Patient Advocacy Organizations, Industry Funding, and Conflicts of Interest.

Importance: Patient advocacy organizations (PAOs) are influential health care stakeholders that provide direct counseling and education for patients, engage in policy advocacy, and shape research agendas. Many PAOs report having financial relationships with for-profit industry, yet little is known about the nature of these relationships. Objective: To describe the nature of industry funding and partnerships between PAOs and for-profit companies in the United States. Design, Setting, and Participants: A survey was conducted from September 1, 2013, to June 30, 2014, of a nationally representative random sample of 439 PAO leaders, representing 5.6% of 7865 PAOs identified in the United States. Survey questions addressed the nature of their activities, their financial relationships with industry, and the perceived effectiveness of their conflict of interest policies. Main Outcomes and Measures: Amount and sources of revenue as well as organizational experiences with and policies regarding financial conflict of interest. Results: Of the 439 surveys mailed to PAO leaders, 289 (65.8%) were returned with at least 80% of the questions answered. The PAOs varied widely in terms of size, funding, activities, and disease focus. The median total revenue among responding organizations was $299 140 (interquartile range, $70 000-$1 200 000). A total of 165 of 245 PAOs (67.3%) reported receiving industry funding, with 19 of 160 PAOs (11.9%) receiving more than half of their funding from industry. Among the subset of PAOs that received industry funding, the median amount was $50 000 (interquartile range, $15 000-$200 000); the median proportion of industry support derived from the pharmaceutical, device, and/or biotechnology sectors was 45% (interquartile range, 0%-100%). A total of 220 of 269 respondents (81.8%) indicated that conflicts of interest are very or moderately relevant to PAOs, and 94 of 171 (55.0%) believed that their organizations' conflict of interest policies were very good. A total of 22 of 285 PAO leaders (7.7%) perceived pressure to conform their positions to the interests of corporate donors. Conclusions and Relevance: Patient advocacy organizations engage in wide-ranging health activities. Although most PAOs receive modest funding from industry, a minority receive substantial industry support, raising added concerns about independence. Many respondents report a need to improve their conflict of interest policies to help maintain public trust.

Gender Differences in Physicians' Financial Ties to Industry: A Study of National Disclosure Data.

BACKGROUND: Academic literature extensively documents gender disparities in the medical profession with regard to salary, promotion, and government funded research. However, gender differences in the value of financial ties to industry have not been adequately studied despite industry's increasing contribution to income and research funding to physicians in the U.S. METHODS & FINDINGS: We analyzed publicly reported financial relationships among 747,603 physicians and 432 pharmaceutical, device and biomaterials companies. Demographic and payment information were analyzed using hierarchical regression models to determine if statistically significant gender differences exist in physician-industry interactions regarding financial ties, controlling for key covariates. In 2011, 432 biomedical companies made an excess of $17,991,000 in payments to 220,908 physicians. Of these physicians, 75.1% were male. Female physicians, on average, received fewer total dollars (-$3,598.63, p<0.001) per person than men. Additionally, female physicians received significantly lower amounts for meals (-$41.80, p<0.001), education (-$1,893.14, p<0.001), speaker fees (-$2,898.44, p<0.001), and sponsored research (-$15,049.62, p=0.05). For total dollars, an interaction between gender and institutional reputation was statistically significant, implying that the differences between women and men differed based on industry's preference for an institution, with larger differences at higher reputation institutions. CONCLUSIONS: Female physicians receive significantly lower compensation for similarly described activities than their male counterparts after controlling for key covariates. As regulations lead to increased transparency regarding these relationships, efforts to standardize compensation should be considered to promote equitable opportunities for all physicians.

Rhabdoid differentiation is associated with aggressive behavior in renal cell carcinoma: a clinicopathologic analysis of 76 cases with clinical follow-up.

Rhabdoid differentiation has been associated with aggressive behavior in carcinomas from different organ systems. A recent consensus statement of the International Society of Urological Pathology (ISUP), in addition to proposing a nucleolar grading system (ISUP grade) for renal cell carcinoma (RCC) to replace the Fuhrman system, recommended reporting the presence of rhabdoid differentiation in RCC and considering tumors with rhabdoid differentiation to be ISUP grade 4. Although it has been shown that rhabdoid differentiation is associated with increased grade and stage of RCC, it has not been fully demonstrated whether it has an adverse effect independent of this association with increased grade and stage. We provide the largest clinicopathologic analysis of RCC with rhabdoid differentiation to date (76 cases), including characterization of metastatic disease. In addition, by constructing a multivariable model including tumor grade, stage, necrosis, and distant metastasis to compare a series of 49 clear cell RCC with rhabdoid differentiation with a cohort of 41 clear cell RCCs without rhabdoid differentiation, we demonstrate that the presence of rhabdoid differentiation in clear cell RCC confers an increased risk of death (hazard ratio=5.25; 95% confidence interval, 2.1-14.3) independent of these other adverse prognostic factors. These findings underscore the significance of rhabdoid differentiation in RCC as an adverse prognostic factor and support the recent reporting and grading recommendations of the ISUP.

