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Milwaukee, WI, United States

Santana-Davila R.,Clement blocki Va Medical Center | Szabo A.,Medical College of Wisconsin | Arce-Lara C.,Clement blocki Va Medical Center | Williams C.D.,Durham Medical Center | And 2 more authors.
Journal of Thoracic Oncology | Year: 2014

BACKGROUND:: While platinum-based doublet chemotherapy is standard of care for patients presenting with metastatic non-small-cell lung cancer, the optimal platinum agent (cisplatin versus carboplatin) is unclear. We therefore compared survival and toxicity among persons receiving these agents at Department of Veterans Affairs hospitals. METHODS:: We used the Veterans Affairs Central Cancer Registry to identify veterans presented between 2001 and 2008 with metastatic non-small-cell lung cancer, then selected those receiving initial platinum doublet chemotherapy. We compared survival between those receiving cisplatin and carboplatin using multivariable Cox proportional hazards models and propensity score analyses to adjust for imbalances in demographics and clinical characteristics. RESULTS:: We identified 4352 eligible persons; 4061 (93%) received carboplatin. Patients treated with cisplatin were younger (median age 61 versus 63, p < 0.01) and had less comorbidities (summary comorbidity score > 2, 7.7% versus 12.8%, p = 0.01) and higher eGFR (87 versus 84 mL/min/1.73 m). Median survival was similar for persons receiving cisplatin and carboplatin (8.1 versus 7.5 months, p = 0.54). In an adjusted survival analyses, the use of cisplatin was not associated with a better survival (hazard ratio 0.98, 95% confidence interval 0.84-1.14, p = 0.79). We performed subgroup analysis defined by histology and second agent, the hazard ratio for mortality ranged spanned 1 and none of these approached statistical significance (all p values > 0.20). Cisplatin-treated patients were more likely to have more hospitalization (1.7 versus 1.3, p < 0.01) and outpatient visits (11 versus 9.6, p < 0.01). Cisplatin-treated patient had more subsequent encounters for infection (41.6% versus 34.3%, p < 0.01) and acute kidney injury/dehydration (29.2% versus 15.5%, p < 0.01) CONCLUSIONS:: Patients receiving cisplatin and carboplatin-based doublets did not have significantly different survival, but cisplatin use was associated with an increase morbidity and healthcare use. © 2014 by the International Association for the Study of Lung Cancer. Source

Kidambi S.,Medical College of Wisconsin | Kidambi S.,Clement blocki Va Medical Center | Kotchen T.A.,Medical College of Wisconsin
American Journal of Cardiovascular Drugs | Year: 2013

Obesity is a global pandemic and with its rise, its associated co-morbidities are increasing in prevalence, particularly uncontrolled hypertension. Lifestyle changes should be an anchor for the management of obesity-related hypertension; however, they are difficult to sustain. Drug therapy is often necessary to achieve blood pressure control. Diuretics, inhibitors of the renin-angiotensin system, and dihydropyridine calcium channel blockers are often used as first trio, with subsequent additions of mineralocorticoid receptor antagonists and/or dual alpha/beta blocking agents. While a number of agents are currently available, 50 % of hypertensive patients remain uncontrolled. A number of novel drug and invasive therapies are in development and hold significant potential for the effective management of obesity-related hypertension. © 2013 Springer International Publishing Switzerland. Source

Pabbidi M.R.,University of Mississippi Medical Center | Mazur O.,University of Mississippi Medical Center | Fan F.,University of Mississippi Medical Center | Farley J.M.,University of Mississippi Medical Center | And 4 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2014

Recent studies have indicated that the myogenic response (MR) in cerebral arteries is impaired in Fawn Hooded Hypertensive (FHH) rats and that transfer of a 2.4 megabase pair region of chromosome 1 (RNO1) containing 15 genes from the Brown Norway rat into the FHH genetic background restores MR in a FHH.1BN congenic strain. However, the mechanisms involved remain to be determined. The present study examined the role of the large conductance calcium-activated potassium (BK) channel in impairing the MR in FHH rats. Whole-cell patch-clamp studies of cerebral vascular smooth muscle cells (VSMCs) revealed that iberiotoxin (IBTX; BK inhibitor)-sensitive outward potassium (K+) channel current densities are four- to fivefold greater in FHH than in FHH.1BN congenic strain. Inside-out patches indicated that the BK channel open probability (NPo) is 10-fold higher and IBTX reduced NPo to a greater extent in VSMCs isolated from FHH than in FHH.1BN rats. Voltage sensitivity of the BK channel is enhanced in FHH as compared with FHH.1BN rats. The frequency and amplitude of spontaneous transient outward currents are significantly greater in VSMCs isolated from FHH than in FHH.1BN rats. However, the expression of the BK-α and -β-subunit proteins in cerebral vessels as determined by Western blot is similar between the two groups. Middle cerebral arteries (MCAs) isolated from FHH rats exhibited an impaired MR, and administration of IBTX restored this response. These results indicate that there is a gene on RNO1 that impairs MR in the MCAs of FHH rats by enhancing BK channel activity. © 2014 the American Physiological Society. Source

