used to determine the odds of experiencing an infectious complication in patients with obesity while controlling for age, gender, diabetes, number of comorbidities, injury severity, injury mechanism, head injury, and surgical procedure. Results Patients with a body mass index of 30 or greater compared with nonobese patients had increased odds of having an infectious complication (Odds Ratio, 1.59; 1.49-1.69). In addition to obesity, injury severity score greater than 29, age 40 y or older, diabetes, comorbid conditions, and having a surgical procedure were also predictive of an infectious complication. Conclusions Our results indicate that trauma patients with obesity are nearly 60% more likely to develop an infectious complication in the hospital. Infection prevention and control measures should be implemented soon after hospital arrival for patients with obesity, particularly those with operative trauma.Item Is it a cold or the flu?(2005-09) National Institute of Allergy and Infectious Diseases (U.S.)Information sheet comparing the common cold with the flu.Item Loss of survival factors and activation of inflammatory cascades in brain sympathetic centers in type 1 diabetic mice(American Physiological Society, 2015-04-15) Hu, Ping; Thinschmidt, Jeffrey S.; Caballero, Sergio; Adamson, Samuel; Cole, Louise; Chan-Ling, Tailoi; Grant, Maria B.; Department of Ophthalmology, IU School of MedicineNeuroinflammation and neurodegeneration have been observed in the brain in type 1 diabetes (T1D). However, little is known about the mediators of these effects. In T1D mice with 12- and 35-wk duration of diabetes we examined two mechanisms of neurodegeneration, loss of the neuroprotective factors insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) and changes in indoleamine 2,3-dioxygenase (IDO) expression in the brain, and compared the response to age-matched controls. Furthermore, levels of matrix metalloproteinase-2 (MMP-2), nucleoside triphosphate diphosphohydrolase-1 (CD39), and ionized calcium-binding adaptor molecule 1 (Iba-1) were utilized to assess inflammatory changes in astrocytes, microglia, and blood vessels. In the diabetic hypothalamus (HYPO), we observed 20% reduction in neuronal soma diameter (P<0.05) and reduced neuronal expression of IGFBP-3 (-32%, P<0.05) and IGF-I (-15%, P<0.05) compared with controls at 35 wk. In diabetic HYPO, MMP-2 expression was increased in astrocytes (46%, P<0.01), and IDO⁺ cell density rose by (62%, P<0.05). CD39 expression dropped by 30% (P<0.05) in microglia and blood vessels. With 10 wk of systemic treatment using minocycline, an anti-inflammatory agent that crosses the blood-brain barrier, MMP-2, IDO, and CD39 levels normalized (P<0.05). Our results suggest that increased IDO and early loss of CD39⁺ protective cells lead to activation of inflammation in sympathetic centers of the CNS. As a downstream effect, the loss of the neuronal survival factors IGFBP-3 and IGF-I and the neurotoxic products of the kynurenine pathway contribute to the loss of neuronal density observed in the HYPO in T1D.
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