Four-item fatigue screen: replacing the Brief Fatigue Index.

INTRODUCTION: To develop a shorter and less burdensome cancer-related fatigue (CRF) questionnaire, the Four-Item Fatigue Scale (FIFS) was tested for validity against the Brief Fatigue Index (BFI). METHODS: On day 1, patients with cancer completed the BFI and FIFS in a random order and the reverse on day 7. Sixty-five patients were needed for an 80% power and a Spearman correlation of .7 or greater. The FIFS was compared with the BFI in fatigue severity and changes in fatigue over time. Bonferroni corrections were made for multiple comparisons with International Classification of Diseases, Tenth Revision (ICD-10) fatigue criteria. RESULTS: Seventy-nine patients were enrolled, 65 patients completed both surveys. Spearman correlation between FIFS and BFI for day 1 was 0.69 (95% confidence interval [CI] 0.50-0.87) and 0.73 (95% CI 0.56-0.90) 1 week later. Fatigue severity did not predict survival with either questionnaire. Brief Fatigue Index severity correlated with ICD-10 items 1, 3, 7, and 10B. Regression analysis showed that on day 7 BFI correlated with ICD-10 items 1, 7, and 10. When the model was adjusted for day 1, only the ICD-10 item 5 correlated well in BFI over 1 week. The ICD-10 items 7 and 10 significantly correlated with day 1 FIFS fatigue changes over 7 days after adjustment for FIFS baseline score. CONCLUSIONS: Four-Item Fatigue Scale has concurrent validity for fatigue using the BFI. The FIFS and BFI correlated modestly over time. Certain ICD-10 items correlated with CRF severity depending on the questionnaire.

Nomogram to predict successful placement in surgical subspecialty fellowships using applicant characteristics.

PURPOSE: The purpose of the study was to develop a model that predicts an individual applicant's probability of successful placement into a surgical subspecialty fellowship program. METHODS: Candidates who applied to surgical fellowships during a 3-year period were identified in a set of databases that included the electronic application materials. RESULTS: Of the 1281 applicants who were available for analysis, 951 applicants (74%) successfully placed into a colon and rectal surgery, thoracic surgery, vascular surgery, or pediatric surgery fellowship. The optimal final prediction model, which was based on a logistic regression, included 14 variables. This model, with a c statistic of 0.74, allowed for the determination of a useful estimate of the probability of placement for an individual candidate. CONCLUSIONS: Of the factors that are available at the time of fellowship application, 14 were used to predict accurately the proportion of applicants who will successfully gain a fellowship position.

The relationship between symptom prevalence and severity and cancer primary site in 796 patients with advanced cancer.

Knowledge of differences in symptom experience between cancer sites may help better understand symptom pathophysiology. A total of 38 symptoms in 796 consecutive patients with advanced cancer were retrospectively analyzed. Symptom prevalence and severity were compared among the 12 primary site groups (PSGs) by the chi-square test. Pairwise comparisons determined which sites differed. Pain, fatigue, weakness, lack of energy, and anorexia had the highest overall prevalence but did not differ among PSGs. The 3 most common neuropsychological symptoms (insomnia, depression, and anxiety) also did not vary among PSGs. Nineteen (50%) symptoms varied significantly between PSGs, in prevalence (17), severity (14), or both (12). Nine of 17, 6 of 14, and 6 of 12 were gastrointestinal symptoms. Symptoms which varied by PSGs can be included in cancer site-specific symptom assessment instruments.

Bioelectrical impedance phase angle changes during hydration and prognosis in advanced cancer.