Nanchal R.,Medical College of Wisconsin | Kumar G.,Medical College of Wisconsin | Taneja A.,Medical College of Wisconsin | Patel J.,Medical College of Wisconsin | And 5 more authors.
Chest | Year: 2012

Background: Pulmonary embolism is a common, often fatal condition that requires timely recognition and rapid institution of therapy. Previous studies have documented worse outcomes for weekend admissions for a variety of time-sensitive medical conditions. This phenomenon has not been clearly demonstrated for pulmonary embolism. Methods: We used the Healthcare Cost and Utilization Project Nationwide Inpatient Sample for the years 2000 to 2008 to identify people with a principal discharge diagnosis of pulmonary embolism. We classified admissions as weekend if they occurred between midnight Friday and midnight Sunday. We compared all-cause in-hospital mortality between weekend and weekday admissions and investigated the timing of inferior vena cava (IVC) filter placement and thrombolytic infusion as potential explanations for differences in mortality. Results: Unadjusted mortality was higher for weekend admissions than weekday admissions (OR, 1.19;95% CI, 1.13-1.24). This increase in mortality remained statistically significant after controlling for potential confounding variables (OR, 1.17;95% CI, 1.11-1.22). Among patients who received an IVC filter, a larger proportion of those admitted on a weekday than on the weekend received it on their first hospital day (38% vs 29%, P <.001). The timing of thrombolytic therapy did not differ between weekday and weekend admissions. Conclusions: Weekend admissions for pulmonary embolism were associated with higher mortality than weekday admissions. Our finding that IVC filter placement occurred later in the hospital course for patients admitted on weekends with pulmonary embolism suggests differences in the timeliness of diagnosis and treatment between weekday and weekend admissions. Regardless of cause, physicians should be aware that weekend admissions for pulmonary embolism have a 20% increased risk of death and warrant closer attention than provided during the week. © 2012 American College of Chest Physicians. Source

Kumar G.,Medical College of Wisconsin | Majumdar T.,Medical College of Wisconsin | Jacobs E.R.,Medical College of Wisconsin | Jacobs E.R.,Clement blocki Va Medical Center | And 5 more authors.
Chest | Year: 2013

Background: Critically ill, morbidly obese patients (BMI > 40 kg/m 2) are at high risk of respiratory failure requiring invasive mechanical ventilation (IMV). It is not clear if outcomes of critically ill, obese patients are affected by obesity. Due to limited cardiopulmonary reserve, they may have poor outcomes. However, literature to this effect is limited and conflicted. Methods: We used the Nationwide Inpatient Sample from 2004 to 2008 to examine the outcomes of morbidly obese people receiving IMV and compared them to nonobese people. We identified hospitalizations requiring IMV and morbid obesity using International Classification of Diseases, 9th Revision, Clinical Modification codes. Primary outcomes studied were inhospital mortality, rates of prolonged mechanical ventilation (> 96 h), and tracheostomy. Multivariable logistic regression was used to adjust for potential confounding variables. We also examined outcomes stratified by number of organs failing. Results: Of all hospitalized, morbidly obese people, 2.9% underwent IMV. Mean age, comorbidity score, and severity of illness were lower in morbidly obese people. The adjusted mortality was not significantly different in morbidly obese people (OR 0.89; 95% CI, 0.74-1.06). When stratified by severity of disease, there was a stepwise increase in risk for mortality among morbidly obese people relative to nonobese people (range: OR, 0.77; 95% CI, 0.58-1.01 for only respiratory failure, to OR, 4.14; 95% CI, 1.11-15.3 for four or more organs failing). Rates of prolonged mechanical ventilation were similar, but rate of tracheostomy (OR 2.19; 95% CI, 1.77-2.69) was significantly higher in patients who were morbidly obese. Conclusions: Morbidly obese people undergoing IMV have a similar risk for death as nonobese people if only respiratory failure is present. When more organs fail, morbidly obese people have increased risk for mortality compared with nonobese people. © 2013 American College of Chest Physicians. Source

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