INTRODUCTION: We wished to determine bioelectrical impedance (BIA) correlates before hydration or changes during hydration and determine if these changes were prognostically important. METHODS AND MATERIALS: Fifty eligible patients underwent BIA measurements 3 consecutive days. Laboratory studies (electrolytes, creatinine, and hemoglobin) on day 1; weights and vital signs were recorded. Kaplan-Meier survival estimates were made at 30 and 60 days. Hazard ratios (HRs) based on Cox proportional hazards model were calculated. RESULTS: Weight loss was associated with shorter survival. A higher phase angle (PA) on day 1 predicted longer survival. Increased PA during hydration predicted shorter survival: increased weight during hydration predicted longer survival. DISCUSSION: Higher phase angle before hydration predicts poorer survival and, paradoxically, an increase in phase angle during hydration predicted poorer survival and preexisting intracellular dehydration, cachexia, or poor membrane function. CONCLUSIONS: Phase angle and weight during hydration predict survival in cancer.

Substitution of methotrexate for cyclophosphamide in Wegener granulomatosis: a 12-year single-practice experience.

We conducted a retrospective review to assess outcomes of therapy in patients with newly diagnosed Wegener granulomatosis (WG) using methotrexate (MTX) for mild to moderate disease and short-term treatment with cyclophosphamide (CYC) followed by MTX for severe disease. Patients with WG were included if their initial plan of therapy and subsequent care were directly supervised by the Cleveland Clinic Center for Vasculitis Care and Research. Severe disease (immediately life-threatening or involving critical organs) was initially treated with CYC and glucocorticoids. Mild to moderate disease was initially treated with MTX and glucocorticoids if serum creatinine was less than 2 mg/dL. Following initial improvement of severe disease, treatment was changed to MTX if serum creatinine was originally less than 2 mg/dL or had diminished to less than 2 mg/dL. Disease activity was determined at each visit and later converted to a Birmingham Vasculitis Activity Score, as modified for Wegener granulomatosis (BVAS/WG). Laboratory monitoring of disease and treatment toxicity was initially weekly and never less than monthly.Eighty-two (32%) of 253 patients with WG referred to the Center for Vasculitis Care and Research met eligibility criteria. Ineligible patients did not have new-onset disease or were not able to be followed principally in our center. Seventy percent of patients (57/82) initially had severe disease and received a short course of CYC for remission induction. In over half of these patients, illness was judged to be severe because of pulmonary hemorrhage; rapidly progressive glomerulonephritis, including need for dialysis; or neurologic abnormalities. All patients improved: remission was achieved in 50% (41/82) of patients within 6 months and in 72% (59/82) within 12 months. Sustained remission (BVAS/WG = 0 for at least 6 consecutive months) was ultimately achieved in 78% (64/82) of patients. Among the 75 (91%) patients who achieved remission of any duration, 45% relapsed within 1 year and 66% relapsed within 2 years following remission. Eighty-two percent of relapsed patients achieved subsequent remissions after additional treatment. About three-quarters of relapses were mild and promptly responded to treatment. Seventeen percent of patients developed serious infections. CYC-associated cystitis or bladder cancer did not occur in any patients. At least 1 form of permanent morbidity from WG alone was noted in 74.0% of patients. Three patients (3.7%) died over a median follow-up period of 4.5 years; no deaths were due to active disease. Although treatment was primarily directed toward achieving clinical improvement and not calculated to achieve marked lymphopenia, patients in whom treatment produced lymphocyte counts of 1000/mm was associated with a hazard ratio for relapse of 3.0, although the latter difference was not statistically significant. In patients with WG, a strategy that limits or avoids CYC therapy produced a frequency of remission comparable to that achieved with conventional CYC protocols, excellent survival, and avoidance of long-term CYC toxicity. However, relapses were common and incremental permanent morbidity occurred in most patients. While not a goal of therapy, when treatment produced marked lymphopenia, prolonged remissions were more likely.

Lung volume reduction surgery in patients with emphysema and alpha-1 antitrypsin deficiency.

BACKGROUND: The role of lung volume reduction surgery (LVRS) for individuals with alpha-1 antitrypsin (AAT) deficiency is unclear. METHODS: To assess the role of LVRS in individuals with severe deficiency of AAT, outcomes within the National Emphysema Treatment Trial were analyzed. RESULTS: Of 1218 randomized subjects, 16 (1.3%) had severe AAT deficiency (serum level < 80 mg/dL) and a consistent phenotype (when available). Characteristics of these 16 patients include 87.5% male; median serum AAT level, 55.5 mg/dL; age, 66 years; forced expiratory volume in 1 second (FEV1), 27% predicted; and 50% had upper-lobe-predominant emphysema. All 10 subjects randomized to LVRS underwent the procedure. Although the small number of subjects hampered statistical analysis, 2-year mortality was higher with surgery (20% versus 0%) than with medical treatment. Comparison of outcomes between the 10 AAT-deficient and the 554 AAT-replete subjects undergoing LVRS showed a greater increase in exercise capacity at 6 months in replete subjects and a trend toward lower and shorter duration FEV1 rise in deficient individuals. CONCLUSIONS: This study extends to 49 cases the published experience of LVRS in severe AAT deficiency. Although the small number of subjects precludes firm conclusions, trends of lower magnitude and duration of FEV1 rise after surgery in AAT-deficient versus AAT-replete subjects and higher mortality in deficient individuals randomized to surgery versus medical treatment suggest caution in recommending LVRS in AAT deficiency.

Safety of targeted perioperative mupirocin treatment for preventing infections after cardiac surgery.

BACKGROUND: Indiscriminate antibiotic use may lead to development of antibiotic resistance. Preoperative mupirocin treatment decreases Staphylococcus aureus carriage and may reduce subsequent surgical site infection, but is unlikely to benefit noncarriers. This study was undertaken to evaluate whether avoiding mupirocin in noncarriers places them at increased risk for subsequent postoperative infection. METHODS: We conducted a retrospective cohort study examining incidence of postoperative infection in patients undergoing cardiac surgery at the Cleveland Clinic after introduction of a protocol of polymerase chain reaction screening for nasal S aureus carriage, and avoiding mupirocin treatment of noncarriers. RESULTS: Between August 1, 2002, and May 31, 2004, 6,334 patients were screened for nasal carriage of S aureus before undergoing cardiac surgery. There was no significant difference in infection rates between carriers and noncarriers when examining the incidence of all infections (5.6% and 5.0%; relative risk [RR] 1.11 [95% confidence interval (CI): 0.86 to 1.43]), infections caused specifically by S aureus (1.04% and 0.80%; RR 1.30 [95% CI: 0.71 to 2.39]), any surgical site infection (3.1% and 3.2%; RR 0.97 [95% CI: 0.69 to 1.36]), S aureus surgical site infection (0.82% and 0.58%; RR 1.41 [95% CI: 0.71 to 2.82]), any bloodstream infection (3.1% and 2.5%; RR 1.21 [95% CI: 0.86 to 1.71]), and S aureus bloodstream infection (0.37% and 0.48%; RR 0.77 [95% CI: 0.30 to 2.03]). Mupirocin use declined substantially after introduction of the protocol. CONCLUSIONS: A strategy of targeting perioperative mupirocin treatment to carriers leads to significant reduction in mupirocin use without increasing early postoperative infectious complications in noncarriers.

A multivariate analysis of risk factors associated with subcapsular hematoma formation following electromagnetic shock wave lithotripsy.

PURPOSE: Subcapsular or perinephric hematoma is one of the most frequent and potentially serious complications of extracorporeal shock wave lithotripsy (SWL). We determined the incidence of and risk factors for renal hematomas following electromagnetic shock wave lithotripsy. MATERIALS AND METHODS: Between February 1999 and August 2003, 570 SWL treatments were performed using a Modulith SLX electromagnetic lithotriptor (Storz, St. Louis, Missouri). A total of 415 of these treatments in 317 patients were performed for stones in the renal pelvis or calices and these treatment episodes represent the study group reported. Treatment episodes were reviewed from a prospective institutional review board approved registry and analyzed for patient age, gender, body mass index, mean arterial pressure at induction, stone location, total number of shock waves and peak shock wave intensity. RESULTS: Following these 415 episodes subcapsular or perinephric hematomas developed in 17 patients for an overall incidence of 4.1%. The probability of hematoma after shock wave lithotripsy increased significantly as patient age at treatment increased, such that the probability of hematoma was estimated to be 1.67 times greater for each 10-year incremental increase in patient age. None of the other variables analyzed were significantly related to the incidence of hematoma formation at the 0.05 level. CONCLUSIONS: The incidence of renal hematoma formation following electromagnetic SWL for renal calculus was 4.1%. The probability of hematoma increased significantly with increasing patient age but it was not associated with increasing mean arterial pressure at treatment. These findings are in contrast to previous reports of hematoma associated with electrohydraulic SWL. These differences may be a consequence of the smaller focal zone and higher peak pressure associated with Storz Modulith electromagnetic SWL and, just as importantly, a consequence of the difference in the manner in which blood pressure was defined.

A mathematical model of cell salvage compared and combined with normovolemic hemodilution.

BACKGROUND: Mathematical models have been used to describe the factors that affect cell salvage (CS) and normovolemic hemodilution (ANH). Here, the CS and ANH models were used to compare these two techniques alone or in combination with each other. STUDY DESIGN AND METHODS: Variables used for a hypothetical patient included an estimated blood volume of 5000 mL, a presurgery hematocrit (Hct) of 45 percent, and a transfusion trigger of 21 percent. The model accounts for both the effect of decreasing the Hct due to blood loss and the effect of increasing Hct due to the readministration of blood in an isovolemic patient. The efficacy of CS and ANH is defined to be the maximum allowable blood loss for a fixed blood volume and a fixed transfusion trigger. RESULTS: Comparison of CS with ANH showed that 3 units of ANH was comparable to CS when CS recovery rates ranged from 19 to 24 percent. For a patient with a blood volume of 5000 mL and a starting Hct of 40 percent, 3 units of ANH would allow for 3972 mL of blood to be lost before crossing a 21-percent transfusion trigger, whereas CS with a 125-mL bowl would allow for 7611 mL. CONCLUSION: When comparing ANH to CS, this mathematical model would suggest that CS has the potential to offer significantly greater red blood cell avoidance than does ANH; however, the combination of ANH with CS may offer allogeneic avoidance superior to either technique alone.

A clinicopathologic evaluation of follicular lymphoma grade 3A versus grade 3B reveals no survival differences.

CONTEXT: The World Health Organization classification recommends categorizing grade 3 follicular lymphomas based on the presence of centrocytes (grade 3A) or of sheets of centroblasts (grade 3B). The clinical significance of this practice is not known. OBJECTIVE: To determine whether grade 3 follicular lymphoma subtype is associated with prognosis. DESIGN: Multi-institutional retrospective case series. MAIN OUTCOME MEASURE: Overall survival. RESULTS: Forty-five cases of grade 3 follicular lymphoma without diffuse large B-cell lymphoma were studied (35 cases of grade 3A, 10 cases of grade 3B) from 21 men and 24 women (median age, 67 years; mean age, 63.8 years; range, 26-86 years). Follow-up information from the time of diagnosis was available in all patients, with a median follow-up time of 24 months (mean, 34 months; range, 2- 115 months). Treatment information was available in 40 patients. There was no difference in age (P =.45, Wilcoxon test) or stage (P =.76, Fisher exact test) between patients with follicular lymphoma of grade 3A or grade 3B. Furthermore, the Cochran-Armitage test for trends showed no evidence that the proportion of patients with follicular lymphoma grade 3A or 3B increased or decreased with increasing stage at presentation. Kaplan-Meier analysis showed a median overall survival of 44 months from the time grade 3 follicular lymphoma was diagnosed, with no significant difference between cases diagnosed as grade 3A or grade 3B (P =.14, log-rank test). Univariable Cox proportional hazards modeling showed no evidence that an anthracycline-containing chemotherapy regimen or history of lower grade follicular lymphoma affected overall survival. CONCLUSIONS: In this retrospective series, subclassification of grade 3 follicular lymphoma into type 3A and 3B categories had limited clinical and prognostic significance. However, the study was limited by lack of statistical power. Since morphology often provides clues for progress in defining biologic differences, subtyping may still be useful, particularly in the setting of prospective clinical studies.

Leukocyte reduction during orthotopic liver transplantation and postoperative outcome: a pilot study.

STUDY OBJECTIVE: To investigate the effect of intraoperative leukocyte reduction of administered blood products on the incidence of acute cellular rejection and postoperative patient outcome. DESIGN: Prospective, nonrandomized, historical control study. SETTING: Academic tertiary medical center. PATIENTS: The study group (Group 1) consisted of 30 consecutive adult patients with end-stage liver disease scheduled to undergo orthotopic liver transplantation (OLT) between 1998 and 2000. The historical control group (Group 2) consisted of 30 adult patients with end-stage liver disease matched to study group patients as closely as possible for age, gender, and etiology of liver disease who underwent OLT between 1995 and 1999. INTERVENTIONS: Group 1 patients had all intraoperative allogeneic and cell salvaged blood products leukocyte reduced before administration. Group 2 patients underwent OLT without leukocyte filtration of any administered blood products. MEASUREMENTS: Demographic data were collected for both patient groups and included age, gender, etiology of liver disease, and both intraoperative and postoperative immunosuppression. Demographic allograft donor data for both patient groups were collected and included age, gender, use of vasopressors during procurement, and cold and warm donor organ ischemic times. Outcome variables measured included incidence of acute cellular rejection, length of intensive care unit (ICU) and length of hospital stay, incidence of both graft loss and retransplantation, and mortality. MAIN RESULTS: The incidence of acute cellular rejection was 40% in Group 1 and 66.7% in Group 2 (p = 0.037). Length of ICU stay was 3.0 (2.0, 5.0) days in Group 1 and 4.0 (3.0, 6.0) days in Group 2 (p = 0.16). Length of hospital stay was 14.0 (11.0, 18.0) days in Group 1 and 18.0 (14.0, 27.0) days in Group 2 (p = 0.035). One allograft was lost in Group 2 because of primary nonfunction requiring retransplantation (p = 0.31), and three postoperative deaths occurred in Group 1 as a result of multisystem organ failure (p = 0.08). CONCLUSIONS: Coincident with leukocyte reduction of all administered blood products during OLT, an improved outcome was observed in Group 1 patients as demonstrated by both a decreased incidence of acute cellular rejection and length of hospital stay.

Interferon gamma responses to myelin peptides in multiple sclerosis correlate with a new clinical measure of disease progression.

The relationship between autoreactivity to myelin antigens and disease progression in multiple sclerosis (MS) is not fully understood. We addressed this relationship by cross-sectionally comparing an objective measure of MS disability with immune cytokine responses to myelin proteins. The ELISPOT assay was used to determine the ex vivo interferon gamma (IFNgamma) and interleukin-10 (IL-10) production by peripheral blood mononuclear cells (PBMCs) in response to peptides spanning the entire proteolipid protein (PLP) and myelin basic protein (MBP) molecules in 20 patients with relapsing-remitting (RR) MS and 27 age- and sex-matched healthy controls. MS patients showed significantly higher MBP-induced IFNgamma responses and PLP-induced IL-10 responses compared with healthy controls. Using the Multiple Sclerosis Functional Composite (MSFC), a new multifactorial measure of disability, MS patients showed a significant correlation between the IFNgamma response to PLP peptides and MBP peptides, and disability. In contrast, in MS patients, there was no correlation between the MSFC and the response to unrelated control antigens or mitogens. These data show that myelin-specific T lymphocytes secreting the inflammatory cytokine IFNgamma correlate with functional impairment in MS, supporting an antigen-specific link between the immune response to myelin and disability in MS.

Nature, frequency, and predictors of secondary procedures after endovascular repair of abdominal aortic aneurysm.

OBJECTIVES: Endovascular stent grafting offers a potentially less invasive option for treatment of abdominal aortic aneurysm. Clinical benefit has been demonstrated with respect to early parameters such as blood transfusion, return of gastrointestinal function, and length of hospital stay. Endovascular repair, however, has been criticized on the basis of inferior long-term outcome. Secondary procedures may be necessary to address durability issues such as migration, high-pressure endoleak, graft limb thrombosis, and degeneration of the stent-fabric structure itself, issues that may compromise the primary goal of aneurysm repair, protection from rupture. METHODS: Between 1996 and 2002, 703 patients underwent endovascular treatment of infrarenal abdominal aortic aneurysm at The Cleveland Clinic Foundation. During this time, five devices were used: Ancure, AneuRx, Excluder, Talent, and Zenith. Outcome was assessed with physical examination, lower extremity arterial studies, plain abdominal radiography, and computed tomography at discharge, at 1, 6, and 12 months postoperatively, and annually thereafter. Secondary procedures were defined as any procedure, exclusive of diagnostic angiography, performed after stent graft implantation, directed at treatment of aneurysm-related events. Multivariable statistical techniques for censored data (Cox proportional hazards modeling) were used to determine baseline parameters associated with need for secondary procedures over follow-up, with calculation of hazards ratio (HR) and 95% confidence interval (CI). RESULTS: Patient follow-up averaged 12.2 +/- 11.7 months. Patient survival was 90% +/- 1.4% at 1 year, 78% +/- 2.6% at 2 years, and 70% +/- 3.8% at 3 years. Aneurysm rupture occurred in 3 patients (0.4%), accounting for rupture risk of 1.4% over the first 2 years of follow-up (Kaplan-Meier method). Overall, 128 secondary procedures were required in 104 patients (15%), with a cumulative risk of 12% +/- 1.5% at 1 year, 24% +/- 2.8% at 2 years, and 35% +/- 4.4% at 3 years after stent graft implantation. Among the secondary procedures, new stent grafts and extensions were placed in 34 patients (27%), embolization of endoleak was performed in 33 patients (26%), and open surgical conversion was undertaken in 11 patients (9%). Periprocedural mortality of secondary procedures was 8% overall, but was 18% for patients undergoing open surgical conversion. Multivariable modeling identified the date the procedure was performed (HR, 1.53 per 3-month period of study; CI, 1.22-1.92; P <.001) and aneurysm size (HR, 1.35 per centimeter of minor axis; CI, 1.13-1.60; P <.001) as independent predictors of need for secondary procedures. CONCLUSIONS: Current endovascular devices are associated with a relatively high rate of complications over mid-term follow-up, culminating in frequent need for secondary remedial procedures. With strict follow-up imaging compliance, however, risk for rupture and aneurysm-related death remain exceedingly low. Newer technology may achieve improved durability and a lower requirement for secondary procedures, while maintaining the minimally invasive nature of presently available devices.

Weekly versus daily changes of in-line suction catheters: impact on rates of ventilator-associated pneumonia and associated costs.

BACKGROUND: An earlier randomized, controlled trial showed that weekly or as-needed (as opposed to daily) changes of in-line suction catheters were associated with substantial cost savings, without a higher rate of ventilator-associated pneumonia (VAP). To examine the impact of decreasing the frequency of in-line suction catheter changes in our medical intensive care unit, we conducted an observational study, comparing the catheter costs and frequency of VAP during (1) a control period, during which in-line suction catheters were changed daily, and (2) a treatment period, during which the catheters were changed every 7 days or sooner if needed, for mechanical failure or soilage. METHODS: All adult patients admitted to our 18-bed medical intensive care unit were evaluated for the 3-month interval 1 year prior to the practice change (May through July 1998) and for the 3 months after implementing the new policy (May through July 1999). To avoid bias related to usual seasonal variation in VAP frequency, we also determined (via medical records) the VAP rate during May through July 1997. The occurrence of VAP was ascertained by an infection control practitioner, using criteria established by the Centers for Disease Control and applied in a standard fashion. The VAP rate was calculated as the mean number of VAPs per 100 ventilator-days for each 3-month interval. Use of ventilators, humidifiers, and non-heated-wire, disposable circuits was uniform during the study, as were policies regarding humidity, temperature settings, and frequency of routine ventilator circuit changes. RESULTS: During the control period 146 patients accounted for 1,075 ventilator-days and there were 2 VAPs (0.19 VAPs per 100 ventilator-days). During the treatment period 143 patients accounted for 1,167 ventilator-days and there were no VAPs. The mean +/- SD duration of in-line suction catheter use during the treatment period was 3.8 +/- 0.8 days, and 51% of the patients had the same catheter in place for > 3 days (range 4-9 days). The actual cost of catheters used during the treatment period was lower than during the control period ($1,330 vs $6,026), predicting annual catheter cost savings of $18,782. CONCLUSIONS: We conclude that (1) a policy of weekly (vs daily) change of in-line suction catheter is associated with substantial cost savings, with no significant increase in the frequency of VAP, and (2) to the extent that these findings confirm the results of prior studies they support a policy of changing in-line suction catheters weekly rather than daily.

Correlation between ammonia levels and the severity of hepatic encephalopathy.

PURPOSE: Because the correlation between ammonia levels and the severity of hepatic encephalopathy remains controversial, we prospectively evaluated the correlation in 121 consecutive patients with cirrhosis. METHODS: The diagnosis of hepatic encephalopathy was based on clinical criteria, and the severity of hepatic encephalopathy was based on the West Haven Criteria for grading of mental status. Arterial and venous blood samples were obtained from each patient. Four types of ammonia measurements were analyzed: arterial and venous total ammonia, and arterial and venous partial pressure of ammonia. Spearman rank correlations (r(s)) were calculated. RESULTS: Of the 121 patients, 30 (25%) had grade 0 encephalopathy (no signs or symptoms), 27 (22%) had grade 1, 23 (19%) had grade 2, 28 (23%) had grade 3, and 13 (11%) had grade 4 (the most severe signs and symptoms). Each of the four measures of ammonia increased with the severity of hepatic encephalopathy: arterial total ammonia (r(s) = 0.61, P < or = 0.001), venous total ammonia (r(s) = 0.56, P < or = 0.001), arterial partial pressure of ammonia (r(s) = 0.55, P < or = 0.001), and venous partial pressure of ammonia (r(s) = 0.52, P < or = 0.001). CONCLUSION: Ammonia levels correlate with the severity of hepatic encephalopathy. Venous sampling is adequate for ammonia measurement. There appears to be no additional advantage of measuring the partial pressure of ammonia compared with total ammonia levels.

A mathematical model of cell salvage efficiency.

UNLABELLED: Cell salvage (CS) is one of the modalities that can be used during surgery to decrease the use of allogeneic blood. Unlike acute normovolemic hemodilution, the efficiency of CS has not been mathematically modeled. In this article, we hypothesized that a mathematical model could predict the decline of hematocrit during CS. The model that was developed accounts for both the effect of decreasing the hematocrit because of blood loss and the effect of increasing hematocrit because of the readministration of washed blood in an isovolemic patient. The efficiency of CS is defined to be the maximum allowable blood loss (MABL) for a fixed blood volume and a fixed transfusion trigger. For demonstration purposes, variables used for a hypothetical patient included an estimated blood volume of 5000 mL, a presurgery hematocrit of 45%, and a transfusion trigger of 21%. The MABL in a typical case was 9600 mL, with a CS red cell recovery rate of 60%. Patient records from a convenience sample showed an average recovery rate of 57% with 20% variability. This mathematical model suggests that CS can be a highly effective blood conservation method when red blood cell collection is optimal. IMPLICATIONS: In this study, a mathematical model of cell salvage was developed. The model was then matched against real clinical cases to gain an understanding of the variables that modify cell salvage efficiency. The model illustrates that cell salvage can be a highly effective method of avoiding blood transfusion.

Gender as a primary predictor of outcome after carotid endarterectomy.

OBJECTIVE: Post hoc analysis results of the North American Symptomatic Carotid Endarterectomy Trial and the Asymptomatic Carotid Atherosclerosis Study suggest that carotid endarterectomy (CEA) may not be as efficacious in women as it is in men. This study was undertaken for the evaluation of whether there is a difference between men and women in early postoperative outcome after CEA and whether such a difference is consistent across other predictors. METHODS: We conducted a retrospective review of all CEAs entered into our departmental registry between January 1, 1989, and November 30, 2000. A total of 3422 CEAs was performed in 3077 consecutive patients. The ratio of men to women was 2:1, and the ratio of patients who were asymptomatic to patients who were symptomatic was 2.3:1. The following in-hospital outcome data were analyzed: transient ischemic attack (TIA), stroke, mortality, combined TIA or stroke, and combined stroke or mortality. Univariate and multivariate analysis results of selected risk factors for an adverse perioperative event were assessed with generalized estimating equation analysis with backwards selection. The following risk factors were considered: gender, preoperative neurologic status, urgency of operation, type of arteriotomy repair, reoperative CEA for recurrent stenosis, history of cardiopulmonary disease, previous coronary artery intervention, simultaneous CEA and coronary bypass grafting surgery, renal failure, and diabetes. RESULTS: Univariate analysis results of gender differences revealed that women were at higher risk for a postoperative TIA or stroke (3.3% for women versus 2.1% for men; odds ratio [OR], 1.6; confidence interval [CI], 1.04 to 2.5; P =.03) and for postoperative stroke or mortality (3.1% for women versus 2.1% for men; OR, 1.6; CI, 1.04 to 2.5; P =.03). Multivariate analysis results showed that female gender was an independent predictor for a postoperative TIA or stroke (OR, 1.7; CI, 1.1 to 2.6; P =.03). Further analysis disclosed that women who were asymptomatic were at greater risk than were men for postoperative stroke or mortality (OR, 2.3; CI, 1.3 to 3.9; P =.003). Conversely, there was no gender association for postoperative stroke or mortality in the consideration of only patients who were symptomatic (OR, 1.0; CI, 0.45 to 2.1; P =.95). The interaction between women and preoperative symptoms approached significance (P =.07) with respect to postoperative stroke and mortality rate, which suggests that the gender effect could be influenced by the clinical presentation. CONCLUSION: The combined TIA or stroke and stroke or mortality rates are higher in women as compared with men in the postoperative period, but these risks remain acceptable when CEA is performed for appropriate indications. The interaction between symptoms and gender suggests that, in patients who are asymptomatic, women are more likely than are men to have early complications. However, there is no gender difference in patients who are symptomatic. Therefore, despite a low postoperative complication rate, CEA is appropriate in both women who are asymptomatic and women who are symptomatic only if the postoperative TIA, stroke, and mortality rates are appreciably lower than in the natural history of medical management of these patients.